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Sample records for 3d qsar models

  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. Exploring conformational search protocols for ligand-based virtual screening and 3-D QSAR modeling.

    PubMed

    Cappel, Daniel; Dixon, Steven L; Sherman, Woody; Duan, Jianxin

    2015-02-01

    3-D ligand conformations are required for most ligand-based drug design methods, such as pharmacophore modeling, shape-based screening, and 3-D QSAR model building. Many studies of conformational search methods have focused on the reproduction of crystal structures (i.e. bioactive conformations); however, for ligand-based modeling the key question is how to generate a ligand alignment that produces the best results for a given query molecule. In this work, we study different conformation generation modes of ConfGen and the impact on virtual screening (Shape Screening and e-Pharmacophore) and QSAR predictions (atom-based and field-based). In addition, we develop a new search method, called common scaffold alignment, that automatically detects the maximum common scaffold between each screening molecule and the query to ensure identical coordinates of the common core, thereby minimizing the noise introduced by analogous parts of the molecules. In general, we find that virtual screening results are relatively insensitive to the conformational search protocol; hence, a conformational search method that generates fewer conformations could be considered "better" because it is more computationally efficient for screening. However, for 3-D QSAR modeling we find that more thorough conformational sampling tends to produce better QSAR predictions. In addition, significant improvements in QSAR predictions are obtained with the common scaffold alignment protocol developed in this work, which focuses conformational sampling on parts of the molecules that are not part of the common scaffold. PMID:25408244

  3. 2D and 3D QSAR models for identifying diphenylpyridylethanamine based inhibitors against cholesteryl ester transfer protein.

    PubMed

    Chen, Meimei; Yang, Xuemei; Lai, Xinmei; Gao, Yuxing

    2015-10-15

    Cholesteryl ester transfer protein (CETP) inhibitors hold promise as new agents against coronary heart disease. Molecular modeling techniques such as 2D-QSAR and 3D-QSAR analysis were applied to establish models to distinguish potent and weak CETP inhibitors. 2D and 3D QSAR models-based a series of diphenylpyridylethanamine (DPPE) derivatives (newly identified as CETP inhibitors) were then performed to elucidate structural and physicochemical requirements for higher CETP inhibitory activity. The linear and spline 2D-QSAR models were developed through multiple linear regression (MLR) and support vector machine (SVM) methods. The best 2D-QSAR model obtained by SVM gave a high predictive ability (R(2)train=0.929, R(2)test=0.826, Q(2)LOO=0.780). Also, the 2D-QSAR models uncovered that SlogP_VSA0, E_sol and Vsurf_DW23 were important features in defining activity. In addition, the best 3D-QSAR model presented higher predictive ability (R(2)train=0.958, R(2)test=0.852, Q(2)LOO=0.734) based on comparative molecular field analysis (CoMFA). Meanwhile, the derived contour maps from 3D-QSAR model revealed the significant structural features (steric and electronic effects) required for improving CETP inhibitory activity. Consequently, twelve newly designed DPPE derivatives were proposed to be robust and potent CETP inhibitors. Overall, these derived models may help to design novel DPPE derivatives with better CETP inhibitory activity. PMID:26346366

  4. The continuous molecular fields approach to building 3D-QSAR models.

    PubMed

    Baskin, Igor I; Zhokhova, Nelly I

    2013-05-01

    The continuous molecular fields (CMF) approach is based on the application of continuous functions for the description of molecular fields instead of finite sets of molecular descriptors (such as interaction energies computed at grid nodes) commonly used for this purpose. These functions can be encapsulated into kernels and combined with kernel-based machine learning algorithms to provide a variety of novel methods for building classification and regression structure-activity models, visualizing chemical datasets and conducting virtual screening. In this article, the CMF approach is applied to building 3D-QSAR models for 8 datasets through the use of five types of molecular fields (the electrostatic, steric, hydrophobic, hydrogen-bond acceptor and donor ones), the linear convolution molecular kernel with the contribution of each atom approximated with a single isotropic Gaussian function, and the kernel ridge regression data analysis technique. It is shown that the CMF approach even in this simplest form provides either comparable or enhanced predictive performance in comparison with state-of-the-art 3D-QSAR methods. PMID:23719959

  5. DYNAMIC 3D QSAR TECHNIQUES: APPLICATIONS IN TOXICOLOGY

    EPA Science Inventory

    Two dynamic techniques recently developed to account for conformational flexibility of chemicals in 3D QSARs are presented. In addition to the impact of conformational flexibility of chemicals in 3D QSAR models, the applicability of various molecular descriptors is discussed. The...

  6. Local intersection volume: a new 3D descriptor applied to develop a 3D-QSAR pharmacophore model for benzodiazepine receptor ligands.

    PubMed

    Verli, Hugo; Albuquerque, Magaly Girão; Bicca de Alencastro, Ricardo; Barreiro, Eliezer J

    2002-03-01

    In this work, we have developed a new descriptor, named local intersection volume (LIV), in order to compose a 3D-QSAR pharmacophore model for benzodiazepine receptor ligands. The LIV can be classified as a 3D local shape descriptor in contraposition to the global shape descriptors. We have selected from the literature 49 non-benzodiazepine compounds as a training data set and the model was obtained and evaluated by genetic algorithms (GA) and partial least-squares (PLS) methods using LIVs as descriptors. The LIV 3D-QSAR model has a good predictive capacity according the cross-validation test by "leave-one-out" procedure (Q(2)=0.72). The developed model was compared to a comprehensive and extensive SAR pharmacophore model, recently proposed by Cook and co-workers, for benzodiazepine receptor ligands [J. Med. Chem. 43 (2000) 71]. It showed a relevant correlation with the pharmacophore groups pointed out in that work. Our LIV 3D-QSAR model was also able to predict affinity values for a series of nine compounds (test data set) that was not included into the training data set. PMID:11900866

  7. Pharmacophore modeling, 3D-QSAR and docking study of 2-phenylpyrimidine analogues as selective PDE4B inhibitors.

    PubMed

    Tripuraneni, Naga Srinivas; Azam, Mohammed Afzal

    2016-04-01

    Pharmacophore modeling, molecular docking, and molecular dynamics (MD) simulation studies have been performed, to explore the putative binding modes of 2-phenylpyrimidine series as PDE4B selective inhibitors. A five point pharmacophore model was developed using 87 molecules having pIC50 ranging from 8.52 to 5.07. The pharmacophore hypothesis yielded a statistically significant 3D-QSAR model, with a high correlation coefficient (R(2)=0.918), cross validation coefficient (Q(2)=0.852), and F value (175) at 4 component PLS factor. The external validation indicated that our QSAR model possessed high predictive power (R(2)=0.70). The generated model was further validated by enrichment studies using the decoy test. To evaluate the effectiveness of docking protocol in flexible docking, we have selected crystallographic bound compound to validate our docking procedure as evident from root mean square deviation. A 10ns molecular dynamics simulation confirmed the docking results of both stability of the 1XMU-ligand complex and the presumed active conformation. Further, similar orientation was observed between the superposition of the conformations of 85 after MD simulation and best XP-docking pose; MD simulation and 3D-QSAR pose; best XP-docking and 3D-QSAR poses. Outcomes of the present study provide insight in designing novel molecules with better PDE4B selective inhibitory activity. PMID:26804643

  8. 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.

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

    PubMed

    Kim, J; Lee, C; Chong, Y

    2009-01-01

    Influenza endonucleases have appeared as an attractive target of antiviral therapy for influenza infection. With the purpose of designing a novel antiviral agent with enhanced biological activities against influenza endonuclease, a three-dimensional quantitative structure-activity relationships (3D-QSAR) model was generated based on 34 influenza endonuclease inhibitors. The comparative molecular similarity index analysis (CoMSIA) with a steric, electrostatic and hydrophobic (SEH) model showed the best correlative and predictive capability (q(2) = 0.763, r(2) = 0.969 and F = 174.785), which provided a pharmacophore composed of the electronegative moiety as well as the bulky hydrophobic group. The CoMSIA model was used as a pharmacophore query in the UNITY search of the ChemDiv compound library to give virtual active compounds. The 3D-QSAR model was then used to predict the activity of the selected compounds, which identified three compounds as the most likely inhibitor candidates. PMID:19343586

  10. Predictive Modeling of Antioxidant Coumarin Derivatives Using Multiple Approaches: Descriptor-Based QSAR, 3D-Pharmacophore Mapping, and HQSAR.

    PubMed

    Mitra, Indrani; Saha, Achintya; Roy, Kunal

    2013-03-01

    The inability of the systemic antioxidants to alleviate the exacerbation of free radical formation from metabolic outputs and environmental pollutants claims an urgent demand for the identification and design of new chemical entities with potent antioxidant activity. In the present work, different QSAR approaches have been utilized for identifying the essential structural attributes imparting a potential antioxidant activity profile of the coumarin derivatives. The descriptor-based QSAR model provides a quantitative outline regarding the structural prerequisites of the molecules, while 3D pharmacophore and HQSAR models emphasize the favourable spatial arrangement of the various chemical features and the crucial molecular fragments, respectively. All the models infer that the fused benzene ring and the oxygen atom of the pyran ring constituting the parent coumarin nucleus capture the prime pharmacophoric features, imparting superior antioxidant activity to the molecules. The developed models may serve as indispensable query tools for screening untested molecules belonging to the class of coumarin derivatives. PMID:23641329

  11. 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

  12. Structure based 3D-QSAR studies of Interleukin-2 inhibitors: Comparing the quality and predictivity of 3D-QSAR models obtained from different alignment methods and charge calculations.

    PubMed

    Halim, Sobia Ahsan; Zaheer-ul-Haq

    2015-08-01

    Interleukin-2 is an essential cytokine in an innate immune response, and is a promising drug target for several immunological disorders. In the present study, structure-based 3D-QSAR modeling was carried out via Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Index Analysis (CoMSIA) methods. Six different partial charge calculation methods were used in combination with two different alignment methods to scrutinize their effects on the predictive power of 3D-QSAR models. The best CoMFA and CoMSIA models were obtained with the AM1 charges when used with co-conformer based substructure alignment (CCBSA) method. The obtained models posses excellent correlation coefficient value and also exhibited good predictive power (for CoMFA: q(2)=0.619; r(2)=0.890; r(2)Pred=0.765 and for CoMSIA: q(2)=0.607; r(2)=0.884; r(2)Pred=0.655). The developed models were further validated by using a set of another sixteen compounds as external test set 2 and both models showed strong predictive power with r(2)Pred=>0.8. The contour maps obtained from these models better interpret the structure activity relationship; hence the developed models would help to design and optimize more potent IL-2 inhibitors. The results might have implications for rational design of specific anti-inflammatory compounds with improved affinity and selectivity. PMID:26051521

  13. Automatic generation of alignments for 3D QSAR analyses.

    PubMed

    Jewell, N E; Turner, D B; Willett, P; Sexton, G J

    2001-01-01

    Many 3D QSAR methods require the alignment of the molecules in a dataset, which can require a fair amount of manual effort in deciding upon a rational basis for the superposition. This paper describes the use of FBSS, a program for field-based similarity searching in chemical databases, for generating such alignments automatically. The CoMFA and CoMSIA experiments with several literature datasets show that the QSAR models resulting from the FBSS alignments are broadly comparable in predictive performance with the models resulting from manual alignments. PMID:11774998

  14. 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...

  15. 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.

  16. Vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors: development and validation of predictive 3-D QSAR models through extensive ligand- and structure-based approaches.

    PubMed

    Ragno, Rino; Ballante, Flavio; Pirolli, Adele; Wickersham, Richard B; Patsilinakos, Alexandros; Hesse, Stéphanie; Perspicace, Enrico; Kirsch, Gilbert

    2015-08-01

    Vascular endothelial growth factor receptor-2, (VEGFR-2), is a key element in angiogenesis, the process by which new blood vessels are formed, and is thus an important pharmaceutical target. Here, 3-D quantitative structure-activity relationship (3-D QSAR) were used to build a quantitative screening and pharmacophore model of the VEGFR-2 receptors for design of inhibitors with improved activities. Most of available experimental data information has been used as training set to derive optimized and fully cross-validated eight mono-probe and a multi-probe quantitative models. Notable is the use of 262 molecules, aligned following both structure-based and ligand-based protocols, as external test set confirming the 3-D QSAR models' predictive capability and their usefulness in design new VEGFR-2 inhibitors. From a survey on literature, this is the first generation of a wide-ranging computational medicinal chemistry application on VEGFR2 inhibitors. PMID:26194852

  17. 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

  18. 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. PMID:26416560

  19. 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

  20. Development and validation of hydrophobic molecular fields derived from the quantum mechanical IEF/PCM-MST solvation models in 3D-QSAR.

    PubMed

    Ginex, Tiziana; Muñoz-Muriedas, Jordi; Herrero, Enric; Gibert, Enric; Cozzini, Pietro; Luque, F J

    2016-05-15

    Since the development of structure-activity relationships about 50 years ago, 3D-QSAR methods belong to the most refined ligand-based in silico techniques for prediction of biological data using physicochemical molecular fields. In this scenario, this study reports the development and validation of quantum mechanical (QM)-based hydrophobic descriptors derived from the parametrized MST continuum solvation model to be used in 3D-QSAR studies within the framework of the Hydrophobic Pharmacophore (HyPhar) method. To this end, five sets of compounds reported in the literature (dopamine D2/D4 antagonists, antifungal 2-aryl-4-chromanones, and inhibitors of GSK-3, cruzain and thermolysin) have been revisited. The results derived from the QM/MST-based hydrophobic descriptors have been compared with previous CoMFA and CoMSIA studies, and examined in light of the available X-ray crystallographic structures of the targets. The analysis reveals that the combination of electrostatic and nonelectrostatic components of the octanol/water partition coefficient yields pharmacophoric models fully comparable with the predictive potential of standard 3D-QSAR techniques. Moreover, the graphical representation of the hydrophobic maps provides a direct linkage with the pattern of interactions found in crystallographic structures. Overall, the introduction of the QM/MST-based descriptors, which could be easily adapted to other continuum solvation formalisms, paves the way to novel computational strategies for disclosing structure-activity relationships in drug design. © 2016 Wiley Periodicals, Inc. PMID:26813046

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

    PubMed

    Lee, Sehan; Barron, Mace G

    2015-11-01

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

  2. Binding affinity prediction of novel estrogen receptor ligands using receptor-based 3-D QSAR methods.

    PubMed

    Sippl, Wolfgang

    2002-12-01

    We have recently reported the development of a 3-D QSAR model for estrogen receptor ligands showing a significant correlation between calculated molecular interaction fields and experimentally measured binding affinity. The ligand alignment obtained from docking simulations was taken as basis for a comparative field analysis applying the GRID/GOLPE program. Using the interaction field derived with a water probe and applying the smart region definition (SRD) variable selection procedure, a significant and robust model was obtained (q(2)(LOO)=0.921, SDEP=0.345). To further analyze the robustness and the predictivity of the established model several recently developed estrogen receptor ligands were selected as external test set. An excellent agreement between predicted and experimental binding data was obtained indicated by an external SDEP of 0.531. Two other traditionally used prediction techniques were applied in order to check the performance of the receptor-based 3-D QSAR procedure. The interaction energies calculated on the basis of receptor-ligand complexes were correlated with experimentally observed affinities. Also ligand-based 3-D QSAR models were generated using program FlexS. The interaction energy-based model, as well as the ligand-based 3-D QSAR models yielded models with lower predictivity. The comparison with the interaction energy-based model and with the ligand-based 3-D QSAR models, respectively, indicates that the combination of receptor-based and 3-D QSAR methods is able to improve the quality of prediction. PMID:12413831

  3. 3D-QSAR studies on Plasmodium falciparam proteins: a mini-review.

    PubMed

    Divakar, Selva; Hariharan, Sivaram

    2015-01-01

    3D-QSAR has become a very important tool in the field of Drug Discovery, especially in important areas like malarial research. The 3D-QSAR is principally a ligand-based drug design but the bioactive conformation of the ligand can also be taken into account in constructing a 3D-QSAR model. The induction of receptor-based 3D-QSAR has been proven to give more robust statistical models. In this review, we have discussed the various 3D-QSAR works done so far which were aimed at combating malaria caused by Plasmodium falciparam. We have also discussed the various enzymes/receptors (targets) in Plasmodium falciparam for which the 3D-QSAR had been generated. The enzymes - wild and mutated dihydrofolate reductase, enoyl acyl protein carrier protein reductase, farnesyltransferase, cytochrome bc1, and falcipains were the major targets for pharmacophore-based drug design. Apart from the above-mentioned targets there were many scaffolds for which the target macromolecule was undefined and could have single/multiple targets. The generated 3D-QSAR model can be used to identify hits by screening the pharmacophore against a chemical library. In this review, the hits identified against various targets of plasmodium falciparam that have been discussed along with their basic scaffold. The various software programs and chemical databases that have been used in the generation of 3D-QSAR and screening were given. From this review, we understand that there is a considerable need to develop novel scaffolds that are different from the existing ligands to overcome cross-resistance. PMID:25543683

  4. Development of docking-based 3D QSAR models for the design of substituted quinoline derivatives as human dihydroorotate dehydrogenase (hDHODH) inhibitors.

    PubMed

    Vyas, V K; Ghate, M

    2013-08-01

    This study has investigated docking-based 3D quantitative structure-activity relationships (QSARs) for a range of quinoline carboxylic acid derivatives by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). A docking study has shown that most of the compounds formed H-bonds with Arg136 and Gln47, which have already been shown to be essential for the binding of ligands at the active site of the hydroorotate dehydrogenase adenovirus (hDHODH). Bioactive conformations of all the molecules obtained from the docking study were used for the 3D QSAR study. The best CoMFA and CoMSIA models were obtained for the training set and were found to be statistically significant, with cross-validated coefficients (q²) of 0.672 and 0.613, r² cv of 0.635 and 0.598 and coefficients of determination (r²) of 0.963 and 0.896, respectively. Both models were validated by a test set of 15 compounds, giving satisfactory predicted correlation coefficients (r² pred) of 0.824 and 0.793 for the CoMFA and CoMSIA models, respectively. From the docking-based 3D QSAR study we designed 34 novel quinoline-based compounds and performed structure-based virtual screening. Finally, in silico pharmacokinetics and toxicities were predicted for 24 of the best docked molecules. The study provides valuable information for the understanding of interactions between hDHODH and the novel compounds. PMID:23714018

  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. Ligand-based Pharmacophore Modeling; Atom-based 3D-QSAR Analysis and Molecular Docking Studies of Phosphoinositide-Dependent Kinase-1 Inhibitors

    PubMed Central

    Kirubakaran, P.; Muthusamy, K.; Singh, K. H. D.; Nagamani, S.

    2012-01-01

    Phosphoinositide-dependent kinase-1 plays a vital role in the PI3-kinase signaling pathway that regulates gene expression, cell cycle growth and proliferation. The common human cancers include lung, breast, blood and prostate possess over stimulation of the phosphoinositide-dependent kinase-1 signaling and making phosphoinositide-dependent kinase-1 an interesting therapeutic target in oncology. A ligand-based pharmacophore and atom-based 3D-QSAR studies were carried out on a set of 82 inhibitors of PDK1. A six point pharmacophore with two hydrogen bond acceptors (A), three hydrogen bond donors (D) and one hydrophobic group (H) was obtained. The pharmacophore hypothesis yielded a 3D-QSAR model with good partial least square statistics results. The training set correlation is characterized by partial least square factors (R2 = 0.9557, SD = 0.2334, F = 215.5, P = 1.407e-32). The test set correlation is characterized by partial least square factors (Q2 ext = 0.7510, RMSE = 0.5225, Pearson-R =0.8676). The external validation indicated that our QSAR model possess high predictive power with good value of 0.99 and value of 0.88. The docking results show the binding orientations of these inhibitors at active site amino acid residues (Ala162, Thr222, Glu209 and Glu166) of phosphoinositide-dependent kinase-1 protein. The binding free energy interactions of protein-ligand complex have been calculated, which plays an important role in molecular recognition and drug design approach. PMID:23325995

  7. 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

  8. Molecular modelling on small molecular CDK2 inhibitors: an integrated approach using a combination of molecular docking, 3D-QSAR and pharmacophore modelling.

    PubMed

    Yuan, H; Liu, H; Tai, W; Wang, F; Zhang, Y; Yao, S; Ran, T; Lu, S; Ke, Z; Xiong, X; Xu, J; Chen, Y; Lu, T

    2013-10-01

    Cyclin-dependent kinase 2 (CDK2) has been identified as an important target for developing novel anticancer agents. Molecular docking, three-dimensional quantitative structure-activity relationship (3D-QSAR) and pharmacophore modelling were combined with the ultimate goal of studying the structure-activity relationship of CDK2 inhibitors. The comparative molecular similarity indices analysis (CoMSIA) model constructed based on a set of 3-aminopyrazole derivatives as CDK2 inhibitors gave statistically significant results (q (2) = 0.700; r (2) = 0.982). A HypoGen pharmacophore model, constructed using diverse CDK2 inhibitors, also showed significant statistics ([Formula: see text]Cost = 61.483; RMSD = 0.53; Correlation coefficient = 0.98). The small residues and error values between the estimated and experimental activities of the training and test set compounds proved their strong capability of activity prediction. The structural insights obtained from these two models were consistent with each other. The pharmacophore model summarized the important pharmacophoric features required for protein-ligand binding. The 3D contour maps in combination with the comprehensive pharmacophoric features helped to better interpret the structure-activity relationship. The results will be beneficial for the discovery and design of novel CDK2 inhibitors. The simplicity of this approach provides expansion to its applicability in optimizing other classes of small molecular CDK2 inhibitors. PMID:23941641

  9. Pharmacophore model prediction, 3D-QSAR and molecular docking studies on vinyl sulfones targeting Nrf2-mediated gene transcription intended for anti-Parkinson drug design.

    PubMed

    Athar, Mohd; Lone, Mohsin Yousuf; Khedkar, Vijay M; Jha, Prakash Chandra

    2016-06-01

    Despite intense research efforts towards clinical and molecular causes of Parkinson disease (PD), the etiology of disease still remains unclear. However, recent studies have provided ample evidences that the oxidative stress is the key player that contributes a lot to dopaminergic (DAergic) neurodegeneration in brain. It is due to the discrepancy of antioxidant defence system of which nuclear factor erythroid 2-related factor 2 (Nrf2) signalling is of central contour. In the current study, potent heme oxygenase-1 agonists (Nrf2 signalling regulator), vinyl sulfones, were selected and an optimal pharmacophore model was brought forth which was examined using a decoy set by atom-based 3D-QSAR. The best four-feature model consists of two hydrogen bond acceptors and two aromatic rings, which has the highest correlation coefficient, R(2) = .71 and [Formula: see text] = .73 in QSAR. These ligands were further studied for molecular docking with Nrf2-keap protein to gain insight into the major binding motifs followed by analysing pharmacokinetic properties to evaluate their bioavailability dominance. From this study, it is concluded that vinyl sulfones could be ideal compounds for targeting Nrf2 pathway which in turn halt the PD progression. Hence, these can be considered as potential leads for drug development against the same. PMID:26222438

  10. 3D QSAR and docking study of gliptin derivatives as DPP-IV inhibitors.

    PubMed

    Agrawal, Ritesh; Jain, Pratima; Dikshit, Subodh Narayan; Bahare, Radhe Shyam

    2013-05-01

    The article describes the development of a robust pharmacophore model and the investigation of structure activity relationship analysis of 46 xanthine derivatives reported for DPP-IV inhibition using PHASE module of Schrodinger software. The present works also encompasses molecular interaction of 46 xanthine ligand through maestro 8.5 software. The QSAR study comprises AHHR.7 pharmacophore hypothesis, which elaborates the three points, e.g. one hydrogen bond acceptor (A), two hydrophobic rings (H) and one aromatic ring (R). The discrete geometries as pharmacophoric feature were developed and the generated pharmacophore model was used to derive a predictive atom-based 3D QSAR model for the studied data set. The obtained 3D QSAR model has an excellent correlation coefficient value (r(2)= 0.9995) along with good statistical significance which is indicated by high Fisher ratio (F= 8537.4). The model also exhibits good predictive power confirmed by the high value of cross validated correlation coefficient (q(2) = 0.6919). The QSAR model suggests that hydrophobic character is crucial for the DPP-IV inhibitory activity exhibited by these compounds and inclusion of hydrophobic substituents will enhance the DPP-IV inhibition. In addition to the hydrophobic character, electron withdrawing groups positively contribute to the DPP-IV inhibition potency. The findings of the QSAR study provide a set of guidelines for designing compounds with better DPP-IV inhibitory potency. PMID:23305140

  11. Synthesis, antifeedant activity against Coleoptera and 3D QSAR study of alpha-asarone derivatives.

    PubMed

    Łozowicka, B; Kaczyński, P; Magdziarz, T; Dubis, A T

    2014-01-01

    For the first time, a set of 56 compounds representing structural derivatives of naturally occurring alpha-asarone as an antifeedants against stored product pests Sitophilus granarius L., Trogoderma granarium Ev., and Tribolium confusum Duv., were subjected to the 3D QSAR studies. Three-dimensional quantitative structure-activity relationships (3D-QSAR) for 56 compounds, including 15 newly synthesized, were performed using comparative molecular field analysis s-CoMFA and SOM-CoMSA techniques. QSAR was conducted based on a combination of biological activity (against Coleoptera larvae and beetles) and various geometrical, topological, quantum-mechanical, electronic, and chromatographic descriptors. The CoMSA formalism coupled with IVE (CoMSA-IVE) allowed us to obtain highly predictive models for Trogoderma granarium Ev. larvae. We have found that this novel method indicates a clear molecular basis for activity and lipophilicity. This investigation will facilitate optimization of the design of new potential antifeedants. PMID:24601760

  12. 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

  13. 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

  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. Alpha(1) adrenoceptor subtype selectivity. 3D-QSAR models for a new class of alpha(1) adrenoceptor antagonists derived from the novel antipsychotic sertindole.

    PubMed

    Balle, Thomas; Andersen, Kim; Søby, Karina Krøjer; Liljefors, Tommy

    2003-06-01

    Receptor-binding affinities for the alpha(1) adrenoceptor subtypes alpha(1a), alpha(1b) and alpha(1d) for a series of 39 alpha(1) adrenoceptor antagonists derived from the antipsychotic sertindole are reported. The SAR of the compounds with respect to affinity for the alpha(1a), alpha(1b) and alpha(1d) adrenoceptor subtypes as well as affinity obtained by an alpha(1) assay (rat brain membranes) were investigated using a 3D-QSAR approach based on the GRID/GOLPE methodology. Good statistics (r(2)=0.91-0.96; q(2)=0.65-0.73) were obtained with the combination of the water (OH2) and methyl (C3) probes. The combination of steric repulsion and electrostatic attractions explain the affinities of the included molecules. The adrenergic alpha(1a) receptor seems to be more tolerant to large substituents in the area between the indole 5- and 6-positions compared to the adrenergic alpha(1b) and alpha(1d) receptor subtypes. There seems to be minor differences in the position of areas in the alpha(1b) receptor compared to alpha(1a) and alpha(1d) receptors where electrostatic interaction between the molecules and the receptor (OH2 probe) contribute to increased affinity. These observations may be used in the design of new subtype selective compounds. In addition, the model based on biological data from an alpha(1) assay (rat brain membranes) resembles the model for the alpha(1b) adrenoceptor subtype. PMID:12676239

  16. 3D QSAR of aminophenyl benzamide derivatives as histone deacetylase inhibitors.

    PubMed

    Mahipal; Tanwar, Om Prakash; Karthikeyan, C; Moorthy, N S Hari Narayana; Trivedi, Piyush

    2010-09-01

    The article describes the development of a robust pharmacophore model and the investigation of structure activity relationship analysis of 48 aminophenyl benzamide derivatives reported for Histone Deacetylase (HDAC) inhibition using PHASE module of Schrodinger software. A five point pharmacophore model consisting of two aromatic rings (R), two hydrogen bond donors (D) and one hydrogen bond acceptor (A) with discrete geometries as pharmacophoric features was developed and the generated pharmacophore model was used to derive a predictive atom-based 3D QSAR model for the studied dataset. The obtained 3D QSAR model has an excellent correlation coefficient value (r(2)=0.99) along with good statistical significance as shown by high Fisher ratio (F=631.80). The model also exhibits good predictive power confirmed by the high value of cross validated correlation coefficient (q(2) = 0.85). The QSAR model suggests that hydrophobic character is crucial for the HDAC inhibitory activity exhibited by these compounds and inclusion of hydrophobic substituents will enhance the HDAC inhibition. In addition to the hydrophobic character, hydrogen bond donating groups positively contributes to the HDAC inhibition whereas electron withdrawing groups has a negative influence in HDAC inhibitory potency. The findings of the QSAR study provide a set of guidelines for designing compounds with better HDAC inhibitory potency. PMID:20977417

  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. Pharmacophore modeling, 3D-QSAR, and docking study of pyrozolo[1,5-a]pyridine/4,4-dimethylpyrazolone analogues as PDE4 selective inhibitors.

    PubMed

    Tripuraneni, Naga Srinivas; Azam, Mohammed Afzal

    2015-11-01

    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 pyrozolo[1,5-a]pyridine/4,4-dimethylpyrazolone analogues. A five point pharmacophore model was developed using 52 molecules having pIC50 values ranging from 9.959 to 3.939. The best predictive pharmacophoric hypothesis AHHRR.3 was characterized by survival score (2.944), cross validated (r(2) = 0.8147), regression coefficient (R(2) = 0.9545) and Fisher ratio (F =173) with 4 component PLS factor. Results explained that one hydrogen bond acceptor, two aromatic rings and two hydrophobic groups are crucial for the PDE4 inhibition. The docking studies of all selected inhibitors in the active site of PDE4 showed crucial hydrogen bond interactions with Asp392, Asn395 Tyr233, and Gln443 residues. The pharmacophoric features R15 and R16 exhibited π-π stacking with His234, Phe414, and Phe446 residues. The generated model was further validated by carrying out the decoy test. The binding free energies of these inhibitors in the catalytic domain of 1XMU were calculated by the molecular mechanics/generalized Born surface area VSGB 2.0 method. The results of molecular dynamics simulation confirmed the extra precision docking-predicted priority for binding sites, the accuracy of docking, and the reliability of active conformations. Pyrozolo[1,5-a]pyridine/4,4-dimethylpyrazolone analogues in this study showed lower binding affinity toward PDE3A in comparison to PDE4. Outcomes of the present study provide insight in designing novel molecules with better PDE4 inhibitory activity. Graphical Abstract Pyrozolo[1,5-a]pyridines/4,4-dimethylpyrazolones. PMID:26499496

  19. 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.

  20. 3D QSAR Pharmacophore Modeling, in Silico Screening, and Density Functional Theory (DFT) Approaches for Identification of Human Chymase Inhibitors

    PubMed Central

    Arooj, Mahreen; Thangapandian, Sundarapandian; John, Shalini; Hwang, Swan; Park, Jong Keun; Lee, Keun Woo

    2011-01-01

    Human chymase is a very important target for the treatment of cardiovascular diseases. Using a series of theoretical methods like pharmacophore modeling, database screening, molecular docking and Density Functional Theory (DFT) calculations, an investigation for identification of novel chymase inhibitors, and to specify the key factors crucial for the binding and interaction between chymase and inhibitors is performed. A highly correlating (r = 0.942) pharmacophore model (Hypo1) with two hydrogen bond acceptors, and three hydrophobic aromatic features is generated. After successfully validating “Hypo1”, it is further applied in database screening. Hit compounds are subjected to various drug-like filtrations and molecular docking studies. Finally, three structurally diverse compounds with high GOLD fitness scores and interactions with key active site amino acids are identified as potent chymase hits. Moreover, DFT study is performed which confirms very clear trends between electronic properties and inhibitory activity (IC50) data thus successfully validating “Hypo1” by DFT method. Therefore, this research exertion can be helpful in the development of new potent hits for chymase. In addition, the combinational use of docking, orbital energies and molecular electrostatic potential analysis is also demonstrated as a good endeavor to gain an insight into the interaction between chymase and inhibitors. PMID:22272131

  1. 2D and 3D-QSAR studies on antiproliferative thiazolidine analogs

    NASA Astrophysics Data System (ADS)

    Liao, Si Yan; Qian, Li; Chen, Jin Can; Lu, Hai Liang; Zheng, Kang Cheng

    Two-dimensional (2D) and three-dimensional (3D) quantitative structure-activity relationships (QSARs) of 22 thiazolidine analogs with antiproliferative activity expressed as pIC50, which is defined as the negative value of the logarithm of necessary molar concentration of these compounds to cause 50% growth inhibition against melanoma cell lines WM-164, have been studied by using a combined method of the DFT, MM2 and statistics for 2D, as well as the comparative molecular field analysis (CoMFA) method for 3D. The established 2D-QSAR model in training set comprised of random 18 compounds shows not only significant statistical quality, but also predictive ability, with the square of adjusted correlation coefficient (R2A = 0.832) and the square of the cross-validation coefficient (q2 = 0.803). The same model was further applied to predict pIC50 values of the four compounds in the test set, and the resulting R2pred reaching 0.784, further confirms that this 2D-QSAR model has high predictive ability. The 3D-QSAR model also shows good correlative and predictive capabilities in terms of R2 (0.956) and q2 (0.615) obtained from CoMFA model. Further, the robustness of the CoMFA model was verified by bootstrapping analysis (100 runs) with R2bs (0.979) and SDbs (0.056). It is very interesting to find that the results from 2D- and 3D-QSAR analyses accord with each other, and they all show that the steric interaction plays a crucial role in determining the cytotoxicities of the compounds, and that selecting a moderate-size or appropriate-hydrophobicity substituent R as well as increasing the negative charges of C4 on phenyl ring at the same time are advantageous to improving the cytotoxicity. Such results can offer some useful theoretical references for directing the molecular design and understanding the action mechanism of this kind of compound with antiproliferative activity.

  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. 3-D QSARS FOR RANKING AND PRIORITIZATION OF LARGE CHEMICAL DATASETS: AN EDC CASE STUDY

    EPA Science Inventory

    The COmmon REactivity Pattern (COREPA) approach is a three-dimensional structure activity (3-D QSAR) technique that permits identification and quantification of specific global and local steroelectronic characteristics associated with a chemical's biological activity. It goes bey...

  4. 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.

  5. Molecular modeling studies of [6,6,5] Tricyclic Fused Oxazolidinones as FXa inhibitors using 3D-QSAR, Topomer CoMFA, molecular docking and molecular dynamics simulations.

    PubMed

    Xu, Cheng; Ren, Yujie

    2015-10-15

    Coagulation factor Xa (Factor Xa, FXa) is a particularly promising target for novel anticoagulant therapy. The first oral factor Xa inhibitor has been approved in the EU and Canada in 2008. In this work, 38 [6,6,5] Tricyclic Fused Oxazolidinones were studied using a combination of molecular modeling techniques including three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking, molecular dynamics and Topomer CoMFA (comparative molecular field analysis) were used to build 3D-QSAR models. The results show that the best CoMFA model has q(2)=0.511 and r(2)=0.984, the best CoMSIA (comparative molecular similarity indices analysis) model has q(2)=0.700 and r(2)=0.993 and the Topomer CoMFA analysis has q(2)=0.377 and r(2)=0.886. The results indicated the steric, hydrophobic, H-acceptor and electrostatic fields play key roles in models. Molecular docking and molecular dynamics explored the binding relationship of the ligand and the receptor protein. PMID:26343829

  6. Validation of formylchromane derivatives as protein tyrosine phosphatase 1B inhibitors by pharmacophore modeling, atom-based 3D-QSAR and docking studies.

    PubMed

    Malla, Priyanka; Kumar, Rajnish; Kumar, Manoj

    2013-07-01

    Formylchromane derivatives were reported to possess irreversible and selective inhibition on human protein tyrosine phosphatase 1B (PTP 1B). Inhibition of PTP 1B is a molecular level legitimate approach for the management of type 2 diabetes mellitus (T2DM). 3D-QSAR studies were performed on a series of formylchromane derivatives using partial least square (PLS) analysis for correlating molecular architecture of the analogs with their PTP 1B inhibitory activity. A five-point pharmacophore hypothesis with three hydrogen bond acceptors (A) and two aromatic rings (R) as pharmacophoric features was developed using phase module of Schrödinger suite. The hypothesis AAARR.160 was considered as best hypothesis in this study characterized by survival score (3.483), the best cross-validated r² (Q²) (0.774), regression coefficient (0.960), Pearson-R (0.891), and F value (100.3). The results of hypothesis AAARR.160 complimented very closely to interactions witnessed in active site of the ligand-bound complex. The molecular docking simulations into PTP 1B active site also highlighted that biphenyl moiety favorably interacted with amino acid residues lining the lipophilic pocket, and provided hydrophobic interactions with receptor active site. These observations might be useful for further development and optimization of new chemical entities as potential PTP 1B inhibitors prior to its synthesis. PMID:23506477

  7. Exploring clotrimazole-based pharmacophore: 3D-QSAR studies and synthesis of novel antiplasmodial agents.

    PubMed

    Brogi, Simone; Brindisi, Margherita; Joshi, Bhupendra P; Sanna Coccone, Salvatore; Parapini, Silvia; Basilico, Nicoletta; Novellino, Ettore; Campiani, Giuseppe; Gemma, Sandra; Butini, Stefania

    2015-11-15

    We report herein the generation and validation of a 3D-QSAR model based on a set of antimalarials previously described by us and characterized by a clotrimazole-based pharmacophore. A novel series of derivatives was synthesized and showed activity against Plasmodium falciparum chloroquine-sensitive (CQ-S) and chloroquine-resistant (CQ-R) strains. Gratifyingly, compounds 35a-c showed interesting activity against P. falciparum CQ-R strains with improved predicted physico-chemical properties. PMID:26428874

  8. 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

  9. 3D QSAR studies on substituted benzimidazole derivatives as angiotensin II-AT1 receptor antagonist.

    PubMed

    Vyas, Vivek K; Ghate, Manjunath; Chintha, Chetan; Patel, Paresh

    2013-09-01

    This study investigated 3D quantitative structure-activity relationships (QSAR) for a range of substituted benzimidazole derivatives as AngII-AT1 receptor antagonists by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices (CoMSIA). The alignment strategy was used for these compounds by means of Distill function defined in SYBYL X 1.2. The best CoMFA and CoMSIA models were obtained for the training set compounds was statistically significant with leave-one-out (LOO) validation correlation coefficient (q²) of 0.613 and 0.622, cross validated coefficient (r²cv) of 0.617 and 0.607, respectively and conventional coefficient (r²ncv) of 0.886 and 0.859, respectively. Both the models were validated by a test set of 18 compounds giving satisfactory predicted correlation coefficient (r²pred) of 0.714 and 0.549 for CoMFA and CoMSIA models, respectively. Generated 3D QSAR models were used for the prediction of pIC50 of an external dataset of 10 compounds for predictive validation, which gave conventional r² of 0.893 for CoMFA model, and 0.774 for CoMSIA model. We identified some key features in substituted benzimidazole derivatives, such as the importance of lipophilicity and H-bonding at 2- and 5, 6, 7- position of benzimidazole ring, respectively, for good antagonistic activity. CoMFA and CoMSIA models generated in this work provide useful information for the design of new compounds and helped in prediction of antagonistic activity. PMID:24010938

  10. 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.

  11. 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

  12. 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

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

    PubMed

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

    2014-10-01

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

  14. 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

  15. 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.

  16. 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

  17. 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

  18. Synthesis, characterization, antifungal evaluation and 3D-QSAR study of phenylhydrazine substituted tetronic acid derivatives.

    PubMed

    Hu, Ying; Wang, Junjun; Lu, Aimin; Yang, Chunlong

    2014-08-15

    A series of 3-(1-(2-(substituted phenyl)hydrazinyl)alkylidene)furan-2,4(3H,5H)-diones were designed and prepared using two synthetic routes. Their structures were confirmed by FT-IR, (1)H NMR, (13)C NMR, MS, elemental analysis and single-crystal X-ray diffraction. Their bioactivity was evaluated against Botrytis cinerea in vitro. Most target compounds exhibited remarkable antifungal activity. Two compounds 7f and 7h were highly effective and their EC50 values were 0.241 μg/mL and 0.167 μg/mL, respectively, close to that of the control drug procymidone. 3D-QSAR studies of CoMFA and CoMSIA were carried out. Models with good predictive ability were generated with the cross validated q(2) values for CoMFA and CoMSIA being 0.565 and 0.823. Conventional r(2) values were 0.983 and 0.945, respectively. The results provided a practical tool for guiding the design and synthesis of novel and more potent tetronic acid derivatives containing substituted phenylhydrazine moiety. PMID:25042337

  19. A highly predictive 3D-QSAR model for binding to the voltage-gated sodium channel: design of potent new ligands.

    PubMed

    Zha, Congxiang; Brown, George B; Brouillette, Wayne J

    2014-01-01

    A comprehensive comparative molecular field analysis (CoMFA) model for the binding of ligands to the neuronal voltage-gated sodium channel was generated based on 67 diverse compounds. Earlier published CoMFA models for this target provided μM ligands, but the improved model described here provided structurally novel compounds with low nM IC₅₀. For example, new compounds 94 and 95 had IC₅₀ values of 129 and 119 nM, respectively. PMID:24332655

  20. 3D-QSAR studies on CCR2B receptor antagonists: Insight into the structural requirements of (R)-3-aminopyrrolidine series of molecules based on CoMFA/CoMSIA models

    PubMed Central

    Gade, Swetha; Mahmood, Shaik

    2012-01-01

    Objective: Monocyte chemo attractant protein-1 (MCP-1) is a member of the CC-chemokine family and it selectively recruits leukocytes from the circulation to the site of inflammation through binding with the chemotactic cytokine receptor 2B (CCR2B). The recruitment and activation of selected populations of leukocytes is a key feature in a variety of inflammatory conditions. Thus MCP-1 receptor antagonist represents an attractive target for drug discovery. To understand the structural requirements that will lead to enhanced inhibitory potencies, we have carried out 3D-QSAR (quantitative structure–activity relationship) studies on (R)-3-aminopyrrolidine series of molecules as CCR2B receptor antagonists. Materials and Methods: Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on a series of (R)-3-aminopyrrolidine derivatives as antagonists of CCR2B receptor with Sybyl 6.7v. Results: We have derived statistically significant model from 37 molecules and validated it against an external test set of 13 compounds. The CoMFA model yielded a leave one out r2 (r2loo) of 0.847, non-cross-validated r2 (r2ncv) of 0.977, F value of 267.930, and bootstrapped r2 (r2bs) of 0.988. We have derived the standard error of prediction value of 0.367, standard error of estimate 0.141, and a reliable external predictivity, with a predictive r2 (r2pred) of 0.673. While the CoMSIA model yielded an r2loo of 0.719, r2ncv of 0.964,F value of 135.666, r2bs of 0.975, standard error of prediction of 0.512, standard error of estimate of 0.180, and an external predictivity with an r2pred of 0.611. These validation tests not only revealed the robustness of the models but also demonstrated that for our models r2pred, based on the mean activity of test set compounds can accurately estimate external predictivity. Conclusion: The QSAR model gave satisfactory statistical results in terms of q2 and r2 values. We analyzed the contour

  1. 3D QSAR and docking studies of various amido and benzyl-substituted 3-amino-4-(2-cyanopyrrolidide)pyrrolidinyl analogs as DPP-IV inhibitors.

    PubMed

    Agrawal, Ritesh; Jain, Pratima; Dikshit, Subodh Narayan; Jain, Sourabh

    2013-09-01

    The article describes the development of a robust pharmacophore model and the investigation of structure activity relationship analysis of 3-amino-4-(2-cyanopyrrolidide)pyrrolidinyl analogs reported for DPP-IV inhibition using PHASE module of Schrodinger software. The present works also encompass molecular interaction study of 3-amino-4-(2- cyanopyrrolidide)pyrrolidinyl analogs on maestro 8.5 workstation. The Phase study module comprises the five points pharmacophore model (AAHPR.617), consisting two hydrogen bond acceptor (A), one Hydrophobic (H), one Positive(P) and one aromatic ring (R) and with discrete geometries as pharmacophoric feature. The developed pharmacophore model was used to derive a predictive atom-based 3D QSAR model. The obtained 3D QSAR model has an excellent correlation coefficient value (r2=0.9926) along with good statistical significance as shown by high Fisher ratio (F=671.7). The model also exhibits good predictive power, which is confirmed by high value of cross validated correlation coefficient (q2 = 0.7311). The QSAR model suggests that hydrophobic and aromatic characters are crucial for the DPP-IV inhibitory activity. The QSAR model also suggests that the inclusion of hydrophobic substituents would enhance the DPP-IV inhibition. In addition to the hydrogen bond acceptor, hydrophobic character, electro withdrawing character positively contributes to the DPP-IV inhibition. This study provides a set of guidelines for designing compounds with better DPP-IV inhibitory potency. PMID:23607811

  2. 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

  3. Biological evaluation and 3D-QSAR studies of curcumin analogues as aldehyde dehydrogenase 1 inhibitors.

    PubMed

    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

  4. 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

  5. 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.

  6. Ligand-based 3D QSAR analysis of reactivation potency of mono- and bis-pyridinium aldoximes toward VX-inhibited rat acetylcholinesterase.

    PubMed

    Dolezal, Rafael; Korabecny, Jan; Malinak, David; Honegr, Jan; Musilek, Kamil; Kuca, Kamil

    2015-03-01

    To predict unknown reactivation potencies of 12 mono- and bis-pyridinium aldoximes for VX-inhibited rat acetylcholinesterase (rAChE), three-dimensional quantitative structure-activity relationship (3D QSAR) analysis has been carried out. Utilizing molecular interaction fields (MIFs) calculated by molecular mechanical (MMFF94) and quantum chemical (B3LYP/6-31G*) methods, two satisfactory ligand-based CoMFA models have been developed: 1. R(2)=0.9989, Q(LOO)(2)=0.9090, Q(LTO)(2)=0.8921, Q(LMO(20%))(2)=0.8853, R(ext)(2)=0.9259, SDEP(ext)=6.8938; 2. R(2)=0.9962, Q(LOO)(2)=0.9368, Q(LTO)(2)=0.9298, Q(LMO(20%))(2)=0.9248, R(ext)(2)=0.8905, SDEP(ext)=6.6756. High statistical significance of the 3D QSAR models has been achieved through the application of several data noise reduction techniques (i.e. smart region definition SRD, fractional factor design FFD, uninformative/iterative variable elimination UVE/IVE) on the original MIFs. Besides the ligand-based CoMFA models, an alignment molecular set constructed by flexible molecular docking has been also studied. The contour maps as well as the predicted reactivation potencies resulting from 3D QSAR analyses help better understand which structural features are associated with increased reactivation potency of studied compounds. PMID:25588616

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

    PubMed

    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

  8. 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...

  9. 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. PMID:22620261

  10. 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

  11. 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

  12. Predictive QSAR modeling of phosphodiesterase 4 inhibitors.

    PubMed

    Kovalishyn, Vasyl; Tanchuk, Vsevolod; Charochkina, Larisa; Semenuta, Ivan; Prokopenko, Volodymyr

    2012-02-01

    A series of diverse organic compounds, phosphodiesterase type 4 (PDE-4) inhibitors, have been modeled using a QSAR-based approach. 48 QSAR models were compared by following the same procedure with different combinations of descriptors and machine learning methods. QSAR methodologies used random forests and associative neural networks. The predictive ability of the models was tested through leave-one-out cross-validation, giving a Q² = 0.66-0.78 for regression models and total accuracies Ac=0.85-0.91 for classification models. Predictions for the external evaluation sets obtained accuracies in the range of 0.82-0.88 (for active/inactive classifications) and Q² = 0.62-0.76 for regressions. The method showed itself to be a potential tool for estimation of IC₅₀ of new drug-like candidates at early stages of drug development. PMID:22023934

  13. 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

  14. 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

    2016-02-01

    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

  15. 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.

  16. 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

  17. 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…

  18. 3D-QSAR study of tetrahydro-3H-imidazo[4,5-c]pyridine derivatives as VEGFR-2 kinase inhibitors using various charge schemes.

    PubMed

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

    2015-08-01

    Vascular endothelial growth factor-2 receptor (VEGFR-2) kinase is a promising target for the development of novel anticancer drugs. Three-dimensional quantitative structure-activity relationship (3D-QSAR) study was performed on a series of tetrahydro-3H-imidazo[4,5-c]pyridine derivatives to understand the structural basis for VEGFR-2 inhibitory activity. Several 3D-QSAR models were developed using various partial atomic charge schemes. Comparative molecular field analysis (CoMFA) and Comparative molecular similarity indices analysis (CoMSIA) methods were employed to derive these models. The CoMFA models performed better than the CoMSIA models. The reliable CoMFA model was obtained with the Gasteiger-Marsili charge scheme. The model produced statistically significant results with a cross-validated correlation coefficient (q(2)) of 0.635 and a coefficient of determination (r(2)) of 0.930. The model showed reasonable predictive power with predictive correlation coefficient ([Formula: see text]) of 0.582. Robustness of the model was further checked by leave-five-out cross-validation, bootstrapping and progressive scrambling analysis. The model was found to be statistically robust and expected to assist in the design of novel compounds with enhanced VEGFR-2 inhibitory activity. PMID:25874606

  19. 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

  20. Analysis of B-Raf[Formula: see text] inhibitors using 2D and 3D-QSAR, molecular docking and pharmacophore studies.

    PubMed

    Aalizadeh, Reza; Pourbasheer, Eslam; Ganjali, Mohammad Reza

    2015-11-01

    In the present work, a molecular modeling study was carried out using 2D and 3D quantitative structure-activity relationships for the various series of compounds known as B-Raf[Formula: see text] inhibitors. For 2D-QSAR analysis, a linear model was developed by MLR based on GA-OLS with appropriate results [Formula: see text], which was validated by several external validation techniques. To perform a 3D-QSAR analysis, CoMFA and CoMSIA methods were used. The selected CoMFA model could provide reliable statistical values [Formula: see text] based on the training set in the biases of the selected alignment. Using the same selected alignment, a statistically reliable CoMSIA model, out of thirty-one different combinations, was also obtained [Formula: see text]. The predictive accuracy of the derived models was rigorously evaluated with the external test set of nineteen compounds based on several validation techniques. Molecular docking simulations and pharmacophore analyses were also performed to derive the true conformations of the most potent inhibitors with B-Raf[Formula: see text] kinase. PMID:26276566

  1. Molecular determinants of thyroid hormone receptor selectivity in a series of phosphonic acid derivatives: 3D-QSAR analysis and molecular docking.

    PubMed

    Wang, Fang-Fang; Yang, Wei; Shi, Yong-Hui; Le, Guo-Wei

    2015-10-01

    A mathematical study was performed on a set of phosphonic acid derivatives that are substrates for thyroid hormone receptor β (TRβ) and thyroid hormone receptor α (TRα), three-dimensional quantitative structure-activity relationship (3D-QSAR) models using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods were employed to investigate the structural requirements for this series of compounds with improved activity. Some descriptors were also employed to significantly improve the performance of the derived models. The CoMFA model for TRβ exhibited Rcv(2) of 0.612, Rpred(2) of 0.7218, whereas CoMSIA model showed Rcv(2) of 0.621, R(2)pred of 0.7358; the CoMFA model for TRα displayed Rcv(2) of 0.678, Rpred(2) of 0.6424, and the CoMSIA model had Rcv(2) of 0.671, Rpred(2) of 0.6932, which indicate that the constructed models are statistically significant. The derived contour maps further pointed out the regions where interactive fields may influence the activity. In order to validate the QSAR models and explore the origin of the selectivity at the amino acid level, molecular docking was developed, and the results indicate that Arg282, Arg320, Asn331, Gly332, Thr329 and His435 for TRβ, but Ala225, Arg228, Met259, Arg262 and His381 for TRα, respectively are important residues. The information obtained from the QSAR models can be used in the design of more potent TR agonists. PMID:26363198

  2. 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

  3. 3D-QSAR (CoMFA and CoMSIA) and pharmacophore (GALAHAD) studies on the differential inhibition of aldose reductase by flavonoid compounds.

    PubMed

    Caballero, Julio

    2010-11-01

    Inhibitory activities of flavonoid derivatives against aldose reductase (AR) enzyme were modelled by using CoMFA, CoMSIA and GALAHAD methods. CoMFA and CoMSIA methods were used for deriving quantitative structure-activity relationship (QSAR) models. All QSAR models were trained with 55 compounds, after which they were evaluated for predictive ability with additional 14 compounds. The best CoMFA model included both steric and electrostatic fields, meanwhile, the best CoMSIA model included steric, hydrophobic and H-bond acceptor fields. These models had a good predictive quality according to both internal and external validation criteria. On the other hand, GALAHAD was used for deriving a 3D pharmacophore model. Twelve active compounds were used for deriving this model. The obtained model included hydrophobe, hydrogen bond acceptor and hydrogen bond donor features; it was able to identify the active AR inhibitors from the remaining compounds. These in silico tools might be useful in the rational design of new AR inhibitors. PMID:20863730

  4. 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

  5. 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.

  6. 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

  7. Synthesis, biological evaluation and 3D-QSAR studies of new chalcone derivatives as inhibitors of human P-glycoprotein.

    PubMed

    Parveen, Zahida; Brunhofer, Gerda; Jabeen, Ishrat; Erker, Thomas; Chiba, Peter; Ecker, Gerhard F

    2014-04-01

    P-glycoprotein (P-gp) is an ATP-dependent multidrug resistance efflux transporter that plays an important role in anticancer drug resistance and in pharmacokinetics of medicines. Despite a large number of structurally and functionally diverse compounds, also flavonoids and chalcones have been reported as inhibitors of P-gp. The latter share some similarity with the well studied class of propafenones, but do not contain a basic nitrogen atom. Furthermore, due to their rigidity, they are suitable candidates for 3D-QSAR studies. In this study, a set of 22 new chalcone derivatives were synthesized and evaluated in a daunomycin efflux inhibition assay using the CCRF.CEM.VCR1000 cell line. The compound 10 showed the highest activity (IC50=42nM), which is one order of magnitude higher than the activity for an equilipohillic propafenone analogue. 2D- and 3D-QSAR studies indicate the importance of H-bond acceptors, methoxy groups, hydrophobic groups as well as the number of rotatable bonds as pharmacophoric features influencing P-gp inhibitory activity. PMID:24613626

  8. 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

  9. Studies of New Fused Benzazepine as Selective Dopamine D3 Receptor Antagonists Using 3D-QSAR, Molecular Docking and Molecular Dynamics

    PubMed Central

    Liu, Jing; Li, Yan; Zhang, Shuwei; Xiao, Zhengtao; Ai, Chunzhi

    2011-01-01

    In recent years, great interest has been paid to the development of compounds with high selectivity for central dopamine (DA) D3 receptors, an interesting therapeutic target in the treatment of different neurological disorders. In the present work, based on a dataset of 110 collected benzazepine (BAZ) DA D3 antagonists with diverse kinds of structures, a variety of in silico modeling approaches, including comparative molecular field analysis (CoMFA), comparative similarity indices analysis (CoMSIA), homology modeling, molecular docking and molecular dynamics (MD) were carried out to reveal the requisite 3D structural features for activity. Our results show that both the receptor-based (Q2 = 0.603, R2ncv = 0.829, R2pre = 0.690, SEE = 0.316, SEP = 0.406) and ligand-based 3D-QSAR models (Q2 = 0.506, R2ncv =0.838, R2pre = 0.794, SEE = 0.316, SEP = 0.296) are reliable with proper predictive capacity. In addition, a combined analysis between the CoMFA, CoMSIA contour maps and MD results with a homology DA receptor model shows that: (1) ring-A, position-2 and R3 substituent in ring-D are crucial in the design of antagonists with higher activity; (2) more bulky R1 substituents (at position-2 of ring-A) of antagonists may well fit in the binding pocket; (3) hydrophobicity represented by MlogP is important for building satisfactory QSAR models; (4) key amino acids of the binding pocket are CYS101, ILE105, LEU106, VAL151, PHE175, PHE184, PRO254 and ALA251. To our best knowledge, this work is the first report on 3D-QSAR modeling of the new fused BAZs as DA D3 antagonists. These results might provide information for a better understanding of the mechanism of antagonism and thus be helpful in designing new potent DA D3 antagonists. PMID:21541053

  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. Volume learning algorithm artificial neural networks for 3D QSAR studies.

    PubMed

    Tetko, I V; Kovalishyn, V V; Livingstone, D J

    2001-07-19

    The current study introduces a new method, the volume learning algorithm (VLA), for the investigation of three-dimensional quantitative structure-activity relationships (QSAR) of chemical compounds. This method incorporates the advantages of comparative molecular field analysis (CoMFA) and artificial neural network approaches. VLA is a combination of supervised and unsupervised neural networks applied to solve the same problem. The supervised algorithm is a feed-forward neural network trained with a back-propagation algorithm while the unsupervised network is a self-organizing map of Kohonen. The use of both of these algorithms makes it possible to cluster the input CoMFA field variables and to use only a small number of the most relevant parameters to correlate spatial properties of the molecules with their activity. The statistical coefficients calculated by the proposed algorithm for cannabimimetic aminoalkyl indoles were comparable to, or improved, in comparison to the original study using the partial least squares algorithm. The results of the algorithm can be visualized and easily interpreted. Thus, VLA is a new convenient tool for three-dimensional QSAR studies. PMID:11448223

  12. 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

  13. Modular 3-D Transport model

    EPA Science Inventory

    MT3D was first developed by Chunmiao Zheng in 1990 at S.S. Papadopulos & Associates, Inc. with partial support from the U.S. Environmental Protection Agency (USEPA). Starting in 1990, MT3D was released as a pubic domain code from the USEPA. Commercial versions with enhanced capab...

  14. 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.

  15. 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

  16. Docking and 3D-QSAR (quantitative structure activity relationship) studies of flavones, the potent inhibitors of p-glycoprotein targeting the nucleotide binding domain.

    PubMed

    Kothandan, Gugan; Gadhe, Changdev G; Madhavan, Thirumurthy; Choi, Cheol Hee; Cho, Seung Joo

    2011-09-01

    In order to explore the interactions between flavones and P-gp, in silico methodologies such as docking and 3D-QSAR were performed. CoMFA and CoMSIA analyses were done using ligand based and receptor guided alignment schemes. Validation statistics include leave-one-out cross-validated R(2) (q(2)), internal prediction parameter by progressive scrambling (Q(*2)), external prediction with test set. They show that models derived from this study are quite robust. Ligand based CoMFA (q(2) = 0.747, Q(*2) = 0.639, r(pred)(2)=0.802) and CoMSIA model (q(2) = 0.810, Q(*2) = 0.676, r(pred)(2)=0.785) were developed using atom by atom matching. Receptor guided CoMFA (q(2) = 0.712, Q(*2) = 0.497, r(pred)(2) = 0.841) and for CoMSIA (q(2) = 0.805, Q(*2) = 0.589, r(pred)(2) = 0.937) models were developed by docking of highly active flavone into the proposed NBD (nucleotide binding domain) of P-gp. The 3D-QSAR models generated here predicted that hydrophobic and steric parameters are important for activity toward P-gp. Our studies indicate the important amino acid in NBD crucial for binding in accordance with the previous results. This site forms a hydrophobic site. Since flavonoids have potential without toxicity, we propose to inspect this hydrophobic site including Asn1043 and Asp1049 should be considered for future inhibitor design. PMID:21723648

  17. Imidazo[1,2-a]pyrazine inhibitors of phosphoinositide 3-kinase alpha (PI3Kα): 3D-QSAR analysis utilizing the Hybrid Monte Carlo algorithm to refine receptor-ligand complexes for molecular alignment.

    PubMed

    Chadha, N; Jasuja, H; Kaur, M; Singh Bahia, M; Silakari, O

    2014-01-01

    Phosphoinositide 3-kinase alpha (PI3Kα) is a lipid kinase involved in several cellular functions such as cell growth, proliferation, differentiation and survival, and its anomalous regulation leads to cancerous conditions. PI3Kα inhibition completely blocks the cancer signalling pathway, hence it can be explored as an important therapeutic target for cancer treatment. In the present study, docking analysis of 49 selective imidazo[1,2-a]pyrazine inhibitors of PI3Kα was carried out using the QM-Polarized ligand docking (QPLD) program of the Schrödinger software, followed by the refinement of receptor-ligand conformations using the Hybrid Monte Carlo algorithm in the Liaison program, and alignment of refined conformations of inhibitors was utilized for the development of an atom-based 3D-QSAR model in the PHASE program. Among the five generated models, the best model was selected corresponding to PLS factor 2, displaying the highest value of Q(2)test (0.650). The selected model also displayed high values of r(2)train (0.917), F-value (166.5) and Pearson-r (0.877) and a low value of SD (0.265). The contour plots generated for the selected 3D-QSAR model were correlated with the results of docking simulations. Finally, this combined information generated from 3D-QSAR and docking analysis was used to design new congeners. PMID:24601789

  18. 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...

  19. 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

  20. The Esri 3D city information model

    NASA Astrophysics Data System (ADS)

    Reitz, T.; Schubiger-Banz, S.

    2014-02-01

    With residential and commercial space becoming increasingly scarce, cities are going vertical. Managing the urban environments in 3D is an increasingly important and complex undertaking. To help solving this problem, Esri has released the ArcGIS for 3D Cities solution. The ArcGIS for 3D Cities solution provides the information model, tools and apps for creating, analyzing and maintaining a 3D city using the ArcGIS platform. This paper presents an overview of the 3D City Information Model and some sample use cases.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. Synthesis, biological evaluation and 3D-QSAR studies of imidazolidine-2,4-dione derivatives as novel protein tyrosine phosphatase 1B inhibitors.

    PubMed

    Wang, Mei-Yan; Jin, Yuan-Yuan; Wei, Hui-Yu; Zhang, Li-Song; Sun, Su-Xia; Chen, Xiu-Bo; Dong, Wei-Li; Xu, Wei-Ren; Cheng, Xian-Chao; Wang, Run-Ling

    2015-10-20

    Protein tyrosine phosphatase 1B (PTP1B) plays a vital role in the regulation of insulin sensitivity and dephosphorylation of the insulin receptor, so PTP1B inhibitors may be potential agents to treat type 2 diabetes. In this work, a series of novel imidazolidine-2,4-dione derivatives were designed, synthesized and assayed for their PTP1B inhibitory activities. These compounds exhibited potent activities with IC50 values at 0.57-172 μM. A 3D-QSAR study using CoMFA and CoMSIA techniques was carried out to explore structure activity relationship of these molecules. The CoMSIA model was more predictive with q(2) = 0.777, r(2) = 0.999, SEE = 0.013 and r(2)pred = 0.836, while the CoMFA model gave q(2) = 0.543, r(2) = 0.998, SEE = 0.029 and r(2)pred = 0.754. The contour maps derived from the best CoMFA and CoMSIA models combined with docking analysis provided good insights into the structural features relevant to the bioactivity, and could be used in the molecular design of novel imidazolidine-2,4-dione derivatives. PMID:26342135

  6. 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.

  7. Radiosity diffusion model in 3D

    NASA Astrophysics Data System (ADS)

    Riley, Jason D.; Arridge, Simon R.; Chrysanthou, Yiorgos; Dehghani, Hamid; Hillman, Elizabeth M. C.; Schweiger, Martin

    2001-11-01

    We present the Radiosity-Diffusion model in three dimensions(3D), as an extension to previous work in 2D. It is a method for handling non-scattering spaces in optically participating media. We present the extension of the model to 3D including an extension to the model to cope with increased complexity of the 3D domain. We show that in 3D more careful consideration must be given to the issues of meshing and visibility to model the transport of light within reasonable computational bounds. We demonstrate the model to be comparable to Monte-Carlo simulations for selected geometries, and show preliminary results of comparisons to measured time-resolved data acquired on resin phantoms.

  8. Sulfonamide derivatives containing dihydropyrazole moieties selectively and potently inhibit MMP-2/MMP-9: Design, synthesis, inhibitory activity and 3D-QSAR analysis.

    PubMed

    Yan, Xiao-Qiang; Wang, Zhong-Chang; Li, Zhen; Wang, Peng-Fei; Qiu, Han-Yue; Chen, Long-Wang; Lu, Xiao-Yuan; Lv, Peng-Cheng; Zhu, Hai-Liang

    2015-10-15

    New series of sulfonamide derivatives containing a dihydropyrazole moieties inhibitors of MMP-2/MMP-9 were discovered using structure-based drug design. Synthesis, antitumor activity, structure-activity relationship and optimization of physicochemical properties were described. In vitro the bioassay results revealed that most target compounds showed potent inhibitory activity in the enzymatic and cellular assays. Among the compounds, compound 3i exhibited the most potent inhibitory activity with IC50 values of 0.21 μM inhibiting MMP-2 and 1.87 μM inhibiting MMP-9, comparable to the control positive compound CMT-1 (1.26 μM, 2.52 μM). Docking simulation was performed to position compound 3i into the MMP-2 active site to determine the probable binding pose. Docking simulation was further performed to position compound 3i into the MMP-2 active site to determine the probable binding model the 3D-QSAR models were built for reasonable design of MMP-2/MMP-9 inhibitors at present and in future. PMID:26346367

  9. 3D model reconstruction of underground goaf

    NASA Astrophysics Data System (ADS)

    Fang, Yuanmin; Zuo, Xiaoqing; Jin, Baoxuan

    2005-10-01

    Constructing 3D model of underground goaf, we can control the process of mining better and arrange mining work reasonably. However, the shape of goaf and the laneway among goafs are very irregular, which produce great difficulties in data-acquiring and 3D model reconstruction. In this paper, we research on the method of data-acquiring and 3D model construction of underground goaf, building topological relation among goafs. The main contents are as follows: a) The paper proposed an efficient encoding rule employed to structure the field measurement data. b) A 3D model construction method of goaf is put forward, which by means of combining several TIN (triangulated irregular network) pieces, and an efficient automatic processing algorithm of boundary of TIN is proposed. c) Topological relation of goaf models is established. TIN object is the basic modeling element of goaf 3D model, and the topological relation among goaf is created and maintained by building the topological relation among TIN objects. Based on this, various 3D spatial analysis functions can be performed including transect and volume calculation of goaf. A prototype is developed, which can realized the model and algorithm proposed in this paper.

  10. 3D-QSAR and molecular mechanics study for the differences in the azole activity against yeastlike and filamentous fungi and their relation to P450DM inhibition. 1. 3-substituted-4(3H)-quinazolinones.

    PubMed

    Fratev, Filip; Benfenati, Emilio

    2005-01-01

    A combination between 3D-QSAR and molecular mechanics (MM)-docking study was used as a tool to detail and model the mechanism of action of 46 antifungal azoles. Two methods of alignment of the ligands were performed: (i) alignment of the main skeleton without substituents and (ii) alignment of a defined substructure. The best model is characterized by q(2) with the values of 0.70 for yeastlike (yeast), 0.66 for filamentous fungi, and 0.70 for the selectivity against filamentous fungi. 3D-QSAR regression maps derived from six models were used to identify the regions responsible for the differences in the compounds activity against yeast and filamentous fungi. The binding energy of the important substructures (Local Binding Energy-LBE) and its standard deviation were calculated in order to demonstrate quantitatively the contribution of substituents reflecting the diversity of the antifungal activity. The comparisons of these results with the same regions of the contour maps indicated a good correspondence between the 3D-QSAR and MM (LBE) approaches allowing association between the maps and the participating residues in the active sites of P450DM of C. albicans and A. fumigatus. The pi-pi interactions of two or more aromatic groups of the ligands with Phe228 and Tyr132 prove to be most important for the differences in activity against C. albicans. In A. fumigatus there was a better occupation of the inner central I-spiral in the areas around the heme. For the activity against A. fumigatus the pi-pi interactions of aromatic groups of the compounds with Phe509, Phe228, and Tyr132 are significant for the activity. PMID:15921453

  11. Molecular docking based virtual screening of natural compounds as potential BACE1 inhibitors: 3D QSAR pharmacophore mapping and molecular dynamics analysis.

    PubMed

    Kumar, Akhil; Roy, Sudeep; Tripathi, Shubhandra; Sharma, Ashok

    2016-01-01

    Beta-site APP cleaving enzyme1 (BACE1) catalyzes the rate determining step in the generation of Aβ peptide and is widely considered as a potential therapeutic drug target for Alzheimer's disease (AD). Active site of BACE1 contains catalytic aspartic (Asp) dyad and flap. Asp dyad cleaves the substrate amyloid precursor protein with the help of flap. Currently, there are no marketed drugs available against BACE1 and existing inhibitors are mostly pseudopeptide or synthetic derivatives. There is a need to search for a potent inhibitor with natural scaffold interacting with flap and Asp dyad. This study screens the natural database InterBioScreen, followed by three-dimensional (3D) QSAR pharmacophore modeling, mapping, in silico ADME/T predictions to find the potential BACE1 inhibitors. Further, molecular dynamics of selected inhibitors were performed to observe the dynamic structure of protein after ligand binding. All conformations and the residues of binding region were stable but the flap adopted a closed conformation after binding with the ligand. Bond oligosaccharide interacted with the flap as well as catalytic dyad via hydrogen bond throughout the simulation. This led to stabilize the flap in closed conformation and restricted the entry of substrate. Carbohydrates have been earlier used in the treatment of AD because of their low toxicity, high efficiency, good biocompatibility, and easy permeability through the blood-brain barrier. Our finding will be helpful in identify the potential leads to design novel BACE1 inhibitors for AD therapy. PMID:25707809

  12. 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

  13. 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

  14. 3D QSAR STUDIES ON A SERIES OF QUINAZOLINE DERRIVATIVES AS TYROSINE KINASE (EGFR) INHIBITOR: THE K-NEAREST NEIGHBOR MOLECULAR FIELD ANALYSIS APPROACH

    PubMed Central

    Noolvi, Malleshappa N.; Patel, Harun M.

    2010-01-01

    Epidermal growth factor receptor (EGFR) protein tyrosine kinases (PTKs) are known for its role in cancer. Quinazoline have been reported to be the molecules of interest, with potent anticancer activity and they act by binding to ATP site of protein kinases. ATP binding site of protein kinases provides an extensive opportunity to design newer analogs. With this background, we report an attempt to discern the structural and physicochemical requirements for inhibition of EGFR tyrosine kinase. The k-Nearest Neighbor Molecular Field Analysis (kNN-MFA), a three dimensional quantitative structure activity relationship (3D- QSAR) method has been used in the present case to study the correlation between the molecular properties and the tyrosine kinase (EGFR) inhibitory activities on a series of quinazoline derivatives. kNNMFA calculations for both electrostatic and steric field were carried out. The master grid maps derived from the best model has been used to display the contribution of electrostatic potential and steric field. The statistical results showed significant correlation coefficient r2 (q2) of 0.846, r2 for external test set (pred_r2) 0.8029, coefficient of correlation of predicted data set (pred_r2se) of 0.6658, degree of freedom 89 and k nearest neighbor of 2. Therefore, this study not only casts light on binding mechanism between EGFR and its inhibitors, but also provides hints for the design of new EGFR inhibitors with observable structural diversity PMID:24825983

  15. 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

  16. 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

  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. 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.

  19. 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.

  20. 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.

  1. Solar abundances and 3D model atmospheres

    NASA Astrophysics Data System (ADS)

    Ludwig, Hans-Günter; Caffau, Elisabetta; Steffen, Matthias; Bonifacio, Piercarlo; Freytag, Bernd; Cayrel, Roger

    2010-03-01

    We present solar photospheric abundances for 12 elements from optical and near-infrared spectroscopy. The abundance analysis was conducted employing 3D hydrodynamical (CO5BOLD) as well as standard 1D hydrostatic model atmospheres. We compare our results to others with emphasis on discrepancies and still lingering problems, in particular exemplified by the pivotal abundance of oxygen. We argue that the thermal structure of the lower solar photosphere is very well represented by our 3D model. We obtain an excellent match of the observed center-to-limb variation of the line-blanketed continuum intensity, also at wavelengths shortward of the Balmer jump.

  2. 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…

  3. Study of differences in the VEGFR2 inhibitory activities between semaxanib and SU5205 using 3D-QSAR, docking, and molecular dynamics simulations.

    PubMed

    Muñoz, Camila; Adasme, Francisco; Alzate-Morales, Jans H; Vergara-Jaque, Ariela; Kniess, Torsten; Caballero, Julio

    2012-02-01

    Semaxanib (SU5416) and 3-[4'-fluorobenzylidene]indolin-2-one (SU5205) are structurally similar drugs that are able to inhibit vascular endothelial growth factor receptor-2 (VEGFR2), but the former is 87 times more effective than the latter. Previously, SU5205 was used as a radiolabelled inhibitor (as surrogate for SU5416) and a radiotracer for positron emission tomography (PET) imaging, but the compound exhibited poor stability and only a moderate IC(50) toward VEGFR2. In the current work, the relationship between the structure and activity of these drugs as VEGFR2 inhibitors was studied using 3D-QSAR, docking and molecular dynamics (MD) simulations. First, comparative molecular field analysis (CoMFA) was performed using 48 2-indolinone derivatives and their VEGFR2 inhibitory activities. The best CoMFA model was carried out over a training set including 40 compounds, and it included steric and electrostatic fields. In addition, this model gave satisfactory cross-validation results and adequately predicted 8 compounds contained in the test set. The plots of the CoMFA fields could explain the structural differences between semaxanib and SU5205. Docking and molecular dynamics simulations showed that both molecules have the same orientation and dynamics inside the VEGFR2 active site. However, the hydrophobic pocket of VEGFR2 was more exposed to the solvent media when it was complexed with SU5205. An energetic analysis, including Embrace and MM-GBSA calculations, revealed that the potency of ligand binding is governed by van der Waals contacts. PMID:22070999

  4. 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. PMID:26382665

  5. 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.

  6. 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

  7. 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

  8. Receptor-based 3D QSAR analysis of estrogen receptor ligands--merging the accuracy of receptor-based alignments with the computational efficiency of ligand-based methods.

    PubMed

    Sippl, W

    2000-08-01

    One of the major challenges in computational approaches to drug design is the accurate prediction of binding affinity of biomolecules. In the present study several prediction methods for a published set of estrogen receptor ligands are investigated and compared. The binding modes of 30 ligands were determined using the docking program AutoDock and were compared with available X-ray structures of estrogen receptor-ligand complexes. On the basis of the docking results an interaction energy-based model, which uses the information of the whole ligand-receptor complex, was generated. Several parameters were modified in order to analyze their influence onto the correlation between binding affinities and calculated ligand-receptor interaction energies. The highest correlation coefficient (r2 = 0.617, q2Loo = 0.570) was obtained considering protein flexibility during the interaction energy evaluation. The second prediction method uses a combination of receptor-based and 3D quantitative structure-activity relationships (3D QSAR) methods. The ligand alignment obtained from the docking simulations was taken as basis for a comparative field analysis applying the GRID/GOLPE program. Using the interaction field derived with a water probe and applying the smart region definition (SRD) variable selection, a significant and robust model was obtained (r2 = 0.991, q2LOO = 0.921). The predictive ability of the established model was further evaluated by using a test set of six additional compounds. The comparison with the generated interaction energy-based model and with a traditional CoMFA model obtained using a ligand-based alignment (r2 = 0.951, q2L00 = 0.796) indicates that the combination of receptor-based and 3D QSAR methods is able to improve the quality of the underlying model. PMID:10921772

  9. Illustrative visualization of 3D city models

    NASA Astrophysics Data System (ADS)

    Doellner, Juergen; Buchholz, Henrik; Nienhaus, Marc; Kirsch, Florian

    2005-03-01

    This paper presents an illustrative visualization technique that provides expressive representations of large-scale 3D city models, inspired by the tradition of artistic and cartographic visualizations typically found in bird"s-eye view and panoramic maps. We define a collection of city model components and a real-time multi-pass rendering algorithm that achieves comprehensible, abstract 3D city model depictions based on edge enhancement, color-based and shadow-based depth cues, and procedural facade texturing. Illustrative visualization provides an effective visual interface to urban spatial information and associated thematic information complementing visual interfaces based on the Virtual Reality paradigm, offering a huge potential for graphics design. Primary application areas include city and landscape planning, cartoon worlds in computer games, and tourist information systems.

  10. Integrated Biogeomorphological Modeling Using Delft3D

    NASA Astrophysics Data System (ADS)

    Ye, Q.; Jagers, B.

    2011-12-01

    The skill of numerical morphological models has improved significantly from the early 2D uniform, total load sediment models (with steady state or infrequent wave updates) to recent 3D hydrodynamic models with multiple suspended and bed load sediment fractions and bed stratigraphy (online coupled with waves). Although there remain many open questions within this combined field of hydro- and morphodynamics, we observe an increasing need to include biological processes in the overall dynamics. In riverine and inter-tidal environments, there is often an important influence by riparian vegetation and macrobenthos. Over the past decade more and more researchers have started to extend the simulation environment with wrapper scripts and other quick code hacks to estimate their influence on morphological development in coastal, estuarine and riverine environments. Although one can in this way quickly analyze different approaches, these research tools have generally not been designed with reuse, performance and portability in mind. We have now implemented a reusable, flexible, and efficient two-way link between the Delft3D open source framework for hydrodynamics, waves and morphology, and the water quality and ecology modules. The same link will be used for 1D, 2D and 3D modeling on networks and both structured and unstructured grids. We will describe the concepts of the overall system, and illustrate it with some first results.

  11. 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.

  12. 3D modeling of optically challenging objects.

    PubMed

    Park, Johnny; Kak, Avinash

    2008-01-01

    We present a system for constructing 3D models of real-world objects with optically challenging surfaces. The system utilizes a new range imaging concept called multi-peak range imaging, which stores multiple candidates of range measurements for each point on the object surface. The multiple measurements include the erroneous range data caused by various surface properties that are not ideal for structured-light range sensing. False measurements generated by spurious reflections are eliminated by applying a series of constraint tests. The constraint tests based on local surface and local sensor visibility are applied first to individual range images. The constraint tests based on global consistency of coordinates and visibility are then applied to all range images acquired from different viewpoints. We show the effectiveness of our method by constructing 3D models of five different optically challenging objects. To evaluate the performance of the constraint tests and to examine the effects of the parameters used in the constraint tests, we acquired the ground truth data by painting those objects to suppress the surface-related properties that cause difficulties in range sensing. Experimental results indicate that our method significantly improves upon the traditional methods for constructing reliable 3D models of optically challenging objects. PMID:18192707

  13. 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.

  14. 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.

  15. 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.

  16. Inferential modeling of 3D chromatin structure

    PubMed Central

    Wang, Siyu; Xu, Jinbo; Zeng, Jianyang

    2015-01-01

    For eukaryotic cells, the biological processes involving regulatory DNA elements play an important role in cell cycle. Understanding 3D spatial arrangements of chromosomes and revealing long-range chromatin interactions are critical to decipher these biological processes. In recent years, chromosome conformation capture (3C) related techniques have been developed to measure the interaction frequencies between long-range genome loci, which have provided a great opportunity to decode the 3D organization of the genome. In this paper, we develop a new Bayesian framework to derive the 3D architecture of a chromosome from 3C-based data. By modeling each chromosome as a polymer chain, we define the conformational energy based on our current knowledge on polymer physics and use it as prior information in the Bayesian framework. We also propose an expectation-maximization (EM) based algorithm to estimate the unknown parameters of the Bayesian model and infer an ensemble of chromatin structures based on interaction frequency data. We have validated our Bayesian inference approach through cross-validation and verified the computed chromatin conformations using the geometric constraints derived from fluorescence in situ hybridization (FISH) experiments. We have further confirmed the inferred chromatin structures using the known genetic interactions derived from other studies in the literature. Our test results have indicated that our Bayesian framework can compute an accurate ensemble of 3D chromatin conformations that best interpret the distance constraints derived from 3C-based data and also agree with other sources of geometric constraints derived from experimental evidence in the previous studies. The source code of our approach can be found in https://github.com/wangsy11/InfMod3DGen. PMID:25690896

  17. 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.

  18. Structure-based modeling of dye-fiber affinity with SOM-4D-QSAR paradigm: application to set of anthraquinone derivatives.

    PubMed

    Bak, Andrzej; Wyszomirski, Miroslaw; Magdziarz, Tomasz; Smolinski, Adam; Polanski, Jaroslaw

    2014-01-01

    A comparative structure-affinity study of anthraquinone dyes adsorption on cellulose fibre is presented in this paper. We used receptor-dependent 4D-QSAR methods based on grid and neural (SOM) methodology coupled with IVEPLS procedure. The applied RD 4D-QSAR approach focuses mainly on the ability of mapping dye properties to verify the concept of tinctophore in dye chemistry. Moreover, the stochastic SMV procedure to investigate the predictive ability of the method for a large population of 4D-QSAR models was employed. The obtained findings were compared with the previously published RI 3D/4D-QSAR models for the corresponding anthraquinone trainings sets. The neutral (protonated) and anionic (deprotonated) forms of anthraquinone scaffold were examined in order to deal with the uncertainty of the dye ionization state. The results are comparable to both the neutral and anionic dye sets regardless of the occupancy and charge descriptors applied, respectively. It is worth noting that the SOM-4D-QSAR behaves comparably to the cubic counterpart which is observed in each training/test subset specification (4D-QSAR-Jo vs SOM- 4D-QSARo and 4D-QSAR-Jq vs SOM-4D-QSARq). Additionally, an attempt was made to specify a common set of variables contributing significantly to dye-fiber binding affinity; it was simultaneously performed for some arbitrary chosen SMV models. The presented RD 4D-QSAR methodology together with IVE-PLS procedure provides a robust and predictive modeling technique, which facilitates detailed specification of the molecular motifs significantly contributing to the fiber-dye affinity. PMID:24499310

  19. 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.

  20. 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

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

    PubMed

    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

  2. Combined 3D-QSAR, Molecular Docking and Molecular Dynamics Study on Derivatives of Peptide Epoxyketone and Tyropeptin-Boronic Acid as Inhibitors Against the β5 Subunit of Human 20S Proteasome

    PubMed Central

    Liu, Jianling; Zhang, Hong; Xiao, Zhengtao; Wang, Fangfang; Wang, Xia; Wang, Yonghua

    2011-01-01

    An abnormal ubiquitin-proteasome is found in many human diseases, especially in cancer, and has received extensive attention as a promising therapeutic target in recent years. In this work, several in silico models have been built with two classes of proteasome inhibitors (PIs) by using 3D-QSAR, homology modeling, molecular docking and molecular dynamics (MD) simulations. The study resulted in two types of satisfactory 3D-QSAR models, i.e., the CoMFA model (Q2 = 0.462, R2pred = 0.820) for epoxyketone inhibitors (EPK) and the CoMSIA model (Q2 = 0.622, R2pred = 0.821) for tyropeptin-boronic acid derivatives (TBA). From the contour maps, some key structural factors responsible for the activity of these two series of PIs are revealed. For EPK inhibitors, the N-cap part should have higher electropositivity; a large substituent such as a benzene ring is favored at the C6-position. In terms of TBA inhibitors, hydrophobic substituents with a larger size anisole group are preferential at the C8-position; higher electropositive substituents like a naphthalene group at the C3-position can enhance the activity of the drug by providing hydrogen bond interaction with the protein target. Molecular docking disclosed that residues Thr60, Thr80, Gly106 and Ser189 play a pivotal role in maintaining the drug-target interactions, which are consistent with the contour maps. MD simulations further indicated that the binding modes of each conformation derived from docking is stable and in accord with the corresponding structure extracted from MD simulation overall. These results can offer useful theoretical references for designing more potent PIs. PMID:21673924

  3. 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

  4. 3D Modeling of Equatorial Plasma Bubbles

    NASA Astrophysics Data System (ADS)

    Huba, Joseph; Joyce, Glenn; Krall, Jonathan

    2011-10-01

    Post-sunset ionospheric irregularities in the equatorial F region were first observed by Booker and Wells (1938) using ionosondes. This phenomenon has become known as equatorial spread F (ESF). During ESF the equatorial ionosphere becomes unstable because of a Rayleigh-Taylor-like instability: large scale (10s km) electron density ``bubbles'' can develop and rise to high altitudes (1000 km or greater at times). Understanding and modeling ESF is important because of its impact on space weather: it causes radio wave scintillation that degrades communication and navigation systems. In fact, it is the focus of of the Air Force Communications/Navigation Outage Forecast Satellite (C/NOFS) mission. We will describe 3D simulation results from the NRL ionosphere models SAMI3 and SAMI3/ESF of this phenomenon. In particular, we will examine the causes of the day-to-day ariability of ESF which is an unresolved problem at this time. Post-sunset ionospheric irregularities in the equatorial F region were first observed by Booker and Wells (1938) using ionosondes. This phenomenon has become known as equatorial spread F (ESF). During ESF the equatorial ionosphere becomes unstable because of a Rayleigh-Taylor-like instability: large scale (10s km) electron density ``bubbles'' can develop and rise to high altitudes (1000 km or greater at times). Understanding and modeling ESF is important because of its impact on space weather: it causes radio wave scintillation that degrades communication and navigation systems. In fact, it is the focus of of the Air Force Communications/Navigation Outage Forecast Satellite (C/NOFS) mission. We will describe 3D simulation results from the NRL ionosphere models SAMI3 and SAMI3/ESF of this phenomenon. In particular, we will examine the causes of the day-to-day ariability of ESF which is an unresolved problem at this time. Research supported by ONR.

  5. Reservoir geology using 3D modelling tools

    SciTech Connect

    Dubrule, O.; Samson, P.; Segonds, D.

    1996-12-31

    The last decade has seen tremendous developments in the area of quantitative geological modelling. These developments have a significant impact on the current practice of constructing reservoir models. A structural model can first be constructed on the basis of depth-converted structural interpretations produced on a seismic interpretation workstation. Surfaces and faults can be represented as geological objects, and interactively modified. Once the tectonic framework has been obtained, intermediate stratigraphic surfaces can be constructed between the main structural surfaces. Within each layer, reservoir attributes can be represented using various techniques. Examples show how the distribution of different facies (i.e. from fine to coarse grain) can be represented, or how various depositional units (for instance channels, crevasses and lobes in a turbidite setting) can be modelled as geological {open_quotes}objects{close_quotes} with complex geometries. Elf Aquitaine, in close co-operation with the GOCAD project in Nancy (France) is investigating how geological models can be made more realistic by developing interactive functionalities. Examples show that, contrary to standard deterministic or geostatistical modelling techniques (which tend to be difficult to control) the use of new 3D tools allows the geologist to interactively modify geological surfaces (including faults) or volumetric properties. Thus, the sensitivity of various economic parameters (oil in place, connected volumes, reserves) to major geological uncertainties can be evaluated. It is argued that future breakthroughs in geological modelling techniques are likely to happen in the development of interactive approaches rather than in the research of new mathematical algorithms.

  6. Reservoir geology using 3D modelling tools

    SciTech Connect

    Dubrule, O. ); Samson, P. ); Segonds, D. )

    1996-01-01

    The last decade has seen tremendous developments in the area of quantitative geological modelling. These developments have a significant impact on the current practice of constructing reservoir models. A structural model can first be constructed on the basis of depth-converted structural interpretations produced on a seismic interpretation workstation. Surfaces and faults can be represented as geological objects, and interactively modified. Once the tectonic framework has been obtained, intermediate stratigraphic surfaces can be constructed between the main structural surfaces. Within each layer, reservoir attributes can be represented using various techniques. Examples show how the distribution of different facies (i.e. from fine to coarse grain) can be represented, or how various depositional units (for instance channels, crevasses and lobes in a turbidite setting) can be modelled as geological [open quotes]objects[close quotes] with complex geometries. Elf Aquitaine, in close co-operation with the GOCAD project in Nancy (France) is investigating how geological models can be made more realistic by developing interactive functionalities. Examples show that, contrary to standard deterministic or geostatistical modelling techniques (which tend to be difficult to control) the use of new 3D tools allows the geologist to interactively modify geological surfaces (including faults) or volumetric properties. Thus, the sensitivity of various economic parameters (oil in place, connected volumes, reserves) to major geological uncertainties can be evaluated. It is argued that future breakthroughs in geological modelling techniques are likely to happen in the development of interactive approaches rather than in the research of new mathematical algorithms.

  7. Regional geothermal 3D modelling in Denmark

    NASA Astrophysics Data System (ADS)

    Poulsen, S. E.; Balling, N.; Bording, T. S.; Nielsen, S. B.

    2012-04-01

    In the pursuit of sustainable and low carbon emission energy sources, increased global attention has been given to the exploration and exploitation of geothermal resources within recent decades. In 2009 a national multi-disciplinary geothermal research project was established. As a significant part of this project, 3D temperature modelling is to be carried out, with special emphasis on temperatures of potential geothermal reservoirs in the Danish area. The Danish subsurface encompasses low enthalpy geothermal reservoirs of mainly Triassic and Jurassic age. Geothermal plants at Amager (Copenhagen) and Thisted (Northern Jutland) have the capacity of supplying the district heating network with up to 14 MW and 7 MW, respectively, by withdrawing warm pore water from the Gassum (Lower Jurassic/Upper Triassic) and Bunter (Lower Triassic) sandstone reservoirs, respectively. Explorative studies of the subsurface temperature regime typically are based on a combination of observations and modelling. In this study, the open-source groundwater modelling code MODFLOW is modified to simulate the subsurface temperature distribution in three dimensions by taking advantage of the mathematical similarity between saturated groundwater flow (Darcy flow) and heat conduction. A numerical model of the subsurface geology in Denmark is built and parameterized from lithological information derived from joint interpretation of seismic surveys and borehole information. Boundary conditions are constructed from knowledge about the heat flow from the Earth's interior and the shallow ground temperature. Matrix thermal conductivities have been estimated from analysis of high-resolution temperature logs measured in deep wells and porosity-depth relations are included using interpreted main lithologies. The model takes into account the dependency of temperature and pressure on thermal conductivity. Moreover, a transient model based correction of the paleoclimatic thermal disturbance caused by the

  8. 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

  9. A new series of 2-phenol-4-aryl-6-chlorophenyl pyridine derivatives as dual topoisomerase I/II inhibitors: Synthesis, biological evaluation and 3D-QSAR study.

    PubMed

    Karki, Radha; Jun, Kyu-Yeon; Kadayat, Tara Man; Shin, Somin; Thapa Magar, Til Bahadur; Bist, Ganesh; Shrestha, Aarajana; Na, Younghwa; Kwon, Youngjoo; Lee, Eung-Seok

    2016-05-01

    As a continuous effort to develop novel antitumor agents, a new series of forty-five 2-phenol-4-aryl-6-chlorophenyl pyridine compounds were synthesized and evaluated for cytotoxicity against four different human cancer cell lines (DU145, HCT15, T47D, and HeLa), and topoisomerase I and II inhibitory activity. Several compounds (10-15, 20, 22, 24, 28, 42, and 49) displayed strong to moderate dual topoisomerase I and II inhibitory activity at 100 μM. It was observed that hydroxyl and chlorine moiety at meta or para position of phenyl ring is favorable for dual topoisomerase inhibitory activity and cytotoxicity. Most of the compounds displayed stronger cytotoxicities than those of all positive controls against the HCT15 and T47D cell lines. For investigation of the structure-activity relationships, a 3D-QSAR analysis using the method of comparative molecular field analysis (CoMFA) was performed. The generated 3D contour maps can be used for further rational design of novel terpyridine derivatives as highly selective and potent cytotoxic agents. PMID:26945111

  10. 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. PMID:15533619

  11. Understanding Substrate Selectivity of Human UDP-glucuronosyltransferases through QSAR modeling and analysis of homologous enzymes

    PubMed Central

    Dong, Dong; Ako, Roland; Hu, Ming; Wu, Baojian

    2015-01-01

    The UDP-glucuronosyltransferase (UGT) enzyme catalyzes the glucuronidation reaction which is a major metabolic and detoxification pathway in humans. Understanding the mechanisms for substrate recognition by UGT assumes great importance in an attempt to predict its contribution to xenobiotic/drug disposition in vivo. Spurred on by this interest, 2D/3D-quantitative structure activity relationships (QSAR) and pharmacophore models have been established in the absence of a complete mammalian UGT crystal structure. This review discusses the recent progress in modeling human UGT substrates including those with multiple sites of glucuronidation. A better understanding of UGT active site contributing to substrate selectivity (and regioselectivity) from the homologous enzymes (i.e., plant and bacterial UGTs, all belong to family 1 of glycosyltransferase (GT1)) is also highlighted, as these enzymes share a common catalytic mechanism and/or overlapping substrate selectivity. PMID:22385482

  12. 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.

  13. 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

  14. 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

  15. 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/. PMID:27185892

  16. 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.

  17. 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.

  18. 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.

  19. A 3-D shape model of Interamnia

    NASA Astrophysics Data System (ADS)

    Sato, Isao

    2015-08-01

    A 3-D shape model of the sixth largest of the main belt asteroids, (704) Interamnia, is presented. The model is reproduced from its two stellar occultation observations and six lightcurves between 1969 and 2011. The first stellar occultation was the occultation of TYC 234500183 on 1996 December 17 observed from 13 sites in the USA. An elliptical cross section of (344.6±9.6km)×(306.2±9.1km), for position angle P=73.4±12.5 was fitted. The lightcurve around the occultation shows that the peak-to-peak amplitude was 0.04 mag. and the occultation phase was just before the minimum. The second stellar occultation was the occultation of HIP 036189 on 2003 March 23 observed from 39 sites in Japan and Hawaii. An elliptical cross section of (349.8±0.9km)×(303.7±1.7km), for position angle P=86.0±1.1 was fitted. A companion of 8.5 mag. of the occulted star was discovered whose separation is 12±2 mas (milli-arcseconds), P=148±11 . A combined analysis of rotational lightcurves and occultation chords can return more information than can be obtained with either technique alone. From follow-up photometric observations of the asteroid between 2003 and 2011, its rotation period is determined to be 8.728967167±0.00000007 hours, which is accurate enough to fix the rotation phases at other occultation events. The derived north pole is λ2000=259±8, β2000=-50±5 (retrograde rotation); the lengths of the three principal axes are 2a=361.8±2.8km, 2b=324.4±5.0km, 2c=297.3±3.5km, and the mean diameter is D=326.8±3.0km. Supposing the mass of Interamnia as (3.5±0.9)×10-11 solar masses, the density is then ρ=3.8±1.0 g cm-3.

  20. 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

  1. 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.

  2. 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. PMID:24010933

  3. 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. PMID:26142156

  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. 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. PMID:20427100

  6. 3D modeling of metallic grain growth

    SciTech Connect

    George, D.; Carlson, N.; Gammel, J.T.; Kuprat, A.

    1999-06-01

    This paper will describe simulating metallic grain growth using the Gradient Weighted Moving Finite Elements code, GRAIN3D. The authors also describe the set of mesh topology change operations developed to respond to changes in the physical topology such as the collapse of grains and to maintain uniform calculational mesh quality. Validation of the method is demonstrated by comparison to analytic calculations. The authors present results of multigrain simulations where grain boundaries evolve by mean curvature motion and include results which incorporate grain boundary orientation dependence.

  7. 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.

  8. 3D-QSAR (CoMFA, CoMFA-RG, CoMSIA) and molecular docking study of thienopyrimidine and thienopyridine derivatives to explore structural requirements for aurora-B kinase inhibition.

    PubMed

    Borisa, Ankit; Bhatt, Hardik

    2015-11-15

    Aurora-B kinase plays a crucial role in cell cycle events and is identified as an important factor in regulation of spindle check point assembly. Thus, it can be proved as an important target in the field of oncology. 3D-QSAR model was generated using 54 molecules reported in literature containing thienopyrimidine and thienopyridine as scaffolds. All molecules were aligned using Distill function in Sybyl X1.2. This generated best model of CoMFA-RG (Region focusing) and CoMSIA were statistically significant with correlation coefficient r(2)ncv of 0.97, for both & Leave one out coefficient (LOO) q(2) of 0.70 and 0.72, respectively. Best CoMSIA model was built up using various combination of descriptors and proved statistical significant among all models. Best CoMFA-RG and CoMSIA models were validated by 12 test set molecules giving satisfactory prediction (r(2)pred) values of 0.86 and 0.88, respectively. External test set validation was performed using 20 molecules and satisfactory prediction of their biological activity was found. Active compounds were docked on protein (PDB ID: 4C2V) by GOLD module and revealed important interactions with amino acids at ATP-binding region. These data explored insight requirements for Aurora-B inhibition which might be fruitful for understanding mechanisms with kinase ligand interactions. PMID:26343315

  9. 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

  10. Life in 3D is never flat: 3D models to optimise drug delivery.

    PubMed

    Fitzgerald, Kathleen A; Malhotra, Meenakshi; Curtin, Caroline M; O' Brien, Fergal J; O' Driscoll, Caitriona M

    2015-10-10

    The development of safe, effective and patient-acceptable drug products is an expensive and lengthy process and the risk of failure at different stages of the development life-cycle is high. Improved biopharmaceutical tools which are robust, easy to use and accurately predict the in vivo response are urgently required to help address these issues. In this review the advantages and challenges of in vitro 3D versus 2D cell culture models will be discussed in terms of evaluating new drug products at the pre-clinical development stage. Examples of models with a 3D architecture including scaffolds, cell-derived matrices, multicellular spheroids and biochips will be described. The ability to simulate the microenvironment of tumours and vital organs including the liver, kidney, heart and intestine which have major impact on drug absorption, distribution, metabolism and toxicity will be evaluated. Examples of the application of 3D models including a role in formulation development, pharmacokinetic profiling and toxicity testing will be critically assessed. Although utilisation of 3D cell culture models in the field of drug delivery is still in its infancy, the area is attracting high levels of interest and is likely to become a significant in vitro tool to assist in drug product development thus reducing the requirement for unnecessary animal studies. PMID:26220617

  11. 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.

  12. 3D scene modeling from multiple range views

    NASA Astrophysics Data System (ADS)

    Sequeira, Vitor; Goncalves, Joao G. M.; Ribeiro, M. Isabel

    1995-09-01

    This paper presents a new 3D scene analysis system that automatically reconstructs the 3D geometric model of real-world scenes from multiple range images acquired by a laser range finder on board of a mobile robot. The reconstruction is achieved through an integrated procedure including range data acquisition, geometrical feature extraction, registration, and integration of multiple views. Different descriptions of the final 3D scene model are obtained: a polygonal triangular mesh, a surface description in terms of planar and biquadratics surfaces, and a 3D boundary representation. Relevant experimental results from the complete 3D scene modeling are presented. Direct applications of this technique include 3D reconstruction and/or update of architectual or industrial plans into a CAD model, design verification of buildings, navigation of autonomous robots, and input to virtual reality systems.

  13. Visualization of 3D Geological Models on Google Earth

    NASA Astrophysics Data System (ADS)

    Choi, Y.; Um, J.; Park, M.

    2013-05-01

    Google Earth combines satellite imagery, aerial photography, thematic maps and various data sets to make a three-dimensional (3D) interactive image of the world. Currently, Google Earth is a popular visualization tool in a variety of fields and plays an increasingly important role not only for private users in daily life, but also for scientists, practitioners, policymakers and stakeholders in research and application. In this study, a method to visualize 3D geological models on Google Earth is presented. COLLAborative Design Activity (COLLADA, an open standard XML schema for establishing interactive 3D applications) was used to represent different 3D geological models such as borehole, fence section, surface-based 3D volume and 3D grid by triangle meshes (a set of triangles connected by their common edges or corners). In addition, we designed Keyhole Markup Language (KML, the XML-based scripting language of Google Earth) codes to import the COLLADA files into the 3D render window of Google Earth. The method was applied to the Grosmont formation in Alberta, Canada. The application showed that the combination of COLLADA and KML enables Google Earth to effectively visualize 3D geological structures and properties.; Visualization of the (a) boreholes, (b) fence sections, (c) 3D volume model and (d) 3D grid model of Grossmont formation on Google Earth

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

    NASA Astrophysics Data System (ADS)

    Haas, Kevin A.; Warner, John C.

    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.

  15. 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.

  16. 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.

  17. 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…

  18. 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

  19. Evaluation of 3D-Jury on CASP7 models

    PubMed Central

    Kaján, László; Rychlewski, Leszek

    2007-01-01

    Background 3D-Jury, the structure prediction consensus method publicly available in the Meta Server , was evaluated using models gathered in the 7th round of the Critical Assessment of Techniques for Protein Structure Prediction (CASP7). 3D-Jury is an automated expert process that generates protein structure meta-predictions from sets of models obtained from partner servers. Results The performance of 3D-Jury was analysed for three aspects. First, we examined the correlation between the 3D-Jury score and a model quality measure: the number of correctly predicted residues. The 3D-Jury score was shown to correlate significantly with the number of correctly predicted residues, the correlation is good enough to be used for prediction. 3D-Jury was also found to improve upon the competing servers' choice of the best structure model in most cases. The value of the 3D-Jury score as a generic reliability measure was also examined. We found that the 3D-Jury score separates bad models from good models better than the reliability score of the original server in 27 cases and falls short of it in only 5 cases out of a total of 38. We report the release of a new Meta Server feature: instant 3D-Jury scoring of uploaded user models. Conclusion The 3D-Jury score continues to be a good indicator of structural model quality. It also provides a generic reliability score, especially important for models that were not assigned such by the original server. Individual structure modellers can also benefit from the 3D-Jury scoring system by testing their models in the new instant scoring feature available in the Meta Server. PMID:17711571

  20. AZOrange - High performance open source machine learning for QSAR modeling in a graphical programming environment

    PubMed Central

    2011-01-01

    Background Machine learning has a vast range of applications. In particular, advanced machine learning methods are routinely and increasingly used in quantitative structure activity relationship (QSAR) modeling. QSAR data sets often encompass tens of thousands of compounds and the size of proprietary, as well as public data sets, is rapidly growing. Hence, there is a demand for computationally efficient machine learning algorithms, easily available to researchers without extensive machine learning knowledge. In granting the scientific principles of transparency and reproducibility, Open Source solutions are increasingly acknowledged by regulatory authorities. Thus, an Open Source state-of-the-art high performance machine learning platform, interfacing multiple, customized machine learning algorithms for both graphical programming and scripting, to be used for large scale development of QSAR models of regulatory quality, is of great value to the QSAR community. Results This paper describes the implementation of the Open Source machine learning package AZOrange. AZOrange is specially developed to support batch generation of QSAR models in providing the full work flow of QSAR modeling, from descriptor calculation to automated model building, validation and selection. The automated work flow relies upon the customization of the machine learning algorithms and a generalized, automated model hyper-parameter selection process. Several high performance machine learning algorithms are interfaced for efficient data set specific selection of the statistical method, promoting model accuracy. Using the high performance machine learning algorithms of AZOrange does not require programming knowledge as flexible applications can be created, not only at a scripting level, but also in a graphical programming environment. Conclusions AZOrange is a step towards meeting the needs for an Open Source high performance machine learning platform, supporting the efficient development of

  1. Computational modeling of RNA 3D structures and interactions.

    PubMed

    Dawson, Wayne K; Bujnicki, Janusz M

    2016-04-01

    RNA molecules have key functions in cellular processes beyond being carriers of protein-coding information. These functions are often dependent on the ability to form complex three-dimensional (3D) structures. However, experimental determination of RNA 3D structures is difficult, which has prompted the development of computational methods for structure prediction from sequence. Recent progress in 3D structure modeling of RNA and emerging approaches for predicting RNA interactions with ions, ligands and proteins have been stimulated by successes in protein 3D structure modeling. PMID:26689764

  2. 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

  3. 3D-QSAR, design, synthesis and characterization of trisubstituted harmine derivatives with in vitro antiproliferative properties.

    PubMed

    Meinguet, Céline; Bruyère, Céline; Frédérick, Raphaël; Mathieu, Véronique; Vancraeynest, Christelle; Pochet, Lionel; Laloy, Julie; Mortier, Jérémie; Wolber, Gerhard; Kiss, Robert; Masereel, Bernard; Wouters, Johan

    2015-04-13

    Apolar trisubstituted derivatives of harmine show high antiproliferative activity on diverse cancer cell lines. However, these molecules present a poor solubility making these compounds poorly bioavailable. Here, new compounds were synthesized in order to improve solubility while retaining antiproliferative activity. First, polar substituents have shown a higher solubility but a loss of antiproliferative activity. Second, a Comparative Molecular Field Analysis (CoMFA) model was developed, guiding the design and synthesis of eight new compounds. Characterization has underlined the in vitro antiproliferative character of these compounds on five cancerous cell lines, combining with a high solubility at physiological pH, making these molecules druggable. Moreover, targeting glioma treatment, human intestinal absorption and blood brain penetration have been calculated, showing high absorption and penetration properties. PMID:25747498

  4. 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.

  5. 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.

  6. Simulation of 3D infrared scenes using random fields model

    NASA Astrophysics Data System (ADS)

    Shao, Xiaopeng; Zhang, Jianqi

    2001-09-01

    Analysis and simulation of smart munitions requires imagery for the munition's sensor to view. The traditional infrared background simulations are always limited in the plane scene studies. A new method is described to synthesize the images in 3D view and with various terrains texture. We develop the random fields model and temperature fields to simulate 3D infrared scenes. Generalized long-correlation (GLC) model, one of random field models, will generate both the 3D terrains skeleton data and the terrains texture in this work. To build the terrain mesh with the random fields, digital elevation models (DEM) are introduced in the paper. And texture mapping technology will perform the task of pasting the texture in the concavo-convex surfaces of the 3D scene. The simulation using random fields model is a very available method to produce 3D infrared scene with great randomicity and reality.

  7. 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.

  8. 3D-QSAR and molecular docking studies of 1,3,5-triazene-2,4-diamine derivatives against r-RNA: novel bacterial translation inhibitors.

    PubMed

    Sekhar, Y Nataraja; Nayana, M Ravi Shashi; Sivakumari, N; Ravikumar, Muttineni; Mahmood, S K

    2008-06-01

    Aminoglycoside mimetics inhibit bacterial translation by interfering with the ribosomal decoding site. To elucidate the structural properties of these compounds important for antibacterial activity, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were applied to a set of 56 aminoglycosides mimetics. The successful CoMFA model yielded the leave-one-out (LOO) cross-validated correlation coefficient (q(2)) of 0.708 and a non-cross-validated correlation coefficient (r(2)) of 0.967. CoMSIA model gave q(2)=0.556 and r(2)=0.935. The CoMFA and CoMSIA models were validated with 36 test set compounds and showed a good r(pred)(2) of 0.624 and 0.640, respectively. Contour maps of the two QSAR approaches show that electronic effects dominantly determine the binding affinities. These obtained results were agreed well with the experimental observations and docking studies. The results not only lead to a better understanding of structural requirements of bacterial translation inhibitors but also can help in the design of novel bacterial translation inhibitors. PMID:18372201

  9. 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.

  10. 3D scanning modeling method application in ancient city reconstruction

    NASA Astrophysics Data System (ADS)

    Ren, Pu; Zhou, Mingquan; Du, Guoguang; Shui, Wuyang; Zhou, Pengbo

    2015-07-01

    With the development of optical engineering technology, the precision of 3D scanning equipment becomes higher, and its role in 3D modeling is getting more distinctive. This paper proposed a 3D scanning modeling method that has been successfully applied in Chinese ancient city reconstruction. On one hand, for the existing architectures, an improved algorithm based on multiple scanning is adopted. Firstly, two pieces of scanning data were rough rigid registered using spherical displacers and vertex clustering method. Secondly, a global weighted ICP (iterative closest points) method is used to achieve a fine rigid registration. On the other hand, for the buildings which have already disappeared, an exemplar-driven algorithm for rapid modeling was proposed. Based on the 3D scanning technology and the historical data, a system approach was proposed for 3D modeling and virtual display of ancient city.

  11. 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

  12. 3-D model-based Bayesian classification

    SciTech Connect

    Soenneland, L.; Tenneboe, P.; Gehrmann, T.; Yrke, O.

    1994-12-31

    The challenging task of the interpreter is to integrate different pieces of information and combine them into an earth model. The sophistication level of this earth model might vary from the simplest geometrical description to the most complex set of reservoir parameters related to the geometrical description. Obviously the sophistication level also depend on the completeness of the available information. The authors describe the interpreter`s task as a mapping between the observation space and the model space. The information available to the interpreter exists in observation space and the task is to infer a model in model-space. It is well-known that this inversion problem is non-unique. Therefore any attempt to find a solution depend son constraints being added in some manner. The solution will obviously depend on which constraints are introduced and it would be desirable to allow the interpreter to modify the constraints in a problem-dependent manner. They will present a probabilistic framework that gives the interpreter the tools to integrate the different types of information and produce constrained solutions. The constraints can be adapted to the problem at hand.

  13. Opportunity Landing Spot Panorama (3-D Model)

    NASA Technical Reports Server (NTRS)

    2004-01-01

    The rocky outcrop traversed by the Mars Exploration Rover Opportunity is visible in this three-dimensional model of the rover's landing site. Opportunity has acquired close-up images along the way, and scientists are using the rover's instruments to closely examine portions of interest. The white fragments that look crumpled near the center of the image are portions of the airbags. Distant scenery is displayed on a spherical backdrop or 'billboard' for context. Artifacts near the top rim of the crater are a result of the transition between the three-dimensional model and the billboard. Portions of the terrain model lacking sufficient data appear as blank spaces or gaps, colored reddish-brown for better viewing. This image was generated using special software from NASA's Ames Research Center and a mosaic of images taken by the rover's panoramic camera.

    [figure removed for brevity, see original site] Click on image for larger view

    The rocky outcrop traversed by the Mars Exploration Rover Opportunity is visible in this zoomed-in portion of a three-dimensional model of the rover's landing site. Opportunity has acquired close-up images along the way, and scientists are using the rover's instruments to closely examine portions of interest. The white fragments that look crumpled near the center of the image are portions of the airbags. Distant scenery is displayed on a spherical backdrop or 'billboard' for context. Artifacts near the top rim of the crater are a result of the transition between the three-dimensional model and the billboard. Portions of the terrain model lacking sufficient data appear as blank spaces or gaps, colored reddish-brown for better viewing. This image was generated using special software from NASA's Ames Research Center and a mosaic of images taken by the rover's panoramic camera.

  14. 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. PMID:26764189

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. Kongsfjorden-MIKE 3D model

    NASA Astrophysics Data System (ADS)

    Przyborska, Anna; Kosecki, Szymon; Jakacki, Jaromir

    2014-05-01

    Kongsfjorden is a West Svalbard fjord with a surface area of about 210 km2. It is obvious that the depths of the outer and central basins are influenced by the open sea, under influence of West Spitsbergen Current (WSC), which curry out warm Atlantic water and cold East Spitsbergen Current, while the shallower, inner basin has a large glacial outflow and its maximum depths do not exceed 100 m. Freshwater stored in Spitsbergen glaciers have strong influence on local hydrology and physical fjord conditions. Both, local and shelf conditions have impact on state of the fjord. External forces like tides, velocities at the boundary and atmospheric forces together with sources of cold and dens fresh water in the fjords will give reliable representation of physical conditions in Kongsfjorden. Modeling could help to solve this problem and we have hope that we find answer which one is the most important for local conditions in fjord. Calculations of balances between cold fresh water and warm and salt will provide additional information that could help to answer the main question of the GAME (Growing of the Arctic Marine Ecosystem) project - what is the reaction of physically controlled Arctic marine ecosystem to temperature rise.

  3. 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.

  4. The 3D model: explaining densification and deformation mechanisms by using 3D parameter plots.

    PubMed

    Picker, Katharina M

    2004-04-01

    The aim of the study was to analyze very differently deforming materials using 3D parameter plots and consequently to gain deeper insights into the densification and deformation process described with the 3D model in order to define an ideal tableting excipient. The excipients used were dicalcium phosphate dihydrate (DCPD), sodium chloride (NaCl), microcrystalline cellulose (MCC), xylitol, mannitol, alpha-lactose monohydrate, maltose, hydroxypropyl methylcellulose (HPMC), sodium carboxymethylcellulose (NaCMC), cellulose acetate (CAC), maize starch, potato starch, pregelatinized starch, and maltodextrine. All of the materials were tableted to graded maximum relative densities (rhorel, max) using an eccentric tableting machine. The data which resulted, namely force, displacement, and time, were analyzed by the application of 3D modeling. Different particle size fractions of DCPD, CAC, and MCC were analyzed in addition. Brittle deforming materials such as DCPD exhibited a completely different 3D parameter plot, with low time plasticity, d, and low pressure plasticity, e, and a strong decrease in omega values when densification increased, in contrast to the plastically deforming MCC, which had much higher d, e, and omega values. e and omega values changed only slightly when densification increased for MCC. NaCl showed less of a decrease in omega values than DCPD did, and the d and e values were between those of MCC and DCPD. The sugar alcohols, xylitol and mannitol, behaved in a similar fashion to sodium chloride. This is also valid for the crystalline sugars, alpha-lactose monohydrate, and maltose. However, the sugars are more brittle than the sugar alcohols. The cellulose derivatives, HPMC, NaCMC, and CAC, are as plastic as MCC, however, their elasticity depends on substitution indicated by lower (more elastic) or higher (less elastic) omega values. The native starches, maize starch and potato starch, are very elastic, and pregelatinized starch and maltodextrine are

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. Metrological validation for 3D modeling of dental plaster casts.

    PubMed

    Brusco, Nicola; Andreetto, Marco; Lucchese, Luca; Carmignato, Simone; Cortelazzo, Guido M

    2007-11-01

    The contribution of this paper is twofold: (1) it presents an automatic 3D modeling technique and (2) it advances a procedure for its metrological evaluation in the context of a medical application, the 3D modeling of dental plaster casts. The motivation for this work is the creation of a "virtual gypsotheque" where cumbersome dental plaster casts can be replaced by numerical 3D models, thereby alleviating storage and access problems and allowing dentists and orthodontists the use of novel and unprecedented software tools for their medical evaluations. Modeling free-form surfaces of anatomical interest is an intriguing mixture of open issues concerning 3D modeling, geometrical metrology, and medicine. Of general interest is both the fact that a widespread use of 3D modeling in non-engineering applications requires automatic procedures of the kind presented in this work and the adopted validation paradigm for free-form surfaces, rather useful for practical purposes. In this latter respect, the metrological analysis we advance is the first seminal attempt in the field of 3D modeling and can be readily extended to contexts other than the medical one discussed in this paper. PMID:17126062

  11. 3D Modeling from Photos Given Topological Information.

    PubMed

    Kim, Young Min; Cho, Junghyun; Ahn, Sang Chul

    2016-09-01

    Reconstructing 3D models given a single-view 2D information is inherently an ill-posed problem and requires additional information such as shape prior or user input.We introduce a method to generate multiple 3D models of a particular category given corresponding photographs when the topological information is known. While there is a wide range of shapes for an object of a particular category, the basic topology usually remains constant.In consequence, the topological prior needs to be provided only once for each category and can be easily acquired by consulting an existing database of 3D models or by user input. The input of topological description is only connectivity information between parts; this is in contrast to previous approaches that have required users to interactively mark individual parts. Given the silhouette of an object and the topology, our system automatically finds a skeleton and generates a textured 3D model by jointly fitting multiple parts. The proposed method, therefore, opens the possibility of generating a large number of 3D models by consulting a massive number of photographs. We demonstrate examples of the topological prior and reconstructed 3D models using photos. PMID:26661474

  12. 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.

  13. 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. PMID:27018829

  14. 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.

  15. 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. PMID:22425566

  16. 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.

  17. 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

  18. 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

  19. Combined registration of 3D tibia and femur implant models in 3D magnetic resonance images

    NASA Astrophysics Data System (ADS)

    Englmeier, Karl-Hans; Siebert, Markus; von Eisenhart-Rothe, Ruediger; Graichen, Heiko

    2008-03-01

    The most frequent reasons for revision of total knee arthroplasty are loosening and abnormal axial alignment leading to an unphysiological kinematic of the knee implant. To get an idea about the postoperative kinematic of the implant, it is essential to determine the position and orientation of the tibial and femoral prosthesis. Therefore we developed a registration method for fitting 3D CAD-models of knee joint prostheses into an 3D MR image. This rigid registration is the basis for a quantitative analysis of the kinematics of knee implants. Firstly the surface data of the prostheses models are converted into a voxel representation; a recursive algorithm determines all boundary voxels of the original triangular surface data. Secondly an initial preconfiguration of the implants by the user is still necessary for the following step: The user has to perform a rough preconfiguration of both remaining prostheses models, so that the fine matching process gets a reasonable starting point. After that an automated gradient-based fine matching process determines the best absolute position and orientation: This iterative process changes all 6 parameters (3 rotational- and 3 translational parameters) of a model by a minimal amount until a maximum value of the matching function is reached. To examine the spread of the final solutions of the registration, the interobserver variability was measured in a group of testers. This variability, calculated by the relative standard deviation, improved from about 50% (pure manual registration) to 0.5% (rough manual preconfiguration and subsequent fine registration with the automatic fine matching process).

  20. 3D Bioprinting of Tissue/Organ Models.

    PubMed

    Pati, Falguni; Gantelius, Jesper; Svahn, Helene Andersson

    2016-04-01

    In vitro tissue/organ models are useful platforms that can facilitate systematic, repetitive, and quantitative investigations of drugs/chemicals. The primary objective when developing tissue/organ models is to reproduce physiologically relevant functions that typically require complex culture systems. Bioprinting offers exciting prospects for constructing 3D tissue/organ models, as it enables the reproducible, automated production of complex living tissues. Bioprinted tissues/organs may prove useful for screening novel compounds or predicting toxicity, as the spatial and chemical complexity inherent to native tissues/organs can be recreated. In this Review, we highlight the importance of developing 3D in vitro tissue/organ models by 3D bioprinting techniques, characterization of these models for evaluating their resemblance to native tissue, and their application in the prioritization of lead candidates, toxicity testing, and as disease/tumor models. PMID:26895542

  1. 3D web visualization of huge CityGML models

    NASA Astrophysics Data System (ADS)

    Prandi, F.; Devigili, F.; Soave, M.; Di Staso, U.; De Amicis, R.

    2015-08-01

    Nowadays, rapid technological development into acquiring geo-spatial information; joined to the capabilities to process these data in a relative short period of time, allows the generation of detailed 3D textured city models that will become an essential part of the modern city information infrastructure (Spatial Data Infrastructure) and, can be used to integrate various data from different sources for public accessible visualisation and many other applications. One of the main bottlenecks, which at the moment limit the use of these datasets to few experts, is a lack on efficient visualization systems through the web and interoperable frameworks that allow standardising the access to the city models. The work presented in this paper tries to satisfy these two requirements developing a 3D web-based visualization system based on OGC standards and effective visualization concepts. The architectural framework, based on Services Oriented Architecture (SOA) concepts, provides the 3D city data to a web client designed to support the view process in a very effective way. The first part of the work is to design a framework compliant to the 3D Portrayal Service drafted by the of the Open Geospatial Consortium (OGC) 3D standardization working group. The latter is related to the development of an effective web client able to render in an efficient way the 3D city models.

  2. 3-D electromagnetic modeling of wakefields in accelerator components

    SciTech Connect

    Poole, B.R.; Caporaso, G.J.; Ng, Wang C.; Shang, C.C.; Steich, D.

    1996-09-18

    We discuss the use of 3-D finite-difference time-domain (FDTD) electromagnetic codes for modeling accelerator components. Computational modeling of cylindrically symmetric structures such as induction accelerator cells has been very successful in predicting the wake potential and wake impedances of these structures, but full 3-D modeling of complex structures has been limited due to substantial computer resources required for a full 3-D model. New massively parallel 3-D time domain electromagnetic codes now under development using conforming unstructured meshes allow a substantial increase in the geometric fidelity of the structures being modeled. Development of these new codes are discussed in context of applicability to accelerator problems. Various 3-D structures are tested with an existing cubical cell FDTD code and wake impedances compared with simple analytic models for the structures; results will be used as benchmarks for testing the new time time domain codes. Structures under consideration include a stripline beam position monitor as well as circular and elliptical apertures in circular waveguides. Excellent agreement for monopole and dipole impedances with models were found for these structures below the cutoff frequency of the beam line.

  3. 3-D electromagnetic modeling of wakefields in accelerator components

    SciTech Connect

    Poole, Brian R.; Caporaso, George J.; Ng, Wang C.; Shang, Clifford C.; Steich, David

    1997-02-01

    We discuss the use of 3-D finite-difference time-domain (FDTD) electromagnetic codes for the modeling of accelerator components. Computational modeling of cylindrically symmetric structures such as induction accelerator cells has been extremely successful in predicting the wake potential and wake impedances of these structures, but fully 3-D modeling of complex structures has been limited due to the substantial computer resources required for a fully 3-D model. New massively parallel 3-D time domain electromagnetic codes now under development using conforming unstructured meshes allow a substantial increase in the geometric fidelity of the structures being modeled. Development of these new codes will be discussed in the context of their applicability to accelerator problems. A variety of 3-D structures are tested with an existing cubical cell FDTD code and the wake impedances are compared with simple analytic models for the structures. These results will provide a set of benchmarks for testing the new time domain codes. Structures under consideration include a stripline beam position monitor as well as circular and elliptical apertures in circular waveguides. Excellent agreement for the monopole and dipole impedances with the models are found for these structures below the cutoff frequency of the beam line.

  4. 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...

  5. The analysis of structure-anticancer and antiviral activity relationships for macrocyclic pyridinophanes and their analogues on the basis of 4D QSAR models (simplex representation of molecular structure).

    PubMed

    Kuz'min, Victor E; Artemenko, Anatoly G; Lozitsky, Victor P; Muratov, Eugene N; Fedtchouk, Alla S; Dyachenko, Natalia S; Nosach, Lidiya N; Gridina, Tatiyana L; Shitikova, Larisa I; Mudrik, Liubov M; Mescheriakov, Aleksey K; Chelombitko, Vladislav A; Zheltvay, Andrey I; Vanden Eynde, Jean-Jaques

    2002-01-01

    A new 4D-QSAR approach has been considered. For all investigated molecules the 3D structural models have been created and the set of conformers (fourth dimension) have been used. Each conformer is represented as a system of different simplexes (tetratomic fragments of fixed structure, chirality and symmetry). The investigation of influence of molecular structure of macrocyclic pyridinophanes, their analogues and certain other compounds on anticancer and antiviral (anti-influenza, antiherpes and antiadenovirus) activity has been carried out by means of the 4D-QSAR. Statistic characteristics for QSAR of PLS (partial least squares) models are satisfactory (R = 0.92-0.97; CVR = 0.63-0.83). Molecular fragments increasing and decreasing biological activity were defined. This information may be useful for design, and direct synthesis of novel anticancer and antiviral agents. PMID:12136936

  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. Perception-based shape retrieval for 3D building models

    NASA Astrophysics Data System (ADS)

    Zhang, Man; Zhang, Liqiang; Takis Mathiopoulos, P.; Ding, Yusi; Wang, Hao

    2013-01-01

    With the help of 3D search engines, a large number of 3D building models can be retrieved freely online. A serious disadvantage of most rotation-insensitive shape descriptors is their inability to distinguish between two 3D building models which are different at their main axes, but appear similar when one of them is rotated. To resolve this problem, we present a novel upright-based normalization method which not only correctly rotates such building models, but also greatly simplifies and accelerates the abstraction and the matching of building models' shape descriptors. Moreover, the abundance of architectural styles significantly hinders the effective shape retrieval of building models. Our research has shown that buildings with different designs are not well distinguished by the widely recognized shape descriptors for general 3D models. Motivated by this observation and to further improve the shape retrieval quality, a new building matching method is introduced and analyzed based on concepts found in the field of perception theory and the well-known Light Field descriptor. The resulting normalized building models are first classified using the qualitative shape descriptors of Shell and Unevenness which outline integral geometrical and topological information. These models are then put in on orderly fashion with the help of an improved quantitative shape descriptor which we will term as Horizontal Light Field Descriptor, since it assembles detailed shape characteristics. To accurately evaluate the proposed methodology, an enlarged building shape database which extends previous well-known shape benchmarks was implemented as well as a model retrieval system supporting inputs from 2D sketches and 3D models. Various experimental performance evaluation results have shown that, as compared to previous methods, retrievals employing the proposed matching methodology are faster and more consistent with human recognition of spatial objects. In addition these performance

  8. Microfluidic 3D cell culture: from tools to tissue models.

    PubMed

    van Duinen, Vincent; Trietsch, Sebastiaan J; Joore, Jos; Vulto, Paul; Hankemeier, Thomas

    2015-12-01

    The transition from 2D to 3D cell culture techniques is an important step in a trend towards better biomimetic tissue models. Microfluidics allows spatial control over fluids in micrometer-sized channels has become a valuable tool to further increase the physiological relevance of 3D cell culture by enabling spatially controlled co-cultures, perfusion flow and spatial control over of signaling gradients. This paper reviews most important developments in microfluidic 3D culture since 2012. Most efforts were exerted in the field of vasculature, both as a tissue on its own and as part of cancer models. We observe that the focus is shifting from tool building to implementation of specific tissue models. The next big challenge for the field is the full validation of these models and subsequently the implementation of these models in drug development pipelines of the pharmaceutical industry and ultimately in personalized medicine applications. PMID:26094109

  9. Evaluating Biomaterial- and Microfluidic-Based 3D Tumor Models.

    PubMed

    Carvalho, Mariana R; Lima, Daniela; Reis, Rui L; Correlo, Vitor M; Oliveira, Joaquim M

    2015-11-01

    Cancer is a major cause of morbidity and mortality worldwide, with a disease burden estimated to increase over the coming decades. Disease heterogeneity and limited information on cancer biology and disease mechanisms are aspects that 2D cell cultures fail to address. Here, we review the current ‘state-of-the-art’ in 3D tissue-engineering (TE) models developed for, and used in, cancer research. We assess the potential for scaffold-based TE models and microfluidics to fill the gap between 2D models and clinical application. We also discuss recent advances in combining the principles of 3D TE models and microfluidics, with a special focus on biomaterials and the most promising chip-based 3D models. PMID:26603572

  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. 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. PMID:27037463

  12. 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. PMID:26851376

  13. 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

  14. 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

  15. 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.

  16. MR image denoising method for brain surface 3D modeling

    NASA Astrophysics Data System (ADS)

    Zhao, De-xin; Liu, Peng-jie; Zhang, De-gan

    2014-11-01

    Three-dimensional (3D) modeling of medical images is a critical part of surgical simulation. In this paper, we focus on the magnetic resonance (MR) images denoising for brain modeling reconstruction, and exploit a practical solution. We attempt to remove the noise existing in the MR imaging signal and preserve the image characteristics. A wavelet-based adaptive curve shrinkage function is presented in spherical coordinates system. The comparative experiments show that the denoising method can preserve better image details and enhance the coefficients of contours. Using these denoised images, the brain 3D visualization is given through surface triangle mesh model, which demonstrates the effectiveness of the proposed method.

  17. Modeling Liver-Related Adverse Effects of Drugs Using kNN QSAR Method

    PubMed Central

    Rodgers, Amie D.; Zhu, Hao; Fourches, Dennis; Rusyn, Ivan; Tropsha, Alexander

    2010-01-01

    Adverse effects of drugs (AEDs) continue to be a major cause of drug withdrawals both in development and post-marketing. While liver-related AEDs are a major concern for drug safety, there are few in silico models for predicting human liver toxicity for drug candidates. We have applied the Quantitative Structure Activity Relationship (QSAR) approach to model liver AEDs. In this study, we aimed to construct a QSAR model capable of binary classification (active vs. inactive) of drugs for liver AEDs based on chemical structure. To build QSAR models, we have employed an FDA spontaneous reporting database of human liver AEDs (elevations in activity of serum liver enzymes), which contains data on approximately 500 approved drugs. Approximately 200 compounds with wide clinical data coverage, structural similarity and balanced (40/60) active/inactive ratio were selected for modeling and divided into multiple training/test and external validation sets. QSAR models were developed using the k nearest neighbor method and validated using external datasets. Models with high sensitivity (>73%) and specificity (>94%) for prediction of liver AEDs in external validation sets were developed. To test applicability of the models, three chemical databases (World Drug Index, Prestwick Chemical Library, and Biowisdom Liver Intelligence Module) were screened in silico and the validity of predictions was determined, where possible, by comparing model-based classification with assertions in publicly available literature. Validated QSAR models of liver AEDs based on the data from the FDA spontaneous reporting system can be employed as sensitive and specific predictors of AEDs in pre-clinical screening of drug candidates for potential hepatotoxicity in humans. PMID:20192250

  18. 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

  19. 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.

  20. 3D head model classification using optimized EGI

    NASA Astrophysics Data System (ADS)

    Tong, Xin; Wong, Hau-san; Ma, Bo

    2006-02-01

    With the general availability of 3D digitizers and scanners, 3D graphical models have been used widely in a variety of applications. This has led to the development of search engines for 3D models. Especially, 3D head model classification and retrieval have received more and more attention in view of their many potential applications in criminal identifications, computer animation, movie industry and medical industry. This paper addresses the 3D head model classification problem using 2D subspace analysis methods such as 2D principal component analysis (2D PCA[3]) and 2D fisher discriminant analysis (2DLDA[5]). It takes advantage of the fact that the histogram is a 2D image, and we can extract the most useful information from these 2D images to get a good result accordingingly. As a result, there are two main advantages: First, we can perform less calculation to obtain the same rate of classification; second, we can reduce the dimensionality more than PCA to obtain a higher efficiency.

  1. 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. PMID:25913312

  2. Vhrs Stereo Images for 3d Modelling of Buildings

    NASA Astrophysics Data System (ADS)

    Bujakiewicz, A.; Holc, M.

    2012-07-01

    The paper presents the project which was carried out in the Photogrammetric Laboratory of Warsaw University of Technology. The experiment is concerned with the extraction of 3D vector data for buildings creation from 3D photogrammetric model based on the Ikonos stereo images. The model was reconstructed with photogrammetric workstation - Summit Evolution combined with ArcGIS 3D platform. Accuracy of 3D model was significantly improved by use for orientation of pair of satellite images the stereo measured tie points distributed uniformly around the model area in addition to 5 control points. The RMS for model reconstructed on base of the RPC coefficients only were 16,6 m, 2,7 m and 47,4 m, for X, Y and Z coordinates, respectively. By addition of 5 control points the RMS were improved to 0,7 m, 0,7 m 1,0 m, where the best results were achieved when RMS were estimated from deviations in 17 check points (with 5 control points)and amounted to 0,4 m, 0,5 m and 0,6 m, for X, Y, and Z respectively. The extracted 3D vector data for buildings were integrated with 2D data of the ground footprints and afterwards they were used for 3D modelling of buildings in Google SketchUp software. The final results were compared with the reference data obtained from other sources. It was found that the shape of buildings (in concern to the number of details) had been reconstructed on level of LoD1, when the accuracy of these models corresponded to the level of LoD2.

  3. 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.

  4. 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.

  5. SAR/QSAR MODELS FOR TOXICITY PREDICTION: APPROACHES AND NEW DIRECTIONS

    EPA Science Inventory

    Abstract

    SAR/QSAR MODELS FOR TOXICITY PREDICTION: APPROACHES AND NEW DIRECTIONS

    Risk assessment typically incorporates some relevant toxicity information upon which to base a sound estimation for a chemical of concern. However, there are many circumstances in whic...

  6. 3D surface digitizing and modeling development at ITRI

    NASA Astrophysics Data System (ADS)

    Hsueh, Wen-Jean

    2000-06-01

    This paper gives an overview of the research and development activities in 3D surface digitizing and modeling conducted at the Industrial Technology Research Institute (ITRI) of Taiwan in the past decade. As a major technology and consulting service provider of the area, ITRI has developed 3D laser scanning digitizers ranging from low-cost compacts, industrial CAD/CAM digitizing, to large human body scanner, with in-house 3D surface modeling software to provide total solution in reverse engineering that requires processing capabilities of large number of 3D data. Based on both hardware and software technologies in scanning, merging, registration, surface fitting, reconstruction, and compression, ITRI is now exploring innovative methodologies that provide higher performances, including hardware-based correlation algorithms with advanced camera designs, animation surface model reconstruction, and optical tracking for motion capture. It is expected that the need for easy and fast high-quality 3D information in the near future will grow exponentially, at the same amazing rate as the internet and the human desire for realistic and natural images.

  7. Diffusion approximation for modeling of 3-D radiation distributions

    SciTech Connect

    Zardecki, A.; Gerstl, S.A.W.; De Kinder, R.E. Jr.

    1985-01-01

    A three-dimensional transport code DIF3D, based on the diffusion approximation, is used to model the spatial distribution of radiation energy arising from volumetric isotropic sources. Future work will be concerned with the determination of irradiances and modeling of realistic scenarios, relevant to the battlefield conditions. 8 refs., 4 figs.

  8. 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

  9. Modelling Gaia CCD pixels with Silvaco 3D engineering software

    NASA Astrophysics Data System (ADS)

    Seabroke, G. M.; Prod'Homme, T.; Hopkinson, G.; Burt, D.; Robbins, M.; Holland, A.

    2011-02-01

    Gaia will only achieve its unprecedented measurement accuracy requirements with detailed calibration and correction for radiation damage. We present our Silvaco 3D engineering software model of the Gaia CCD pixel and two of its applications for Gaia: (1) physically interpreting supplementary buried channel (SBC) capacity measurements (pocket-pumping and first pixel response) in terms of e2v manufacturing doping alignment tolerances; and (2) deriving electron densities within a charge packet as a function of the number of constituent electrons and 3D position within the charge packet as input to microscopic models being developed to simulate radiation damage.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. Creating Physical 3D Stereolithograph Models of Brain and Skull

    PubMed Central

    Kelley, Daniel J.; Farhoud, Mohammed; Meyerand, M. Elizabeth; Nelson, David L.; Ramirez, Lincoln F.; Dempsey, Robert J.; Wolf, Alan J.; Alexander, Andrew L.; Davidson, Richard J.

    2007-01-01

    The human brain and skull are three dimensional (3D) anatomical structures with complex surfaces. However, medical images are often two dimensional (2D) and provide incomplete visualization of structural morphology. To overcome this loss in dimension, we developed and validated a freely available, semi-automated pathway to build 3D virtual reality (VR) and hand-held, stereolithograph models. To evaluate whether surface visualization in 3D was more informative than in 2D, undergraduate students (n = 50) used the Gillespie scale to rate 3D VR and physical models of both a living patient-volunteer's brain and the skull of Phineas Gage, a historically famous railroad worker whose misfortune with a projectile tamping iron provided the first evidence of a structure-function relationship in brain. Using our processing pathway, we successfully fabricated human brain and skull replicas and validated that the stereolithograph model preserved the scale of the VR model. Based on the Gillespie ratings, students indicated that the biological utility and quality of visual information at the surface of VR and stereolithograph models were greater than the 2D images from which they were derived. The method we developed is useful to create VR and stereolithograph 3D models from medical images and can be used to model hard or soft tissue in living or preserved specimens. Compared to 2D images, VR and stereolithograph models provide an extra dimension that enhances both the quality of visual information and utility of surface visualization in neuroscience and medicine. PMID:17971879

  18. 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

  19. 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.

  20. 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. PMID:26200234

  1. 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…

  2. 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. PMID:20439141

  3. A Sketching Interface for Freeform 3D Modeling

    NASA Astrophysics Data System (ADS)

    Igarashi, Takeo

    This chapter introduces Teddy, a sketch-based modeling system to quickly and easily design freeform models such as stuffed animals and other rotund objects. The user draws several 2D freeform strokes interactively on the screen and the system automatically constructs plausible 3D polygonal surfaces. Our system supports several modeling operations, including the operation to construct a 3D polygonal surface from a 2D silhouette drawn by the user: it inflates the region surrounded by the silhouette making a wide area fat, and a narrow area thin. Teddy, our prototype system, is implemented as a Java program, and the mesh construction is done in real-time on a standard PC. Our informal user study showed that a first-time user masters the operations within 10 minutes, and can construct interesting 3D models within minutes. We also report the result of a case study where a high school teacher taught various 3D concepts in geography using the system.

  4. 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…

  5. 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

  6. QSAR as a random event: modeling of nanoparticles uptake in PaCa2 cancer cells.

    PubMed

    Toropov, Andrey A; Toropova, Alla P; Puzyn, Tomasz; Benfenati, Emilio; Gini, Giuseppina; Leszczynska, Danuta; Leszczynski, Jerzy

    2013-06-01

    Quantitative structure-property/activity relationships (QSPRs/QSARs) are a tool to predict various endpoints for various substances. The "classic" QSPR/QSAR analysis is based on the representation of the molecular structure by the molecular graph. However, simplified molecular input-line entry system (SMILES) gradually becomes most popular representation of the molecular structure in the databases available on the Internet. Under such circumstances, the development of molecular descriptors calculated directly from SMILES becomes attractive alternative to "classic" descriptors. The CORAL software (http://www.insilico.eu/coral) is provider of SMILES-based optimal molecular descriptors which are aimed to correlate with various endpoints. We analyzed data set on nanoparticles uptake in PaCa2 pancreatic cancer cells. The data set includes 109 nanoparticles with the same core but different surface modifiers (small organic molecules). The concept of a QSAR as a random event is suggested in opposition to "classic" QSARs which are based on the only one distribution of available data into the training and the validation sets. In other words, five random splits into the "visible" training set and the "invisible" validation set were examined. The SMILES-based optimal descriptors (obtained by the Monte Carlo technique) for these splits are calculated with the CORAL software. The statistical quality of all these models is good. PMID:23566368

  7. Thermal 3D Modeling of Geothermal Area Using Terrestrial Photogrammetry

    NASA Astrophysics Data System (ADS)

    Akcay, Ozgun; Cuneyt Erenoglu, Ramazan; Erenoglu, Oya; Yılmazturk, Ferruh; Karaca, Zeki

    2015-04-01

    Photogrammetry and computer vision, sciences producing high accuracy 3D models from digital images based on projective geometry. 3D models can also be produced using thermal camera images using photogrammetry and computer vision techniques. Thermal images are capable of displaying hotspots on geothermal areas as a heat source in details. In the research, Tuzla geothermal area in Çanakkale province of Turkey is inspected using imaging techniques of terrestrial photogrammetry. Both a digital camera Canon EOS 650D and an infrared camera Optris PI 450 are used to obtain images of the thermal site. Calibration parameters (focal length, principle point, distortion coefficients) of thermal and digital cameras are determined using the calibration test field at the laboratory before the field work. In order to provide the georeferencing and the robustness of the 3D model, aluminum discs having diameter of 30 centimeters as ground control points (GCPs) are set to the geothermal area appropriately before imaging. Aluminum targets are chosen as the GCP because they are determined on the image depending on the contrast reflectance rate of the aluminum. Using GNSS RTK receivers supplying ±1 cm accuracy positioning, GCPs are measured so as to implement photogrammetric process successfully with thermal images. Numerous corresponding points are detected on the overlapped images with image matching techniques. Later on, bundle block adjustment is applied to calculate the revised interior orientation parameters of camera and exterior orientation parameters of camera positions. The 3D model showing details of the surface temperatures of the geothermal area are produced with multi view stereo (MVS) technique. The technique is able to produce 3D representation (point cloud, mesh and textured surface) of the field from both the thermal and digital images. The research presents that photogrammetric evaluation of thermal images is a noteworthy method to obtain a quick- accurate 3D

  8. 3D geometric modelling of hand-woven textile

    NASA Astrophysics Data System (ADS)

    Shidanshidi, H.; Naghdy, F.; Naghdy, G.; Conroy, D. Wood

    2008-02-01

    Geometric modeling and haptic rendering of textile has attracted significant interest over the last decade. A haptic representation is created by adding the physical properties of an object to its geometric configuration. While research has been conducted into geometric modeling of fabric, current systems require time-consuming manual recognition of textile specifications and data entry. The development of a generic approach for construction of the 3D geometric model of a woven textile is pursued in this work. The geometric model would be superimposed by a haptic model in the future work. The focus at this stage is on hand-woven textile artifacts for display in museums. A fuzzy rule based algorithm is applied to the still images of the artifacts to generate the 3D model. The derived model is exported as a 3D VRML model of the textile for visual representation and haptic rendering. An overview of the approach is provided and the developed algorithm is described. The approach is validated by applying the algorithm to different textile samples and comparing the produced models with the actual structure and pattern of the samples.

  9. A biochemical/biophysical 3D FE intervertebral disc model.

    PubMed

    Schroeder, Y; Huyghe, J M; van Donkelaar, C C; Ito, K

    2010-10-01

    Present research focuses on different strategies to preserve the degenerated disc. To assure long-term success of novel approaches, favorable mechanical conditions in the disc tissue are essential. To evaluate these, a model is required that can determine internal mechanical conditions which cannot be directly measured as a function of assessable biophysical characteristics. Therefore, the objective is to evaluate if constitutive and material laws acquired on isolated samples of nucleus and annulus tissue can be used directly in a whole-organ 3D FE model to describe intervertebral disc behavior. The 3D osmo-poro-visco-hyper-elastic disc (OVED) model describes disc behavior as a function of annulus and nucleus tissue biochemical composition, organization and specific constituent properties. The description of the 3D collagen network was enhanced to account for smaller fibril structures. Tissue mechanical behavior tests on isolated nucleus and annulus samples were simulated with models incorporating tissue composition to calculate the constituent parameter values. The obtained constitutive laws were incorporated into the whole-organ model. The overall behavior and disc properties of the model were corroborated against in vitro creep experiments of human L4/L5 discs. The OVED model simulated isolated tissue experiments on confined compression and uniaxial tensile test and whole-organ disc behavior. This was possible, provided that secondary fiber structures were accounted for. The fair agreement (radial bulge, axial creep deformation and intradiscal pressure) between model and experiment was obtained using constitutive properties that are the same for annulus and nucleus. Both tissue models differed in the 3D OVED model only by composition. The composition-based modeling presents the advantage of reducing the numbers of material parameters to a minimum and to use tissue composition directly as input. Hence, this approach provides the possibility to describe internal

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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...

  15. 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.

  16. 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

  17. Analogue-based approaches in anti-cancer compound modelling: the relevance of QSAR models

    PubMed Central

    2011-01-01

    Background QSAR is among the most extensively used computational methodology for analogue-based design. The application of various descriptor classes like quantum chemical, molecular mechanics, conceptual density functional theory (DFT)- and docking-based descriptors for predicting anti-cancer activity is well known. Although in vitro assay for anti-cancer activity is available against many different cell lines, most of the computational studies are carried out targeting insufficient number of cell lines. Hence, statistically robust and extensive QSAR studies against 29 different cancer cell lines and its comparative account, has been carried out. Results The predictive models were built for 266 compounds with experimental data against 29 different cancer cell lines, employing independent and least number of descriptors. Robust statistical analysis shows a high correlation, cross-validation coefficient values, and provides a range of QSAR equations. Comparative performance of each class of descriptors was carried out and the effect of number of descriptors (1-10) on statistical parameters was tested. Charge-based descriptors were found in 20 out of 39 models (approx. 50%), valency-based descriptor in 14 (approx. 36%) and bond order-based descriptor in 11 (approx. 28%) in comparison to other descriptors. The use of conceptual DFT descriptors does not improve the statistical quality of the models in most cases. Conclusion Analysis is done with various models where the number of descriptors is increased from 1 to 10; it is interesting to note that in most cases 3 descriptor-based models are adequate. The study reveals that quantum chemical descriptors are the most important class of descriptors in modelling these series of compounds followed by electrostatic, constitutional, geometrical, topological and conceptual DFT descriptors. Cell lines in nasopharyngeal (2) cancer average R2 = 0.90 followed by cell lines in melanoma cancer (4) with average R2 = 0.81 gave the

  18. A method for building 3D models of barchan dunes

    NASA Astrophysics Data System (ADS)

    Nai, Yang; Li-lan, Su; Lin, Wan; Jie, Yang; Shi-yi, Chen; Wei-lu, Hu

    2016-01-01

    The distributions of barchan dunes are usually represented by digital terrain models (DTMs) overlaid with digital orthophoto maps. Given that most regions with barchan dues have low relief, a 3D map obtained from a DTM may ineffectively show the stereoscopic shape of each dune. The method of building 3D models of barchan dunes using existing modeling software seldom considers the geographical environment. As a result, barchan dune models are often inconsistent with actual DTMs and incompletely express the morphological characteristics of dunes. Manual construction of barchan dune models is also costly and time consuming. Considering these problems, the morphological characteristics of barchan dunes and the mathematical relationships between the morphological parameters of the dunes, such as length, height, and width, are analyzed in this study. The methods of extracting the morphological feature points of barchan dunes, calculating their morphological parameters and building dune outlines and skeleton lines based on the medial axes, are also presented. The dune outlines, skeleton lines, and part of the medial axes of dunes are used to construct a constrained triangulated irregular network. C# and ArcEngine are employed to build 3D models of barchan dunes automatically. Experimental results of a study conducted in Tengger Desert show that the method can be used to approximate the morphological characteristics of barchan dunes and is less time consuming than manual methods.

  19. Geometric and colour data fusion for outdoor 3D models.

    PubMed

    Merchán, Pilar; Adán, Antonio; Salamanca, Santiago; Domínguez, Vicente; Chacón, Ricardo

    2012-01-01

    This paper deals with the generation of accurate, dense and coloured 3D models of outdoor scenarios from scanners. This is a challenging research field in which several problems still remain unsolved. In particular, the process of 3D model creation in outdoor scenes may be inefficient if the scene is digitalized under unsuitable technical (specific scanner on-board camera) and environmental (rain, dampness, changing illumination) conditions. We address our research towards the integration of images and range data to produce photorealistic models. Our proposal is based on decoupling the colour integration and geometry reconstruction stages, making them independent and controlled processes. This issue is approached from two different viewpoints. On the one hand, given a complete model (geometry plus texture), we propose a method to modify the original texture provided by the scanner on-board camera with the colour information extracted from external images taken at given moments and under specific environmental conditions. On the other hand, we propose an algorithm to directly assign external images onto the complete geometric model, thus avoiding tedious on-line calibration processes. We present the work conducted on two large Roman archaeological sites dating from the first century A.D., namely, the Theatre of Segobriga and the Fori Porticus of Emerita Augusta, both in Spain. The results obtained demonstrate that our approach could be useful in the digitalization and 3D modelling fields. PMID:22969327

  20. 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

  1. 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

  2. 3D Babcock-Leighton Solar Dynamo Models

    NASA Astrophysics Data System (ADS)

    Miesch, Mark S.; Hazra, Gopal; Karak, Bidya Binay; Teweldebirhan, Kinfe; Upton, Lisa

    2016-05-01

    We present results from the new STABLE (Surface flux Transport and Babcock Leighton) Dynamo Model. STABLE is a 3D Babcock-Leighton/Flux Transport dynamo model in which the source of poloidal field is the explicit emergence, distortion, and dispersal of bipolar magnetic regions (BMRs). In this talk I will discuss initial results with axisymmetric flow fields, focusing on the operation of the model, the general features of the cyclic solutions, and the challenge of achieving supercritical dynamo solutions using only the Babcock-Leighton source term. Then I will present dynamo simulations that include 3D convective flow fields based on the observed velocity power spectrum inferred from photospheric Dopplergrams. I'll use these simulations to assess how the explicit transport and amplification of fields by surface convection influences the operation of the dynamo. I will also discuss the role of surface magnetic fields in regulating the subsurface toroidal flux budget.

  3. 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.

  4. Texture blending on 3D models using casual images

    NASA Astrophysics Data System (ADS)

    Liu, Xingming; Liu, Xiaoli; Li, Ameng; Liu, Junyao; Wang, Huijing

    2013-12-01

    In this paper, a method for constructing photorealistic textured model using 3D structured light digitizer is presented. Our method acquisition of range images and texture images around object, and range images are registered and integrated to construct geometric model of object. System is calibrated and poses of texture-camera are determined so that the relationship between texture and geometric model is established. After that, a global optimization is applied to assign compatible texture to adjacent surface and followed with a level procedure to remove artifacts due to vary lighting, approximate geometric model and so on. Lastly, we demonstrate the effect of our method on constructing a real model of world.

  5. A 3D alcoholic liver disease model on a chip.

    PubMed

    Lee, JaeSeo; Choi, BongHwan; No, Da Yoon; Lee, GeonHui; Lee, Seung-Ri; Oh, HyunJik; Lee, Sang-Hoon

    2016-03-14

    Alcohol is one of the main causes of liver diseases, and the development of alcoholic liver disease (ALD) treatment methods has been one of the hottest issues. For this purpose, development of in vitro models mimicking the in vivo physiology is one of the critical requirements, and they help to determine the disease mechanisms and to discover the treatment method. Herein, a three-dimensional (3D) ALD model was developed and its superior features in mimicking the in vivo condition were demonstrated. A spheroid-based microfluidic chip was employed for the development of the 3D in vitro model of ALD progression. We co-cultured rat primary hepatocytes and hepatic stellate cells (HSCs) in a fluidic chip to investigate the role of HSCs in the recovery of liver with ALD. An interstitial level of flow derived by an osmotic pump was applied to the chip to provide in vivo mimicking of fluid activity. Using this in vitro tool, we were able to observe structural changes and decreased hepatic functions with the increase in ethanol concentration. The recovery process of liver injured by alcohol was observed by providing fresh culture medium to the damaged 3D liver tissue for few days. A reversibly- and irreversibly-injured ALD model was established. The proposed model can not only be used for the research of alcoholic disease mechanism, but also has the potential for use in studies of hepatotoxicity and drug screening applications. PMID:26857817

  6. Two-equation turbulence modeling for 3-D hypersonic flows

    NASA Technical Reports Server (NTRS)

    Bardina, J. E.; Coakley, T. J.; Marvin, J. G.

    1992-01-01

    An investigation to verify, incorporate and develop two-equation turbulence models for three-dimensional high speed flows is presented. The current design effort of hypersonic vehicles has led to an intensive study of turbulence models for compressible hypersonic flows. This research complements an extensive review of experimental data and the current development of 2D turbulence models. The review of experimental data on 2D and 3D flows includes complex hypersonic flows with pressure profiles, skin friction, wall heat transfer, and turbulence statistics data. In a parallel effort, turbulence models for high speed flows have been tested against flat plate boundary layers, and are being tested against the 2D database. In the present paper, we present the results of 3D Navier-Stokes numerical simulations with an improved k-omega two-equation turbulence model against experimental data and empirical correlations of an adiabatic flat plate boundary layer, a cold wall flat plate boundary layer, and a 3D database flow, the interaction of an oblique shock wave and a thick turbulent boundary layer with a free stream Mach number = 8.18 and Reynolds number = 5 x 10 to the 6th.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. QSAR Modeling Using Large-Scale Databases: Case Study for HIV-1 Reverse Transcriptase Inhibitors.

    PubMed

    Tarasova, Olga A; Urusova, Aleksandra F; Filimonov, Dmitry A; Nicklaus, Marc C; Zakharov, Alexey V; Poroikov, Vladimir V

    2015-07-27

    Large-scale databases are important sources of training sets for various QSAR modeling approaches. Generally, these databases contain information extracted from different sources. This variety of sources can produce inconsistency in the data, defined as sometimes widely diverging activity results for the same compound against the same target. Because such inconsistency can reduce the accuracy of predictive models built from these data, we are addressing the question of how best to use data from publicly and commercially accessible databases to create accurate and predictive QSAR models. We investigate the suitability of commercially and publicly available databases to QSAR modeling of antiviral activity (HIV-1 reverse transcriptase (RT) inhibition). We present several methods for the creation of modeling (i.e., training and test) sets from two, either commercially or freely available, databases: Thomson Reuters Integrity and ChEMBL. We found that the typical predictivities of QSAR models obtained using these different modeling set compilation methods differ significantly from each other. The best results were obtained using training sets compiled for compounds tested using only one method and material (i.e., a specific type of biological assay). Compound sets aggregated by target only typically yielded poorly predictive models. We discuss the possibility of "mix-and-matching" assay data across aggregating databases such as ChEMBL and Integrity and their current severe limitations for this purpose. One of them is the general lack of complete and semantic/computer-parsable descriptions of assay methodology carried by these databases that would allow one to determine mix-and-matchability of result sets at the assay level. PMID:26046311

  18. 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.

  19. Homology modeling and QSAR analysis of 1,3,4-thiadiazole and 1,3,4-triazole derivatives as carbonic anhydrase inhibitors.

    PubMed

    Akula, N V Murali Krishna; Kumar, Surendra; Singh, Vineet; Tiwari, Meena

    2010-08-01

    Carbonic anhydrase (CA) inhibitors are very interesting target for designing anticancer (hypoxic) and antiglaucoma drugs. In the present study, a 3D homology modeling of human carbonic anhydrase-IX (hCA-IX) isozyme, based upon the crystal structure of murine CA-XIVA (PDB CODE 1RJ5) was performed, as no experimental 3D structures are available. A homology model of hCA-IX was developed and validated. To explore the responsible physicochemical properties of 1,3,4-thiadiazole and 1,3,4-triazole derivatives for carbonic anhydrase inhibition, a quantitative structure activity relationship (QSAR) study was performed having hCA-II and hCA-IX inhibitory activity respectively. In hCA-II and hCA-IX inhibitory activities, four significant models with good correlations (> or = 0.945 & > or = 0.926) were obtained; two models (models 1 and 3) were selected based on statistical criterion. The QSAR study revealed that in case of hCA-II, overall increase in size and volume of molecule, introduction of electropositive surfaces might increase the inhibitory activity, whereas in case of hCA-IX, decreasing the hydrophobicity and introduction of electron releasing substituents might increase the hCA-IX inhibitory activity. PMID:21174951

  20. Trust, but verify: On the importance of chemical structure curation in cheminformatics and QSAR modeling research

    PubMed Central

    Fourches, Denis; Muratov, Eugene; Tropsha, Alexander

    2010-01-01

    Molecular modelers and cheminformaticians typically analyze experimental data generated by other scientists. Consequently, when it comes to data accuracy, cheminformaticians are always at the mercy of data providers who may inadvertently publish (partially) erroneous data. Thus, dataset curation is crucial for any cheminformatics analysis such as similarity searching, clustering, QSAR modeling, virtual screening, etc., especially nowadays when the availability of chemical datasets in public domain has skyrocketed in recent years. Despite the obvious importance of this preliminary step in the computational analysis of any dataset, there appears to be no commonly accepted guidance or set of procedures for chemical data curation. The main objective of this paper is to emphasize the need for a standardized chemical data curation strategy that should be followed at the onset of any molecular modeling investigation. Herein, we discuss several simple but important steps for cleaning chemical records in a database including the removal of a fraction of the data that cannot be appropriately handled by conventional cheminformatics techniques. Such steps include the removal of inorganic and organometallic compounds, counterions, salts and mixtures; structure validation; ring aromatization; normalization of specific chemotypes; curation of tautomeric forms; and the deletion of duplicates. To emphasize the importance of data curation as a mandatory step in data analysis, we discuss several case studies where chemical curation of the original “raw” database enabled the successful modeling study (specifically, QSAR analysis) or resulted in a significant improvement of model's prediction accuracy. We also demonstrate that in some cases rigorously developed QSAR models could be even used to correct erroneous biological data associated with chemical compounds. We believe that good practices for curation of chemical records outlined in this paper will be of value to all

  1. 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

  2. 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).

  3. 2D quantum double models from a 3D perspective

    NASA Astrophysics Data System (ADS)

    Bernabé Ferreira, Miguel Jorge; Padmanabhan, Pramod; Teotonio-Sobrinho, Paulo

    2014-09-01

    In this paper we look at three dimensional (3D) lattice models that are generalizations of the state sum model used to define the Kuperberg invariant of 3-manifolds. The partition function is a scalar constructed as a tensor network where the building blocks are tensors given by the structure constants of an involutory Hopf algebra A. These models are very general and are hard to solve in its entire parameter space. One can obtain familiar models, such as ordinary gauge theories, by letting A be the group algebra {C}(G) of a discrete group G and staying on a certain region of the parameter space. We consider the transfer matrix of the model and show that quantum double Hamiltonians are derived from a particular choice of the parameters. Such a construction naturally leads to the star and plaquette operators of the quantum double Hamiltonians, of which the toric code is a special case when A={C}({{{Z}}_{2}}). This formulation is convenient to study ground states of these generalized quantum double models where they can naturally be interpreted as tensor network states. For a surface Σ, the ground state degeneracy is determined by the Kuperberg 3-manifold invariant of \\Sigma \\times {{S}^{1}}. It is also possible to obtain extra models by simply enlarging the allowed parameter space but keeping the solubility of the model. While some of these extra models have appeared before in the literature, our 3D perspective allows for an uniform description of them.

  4. 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.

  5. 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).

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

    NASA Astrophysics Data System (ADS)

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

    2013-11-01

    In this work, we propose a dynamic, flexible and interactive urban digital terrain platform (DTP) with spatial data and query processing capabilities of Geographic Information Systems (GIS), 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 (DSM) 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.

  7. 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.

  8. 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.

  9. 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.

  10. Modeling and Processing of Continuous 3D Elastic Wavefield Data

    NASA Astrophysics Data System (ADS)

    Milkereit, B.; Bohlen, T.

    2001-12-01

    Continuous seismic wavefields are excited by earthquake clustering, induced seismicity in reservoirs, and mining. In hydrocarbon reservoirs, for example, pore pressure changes and fluid flow (mass transfer) will cause incremental deviatoric stresses sufficient to trigger and sustain seismic activity. Here we address three aspects of seismic wavefields in three-dimensional heterogeneous media triggered by distributed sources in space and time: forward modeling, multichannel data processing, and source location imaging. A power law distribution of seismic sources (such as the Gutenberg-Richter law) is used for the modeling of viscoelastic/elastic wave propagation through a realistic earth model. 3D modeling provides new insight in the interaction of multi-source wavefields and the role of scale-dependend elastic model parameters on transmitted and reflected/back-scattered wavefields. There exists a strong correlation between the spatial properties of the compressional, shear wave and density perturbations and the lateral correlation length of the resulting reflected or transmitted seismic wavefields. Modeling is based on the implementation of 3D elastic/viscoelastic FD codes on massive parallel and/or distributed computing resources using MPI (message passing interface). For parallelization, large grid 3D earth models are decomposed into subvolume processing elements whereby each processing element is updating the wavefield within its portion of the grid. Processing of continuous seismic wavefields excited by multiple distributed sources is based on a combination of crosscorrelated or slowness-transformed array data and Kirchhoff or reverse time migration for source location or source volume imaging. The appearance of slowness in both migration and array data processing suggests the possibility of combining them into a single process. In order to place further constraints on the migration, the directivity properties of 3-component receiver arrays can be included in

  11. 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.

  12. 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

  13. 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.

  14. 3D finite element model for treatment of cleft lip

    NASA Astrophysics Data System (ADS)

    Jiao, Chun; Hong, Dongming; Lu, Hongbing; Wang, Jianqi; Lin, Qin; Liang, Zhengrong

    2009-02-01

    Cleft lip is a congenital facial deformity with high occurrence rate in China. Surgical procedure involving Millard or Tennison methods is usually employed for treatment of cleft lip. However, due to the elasticity of the soft tissues and the mechanical interaction between skin and maxillary, the occurrence rate of facial abnormality or dehisce is still high after the surgery, leading to multiple operations of the patient. In this study, a framework of constructing a realistic 3D finite element model (FEM) for the treatment of cleft lip has been established. It consists of two major steps. The first one is the reconstruction of a 3D geometrical model of the cleft lip from scanning CT data. The second step is the build-up of a FEM for cleft lip using the geometric model, where the material property of all the tetrahedrons was calculated from the CT densities directly using an empirical curve. The simulation results demonstrated (1) the deformation procedure of the model step-by-step when forces were applied, (2) the stress distribution inside the model, and (3) the displacement of all elements in the model. With the computer simulation, the minimal force of having the cleft be repaired is predicted, as well as whether a given force sufficient for the treatment of a specific individual. It indicates that the proposed framework could integrate the treatment planning with stress analysis based on a realistic patient model.

  15. 3D statistical shape models incorporating 3D random forest regression voting for robust CT liver segmentation

    NASA Astrophysics Data System (ADS)

    Norajitra, Tobias; Meinzer, Hans-Peter; Maier-Hein, Klaus H.

    2015-03-01

    During image segmentation, 3D Statistical Shape Models (SSM) usually conduct a limited search for target landmarks within one-dimensional search profiles perpendicular to the model surface. In addition, landmark appearance is modeled only locally based on linear profiles and weak learners, altogether leading to segmentation errors from landmark ambiguities and limited search coverage. We present a new method for 3D SSM segmentation based on 3D Random Forest Regression Voting. For each surface landmark, a Random Regression Forest is trained that learns a 3D spatial displacement function between the according reference landmark and a set of surrounding sample points, based on an infinite set of non-local randomized 3D Haar-like features. Landmark search is then conducted omni-directionally within 3D search spaces, where voxelwise forest predictions on landmark position contribute to a common voting map which reflects the overall position estimate. Segmentation experiments were conducted on a set of 45 CT volumes of the human liver, of which 40 images were randomly chosen for training and 5 for testing. Without parameter optimization, using a simple candidate selection and a single resolution approach, excellent results were achieved, while faster convergence and better concavity segmentation were observed, altogether underlining the potential of our approach in terms of increased robustness from distinct landmark detection and from better search coverage.

  16. 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

  17. 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

  18. 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

  19. Bazhenov fm unconventional reservoir 3D geological modeling methodology

    NASA Astrophysics Data System (ADS)

    Telnova, A.; Baranov, V.; Bukhanov, N.

    2016-03-01

    The Bazhenov Formation has been studied for more than 50 years, but its petroleum potential, optimal STOIIP or resource estimation approaches, the methodology used to select a reservoir, determine its properties are still unclear. The distinctive features of bituminous shale are specific geochemical properties chosen as basic parameters to perform the geological modeling of the Bazhenov deposits and determine the key areas. The main objective of this paper is to choose an optimal 3D geological modeling algorithm and test conventional (petrophysical) and specific (geochemical) properties.

  20. Towards Forward Modeling of 3D Heterogeneity in D" region

    NASA Astrophysics Data System (ADS)

    To, A.; Capdeville, Y.; Romanowicz, B.

    2002-12-01

    The presence of strong lateral heterogeneity in D" is now well documented. While tomographic modeling provides constraints on the large scale patterns, strong variations on shorter scales are best addressed by forward modeling. Appropriate tools are needed for forward modeling that will handle strong 3D heterogeneity, at relatively short periods and including diffracted waves. We use a coupled mode/SEM (Spectral Element Method) to compute synthetic seismograms in 3D models of the D" layer down to 1/12s. This coupled method (Capdeville, 2001) affords faster computations than SEM in cases where heterogeneity can be restricted to a specific layer. We compare them with observed waveforms for several events in the Western Pacific. Observed and synthetic travel time trends are very consistent, although in most cases the observed residuals are significantly larger. Waveform amplitudes are less consistent. In order to understand the origin of the amplitude difference, we test the effect of 3D heterogeneity on Sdiff phase. In particular, the results show opposite trends in the amplitude of Sdiff due to heterogeneity located near the CMB or well above it. This provides constraints on the location of the causative velocity heterogeneity. Because the forward modeling approach requires many iterations, the coupled mode/SEM approach is still computationally intensive. It is more efficient to use a less accurate traditional approach to first get closer to a final model, and only then use coupled mode/SEM to refine the model. Ray theory is the most expedient way to calculate travel times. However, it is an infinite frequency approximation and not appropriate to handle diffracting waves. We show that ray theory predicts larger travel time anomaly for Sdiff phase than the one obtained by coupled mode/SEM. Although it is based on a weak heterogeneity assumption, Non-linear Asymptotic Coupling Theory(NACT) (Li and Romanowicz, 1995) helps to overcome this difficulty. It can handle

  1. 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.

  2. 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.

  3. 3D Building Evacuation Route Modelling and Visualization

    NASA Astrophysics Data System (ADS)

    Chan, W.; Armenakis, C.

    2014-11-01

    The most common building evacuation approach currently applied is to have evacuation routes planned prior to these emergency events. These routes are usually the shortest and most practical path from each building room to the closest exit. The problem with this approach is that it is not adaptive. It is not responsively configurable relative to the type, intensity, or location of the emergency risk. Moreover, it does not provide any information to the affected persons or to the emergency responders while not allowing for the review of simulated hazard scenarios and alternative evacuation routes. In this paper we address two main tasks. The first is the modelling of the spatial risk caused by a hazardous event leading to choosing the optimal evacuation route for a set of options. The second is to generate a 3D visual representation of the model output. A multicriteria decision making (MCDM) approach is used to model the risk aiming at finding the optimal evacuation route. This is achieved by using the analytical hierarchy process (AHP) on the criteria describing the different alternative evacuation routes. The best route is then chosen to be the alternative with the least cost. The 3D visual representation of the model displays the building, the surrounding environment, the evacuee's location, the hazard location, the risk areas and the optimal evacuation pathway to the target safety location. The work has been performed using ESRI's ArcGIS. Using the developed models, the user can input the location of the hazard and the location of the evacuee. The system then determines the optimum evacuation route and displays it in 3D.

  4. Variable selection based QSAR modeling on Bisphenylbenzimidazole as Inhibitor of HIV-1 reverse transcriptase.

    PubMed

    Kumar, Surendra; Tiwari, Meena

    2013-11-01

    The emergence of mutant virus in drug therapy for HIV-1 infection has steadily risen in the last decade. Inhibition of reverse transcriptase enzyme has emerged as a novel target for the treatment of HIV infection. The aim to decipher the structural features that interact with receptor, we report a quantitative structure activity relationship (QSAR) study on a dataset of thirty seven compounds belonging to bisphenylbenzimidazoles (BPBIs) as reverse transcriptase inhibitors using enhanced replacement method (ERM), stepwise multiple linear regression (Stepwise-MLR) and genetic function approximation (GFA) method for selecting a subset of relevant descriptors, developing the best multiple linear regression model and defining the QSAR model applicability domain boundaries. The enhanced replacement method was found to give better results r²=0.8542, Q²(loo) = 0.7917, r²pred = 0.7812) at five variables as compared to stepwise MLR and GFA method, evidenced by internal and external validation parameters. The modified r² (r²m) of the training set, test set and whole data set were calculated and are in agreement with the enhanced replacement method. The results of QSAR study rationalize the structural requirement for optimum binding of ligands. The developed QSAR model shows that hydrophobicity, flexibility, three dimensional surface area, volume and shape of molecule are important parameters to be considered for designing new compounds and to decipher reverse transcriptase enzyme inhibition activity of these compounds at molecular level. The applicability domain was defined to find the similar analogs with better prediction power. PMID:23106285

  5. 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.

  6. DFT-based QSAR models to predict the antimycobacterial activity of chalcones.

    PubMed

    Barua, Nilakshi; Sarmah, Pubalee; Hussain, Iftikar; Deka, Ramesh C; Buragohain, Alak K

    2012-04-01

    In this study, antimycobacterial activity of a set of synthesized chalcone derivatives against Mycobacterium tuberculosis H37Rv was investigated by quantitative structure-activity relationship (QSAR) analysis using density functional theory (DFT) and molecular mechanics (MM+)-based descriptors in both gas and solvent phases. The best molecular descriptors identified were hardness, E(HOMO) , MR(A-4) and MR(B-4') that contributed to the antimycobacterial activity of the chalcones as independent factors. The correlation of these four descriptors with their antimycobacterial activity increases with the inclusion of solvent medium, indicating their importance in studying biological activity. QSAR models revealed that in gas phase, lower values of E(HOMO) , MR(A-4) and MR(B-4') increase the antimycobacterial activity of the chalcone molecules. However, in solvent phase, lower values of E(HOMO) and MR(B-4') and higher values of MR(A-4) increase their activity. PMID:22151277

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. Recent progress in modelling 3D lithospheric deformation

    NASA Astrophysics Data System (ADS)

    Kaus, B. J. P.; Popov, A.; May, D. A.

    2012-04-01

    Modelling 3D lithospheric deformation remains a challenging task, predominantly because the variations in rock types, as well as nonlinearities due to for example plastic deformation result in sharp and very large jumps in effective viscosity contrast. As a result, there are only a limited number of 3D codes available, most of which are using direct solvers which are computationally and memory-wise very demanding. As a result, the resolutions for typical model runs are quite modest, despite the use of hundreds of processors (and using much larger computers is unlikely to bring much improvement in this situation). For this reason we recently developed a new 3D deformation code,called LaMEM: Lithosphere and Mantle Evolution Model. LaMEM is written on top of PETSc, and as a result it runs on massive parallel machines and we have a large number of iterative solvers available (including geometric and algebraic multigrid methods). As it remains unclear which solver combinations work best under which conditions, we have implemented most currently suggested methods (such as schur complement reduction or Fully coupled iterations). In addition, we can use either a finite element discretization (with Q1P0, stabilized Q1Q1 or Q2P-1 elements) or a staggered finite difference discretization for the same input geometry, which is based on a marker and cell technique). This gives us he flexibility to test various solver methodologies on the same model setup, in terms of accuracy, speed, memory usage etc. Here, we will report on some features of LaMEM, on recent code additions, as well as on some lessons we learned which are important for modelling 3D lithospheric deformation. Specifically we will discuss: 1) How we combine a particle-and-cell method to make it work with both a finite difference and a (lagrangian, eulerian or ALE) finite element formulation, with only minor code modifications code 2) How finite difference and finite element discretizations compare in terms of

  12. 3-D Modeling of a Nearshore Dye Release

    NASA Astrophysics Data System (ADS)

    Maxwell, A. R.; Hibler, L. F.; Miller, L. M.

    2006-12-01

    The usage of computer modeling software in predicting the behavior of a plume discharged into deep water is well established. Nearfield plume spreading in coastal areas with complex bathymetry is less commonly studied; in addition to geometry, some of the difficulties of this environment include: tidal exchange, temperature, and salinity gradients. Although some researchers have applied complex hydrodynamic models to this problem, nearfield regions are typically modeled by calibration of an empirical or expert system model. In the present study, the 3D hydrodynamic model Delft3D-FLOW was used to predict the advective transport from a point release in Sequim Bay, Washington. A nested model approach was used, wherein a coarse model using a mesh extending to nearby tide gages (cell sizes up to 1 km) was run over several tidal cycles in order to provide boundary conditions to a smaller area. The nested mesh (cell sizes up to 30 m) was forced on two open boundaries using the water surface elevation derived from the coarse model. Initial experiments with the uncalibrated model were conducted in order to predict plume propagation based on the best available field data. Field experiments were subsequently carried out by releasing rhodamine dye into the bay at near-peak flood tidal current and near high slack tidal conditions. Surface and submerged releases were carried out from an anchored vessel. Concurrently collected data from the experiment include temperature, salinity, dye concentration, and hyperspectral imagery, collected from boats and aircraft. A REMUS autonomous underwater vehicle was used to measure current velocity and dye concentration at varying depths, as well as to acquire additional bathymetric information. Preliminary results indicate that the 3D hydrodynamic model offers a reasonable prediction of plume propagation speed and shape. A sensitivity analysis is underway to determine the significant factors in effectively using the model as a predictive tool

  13. Toward a general predictive QSAR model for gamma-secretase inhibitors.

    PubMed

    Ajmani, Subhash; Janardhan, Sridhara; Viswanadhan, Vellarkad N

    2013-08-01

    Gamma secretase (GS) is an appealing drug target for Alzheimer disease and cancer because of its central role in the processing of amyloid precursor protein and the notch family of proteins. In the absence of three-dimensional structure of GS, there is an urgent need for new methods for the prediction and screening of GS inhibitors, for facilitating discovery of novel GS inhibitors. The present study reports QSAR studies on diverse chemical classes comprising 233 compounds collected from the ChEMBL database. Herein, continuous [PLS regression and neural-network (NN)] and categorical QSAR models (NN and linear discriminant analysis) were developed to obtain pertinent descriptors responsible for variation of GS inhibitor potency. Also, SAR within various chemical classes of compounds is analyzed with respect to important QSAR descriptors, which revealed the significance of electronegative substitutions on aryl rings (PEOE3) in determining variation of GS inhibitor potency. Furthermore, substitution of acyclic amines with N-substituted cyclic amines appears to be favorable for enhancing GS inhibitor potency by increasing the values of sssN_Cnt and number of aliphatic rings. The models developed are statistically significant and improve our understanding of compounds contributing toward GS inhibitor potency and aid in the rational design of novel potent GS inhibitors. PMID:23612850

  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 PAGESBeta

    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. Structure-odor correlations in homologous series of alkanethiols and attempts to predict odor thresholds by 3D-QSAR studies.

    PubMed

    Polster, Johannes; Schieberle, Peter

    2015-02-11

    Homologous series of alkane-1-thiols, alkane-2-thiols, alkane-3-thiols, 2-methylalkane-1-thiols, 2-methylalkane-3-thiols, 2-methylalkane-2-thiols, and alkane-1,ω-dithiols were synthesized to study the influence of structural changes on odor qualities and odor thresholds. In particular, the odor thresholds were strongly influenced by steric effects: In all homologous series a minimum was observed for thiols with five to seven carbon atoms, whereas increasing the chain length led to an exponential increase in the odor threshold. Tertiary alkanethiols revealed clearly lower odor thresholds than found for primary or secondary thiols, whereas neither a second mercapto group in the molecule nor an additional methyl substitution lowered the threshold. To investigate the impact of the SH group, odor thresholds and odor qualities of thiols were compared to those of the corresponding alcohols and (methylthio)alkanes. Replacement of the SH group by an OH group as well as S-methylation of the thiols significantly increased the odor thresholds. By using comparative molecular field analysis, a 3D quantitative structure-activity relationship model was created, which was able to simulate the odor thresholds of alkanethiols in good agreement with the experimental results. NMR and mass spectrometric data for 46 sulfur-containing compounds are additionally supplied. PMID:25608797

  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. 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.

  20. 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.

  1. Unstructured 3D grid toolbox for modeling and simulation

    SciTech Connect

    George, D.

    1997-11-01

    Computable 3D grids that accurately represent complex multimaterial geometries are essential for both static and time-dependent modeling and simulation. LaGriT, the grid toolbox developed at Los Alamos provides a sophisticated set of initial grid generation, grid maintenance and grid optimization tools. We present example grids that demonstrate the flexibility of the grid generator. Additionally, we present the results of an electrostatic calculation and a grain growth problem that illustrate the grid optimization features and the utility of the grid server architecture.

  2. Simulation of 3D Global Wave Propagation Through Geodynamic Models

    NASA Astrophysics Data System (ADS)

    Schuberth, B.; Piazzoni, A.; Bunge, H.; Igel, H.; Steinle-Neumann, G.

    2005-12-01

    This project aims at a better understanding of the forward problem of global 3D wave propagation. We use the spectral element program "SPECFEM3D" (Komatitsch and Tromp, 2002a,b) with varying input models of seismic velocities derived from mantle convection simulations (Bunge et al., 2002). The purpose of this approach is to obtain seismic velocity models independently from seismological studies. In this way one can test the effects of varying parameters of the mantle convection models on the seismic wave field. In order to obtain the seismic velocities from the temperature field of the geodynamical simulations we follow a mineral physics approach. Assuming a certain mantle composition (e.g. pyrolite with CMASF composition) we compute the stable phases for each depth (i.e. pressure) and temperature by system Gibbs free energy minimization. Elastic moduli and density are calculated from the equations of state of the stable mineral phases. For this we use a mineral physics database derived from calorimetric experiments (enthalphy and entropy of formation, heat capacity) and EOS parameters.

  3. 3D Model of Melt Distribution in Partially Molten Dunite

    NASA Astrophysics Data System (ADS)

    Garapic, G.; Faul, U.; Brisson, E.

    2010-12-01

    The currently existing model of grain-scale melt geometry in the Earth’s upper mantle is derived from theoretical considerations that stem from material science research, combined with relatively low-resolution observations of polished two-dimensional surfaces. This model predicts a simple, interconnected network of melt along three-grain edges in static surface energy equilibrium. However, due to a continuous rearrangements of neighboring grains caused by grain growth, melt forms complex shapes among the grains. As a result, it is impossible to construct a 3D image of the pore space from 2D surfaces, which makes it particularly challenging to resolve the current controversy on whether all two-grain boundaries are wetted or melt-free. We present a new method for reconstruction of the 3D pore space in partially molten rocks. The method consists of serial sectioning and high resolution imaging (Field Emission SEM) of polished surfaces, followed by image alignment and rendering. The ablation rate during serial sectioning is determined by measuring the depth of a laser hole by interferometry. We removed a total of 25 layers with a spacing of of 1.3.microns between layers. Each layer consists of a mosaic of images approximately 300 x 320 microns in size. Melt regions are identified within each layer by hand-digitizing SEM images. We obtain a 3D model by stacking the slices, registering each slice, and using alpha shapes as a surface reconstruction technique. The sample we investigated is a partially molten dunite consisting of Fo90 olivine with a mean grain size of 33 microns and 4% melt. It was run in a piston cylinder at 1350°C and 1 GPa for 432 hours to achieve steady state grain growth. Rendering of the 3D pore space shows that the larger melt pockets at multi-grain junctions change within only a few microns in depth, whereas thin inclusions along two-grain boundaries persist over the entire depth of the imaged volume, which is similar to the mean grain size

  4. 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…

  5. 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.

  6. 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

  7. SEARCHBreast Workshop Proceedings: 3D Modelling of Breast Cancer.

    PubMed

    Morrissey, Bethny; Blyth, Karen; Carter, Phil; Chelala, Claude; Holen, Ingunn; Jones, Louise; Speirs, Valerie

    2015-12-01

    SEARCHBreast, a UK initiative supported by the NC3Rs, organised a workshop entitled 3D Modelling of Breast Cancer. The workshop focused on providing researchers with solutions to overcome some of the perceived barriers to working with human-derived tumour cells, cell lines and tissues, namely: a) the limited access to human-derived material; and b) the difficulty in working with these samples. The workshop presentations provided constructive advice and information on how to best prepare human cells or tissues for further downstream applications. Techniques in developing primary cultures from patient samples, and considerations when preserving tissue slices, were discussed. A common theme throughout the workshop was the importance of ensuring that the cells are grown in conditions as similar to the in vivo microenvironment as possible. Comparisons of the advantages of several in vitro options, such as primary cell cultures, cell line cultures, explants or tissue slices, suggest that all offer great potential applications for breast cancer research, and highlight that it need not be a case of choosing one over the other. The workshop also offered cutting-edge examples of on-chip technologies and 3-D tumour modelling by using virtual pathology, which can contribute to clinically relevant studies and provide insights into breast cancer metastatic mechanisms. PMID:26753939

  8. 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.

  9. 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

  10. 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.

  11. Development of an aquifer management model AQMAN3D

    USGS Publications Warehouse

    Puig, Juan Carlos; Rolon-Collazo, L. I.; Pagan-Trinidad, Ishmael

    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.

  12. On the number of EINECS compounds that can be covered by (Q)SAR models for acute toxicity.

    PubMed

    Zvinavashe, Elton; Murk, Albertinka J; Rietjens, Ivonne M C M

    2009-01-10

    The new EU legislation for managing chemicals called REACH aims to fill in gaps in toxicity information that exist for the chemicals listed on the European Inventory of Existing Chemical Substances (EINECS). REACH advocates the use of alternatives to animal experimentation including, amongst others, (quantitative) structure-activity relationship models [(Q)SARs] to help fill in the toxicity data gaps. The aim of the present study was to provide a science-based estimate of the number of EINECS compounds that can be covered by (Q)SAR models for acute toxicity. Using the ECOSAR software, 54% of the 100196 EINECS chemicals were classified into 49 classes that can be potentially covered by (Q)SAR models. The largest proportion of the classified compounds (40% of the EINECS list) falls into the classes of non-polar and polar narcotics. Compounds that were not classified include, for example, fish oils, botanical and animal extracts, and crude oil distillates. With rapid improvements in analytical tools, the number of EINECS compounds for which toxicity evaluations may be based on (Q)SAR approaches may be extended by further developing the method recently developed for the safety assessment of natural flavor complexes used as ingredients in food. This method is based on identification of the individual components in a mixture, and judgment of the safety of these identified individual compounds using toxicity information on structurally similar congeners in the respective classes. Such (Q)SAR approaches may be applied to an additional 2938 EINECS compounds, representing botanical and animal extracts, leading to a total estimate of 57% of the EINECS compounds for which (Q)SAR-based approaches may assist in their safety assessment. It is concluded that, despite the fact that individual (Q)SARs may often each cover only a limited number, i.e. less than 1%, of the EINECS compounds, the potential for applying (Q)SAR approaches for safety assessment of EINECS compounds may prove

  13. 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

  14. Daphnia and fish toxicity of (benzo)triazoles: validated QSAR models, and interspecies quantitative activity-activity modelling.

    PubMed

    Cassani, Stefano; Kovarich, Simona; Papa, Ester; Roy, Partha Pratim; van der Wal, Leon; Gramatica, Paola

    2013-08-15

    Due to their chemical properties synthetic triazoles and benzo-triazoles ((B)TAZs) are mainly distributed to the water compartments in the environment, and because of their wide use the potential effects on aquatic organisms are cause of concern. Non testing approaches like those based on quantitative structure-activity relationships (QSARs) are valuable tools to maximize the information contained in existing experimental data and predict missing information while minimizing animal testing. In the present study, externally validated QSAR models for the prediction of acute (B)TAZs toxicity in Daphnia magna and Oncorhynchus mykiss have been developed according to the principles for the validation of QSARs and their acceptability for regulatory purposes, proposed by the Organization for Economic Co-operation and Development (OECD). These models are based on theoretical molecular descriptors, and are statistically robust, externally predictive and characterized by a verifiable structural applicability domain. They have been applied to predict acute toxicity for over 300 (B)TAZs without experimental data, many of which are in the pre-registration list of the REACH regulation. Additionally, a model based on quantitative activity-activity relationships (QAAR) has been developed, which allows for interspecies extrapolation from daphnids to fish. The importance of QSAR/QAAR, especially when dealing with specific chemical classes like (B)TAZs, for screening and prioritization of pollutants under REACH, has been highlighted. PMID:23702385

  15. 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

  16. 3D Tissue-Engineered Model of Ewing Sarcoma

    PubMed Central

    Lamhamedi-Cherradi, Salah-Eddine; Santoro, Marco; Ramammoorthy, Vandhana; Menegaz, Brian A.; Bartholomeusz, Geoffrey; Iles, Lakesla R.; Amin, Hesham M.; Livingston, Andrew J.; Mikos, Antonios G.; Ludwig, Joseph A.

    2015-01-01

    Despite longstanding reliance upon monolayer culture for studying cancer cells, and numerous advantages from both a practical and experimental standpoint, a growing body of evidence suggests more complex three-dimensional (3D) models are necessary to properly mimic many of the critical hallmarks associated with the oncogenesis, maintenance and spread of Ewing sarcoma (ES), the second most common pediatric bone tumor. And as clinicians increasingly turn to biologically-targeted therapies that exert their effects not only on the tumor cells themselves, but also on the surrounding extracellular matrix, it is especially important that preclinical models evolve in parallel to reliably measure antineoplastic effects and possible mechanisms of de novo and acquired drug resistance. Herein, we highlight a number of innovative methods used to fabricate biomimetic ES tumors, encompassing both the surrounding cellular milieu and extracellular matrix (ECM), and suggest potential applications to advance our understanding of ES biology, preclinical drug testing, and personalized medicine. PMID:25109853

  17. 3D Model of the Eta Carinae Little Homunculus Nebula

    NASA Astrophysics Data System (ADS)

    Steffen, Wolfgang; Teodoro, Mairan; Madura, Thomas; Groh, Jose H.; Gull, Theodore R.; Corcoran, Michael F.; Damineli, Augusto; Hamaguchi, Kenji

    2015-01-01

    We extend our morpho-kinematic 3D modeling of the Homunculus nebula (Steffen et al., 2014) to the interior nested Little Homunculus. The model is based on spectroscopic observations from HST/STIS. We find that the structure of the interior Little Homunculus is rather flat in the polar regions and interacts with the main Homunculus nebula only on one side, towards the periastron direction of the binary orbit. Furthermore, the two lobes of the LH are misaligned, also towards the periastron direction. As an explanation for the misalignment we propose that, in both cases, shortly after the eruptions that created the bipolar nebulae from the primary star, the off-center wind of the secondary has pushed the ejecta towards the periastron directions, since the secondary is most of the time near the apastron. Future hydrodynamic simulations are warranted to confirm this scenario.

  18. 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

  19. 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

  20. 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.

  1. Collaboration of 3D context and extracellular matrix in the development of glioma stemness in a 3D model.

    PubMed

    Ma, Nina K L; Lim, Jia Kai; Leong, Meng Fatt; Sandanaraj, Edwin; Ang, Beng Ti; Tang, Carol; Wan, Andrew C A

    2016-02-01

    A hierarchy of cellular stemness exists in certain cancers, and any successful strategy to treat such cancers would have to eliminate the self-renewing tumor-initiating cells at the apex of the hierarchy. The cellular microenvironment, in particular the extracellular matrix (ECM), is believed to have a role in regulating stemness. In this work, U251 glioblastoma cells are cultured on electrospun polystyrene (ESPS) scaffolds coated with an array of 7 laminin isoforms to provide a 3D model for stem cell-related genes and proteins expression studies. We observed collaboration between 3D context and laminins in promoting glioma stemness. Depending on the laminin isoform presented, U251 cells cultured on ESPS scaffolds (3D) exhibited increased expression of stemness markers compared to those cultured on tissue culture polystyrene (2D). Our results indicate the influence of 3D (versus 2D) context on integrin expression, specifically, the upregulation of the laminin-binding integrins alpha 6 and beta 4. By a colony forming assay, we showed enhanced clonogenicity of cells grown on ESPS scaffolds in collaboration with laminins 411, 421, 511 and 521. Evaluation of patient glioma databases demonstrated significant enrichment of integrin and ECM pathway networks in tumors of worse prognosis, consistent with our observations. The present results demonstrate how 3D versus 2D context profoundly affects ECM signaling, leading to stemness. PMID:26684838

  2. 3D density model of the Central Andes

    NASA Astrophysics Data System (ADS)

    Prezzi, Claudia B.; Götze, Hans-Jürgen; Schmidt, Sabine

    2009-12-01

    We developed a 3D density model of the continental crust, the subducted plate and the upper mantle of the Central Andes between 20-29°S and 74-61°W through the forward modelling of Bouguer anomaly. The goal of this contribution is to gain insight on the lithospheric structure integrating the available information (geophysical, geologic, petrologic, and geochemical) in a single model. The geometry of our model is defined and constrained by hypocentre location, reflection and refraction on and offshore seismic lines, travel time and attenuation tomography, receiver function analysis, magnetotelluric studies, thermal models and balanced structural cross-sections. The densities allocated to the different bodies are calculated considering petrologic and geochemical data and pressure and temperature conditions. The model consists of 31 parallel E-W vertical planes, where the continental crust comprises distinct bodies, which represent the different morphotectonic units of the Central Andes. We include a partial melting zone at midcrustal depths under the Altiplano-Puna (low-velocity zone) and consider the presence of a rheologically strong block beneath the Salar de Atacama basin, according to recent seismic studies. Contour maps of the depth of the continental Moho, the thickness of the lower crust and the depth to the bottom of the lithosphere below South America are produced. The possible percentage of partial melt in the Central Andes low-velocity zone is estimated. The residual anomaly is calculated by subtracting from the Bouguer anomaly the gravimetric effect of the modelled subducted slab and of the modelled Moho. Isostatic anomalies are calculated from regional and local isostatic Mohos calculated with and without internal loads, derived from our gravity model, which are then compared to the modelled continental Moho. This study contributes to a more detailed knowledge of the lithospheric structure of this region of the Andes and provides an integrated 3D

  3. 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.

  4. 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

  5. The USGS 3D Seismic Velocity Model for Northern California

    NASA Astrophysics Data System (ADS)

    Brocher, T. M.; Aagaard, B.; Simpson, R. W.; Jachens, R. C.

    2006-12-01

    We present a new regional 3D seismic velocity model for Northern California for use in strong motion simulations of the 1906 San Francisco and other earthquakes. The model includes compressional-wave velocity (Vp), shear-wave velocity (Vs), density, and intrinsic attenuation (Qp, Qs). These properties were assigned for each rock type in a 3D geologic model derived from surface outcrops, boreholes, gravity and magnetic data, and seismic reflection, refraction, and tomography studies. A detailed description of the model, USGS Bay Area Velocity Model 05.1.0, is available online [http://www.sf06simulation.org/geology/velocitymodel]. For ground motion simulations Vs and Qs are more important parameters than Vp and Qp because the strongest ground motions are generated chiefly by shear and surface wave arrivals. Because Vp data are more common than Vs data, however, we first developed Vp versus depth relations for each rock type and then converted these to Vs versus depth relations. For the most important rock types in Northern California we compiled measurements of Vp versus depth using borehole logs, laboratory measurements on hand samples, seismic refraction profiles, and tomography models. These rock types include Salinian and Sierran granitic rocks, metagraywackes and greenstones of the Franciscan Complex, Tertiary and Mesozoic sedimentary and volcanic rocks, and Quaternary and Holocene deposits (Brocher, USGS OFR 05-1317, 2005). Vp versus depth curves were converted to Vs versus depth curves using new empirical nonlinear relations between Vs and Vp (Brocher, BSSA, 2005). These relations, showing that Poisson's ratio is a nonlinear function of Vp, were similarly based on compilations of diverse Vs and Vp measurements on a large suite of rock types, mainly from California and the Pacific Northwest. The model is distributed in a discretized form with routines to query the model using C++, C, and Fortran 77 programming languages. The geologic model was discretized at

  6. A 3D Bubble Merger Model for RTI Mixing

    NASA Astrophysics Data System (ADS)

    Cheng, Baolian

    2015-11-01

    In this work we present a model for the merger processes of bubbles at the edge of an unstable acceleration driven mixing layer. Steady acceleration defines a self-similar mixing process, with a time-dependent inverse cascade of structures of increasing size. The time evolution is itself a renormalization group evolution. The model predicts the growth rate of a Rayleigh-Taylor chaotic fluid-mixing layer. The 3-D model differs from the 2-D merger model in several important ways. Beyond the extension of the model to three dimensions, the model contains one phenomenological parameter, the variance of the bubble radii at fixed time. The model also predicts several experimental numbers: the bubble mixing rate, the mean bubble radius, and the bubble height separation at the time of merger. From these we also obtain the bubble height to the radius aspect ratio, which is in good agreement with experiments. Applications to recent NIF and Omega experiments will be discussed. This work was performed under the auspices of the U.S. Department of Energy by the Los Alamos National Laboratory under Contract No. W-7405-ENG-36.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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…

  12. 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.

  13. 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.

  14. 3D Model of the San Emidio Geothermal Area

    SciTech Connect

    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.

  15. 3D lithography modeling for ground rule development

    NASA Astrophysics Data System (ADS)

    Sarma, Chandra; Bailey, Todd; Lyons, Adam; Shao, Dongbing

    2011-04-01

    The ability to incorporate the effect of patterned underlayers in a 3-dimensional physical resist model that truly mimics the process on real wafers could be used to formulate robust ground rules for design. We have shown as an example block level simulations, where the resist critical dimension is determined by the presence of STI (shallow trench isolation) and/or patterned gate level underneath & their relative spacing, as confirmed on wafer. We will demonstrate how the results of such study could be used for creating ground rules which are truly dependent on the interaction between the current layer resist & the patterned layers underneath. We have also developed a new way to visualize lithographic process variations in 3-D space that is useful for simulation analysis that can prove very helpful in ground rule development and process optimization. Such visualization capability in the dataprep flow to flag issues or dispose critical structures increases speed and efficiency in the mask tapeout process.

  16. Massive fermion model in 3d and higher spin currents

    NASA Astrophysics Data System (ADS)

    Bonora, L.; Cvitan, M.; Prester, P. Dominis; de Souza, B. Lima; Smolić, I.

    2016-05-01

    We analyze the 3d free massive fermion theory coupled to external sources. The presence of a mass explicitly breaks parity invariance. We calculate two- and three-point functions of a gauge current and the energy momentum tensor and, for instance, obtain the well-known result that in the IR limit (but also in the UV one) we reconstruct the relevant CS action. We then couple the model to higher spin currents and explicitly work out the spin 3 case. In the UV limit we obtain an effective action which was proposed many years ago as a possible generalization of spin 3 CS action. In the IR limit we derive a different higher spin action. This analysis can evidently be generalized to higher spins. We also discuss the conservation and properties of the correlators we obtain in the intermediate steps of our derivation.

  17. 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.

  18. QSAR modeling and molecular interaction analysis of natural compounds as potent neuraminidase inhibitors.

    PubMed

    Sun, Jiaying; Mei, Hu

    2016-04-26

    Different QSAR models of 40 natural compounds as neuraminidase inhibitors (NIs) are developed to comprehend chemical-biological interactions and predict activities against neuraminidase (NA) from Clostridium perfringens. Based on the constitutional, topological and conformational descriptors, R(2) and Q(2) values of the obtained SRA model are 0.931 and 0.856. The R(2) and Q(2) values of the constructed HQSAR and almond models are 0.903 and 0.767, 0.904 and 0.511, respectively. Based on the pharmacophore alignment, R(2) and Q(2) values of the optimal CoMSIA model are 0.936 and 0.654. Moreover, Rtest(2) and Qext(2) of values of SRA, HQSAR, almond and CoMSIA models are 0.611 and 0.565, 0.753 and 0.750, 0.612 and 0.582, 0.582 and 0.571, respectively. So, QSAR models have good predictive capability. They can be further used to evaluate and screen new compounds. Moreover, hydrogen bonds and electrostatic factors have high contributions to activities. To understand molecular interactions between natural compounds and NA from Clostridium perfringens, molecular docking is investigated. The docking results elucidate that Arg266, Asp291, Asp328, Tyr485, Glu493, Arg555, Arg615 and Tyr655 are especially the key residues in the active site of 2bf6. Hydrogen bonds and electrostatics are key factors, which impact the interactions between NIs and NA. So, the influential factors of interactions between NIs and NA in the docking results are in agreement with the QSAR results. PMID:27008437

  19. 3D Model of the Tuscarora Geothermal Area

    DOE Data Explorer

    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

  20. A 3D parallel model of Ganymede's exosphere

    NASA Astrophysics Data System (ADS)

    Leclercq, Ludivine; Turc, Lucile; François, Leblanc; Ronan, Modolo

    2013-04-01

    Ganymede is a unique object : it is the biggest moon of our solar system, and the only satellite which has its own intrinsic magnetic field. Its surface is covered by water ice and by regolith. Some previous observations suggest that below its surface may exist an ocean of liquid water. The atmosphere of the planet is poorly known but should be composed essentially of water, hydrogen and oxygen (Marconi et al., Icarus, 2007). These atmospheric particles mainly originate from the surface thanks to sublimation of water-ice and sputtering, a process driven by the magnetospheric Jovian particles impacting Ganymede surface and leading to ejection of atoms and molecules into Ganymede atmosphere. We developed a model of Ganymede's atmosphere based on a 3D Monte Carlo description of the fate of the ejected particles from the surface. This model has been parallelized allowing a much better statistical, spatial and temporal description of Ganymede's environment. This model includes the main sources of the neutral atmosphere and is able to calculate all its characteristics. It was successfully compared to the few known observations as well as to previous modeling. In this presentation, we will present the main characteristics of this model and what it tells us on Ganymede's atmosphere, in terms of spatial structure, composition, temporal variability and relations with both magnetosphere and surface.

  1. 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

  2. Molecular Fingerprint-based Artificial Neural Networks QSAR for Ligand Biological Activity Predictions

    PubMed Central

    Myint, Kyaw-Zeyar; Wang, Lirong; Tong, Qin; Xie, Xiang-Qun

    2012-01-01

    In this manuscript, we have reported a novel 2D fingerprint-based artificial neural network QSAR (FANN-QSAR) method in order to effectively predict biological activities of structurally diverse chemical ligands. Three different types of fingerprints, namely ECFP6, FP2 and MACCS, were used in FANN-QSAR algorithm development, and FANN-QSAR models were compared to known 3D and 2D QSAR methods using five data sets previously reported. In addition, the derived models were used to predict GPCR cannabinoid ligand binding affinities using our manually curated cannabinoid ligand database containing 1699 structurally diverse compounds with reported cannabinoid receptor subtype CB2 activities. To demonstrate its useful applications, the established FANN-QSAR algorithm was used as a virtual screening tool to search a large NCI compound database for lead cannabinoid compounds and we have discovered several compounds with good CB2 binding affinities ranging from 6.70 nM to 3.75 μM. To the best of our knowledge, this is the first report for a fingerprint-based neural network approach validated with a successful virtual screening application in identifying lead compounds. 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:22937990

  3. A hybrid-3D hillslope hydrological model for use in Earth system models

    NASA Astrophysics Data System (ADS)

    Hazenberg, P.; Fang, Y.; Broxton, P.; Gochis, D.; Niu, G.-Y.; Pelletier, J. D.; Troch, P. A.; Zeng, X.

    2015-10-01

    Hillslope-scale rainfall-runoff processes leading to a fast catchment response are not explicitly included in land surface models (LSMs) for use in earth system models (ESMs) due to computational constraints. This study presents a hybrid-3D hillslope hydrological model (h3D) that couples a 1-D vertical soil column model with a lateral pseudo-2D saturated zone and overland flow model for use in ESMs. By representing vertical and lateral responses separately at different spatial resolutions, h3D is computationally efficient. The h3D model was first tested for three different hillslope planforms (uniform, convergent and divergent). We then compared h3D (with single and multiple soil columns) with a complex physically based 3-D model and a simple 1-D soil moisture model coupled with an unconfined aquifer (as typically used in LSMs). It is found that simulations obtained by the simple 1-D model vary considerably from the complex 3-D model and are not able to represent hillslope-scale variations in the lateral flow response. In contrast, the single soil column h3D model shows a much better performance and saves computational time by 2-3 orders of magnitude compared with the complex 3-D model. When multiple vertical soil columns are implemented, the resulting hydrological responses (soil moisture, water table depth, and base flow along the hillslope) from h3D are nearly identical to those predicted by the complex 3-D model, but still saves computational time. As such, the computational efficiency of the h3D model provides a valuable and promising approach to incorporating hillslope-scale hydrological processes into continental and global-scale ESMs.

  4. Efficient sensitivity computations in 3D air quality models

    NASA Astrophysics Data System (ADS)

    Kioutsioukis, Ioannis; Melas, Dimitrios; Zerefos, Christos; Ziomas, Ioannis

    2005-04-01

    The prediction of ground level ozone for air quality monitoring and assessment is simulated through an integrated system of gridded models (meteorological, photochemical), where the atmosphere is represented with a three-dimensional grid that may include thousands of grid cells. The continuity equation solved by the Photochemical Air Quality Model (PAQM) reproduces the atmospheric processes (dynamical, physical, chemical and radiative), such as moving and mixing air parcels from one grid cell to another, calculating chemical reactions, injecting new emissions. The whole modeling procedure includes several sources of uncertainty, especially in the large data sets that describe the status of the domain (boundary conditions, emissions, chemical reaction rates and several others). The robustness of the photochemical simulation is addressed in this work through the deterministic approach of sensitivity analysis. The automatic differentiation tool ADIFOR is applied on the 3D PAQM CAMx and augments its Fortran 77 code by introducing new lines of code that additionally calculate, in only one run, the gradient of the solution vector with respect to its input parameters. The applicability of the approach is evaluated through a sensitivity study of the modeled concentrations to perturbations at the boundary conditions and the emissions, for three essentially dissimilar European Metropolises of the Auto-Oil II programme (Athens, Milan, and London).

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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…

  11. 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

  12. 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

  13. 3D Finite Difference Modelling of Basaltic Region

    NASA Astrophysics Data System (ADS)

    Engell-Sørensen, L.

    2003-04-01

    The main purpose of the work was to generate realistic data to be applied for testing of processing and migration tools for basaltic regions. The project is based on the three - dimensional finite difference code (FD), TIGER, made by Sintef. The FD code was optimized (parallelized) by the author, to run on parallel computers. The parallel code enables us to model large-scale realistic geological models and to apply traditional seismic and micro seismic sources. The parallel code uses multiple processors in order to manipulate subsets of large amounts of data simultaneously. The general anisotropic code uses 21 elastic coefficients. Eight independent coefficients are needed as input parameters for the general TI medium. In the FD code, the elastic wave field computation is implemented by a higher order FD solution to the elastic wave equation and the wave fields are computed on a staggered grid, shifted half a node in one or two directions. The geological model is a gridded basalt model, which covers from 24 km to 37 km of a real shot line in horizontal direction and from the water surface to the depth of 3.5 km. The 2frac {1}{2}D model has been constructed using the compound modeling software from Norsk Hydro. The vertical parameter distribution is obtained from observations in two wells. At The depth of between 1100 m to 1500 m, a basalt horizon covers the whole sub surface layers. We have shown that it is possible to simulate a line survey in realistic (3D) geological models in reasonable time by using high performance computers. The author would like to thank Norsk Hydro, Statoil, GEUS, and SINTEF for very helpful discussions and Parallab for being helpful with the new IBM, p690 Regatta system.

  14. 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

  15. 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

  16. Collision of continental corner from 3-D numerical modeling

    NASA Astrophysics Data System (ADS)

    Li, Zhong-Hai; Xu, Zhiqin; Gerya, Taras; Burg, Jean-Pierre

    2013-10-01

    Continental collision has been extensively investigated with 2-D numerical models assuming infinitely wide plates or insignificant along-strike deformation in the third dimension. However, the corners of natural collision zones normally have structural characteristics that differ from linear parts of mountain belt. We conducted 3-D high-resolution numerical simulations to study the dynamics of a continental corner (lateral continental/oceanic transition zone) during subduction/collision. The results demonstrate different modes between the oceanic subduction side (continuous subduction and retreating trench) and the continental collision side (slab break-off and topography uplift). Slab break-off occurs at a depth (⩽100 km to ˜300 km) that depends on the convergence velocity. The numerical models produce lateral extrusion of the overriding crust from the collisional side to the subduction side, which is also a phenomenon recognized around natural collision of continental corners, for instance around the western corner of the Arabia-Asia collision zone and around the eastern corner of the India-Asia collision zone. Modeling results also indicate that extrusion tectonics may be driven both from above by the topography and gravitational potentials and from below by the trench retreat and asthenospheric mantle return flow, which supports the link between deep mantle dynamics and shallower crustal deformation.

  17. 3D-GEM: Geo-technical extension towards an integrated 3D information model for infrastructural development

    NASA Astrophysics Data System (ADS)

    Tegtmeier, W.; Zlatanova, S.; van Oosterom, P. J. M.; Hack, H. R. G. K.

    2014-03-01

    In infrastructural projects, communication as well as information exchange and (re-)use in and between involved parties is difficult. Mainly this is caused by a lack of information harmonisation. Various specialists are working together on the development of an infrastructural project and all use their own specific software and definitions for various information types. In addition, the lack of and/or differences in the use and definition of thematic semantic information regarding the various information types adds to the problem. Realistic 3D models describing and integrating parts of the earth already exist, but are generally neglecting the subsurface, and especially the aspects of geology and geo-technology. This paper summarises the research towards the extension of an existing integrated semantic information model to include surface as well as subsurface objects and in particular, subsurface geological and geotechnical objects. The major contributions of this research are the definition of geotechnical objects and the mechanism to link them with CityGML, GeoSciML and O&M standard models. The model is called 3D-GEM, short for 3D Geotechnical Extension Model.

  18. Dependence of QSAR models on the selection of trial descriptor sets: a demonstration using nanotoxicity endpoints of decorated nanotubes.

    PubMed

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

    2013-01-28

    Little attention has been given to the selection of trial descriptor sets when designing a QSAR analysis even though a great number of descriptor classes, and often a greater number of descriptors within a given class, are now available. This paper reports an effort to explore interrelationships between QSAR models and descriptor sets. Zhou and co-workers (Zhou et al., Nano Lett. 2008, 8 (3), 859-865) designed, synthesized, and tested a combinatorial library of 80 surface modified, that is decorated, multi-walled carbon nanotubes for their composite nanotoxicity using six endpoints all based on a common 0 to 100 activity scale. Each of the six endpoints for the 29 most nanotoxic decorated nanotubes were incorporated as the training set for this study. The study reported here includes trial descriptor sets for all possible combinations of MOE, VolSurf, and 4D-fingerprints (FP) descriptor classes, as well as including and excluding explicit spatial contributions from the nanotube. Optimized QSAR models were constructed from these multiple trial descriptor sets. It was found that (a) both the form and quality of the best QSAR models for each of the endpoints are distinct and (b) some endpoints are quite dependent upon 4D-FP descriptors of the entire nanotube-decorator complex. However, other endpoints yielded equally good models only using decorator descriptors with and without the decorator-only 4D-FP descriptors. Lastly, and most importantly, the quality, significance, and interpretation of a QSAR model were found to be critically dependent on the trial descriptor sets used within a given QSAR endpoint study. PMID:23252880

  19. Using particle swarms for the development of QSAR models based on K-nearest neighbor and kernel regression.

    PubMed

    Cedeño, Walter; Agrafiotis, Dimitris K

    2003-01-01

    We describe the application of particle swarms for the development of quantitative structure-activity relationship (QSAR) models based on k-nearest neighbor and kernel regression. Particle swarms is a population-based stochastic search method based on the principles of social interaction. Each individual explores the feature space guided by its previous success and that of its neighbors. Success is measured using leave-one-out (LOO) cross validation on the resulting model as determined by k-nearest neighbor kernel regression. The technique is shown to compare favorably to simulated annealing using three classical data sets from the QSAR literature. PMID:13677491

  20. 3D Model Segmentation and Representation with Implicit Polynomials

    NASA Astrophysics Data System (ADS)

    Zheng, Bo; Takamatsu, Jun; Ikeuchi, Katsushi

    When large-scale and complex 3D objects are obtained by range finders, it is often necessary to represent them by algebraic surfaces for such purposes as data compression, multi-resolution, noise elimination, and 3D recognition. Representing the 3D data with algebraic surfaces of an implicit polynomial (IP) has proved to offer the advantages that IP representation is capable of encoding geometric properties easily with desired smoothness, few parameters, algebraic/geometric invariants, and robustness to noise and missing data. Unfortunately, generating a high-degree IP surface for a whole complex 3D shape is impossible because of high computational cost and numerical instability. In this paper we propose a 3D segmentation method based on a cut-and-merge approach. Two cutting procedures adopt low-degree IPs to divide and fit the surface segments simultaneously, while avoiding generating high-curved segments. A merging procedure merges the similar adjacent segments to avoid over-segmentation. To prove the effectiveness of this segmentation method, we open up some new vistas for 3D applications such as 3D matching, recognition, and registration.

  1. 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.

  2. A 3D world model builder with a mobile robot

    SciTech Connect

    Zhang, Z.; Faugeras, O. )

    1992-08-01

    This article describes a system to incrementally build a world model with a mobile robot in an unknown environment. The model is, for the moment, segment based. A trinocular stereo system is used to build a local map about the environment. A global map is obtained by integrating a sequence of stereo frames taken when the robot navigates in the environment. The emphasis of this article is on the representation of the uncertainty of 3D segments from stereo and on the integration of segments from multiple views. The proposed representation is simple and very convenient to characterize the uncertainty of segment. A Kalman filter is used to merge matched line segments. An important characteristic of this integration strategy is that a segment observed by the stereo system corresponds only to one part of the segment in space, so the union of the different observations gives a better estimate on the segment in space. The authors have succeeded in integrating 35 stereo frames taken in their robot room.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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).

  8. EM modeling for GPIR using 3D FDTD modeling codes

    SciTech Connect

    Nelson, S.D.

    1994-10-01

    An analysis of the one-, two-, and three-dimensional electrical characteristics of structural cement and concrete is presented. This work connects experimental efforts in characterizing cement and concrete in the frequency and time domains with the Finite Difference Time Domain (FDTD) modeling efforts of these substances. These efforts include Electromagnetic (EM) modeling of simple lossless homogeneous materials with aggregate and targets and the modeling dispersive and lossy materials with aggregate and complex target geometries for Ground Penetrating Imaging Radar (GPIR). Two- and three-dimensional FDTD codes (developed at LLNL) where used for the modeling efforts. Purpose of the experimental and modeling efforts is to gain knowledge about the electrical properties of concrete typically used in the construction industry for bridges and other load bearing structures. The goal is to optimize the performance of a high-sample-rate impulse radar and data acquisition system and to design an antenna system to match the characteristics of this material. Results show agreement to within 2 dB of the amplitudes of the experimental and modeled data while the frequency peaks correlate to within 10% the differences being due to the unknown exact nature of the aggregate placement.

  9. 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

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

    PubMed

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

    2014-01-01

    A series of new anilides (2a-c, 4-7, 17a-c, 18) and quinolones (3a-b, 8a-b, 9a-b, 10-15, 19) with nitrogen-bearing substituents from benzo[b]thiophene and thieno[2,3-c]thiophene series are prepared. Benzo[b]thieno[2,3-c]- and thieno[3',2':4,5]thieno[2,3-c]quinolones (3a-b, 8a-b) are synthesized by the reaction of photochemical dehydrohalogenation from corresponding anilides. Anilides and quinolones were tested for the antiproliferative activity. Fused quinolones bearing protonated aminium group, quaternary ammonium group, N-methylated and protonated aminium group, amino and protonated amino group (8a, 9b, 10-12) showed very prominent anticancer activity, whereby the hydrochloride salt of N',N'-dimethylaminopropyl-substituted quinolone (14) was the most active one, having the IC50 concentration at submicromolar range in accordance with previous QSAR predictions. On the other hand, flexible anilides were among the less active. Chemometric analysis of investigated compounds was performed. 3D-derived QSAR analysis identified solubility, metabolitic stability and the possibility of the compound to be ionized at pH 4-8 as molecular properties that are positively correlated with anticancer activity of investigated compounds, while molecular flexibility, polarizability and sum of hydrophobic surface areas were found to be negatively correlated. Anilides 2a-b, 4-7 and quinolones 3a-b, 8a-b, 9b and 10-14 were evaluated for DNA binding propensities and topoisomerases I/II inhibition as part of their mechanism of action. Among the anilides, only compound 7 presented some DNA binding propensity whereas the quinolones 8b, 9b and 10-14 intercalate in the DNA base pairs, compounds 8b, 9b and 14 being the most efficient ones. The strongest DNA intercalators, compounds 8b, 9b and 14, were clearly distinguished from the other compounds according to their molecular descriptors by the PCA and PLS analysis. PMID:24334150

  11. 3D Smoothed Particle Hydrodynamics Models of Betelgeuse's Bow Shock

    NASA Astrophysics Data System (ADS)

    Mohamed, S.; Mackey, J.; Langer, N.

    2013-05-01

    Betelgeuse, the bright red supergiant (RSG) in Orion, is a runaway star. Its supersonic motion through the interstellar medium has resulted in the formation of a bow shock, a cometary structure pointing in the direction of motion. We present the first 3D hydrodynamic simulations of the formation and evolution of Betelgeuse's bow shock. We show that the bow shock morphology depends substantially on the growth timescale for Rayleigh-Taylor versus Kelvin-Helmholtz instabilities. We discuss our models in light of the recent Herschel, GALEX and VLA observations. If the mass in the bow shock shell is low (~few × 10-3 M⊙), as seems to be implied by the AKARI and Herschel observations, then Betelgeuse's bow shock is very young and is unlikely to have reached a steady state. The circular, smooth bow shock shell is consistent with this conclusion. We further discuss the implications of our results, in particular, the possibility that Betelgeuse may have only recently entered the RSG phase.

  12. 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

  13. 3-D model of beam kicker in DARHT-2 accelerator

    NASA Astrophysics Data System (ADS)

    Thoma, Carsten; Genoni, Thomas; Hughes, Thomas

    2003-10-01

    The DARHT-2 beamline uses a fast stripline kicker developed at LLNL [1] to create a series of short pulses out of a 2 microsecond pulse for use in high resolution x-ray radiography. Normally, a static bias dipole bends the 2 kA, 18 MeV electron beam off axis into a dump. When the fast stripline kicker is activated, the static dipole kick is cancelled by the dynamic dipole field of the kicker, and the beam travels to the x-ray converter. 3-D PIC simulations are performed to compute the effect of the kicker on the beam. The calculations incorporate the kicker biplate conductor geometry, allowing for accurate modeling of the effects of higher multipole fields as well as beam wakefield effects. Beam emittance growth through the kicker is investigated for various beam loads. [1] B.R. Poole and Y.-J. Chen, "Particle Simulations of DARHT-2 Transport System", Proc. PAC 2001 Conference (http://accelconf.web.cern.ch/AccelConf/p01/PAPERS/RPPH034.PDF).

  14. 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.

  15. 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.

  16. In Silico Model for Developmental Toxicity: How to Use QSAR Models and Interpret Their Results.

    PubMed

    Marzo, Marco; Roncaglioni, Alessandra; Kulkarni, Sunil; Barton-Maclaren, Tara S; Benfenati, Emilio

    2016-01-01

    Modeling developmental toxicity has been a challenge for (Q)SAR model developers due to the complexity of the endpoint. Recently, some new in silico methods have been developed introducing the possibility to evaluate the integration of existing methods by taking advantage of various modeling perspectives. It is important that the model user is aware of the underlying basis of the different models in general, as well as the considerations and assumptions relative to the specific predictions that are obtained from these different models for the same chemical. The evaluation on the predictions needs to be done on a case-by-case basis, checking the analogs (possibly using structural, physicochemical, and toxicological information); for this purpose, the assessment of the applicability domain of the models provides further confidence in the model prediction. In this chapter, we present some examples illustrating an approach to combine human-based rules and statistical methods to support the prediction of developmental toxicity; we also discuss assumptions and uncertainties of the methodology. PMID:27311466

  17. The influence of data curation on QSAR Modeling - examining issues of quality versus quantity of data (American Chemical Society)

    EPA Science Inventory

    This presentation will examine the impact of data quality on the construction of QSAR models being developed within the EPA‘s National Center for Computational Toxicology. We have developed a public-facing platform to provide access to predictive models. As part of the work we ha...

  18. The influence of data curation on QSAR Modeling – examining issues of quality versus quantity of data (SOT)

    EPA Science Inventory

    The construction of QSAR models is critically dependent on the quality of available data. As part of our efforts to develop public platforms to provide access to predictive models, we have attempted to discriminate the influence of the quality versus quantity of data available ...

  19. An examination of data quality on QSAR Modeling in regards to the environmental sciences (UNC-CH talk)

    EPA Science Inventory

    The development of QSAR models is critically dependent on the quality of available data. As part of our efforts to develop public platforms to provide access to predictive models, we have attempted to discriminate the influence of the quality versus quantity of data available to...

  20. INFLUENCE OF MATRIX FORMULATION ON DERMAL PERCUTANEOUS ABSORPTION OF TRIAZOLE FUNGICIDES USING QSAR AND PBPK / PD MODELS

    EPA Science Inventory

    The objective of this work is to use the Exposure Related Dose Estimating Model (ERDEM) and quantitative structure-activity relationship (QSAR) models to develop an assessment tool for human exposure assessment to triazole fungicides. A dermal exposure route is used for the physi...

  1. Approaches to developing alternative and predictive toxicology based on PBPK/PD and QSAR modeling.

    PubMed Central

    Yang, R S; Thomas, R S; Gustafson, D L; Campain, J; Benjamin, S A; Verhaar, H J; Mumtaz, M M

    1998-01-01

    Systematic toxicity testing, using conventional toxicology methodologies, of single chemicals and chemical mixtures is highly impractical because of the immense numbers of chemicals and chemical mixtures involved and the limited scientific resources. Therefore, the development of unconventional, efficient, and predictive toxicology methods is imperative. Using carcinogenicity as an end point, we present approaches for developing predictive tools for toxicologic evaluation of chemicals and chemical mixtures relevant to environmental contamination. Central to the approaches presented is the integration of physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) and quantitative structure--activity relationship (QSAR) modeling with focused mechanistically based experimental toxicology. In this development, molecular and cellular biomarkers critical to the carcinogenesis process are evaluated quantitatively between different chemicals and/or chemical mixtures. Examples presented include the integration of PBPK/PD and QSAR modeling with a time-course medium-term liver foci assay, molecular biology and cell proliferation studies. Fourier transform infrared spectroscopic analyses of DNA changes, and cancer modeling to assess and attempt to predict the carcinogenicity of the series of 12 chlorobenzene isomers. Also presented is an ongoing effort to develop and apply a similar approach to chemical mixtures using in vitro cell culture (Syrian hamster embryo cell transformation assay and human keratinocytes) methodologies and in vivo studies. The promise and pitfalls of these developments are elaborated. When successfully applied, these approaches may greatly reduce animal usage, personnel, resources, and time required to evaluate the carcinogenicity of chemicals and chemical mixtures. Images Figure 6 PMID:9860897

  2. 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

  3. 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.

  4. QSAR Methods.

    PubMed

    Gini, Giuseppina

    2016-01-01

    In this chapter, we introduce the basis of computational chemistry and discuss how computational methods have been extended to some biological properties and toxicology, in particular. Since about 20 years, chemical experimentation is more and more replaced by modeling and virtual experimentation, using a large core of mathematics, chemistry, physics, and algorithms. Then we see how animal experiments, aimed at providing a standardized result about a biological property, can be mimicked by new in silico methods. Our emphasis here is on toxicology and on predicting properties through chemical structures. Two main streams of such models are available: models that consider the whole molecular structure to predict a value, namely QSAR (Quantitative Structure Activity Relationships), and models that find relevant substructures to predict a class, namely SAR. The term in silico discovery is applied to chemical design, to computational toxicology, and to drug discovery. We discuss how the experimental practice in biological science is moving more and more toward modeling and simulation. Such virtual experiments confirm hypotheses, provide data for regulation, and help in designing new chemicals. PMID:27311459

  5. 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

  6. Therapeutic index modeling and predictive QSAR of novel thiazolidin-4-one analogs against Toxoplasma gondii.

    PubMed

    Asadollahi-Baboli, M; Mani-Varnosfaderani, A

    2015-04-01

    The main idea of this study was to find predictive quantitative structure-activity relationships (QSAR) for the therapeutic index of 68 thiazolidin-4-one analogs against Toxoplasma gondii. Multivariate adaptive regression spline (MARS) together with Monte-Carlo (MC) sampling was proposed as a reliable descriptor subset selection strategy. Basis functions and knot points are also determined for each selected descriptor using generalized cross validation after frequency analysis. Least squares-support vector regression (LS-SVR) with optimized hyper-parameters was employed as mapping tool due to its promising empirical performance. The models were validated and tested through the use of the external prediction set of compounds, leave-one-out and leave-many-out cross validation methods, applicability domain analysis and Y-randomization. The robustness and accuracy of the QSAR models were confirmed by the satisfactory statistical parameters for the experimentally reported dataset (R(2)p=0.853, Q(2)LOO=0.785, R(2)L20%O=0.742 and r(2)m=0.715) and low standard error values (RMSEp=0.208, RMSELOO=0.321 and RMSEL20%O=0.376). The comprehensive analysis carried out in the present contribution using the proposed strategy can provide a considerable basis for the design and development of novel drug-like molecules against T.gondii. PMID:25661424

  7. Evaluation of a statistics-based Ames mutagenicity QSAR model and interpretation of the results obtained.

    PubMed

    Barber, Chris; Cayley, Alex; Hanser, Thierry; Harding, Alex; Heghes, Crina; Vessey, Jonathan D; Werner, Stephane; Weiner, Sandy K; Wichard, Joerg; Giddings, Amanda; Glowienke, Susanne; Parenty, Alexis; Brigo, Alessandro; Spirkl, Hans-Peter; Amberg, Alexander; Kemper, Ray; Greene, Nigel

    2016-04-01

    The relative wealth of bacterial mutagenicity data available in the public literature means that in silico quantitative/qualitative structure activity relationship (QSAR) systems can readily be built for this endpoint. A good means of evaluating the performance of such systems is to use private unpublished data sets, which generally represent a more distinct chemical space than publicly available test sets and, as a result, provide a greater challenge to the model. However, raw performance metrics should not be the only factor considered when judging this type of software since expert interpretation of the results obtained may allow for further improvements in predictivity. Enough information should be provided by a QSAR to allow the user to make general, scientifically-based arguments in order to assess and overrule predictions when necessary. With all this in mind, we sought to validate the performance of the statistics-based in vitro bacterial mutagenicity prediction system Sarah Nexus (version 1.1) against private test data sets supplied by nine different pharmaceutical companies. The results of these evaluations were then analysed in order to identify findings presented by the model which would be useful for the user to take into consideration when interpreting the results and making their final decision about the mutagenic potential of a given compound. PMID:26708083

  8. 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

  9. 3d Modelling of Convective Flow In The Rhine Graben

    NASA Astrophysics Data System (ADS)

    Bächler, D.; Kohl, T.; Rybach, L.

    Detailed investigations of the temperature distribution in the Rhine Graben indi- cate regular pattern of thermal anomalies following major north-south striking faults. These anomalies remain unexplained by conventional Rhine Graben studies based on 2D east-west striking sections. First analytical solutions for convective flow in vertical faults are applied for a clearly observable anomalous temperature pattern along ma- jor Rhine Graben faults. By these calculations the fault height, fault aperture, minimal fault permeability and time to convective onset is derived from the observed distances. Since analytical solutions are limited to simple model geometries further improvement was achieved by numerical model simulations, which allow to assume more com- plex initial and boundary conditions. Using the finite volume code TOUGH2 series of anomalies following the same fault were simulated by a 3D numerical model. Fo- cussing on the predominant north-south permeability structure the model consists of a vertical north-south striking fault and surrounding matrix. The fault geometries are based on the analytically predicted fault geometries (aperture=200m, height=3500m) and on the observed temperatures. Comparison of simulation results with observed temperatures shows that the fault is situated between 500 to 600m and 4200m. The fault permeability is taken as 5*10-13m2 and the fluid velocity in the fault is calcu- lated as 10-9 to 10-10 m/s. These results indicate the importance of our considerations since mass flux is much higher in the faults than across them. The minimal age of the anomaly is considered to be 77'000 years, since steady state is reached after this time span. The study proves that the observed temperature anomaly pattern along the gamma fault at Landau can be explained by north-south striking convection systems within fault zones. Similar situations have been found at Soultz. This may be a hint on a general feature of the major north-south striking

  10. 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

  11. Towards an Anisotropic Whole Mantle 3D Elastic Velocity Model

    NASA Astrophysics Data System (ADS)

    Panning, M. P.; Romanowicz, B.; Gung, Y.

    2001-12-01

    Many studies have documented the existence of anisotropy in the earth's upper mantle, concentrated in the top 200 km. This evidence comes from the study of surface waves as well as shear wave splitting. There is also evidence for shear wave splitting in D", at least in well sampled regions. There are some hints of anisotropy at the base of the transition zone. Tomographic models of the upper mantle have been developed with simplifying assumptions about the nature of the anisotropy, in order to minimize the number of free parameters in the inversions. Some assume transverse isotropy (e.g Ekström and Dziewonski, 1997), others include additional degrees of freedom with some realistic constraints on mineralogy (e.g. Montagner and Tanimoto, 1991). Our goal is to investigate anisotropy in the whole mantle, using the framework of waveform inversion, and the nonlinear asymptotic mode coupling theory (NACT), previously developed and applied to the construction of whole-mantle SH velocity models (Li and Romanowicz, 1996; Mégnin and Romanowicz, 2000). For this we require a 3 component dataset, and we have extended our automatic transverse (T) component wavepicking procedures to the vertical (Z) and longitudinal (L) component - a non-trivial task given the large number of phases present in the coupled P-SV system. A useful initial assumption, for which the theory has been readily adapted, is that of transverse isotropy. As a first step towards this, we have been investigating inversions using T component and Z,L component data separately. In particular, this allows us to explore the sampling that can be achieved with Z,L component data alone in the deepest part of the mantle. Indeed, D" is in general much better sampled in SH than in SV, owing to the availability of SHdiff at large distances, while SVdiff decays more rapidly due to mantle-core coupling. We present the results of our resolution experiments and discuss the differences between the 3D SV model obtained in well

  12. 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.

  13. 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.

  14. Research on urban rapid 3D modeling and application based on CGA rule

    NASA Astrophysics Data System (ADS)

    Li, Jing-wen; Jiang, Jian-wu; Zhou, Song; Yin, Shou-qiang

    2015-12-01

    Use CityEngine as the 3D modeling platform, research on urban rapid 3D modeling technology based on the CGA(Computer Generated Architectur) rule , solved the problem of the rapid creation of urban 3D model in large scenes , and research on building texture processing and 3D model optimization techniques based on CGA rule , using component modeling method , solved the problem of texture distortion and model redundancy in the traditional fast modeling 3D model , and development of a three-dimensional view and analysis system based on ArcGIS Engine , realization of 3D model query , distance measurement , specific path flight , 3D marking , Scene export,etc.

  15. 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.

  16. Benefits of statistical molecular design, covariance analysis, and reference models in QSAR: a case study on acetylcholinesterase.

    PubMed

    Andersson, C David; Hillgren, J Mikael; Lindgren, Cecilia; Qian, Weixing; Akfur, Christine; Berg, Lotta; Ekström, Fredrik; Linusson, Anna

    2015-03-01

    Scientific disciplines such as medicinal- and environmental chemistry, pharmacology, and toxicology deal with the questions related to the effects small organic compounds exhort on biological targets and the compounds' physicochemical properties responsible for these effects. A common strategy in this endeavor is to establish structure-activity relationships (SARs). The aim of this work was to illustrate benefits of performing a statistical molecular design (SMD) and proper statistical analysis of the molecules' properties before SAR and quantitative structure-activity relationship (QSAR) analysis. Our SMD followed by synthesis yielded a set of inhibitors of the enzyme acetylcholinesterase (AChE) that had very few inherent dependencies between the substructures in the molecules. If such dependencies exist, they cause severe errors in SAR interpretation and predictions by QSAR-models, and leave a set of molecules less suitable for future decision-making. In our study, SAR- and QSAR models could show which molecular sub-structures and physicochemical features that were advantageous for the AChE inhibition. Finally, the QSAR model was used for the prediction of the inhibition of AChE by an external prediction set of molecules. The accuracy of these predictions was asserted by statistical significance tests and by comparisons to simple but relevant reference models. PMID:25351962

  17. 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)

  18. 3D object-oriented image analysis in 3D geophysical modelling: Analysing the central part of the East African Rift System

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

    Non-uniqueness of satellite gravity interpretation has traditionally been reduced by using a priori information from seismic tomography models. This reduction in the non-uniqueness has been based on velocity-density conversion formulas or user interpretation of the 3D subsurface structures (objects) based on the seismic tomography models and then forward modelling these objects. However, this form of object-based approach has been done without a standardized methodology on how to extract the subsurface structures from the 3D models. In this research, a 3D object-oriented image analysis (3D OOA) approach was implemented to extract the 3D subsurface structures from geophysical data. The approach was applied on a 3D shear wave seismic tomography model of the central part of the East African Rift System. Subsequently, the extracted 3D objects from the tomography model were reconstructed in the 3D interactive modelling environment IGMAS+, and their density contrast values were calculated using an object-based inversion technique to calculate the forward signal of the objects and compare it with the measured satellite gravity. Thus, a new object-based approach was implemented to interpret and extract the 3D subsurface objects from 3D geophysical data. We also introduce a new approach to constrain the interpretation of the satellite gravity measurements that can be applied using any 3D geophysical model.

  19. The rm2 metrics and regression through origin approach: reliable and useful validation tools for predictive QSAR models (Commentary on 'Is regression through origin useful in external validation of QSAR models?').

    PubMed

    Roy, Kunal; Kar, Supratik

    2014-10-01

    Quantitative structure-activity relationship (QSAR) is an in silico technique which can be used in drug discovery, environmental fate modeling, property and toxicity prediction of chemical entities and regulatory toxicology. The predictive potential of a QSAR model is judged from various validation metrics in order to evaluate how well it is capable to predict endpoint values of new untested compounds. The rm2 group of metrics is one of the stringent validation metrics currently used by the QSAR fraternity in different reports. We scrutinized a recently published paper which raised an issue that the constructed criteria based on regression through origin (RTO) are not optimal and there is a significant difference in the rm2 metrics values computed from different statistical software packages. According to our point of view, the conclusion drawn in this paper appears to be misleading. Any inconsistency in the software algorithms has nothing to do with the calculation of rm2 metrics, as such computation is not limited by the use of any specific software, rather it depends only on fundamental mathematical formulae that are well established. However, it is a concern to the QSAR users that Excel and SPSS can return different results for the metrics using the RTO method. Thus, a proper validation of the software tool is required before its use for computation of any validation metric. PMID:24881556

  20. Quasi-Facial Communication for Online Learning Using 3D Modeling Techniques

    ERIC Educational Resources Information Center

    Wang, Yushun; Zhuang, Yueting

    2008-01-01

    Online interaction with 3D facial animation is an alternative way of face-to-face communication for distance education. 3D facial modeling is essential for virtual educational environments establishment. This article presents a novel 3D facial modeling solution that facilitates quasi-facial communication for online learning. Our algorithm builds…

  1. 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.

  2. 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.

  3. 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.

  4. Development and implementation of (Q)SAR modeling within the CHARMMing Web-user interface

    PubMed Central

    Weidlich, Iwona E.; Pevzner, Yuri; Miller, Benjamin T.; Filippov, Igor V.; Woodcock, H. Lee; Brooks, Bernard R.

    2014-01-01

    Recent availability of large publicly accessible databases of chemical compounds and their biological activities (PubChem, ChEMBL) has inspired us to develop a Web-based tool for SAR and QSAR modeling to add to the services provided by CHARMMing (www.charmming.org). This new module implements some of the most recent advances in modern machine learning algorithms – Random Forest, Support Vector Machine (SVM), Stochastic Gradient Descent, Gradient Tree Boosting etc. A user can import training data from Pubchem Bioassay data collections directly from our interface or upload his or her own SD files which contain structures and activity information to create new models (either categorical or numerical). A user can then track the model generation process and run models on new data to predict activity. PMID:25362883

  5. 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

  6. 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

  7. 3D Modeling of the ALICE Photoinjector Upgrade

    SciTech Connect

    McKenzie, J. W.; Militsyn, B. L.; Saveliev, Y. M.

    2009-08-04

    The injector for the ALICE machine (Accelerators and Lasers In Combined Experiments) at Daresbury Laboratory is based around a 350 kV DC photocathode electron gun. An upgrade is proposed to introduce a load-lock GaAs photocathode preparation facility to allow rapid transfer of photocathodes to the gun without breaking the vacuum system. In the current design this requires side-loading of the photocathodes into the cathode ball. An alternative is to relocate the ceramic insulator vertically which will allow back-loading and also backillumination of the photocathodes. 3D electrostatic simulations of the gun chamber are presented for both options along with 3D beam dynamic simulations for an off-axis photocathode, introduced to increase photocathode lifetime by reducing damage by ion backbombardment. Beam dynamic simulations are also presented for the entire injector beamline as well as for a proposed extension to the injector beamline to include a diagnostic section.

  8. Structural and Physico-Chemical Interpretation (SPCI) of QSAR Models and Its Comparison with Matched Molecular Pair Analysis.

    PubMed

    Polishchuk, Pavel; Tinkov, Oleg; Khristova, Tatiana; Ognichenko, Ludmila; Kosinskaya, Anna; Varnek, Alexandre; Kuz'min, Victor

    2016-08-22

    This paper describes the Structural and Physico-Chemical Interpretation (SPCI) approach, which is an extension of a recently reported method for interpretation of quantitative structure-activity relationship (QSAR) models. This approach can efficiently be used to reveal structural motifs and the major physicochemical factors affecting the investigated properties. Its efficacy was demonstrated both on the classical Free-Wilson data set and on several data sets with different end points (permeability of the blood-brain barrier, fibrinogen receptor antagonists, acute oral toxicity). Structure-activity patterns extracted from QSAR models with SPCI were in good correspondence with experimentally observed relationships and molecular docking, regardless of the machine learning method used. Comparison of SPCI with the matched molecular pair (MMP) method clearly shows an advantage of our approach over MMP, especially for small or structurally diverse data sets. The developed approach has been implemented in the SPCI software tool with a graphical user interface, which is publicly available at http://qsar4u.com/pages/sirms_qsar.php . PMID:27419846

  9. 3D numerical model for NGC 6888 Nebula

    NASA Astrophysics Data System (ADS)

    Reyes-Iturbide, J.; Velázquez, P. F.; Rosado, M.

    We present 3D numerical simulations of the NGC6888 nebula considering the proper motion and the evolution of the star, from the red supergiant (RSG) to the Wolf-Rayet (WR) phase. Our simulations reproduce the limb-brightened morphology observed in [OIII] and X-ray emission maps. The synthetic maps computed by the numerical simulations show filamentary and clumpy structures produced by instabilities triggered in the interaction between the WR wind and the RSG shell.

  10. Simulation of Current Generation in a 3-D Plasma Model

    NASA Astrophysics Data System (ADS)

    Tsung, F. S.; Dawson, J. M.

    1996-11-01

    In the advanced tokam