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Sample records for 3d quantitative structure-activity

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

    PubMed

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

    2012-04-23

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

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

    PubMed

    Yuan, Jintao; Pu, Yuepu; Yin, Lihong

    2013-07-01

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

  3. The discovery of novel histone lysine methyltransferase G9a inhibitors (part 1): molecular design based on a series of substituted 2,4-diamino-7- aminoalkoxyquinazoline by molecular-docking-guided 3D quantitative structure-activity relationship studies.

    PubMed

    Feng, Taotao; Wang, Hai; Zhang, Xiaojin; Sun, Haopeng; You, Qidong

    2014-06-01

    Protein lysine methyltransferase G9a, which catalyzes methylation of lysine 9 of histone H3 (H3K9) and lysine 373 (K373) of p53, is overexpressed in human cancers. This suggests that small molecular inhibitors of G9a might be attractive antitumor agents. Herein we report our efforts on the design of novel G9a inhibitor based on the 3D quantitative structure-activity relationship (3D-QSAR) analysis of a series of 2,4-diamino-7-aminoalkoxyquinazolineas G9a inhibitors. The 3D-QSAR model was generated from 47 compounds using docking based molecular alignment. The best predictions were obtained with CoMFA standard model (q2 =0.700, r2 = 0.952) and CoMSIA model combined with steric, electrostatic, hydrophobic, hydrogen bond donor and acceptor fields (q2 = 0.724, r2 =0.960). The structural requirements for substituted 2,4-diamino-7-aminoalkoxyquinazoline for G9a inhibitory activity can be obtained by analysing the COMSIA plots. Based on the information, six novel follow-up analogs were designed.

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

    PubMed

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

    2011-12-01

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

  5. Quantitative data quality metrics for 3D laser radar systems

    NASA Astrophysics Data System (ADS)

    Stevens, Jeffrey R.; Lopez, Norman A.; Burton, Robin R.

    2011-06-01

    Several quantitative data quality metrics for three dimensional (3D) laser radar systems are presented, namely: X-Y contrast transfer function, Z noise, Z resolution, X-Y edge & line spread functions, 3D point spread function and data voids. These metrics are calculated from both raw and/or processed point cloud data, providing different information regarding the performance of 3D imaging laser radar systems and the perceptual quality attributes of 3D datasets. The discussion is presented within the context of 3D imaging laser radar systems employing arrays of Geiger-mode Avalanche Photodiode (GmAPD) detectors, but the metrics may generally be applied to linear mode systems as well. An example for the role of these metrics in comparison of noise removal algorithms is also provided.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-09-01

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

  8. 3D quantitative phase imaging of neural networks using WDT

    NASA Astrophysics Data System (ADS)

    Kim, Taewoo; Liu, S. C.; Iyer, Raj; Gillette, Martha U.; Popescu, Gabriel

    2015-03-01

    White-light diffraction tomography (WDT) is a recently developed 3D imaging technique based on a quantitative phase imaging system called spatial light interference microscopy (SLIM). The technique has achieved a sub-micron resolution in all three directions with high sensitivity granted by the low-coherence of a white-light source. Demonstrations of the technique on single cell imaging have been presented previously; however, imaging on any larger sample, including a cluster of cells, has not been demonstrated using the technique. Neurons in an animal body form a highly complex and spatially organized 3D structure, which can be characterized by neuronal networks or circuits. Currently, the most common method of studying the 3D structure of neuron networks is by using a confocal fluorescence microscope, which requires fluorescence tagging with either transient membrane dyes or after fixation of the cells. Therefore, studies on neurons are often limited to samples that are chemically treated and/or dead. WDT presents a solution for imaging live neuron networks with a high spatial and temporal resolution, because it is a 3D imaging method that is label-free and non-invasive. Using this method, a mouse or rat hippocampal neuron culture and a mouse dorsal root ganglion (DRG) neuron culture have been imaged in order to see the extension of processes between the cells in 3D. Furthermore, the tomogram is compared with a confocal fluorescence image in order to investigate the 3D structure at synapses.

  9. Quantitative 3-D imaging topogrammetry for telemedicine applications

    NASA Technical Reports Server (NTRS)

    Altschuler, Bruce R.

    1994-01-01

    The technology to reliably transmit high-resolution visual imagery over short to medium distances in real time has led to the serious considerations of the use of telemedicine, telepresence, and telerobotics in the delivery of health care. These concepts may involve, and evolve toward: consultation from remote expert teaching centers; diagnosis; triage; real-time remote advice to the surgeon; and real-time remote surgical instrument manipulation (telerobotics with virtual reality). Further extrapolation leads to teledesign and telereplication of spare surgical parts through quantitative teleimaging of 3-D surfaces tied to CAD/CAM devices and an artificially intelligent archival data base of 'normal' shapes. The ability to generate 'topogrames' or 3-D surface numerical tables of coordinate values capable of creating computer-generated virtual holographic-like displays, machine part replication, and statistical diagnostic shape assessment is critical to the progression of telemedicine. Any virtual reality simulation will remain in 'video-game' realm until realistic dimensional and spatial relational inputs from real measurements in vivo during surgeries are added to an ever-growing statistical data archive. The challenges of managing and interpreting this 3-D data base, which would include radiographic and surface quantitative data, are considerable. As technology drives toward dynamic and continuous 3-D surface measurements, presenting millions of X, Y, Z data points per second of flexing, stretching, moving human organs, the knowledge base and interpretive capabilities of 'brilliant robots' to work as a surgeon's tireless assistants becomes imaginable. The brilliant robot would 'see' what the surgeon sees--and more, for the robot could quantify its 3-D sensing and would 'see' in a wider spectral range than humans, and could zoom its 'eyes' from the macro world to long-distance microscopy. Unerring robot hands could rapidly perform machine-aided suturing with

  10. 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.

  11. 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

  12. Quantitative Reconstructions of 3D Chemical Nanostructures in Nanowires.

    PubMed

    Rueda-Fonseca, P; Robin, E; Bellet-Amalric, E; Lopez-Haro, M; Den Hertog, M; Genuist, Y; André, R; Artioli, A; Tatarenko, S; Ferrand, D; Cibert, J

    2016-03-01

    Energy dispersive X-ray spectrometry is used to extract a quantitative 3D composition profile of heterostructured nanowires. The analysis of hypermaps recorded along a limited number of projections, with a preliminary calibration of the signal associated with each element, is compared to the intensity profiles calculated for a model structure with successive shells of circular, elliptic, or faceted cross sections. This discrete tomographic technique is applied to II-VI nanowires grown by molecular beam epitaxy, incorporating ZnTe and CdTe and their alloys with Mn and Mg, with typical size down to a few nanometers and Mn or Mg content as low as 10%.

  13. Breast tumour visualization using 3D quantitative ultrasound methods

    NASA Astrophysics Data System (ADS)

    Gangeh, Mehrdad J.; Raheem, Abdul; Tadayyon, Hadi; Liu, Simon; Hadizad, Farnoosh; Czarnota, Gregory J.

    2016-04-01

    Breast cancer is one of the most common cancer types accounting for 29% of all cancer cases. Early detection and treatment has a crucial impact on improving the survival of affected patients. Ultrasound (US) is non-ionizing, portable, inexpensive, and real-time imaging modality for screening and quantifying breast cancer. Due to these attractive attributes, the last decade has witnessed many studies on using quantitative ultrasound (QUS) methods in tissue characterization. However, these studies have mainly been limited to 2-D QUS methods using hand-held US (HHUS) scanners. With the availability of automated breast ultrasound (ABUS) technology, this study is the first to develop 3-D QUS methods for the ABUS visualization of breast tumours. Using an ABUS system, unlike the manual 2-D HHUS device, the whole patient's breast was scanned in an automated manner. The acquired frames were subsequently examined and a region of interest (ROI) was selected in each frame where tumour was identified. Standard 2-D QUS methods were used to compute spectral and backscatter coefficient (BSC) parametric maps on the selected ROIs. Next, the computed 2-D parameters were mapped to a Cartesian 3-D space, interpolated, and rendered to provide a transparent color-coded visualization of the entire breast tumour. Such 3-D visualization can potentially be used for further analysis of the breast tumours in terms of their size and extension. Moreover, the 3-D volumetric scans can be used for tissue characterization and the categorization of breast tumours as benign or malignant by quantifying the computed parametric maps over the whole tumour volume.

  14. Quantitative 3D data extraction using contiguous volumes

    SciTech Connect

    Dykstra, C.J.; Celler, A.M.; Harrop, R.; Atkins, M.S.

    1996-12-31

    A new image analysis method, called contiguous volume analysis, has been developed to automatically extract 3D information from emission images. The method considers volumes of activity and displays data about them in a format which allows quantitative image comparison. Such rigorous, numerical analysis enables us to show, for example, whether or not important information has been gained, lost or changed through the use of different filters and different reconstruction, attenuation and scatter correction algorithms. Since the analysis method is consistent with a visual inspection of the data, intuitive insights into the meaning of the data are possible, allowing a better understanding of the effects of the different image processing techniques on the images. The data can be used to find patterns of activity in sets of images, and might also be used to quantify noise, allowing an objective determination of which volumes in an image are significant.

  15. Quantitative structure-activity relationships for fluoroelastomer/chlorofluorocarbon systems

    SciTech Connect

    Paciorek, K.J.L.; Masuda, S.R.; Nakahara, J.H. ); Snyder, C.E. Jr.; Warner, W.M. )

    1991-12-01

    This paper reports on swell, tensile, and modulus data that were determined for a fluoroelastomer after exposure to a series of chlorofluorocarbon model fluids. Quantitative structure-activity relationships (QSAR) were developed for the swell as a function of the number of carbons and chlorines and for tensile strength as a function of carbon number and chlorine positions in the chlorofluorocarbons.

  16. Quantitative 3D Optical Imaging: Applications in Dosimetry and Biophysics

    NASA Astrophysics Data System (ADS)

    Thomas, Andrew Stephen

    Optical-CT has been shown to be a potentially useful imaging tool for the two very different spheres of biologists and radiation therapy physicists, but it has yet to live up to that potential. In radiation therapy, researchers have used optical-CT for the readout of 3D dosimeters, but it is yet to be a clinically relevant tool as the technology is too slow to be considered practical. Biologists have used the technique for structural imaging, but have struggled with emission tomography as the reality of photon attenuation for both excitation and emission have made the images quantitatively irrelevant. Dosimetry. The DLOS (Duke Large field of view Optical-CT Scanner) was designed and constructed to make 3D dosimetry utilizing optical-CT a fast and practical tool while maintaining the accuracy of readout of the previous, slower readout technologies. Upon construction/optimization/implementation of several components including a diffuser, band pass filter, registration mount & fluid filtration system the dosimetry system provides high quality data comparable to or exceeding that of commercial products. In addition, a stray light correction algorithm was tested and implemented. The DLOS in combination with the 3D dosimeter it was designed for, PREAGETM, then underwent rigorous commissioning and benchmarking tests validating its performance against gold standard data including a set of 6 irradiations. DLOS commissioning tests resulted in sub-mm isotropic spatial resolution (MTF >0.5 for frequencies of 1.5lp/mm) and a dynamic range of ˜60dB. Flood field uniformity was 10% and stable after 45minutes. Stray light proved to be small, due to telecentricity, but even the residual can be removed through deconvolution. Benchmarking tests showed the mean 3D passing gamma rate (3%, 3mm, 5% dose threshold) over the 6 benchmark data sets was 97.3% +/- 0.6% (range 96%-98%) scans totaling ˜10 minutes, indicating excellent ability to perform 3D dosimetry while improving the speed of

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2013-05-03

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

  20. A novel algorithm for QSAR (quantitative structure-activity relationships)

    SciTech Connect

    Carter, S. ); Nikolic, S.; Trinajstic, N. )

    1989-01-01

    A novel approach to quantitative structure-activity relationships (QSAR) is proposed. It is based on the molecular descriptor named the stereo-identification (SID) number. The applicability of this approach to QSAR studies is tested on aquatic toxicities of phenols against fathead minnows (Phimephales promelas). Our approach reproduced successfully the bioactivities of phenols and is superior to the Hall-Kier model based on Randic's connectivity index.

  1. (Quantitative structure-activity relationships in environmental toxicology)

    SciTech Connect

    Turner, J.E.

    1990-10-04

    The traveler attended the Fourth International Workshop on QSAR (Quantitative Structure-Activity Relationships) in Environmental Toxicology. He was an author or co-author on one platform and two poster presentations. The subject of the workshop offers a framework for analyzing and predicting the fate of chemical pollutants in organisms and the environment. QSAR is highly relevant to the ORNL program on the physicochemical characterization of chemical pollutants for health protection.

  2. Quantitative validation of 3D image registration techniques

    NASA Astrophysics Data System (ADS)

    Holton Tainter, Kerrie S.; Taneja, Udita; Robb, Richard A.

    1995-05-01

    Multimodality images obtained from different medical imaging systems such as magnetic resonance (MR), computed tomography (CT), ultrasound (US), positron emission tomography (PET), single photon emission computed tomography (SPECT) provide largely complementary characteristic or diagnostic information. Therefore, it is an important research objective to `fuse' or combine this complementary data into a composite form which would provide synergistic information about the objects under examination. An important first step in the use of complementary fused images is 3D image registration, where multi-modality images are brought into spatial alignment so that the point-to-point correspondence between image data sets is known. Current research in the field of multimodality image registration has resulted in the development and implementation of several different registration algorithms, each with its own set of requirements and parameters. Our research has focused on the development of a general paradigm for measuring, evaluating and comparing the performance of different registration algorithms. Rather than evaluating the results of one algorithm under a specific set of conditions, we suggest a general approach to validation using simulation experiments, where the exact spatial relationship between data sets is known, along with phantom data, to characterize the behavior of an algorithm via a set of quantitative image measurements. This behavior may then be related to the algorithm's performance with real patient data, where the exact spatial relationship between multimodality images is unknown. Current results indicate that our approach is general enough to apply to several different registration algorithms. Our methods are useful for understanding the different sources of registration error and for comparing the results between different algorithms.

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

    NASA Astrophysics Data System (ADS)

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

    2010-12-01

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

  4. Three dimensional quantitative structure-activity relationships of sulfonamides binding monoclonal antibody by comparative molecular field analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The three-dimensional quantitative structure-activity relationship (3D-QSAR) model of sulfonamide analogs, binding a monoclonal antibody (MabSMR) produced against sulfamerazine was carried out by comparative molecular field analysis (CoMFA). The affinities of MabSMR, expressed as Log10IC50, for 17 ...

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

    PubMed

    Sharma, Mukesh C

    2016-03-01

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

  6. Real Time Quantitative 3-D Imaging of Diffusion Flame Species

    NASA Technical Reports Server (NTRS)

    Kane, Daniel J.; Silver, Joel A.

    1997-01-01

    A low-gravity environment, in space or ground-based facilities such as drop towers, provides a unique setting for study of combustion mechanisms. Understanding the physical phenomena controlling the ignition and spread of flames in microgravity has importance for space safety as well as better characterization of dynamical and chemical combustion processes which are normally masked by buoyancy and other gravity-related effects. Even the use of so-called 'limiting cases' or the construction of 1-D or 2-D models and experiments fail to make the analysis of combustion simultaneously simple and accurate. Ideally, to bridge the gap between chemistry and fluid mechanics in microgravity combustion, species concentrations and temperature profiles are needed throughout the flame. However, restrictions associated with performing measurements in reduced gravity, especially size and weight considerations, have generally limited microgravity combustion studies to the capture of flame emissions on film or video laser Schlieren imaging and (intrusive) temperature measurements using thermocouples. Given the development of detailed theoretical models, more sophisticated studies are needed to provide the kind of quantitative data necessary to characterize the properties of microgravity combustion processes as well as provide accurate feedback to improve the predictive capabilities of the computational models. While there have been a myriad of fluid mechanical visualization studies in microgravity combustion, little experimental work has been completed to obtain reactant and product concentrations within a microgravity flame. This is largely due to the fact that traditional sampling methods (quenching microprobes using GC and/or mass spec analysis) are too heavy, slow, and cumbersome for microgravity experiments. Non-intrusive optical spectroscopic techniques have - up until now - also required excessively bulky, power hungry equipment. However, with the advent of near-IR diode

  7. Determining cleanup levels in bioremediation: Quantitative structure activity relationship techniques

    SciTech Connect

    Arulgnanendran, V.R.J.; Nirmalakhandan, N.

    1995-12-31

    An important feature in the process of planning and initiating bioremediation is the quantification of the toxicity of either an individual chemical or a group of chemicals when multiple chemicals are involved. A laboratory protocol was developed to test the toxicity of single chemicals and mixtures of organic chemicals in a soil medium. Portions of these chemicals are used as a training set to develop Quantitative Structure Activity Relationship (QSAR) models. These predictive models are tested using the chemicals in the testing set, i.e., the remaining chemicals. Moreover mixtures with 10 contaminants in each mixture are tested experimentally to determine joint toxicity for mixtures of chemicals. Using the concepts of Toxic Units, Additivity Index, and Mixture Toxicity Index, the laboratory results are tested for additive, synergistic, or antagonistic effects of the contaminants. These concepts are further validated on mixtures containing eight chemicals that are tested in the laboratory. In addition to the use of the predictive models in evaluating cleanup levels for hazardous waste locations, they are useful to predict microbial toxicity in soils of new chemicals from a congeneric group acting by the same mode of toxicity. These models are applicable when the contaminants act singly or jointly in a mixture.

  8. Improving quantitative structure-activity relationships through multiobjective optimization.

    PubMed

    Nicolotti, Orazio; Giangreco, Ilenia; Miscioscia, Teresa Fabiola; Carotti, Angelo

    2009-10-01

    A multiobjective optimization algorithm was proposed for the automated integration of structure- and ligand-based molecular design. Driven by a genetic algorithm, the herein proposed approach enabled the detection of a number of trade-off QSAR models accounting simultaneously for two independent objectives. The first was biased toward best regressions among docking scores and biological affinities; the second minimized the atom displacements from a properly established crystal-based binding topology. Based on the concept of dominance, 3D QSAR equivalent models profiled the Pareto frontier and were, thus, designated as nondominated solutions of the search space. K-means clustering was, then, operated to select a representative subset of the available trade-off models. These were effectively subjected to GRID/GOLPE analyses for quantitatively featuring molecular determinants of ligand binding affinity. More specifically, it was demonstrated that a) diverse binding conformations occurred on the basis of the ligand ability to profitably contact different part of protein binding site; b) enzyme selectivity was better approached and interpreted by combining diverse equivalent models; and c) trade-off models were successful and even better than docking virtual screening, in retrieving at high sensitivity active hits from a large pool of chemically similar decoys. The approach was tested on a large series, very well-known to QSAR practitioners, of 3-amidinophenylalanine inhibitors of thrombin and trypsin, two serine proteases having rather different biological actions despite a high sequence similarity. PMID:19785453

  9. 3D Slicer as an Image Computing Platform for the Quantitative Imaging Network

    PubMed Central

    Fedorov, Andriy; Beichel, Reinhard; Kalpathy-Cramer, Jayashree; Finet, Julien; Fillion-Robin, Jean-Christophe; Pujol, Sonia; Bauer, Christian; Jennings, Dominique; Fennessy, Fiona; Sonka, Milan; Buatti, John; Aylward, Stephen; Miller, James V.; Pieper, Steve; Kikinis, Ron

    2012-01-01

    Quantitative analysis has tremendous but mostly unrealized potential in healthcare to support objective and accurate interpretation of the clinical imaging. In 2008, the National Cancer Institute began building the Quantitative Imaging Network (QIN) initiative with the goal of advancing quantitative imaging in the context of personalized therapy and evaluation of treatment response. Computerized analysis is an important component contributing to reproducibility and efficiency of the quantitative imaging techniques. The success of quantitative imaging is contingent on robust analysis methods and software tools to bring these methods from bench to bedside. 3D Slicer is a free open source software application for medical image computing. As a clinical research tool, 3D Slicer is similar to a radiology workstation that supports versatile visualizations but also provides advanced functionality such as automated segmentation and registration for a variety of application domains. Unlike a typical radiology workstation, 3D Slicer is free and is not tied to specific hardware. As a programming platform, 3D Slicer facilitates translation and evaluation of the new quantitative methods by allowing the biomedical researcher to focus on the implementation of the algorithm, and providing abstractions for the common tasks of data communication, visualization and user interface development. Compared to other tools that provide aspects of this functionality, 3D Slicer is fully open source and can be readily extended and redistributed. In addition, 3D Slicer is designed to facilitate the development of new functionality in the form of 3D Slicer extensions. In this paper, we present an overview of 3D Slicer as a platform for prototyping, development and evaluation of image analysis tools for clinical research applications. To illustrate the utility of the platform in the scope of QIN, we discuss several use cases of 3D Slicer by the existing QIN teams, and we elaborate on the future

  10. Quantitative structure-activity relationships for organophosphates binding to acetylcholinesterase.

    PubMed

    Ruark, Christopher D; Hack, C Eric; Robinson, Peter J; Anderson, Paul E; Gearhart, Jeffery M

    2013-02-01

    Organophosphates are a group of pesticides and chemical warfare nerve agents that inhibit acetylcholinesterase, the enzyme responsible for hydrolysis of the excitatory neurotransmitter acetylcholine. Numerous structural variants exist for this chemical class, and data regarding their toxicity can be difficult to obtain in a timely fashion. At the same time, their use as pesticides and military weapons is widespread, which presents a major concern and challenge in evaluating human toxicity. To address this concern, a quantitative structure-activity relationship (QSAR) was developed to predict pentavalent organophosphate oxon human acetylcholinesterase bimolecular rate constants. A database of 278 three-dimensional structures and their bimolecular rates was developed from 15 peer-reviewed publications. A database of simplified molecular input line entry notations and their respective acetylcholinesterase bimolecular rate constants are listed in Supplementary Material, Table I. The database was quite diverse, spanning 7 log units of activity. In order to describe their structure, 675 molecular descriptors were calculated using AMPAC 8.0 and CODESSA 2.7.10. Orthogonal projection to latent structures regression, bootstrap leave-random-many-out cross-validation and y-randomization were used to develop an externally validated consensus QSAR model. The domain of applicability was assessed by the William's plot. Six external compounds were outside the warning leverage indicating potential model extrapolation. A number of compounds had residuals >2 or <-2, indicating potential outliers or activity cliffs. The results show that the HOMO-LUMO energy gap contributed most significantly to the binding affinity. A mean training R (2) of 0.80, a mean test set R (2) of 0.76 and a consensus external test set R (2) of 0.66 were achieved using the QSAR. The training and external test set RMSE values were found to be 0.76 and 0.88. The results suggest that this QSAR model can be used in

  11. Synthesis, biological activities, and quantitative structure-activity relationship (QSAR) study of novel camptothecin analogues.

    PubMed

    Wu, Dan; Zhang, Shao-Yong; Liu, Ying-Qian; Wu, Xiao-Bing; Zhu, Gao-Xiang; Zhang, Yan; Wei, Wei; Liu, Huan-Xiang; Chen, An-Liang

    2015-05-13

    In continuation of our program aimed at the development of natural product-based pesticidal agents, three series of novel camptothecin derivatives were designed, synthesized, and evaluated for their biological activities against T. Cinnabarinus, B. brassicae, and B. xylophilus. All of the derivatives showed good-to-excellent activity against three insect species tested, with LC50 values ranging from 0.00761 to 0.35496 mmol/L. Remarkably, all of the compounds were more potent than CPT against T. Cinnabarinus, and compounds 4d and 4c displayed superior activity (LC50 0.00761 mmol/L and 0.00942 mmol/L, respectively) compared with CPT (LC50 0.19719 mmol/L) against T. Cinnabarinus. Based on the observed bioactivities, preliminary structure-activity relationship (SAR) correlations were also discussed. Furthermore, a three-dimensional quantitative structure-activity relationship (3D-QSAR) model using comparative molecular field analysis (CoMFA) was built. The model gave statistically significant results with the cross-validated q2 values of 0.580 and correlation coefficient r2 of 0.991 and  of 0.993. The QSAR analysis indicated that the size of the substituents play an important in the activity of 7-modified camptothecin derivatives. These findings will pave the way for further design, structural optimization, and development of camptothecin-derived compounds as pesticidal agents.

  12. A quantitative structure-activity relationship model for radical scavenging activity of flavonoids.

    PubMed

    Om, A; Kim, J H

    2008-03-01

    A quantitative structure-activity relationship (QSAR) study has been carried out for a training set of 29 flavonoids to correlate and predict the 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity (RSA) values obtained from published data. Genetic algorithm and multiple linear regression were employed to select the descriptors and to generate the best prediction model that relates the structural features to the RSA activities using (1) three-dimensional (3D) Dragon (TALETE srl, Milan, Italy) descriptors and (2) semi-empirical descriptor calculations. The predictivity of the models was estimated by cross-validation with the leave-one-out method. The result showed that a significant improvement of the statistical indices was obtained by deleting outliers. Based on the data for the compounds used in this study, our results suggest a QSAR model of RSA that is based on the following descriptors: 3D-Morse, WHIM, and GETAWAY. Therefore, satisfactory relationships between RSA and the semi-empirical descriptors were found, demonstrating that the energy of the highest occupied molecular orbital, total energy, and energy of heat of formation contributed more significantly than all other descriptors.

  13. 3D-Pathology: a real-time system for quantitative diagnostic pathology and visualisation in 3D

    NASA Astrophysics Data System (ADS)

    Gottrup, Christian; Beckett, Mark G.; Hager, Henrik; Locht, Peter

    2005-02-01

    This paper presents the results of the 3D-Pathology project conducted under the European EC Framework 5. The aim of the project was, through the application of 3D image reconstruction and visualization techniques, to improve the diagnostic and prognostic capabilities of medical personnel when analyzing pathological specimens using transmitted light microscopy. A fully automated, computer-controlled microscope system has been developed to capture 3D images of specimen content. 3D image reconstruction algorithms have been implemented and applied to the acquired volume data in order to facilitate the subsequent 3D visualization of the specimen. Three potential application fields, immunohistology, cromogenic in situ hybridization (CISH) and cytology, have been tested using the prototype system. For both immunohistology and CISH, use of the system furnished significant additional information to the pathologist.

  14. Framework for quantitative evaluation of 3D vessel segmentation approaches using vascular phantoms in conjunction with 3D landmark localization and registration

    NASA Astrophysics Data System (ADS)

    Wörz, Stefan; Hoegen, Philipp; Liao, Wei; Müller-Eschner, Matthias; Kauczor, Hans-Ulrich; von Tengg-Kobligk, Hendrik; Rohr, Karl

    2016-03-01

    We introduce a framework for quantitative evaluation of 3D vessel segmentation approaches using vascular phantoms. Phantoms are designed using a CAD system and created with a 3D printer, and comprise realistic shapes including branches and pathologies such as abdominal aortic aneurysms (AAA). To transfer ground truth information to the 3D image coordinate system, we use a landmark-based registration scheme utilizing fiducial markers integrated in the phantom design. For accurate 3D localization of the markers we developed a novel 3D parametric intensity model that is directly fitted to the markers in the images. We also performed a quantitative evaluation of different vessel segmentation approaches for a phantom of an AAA.

  15. A Workstation for Interactive Display and Quantitative Analysis of 3-D and 4-D Biomedical Images

    PubMed Central

    Robb, R.A.; Heffeman, P.B.; Camp, J.J.; Hanson, D.P.

    1986-01-01

    The capability to extract objective and quantitatively accurate information from 3-D radiographic biomedical images has not kept pace with the capabilities to produce the images themselves. This is rather an ironic paradox, since on the one hand the new 3-D and 4-D imaging capabilities promise significant potential for providing greater specificity and sensitivity (i.e., precise objective discrimination and accurate quantitative measurement of body tissue characteristics and function) in clinical diagnostic and basic investigative imaging procedures than ever possible before, but on the other hand, the momentous advances in computer and associated electronic imaging technology which have made these 3-D imaging capabilities possible have not been concomitantly developed for full exploitation of these capabilities. Therefore, we have developed a powerful new microcomputer-based system which permits detailed investigations and evaluation of 3-D and 4-D (dynamic 3-D) biomedical images. The system comprises a special workstation to which all the information in a large 3-D image data base is accessible for rapid display, manipulation, and measurement. The system provides important capabilities for simultaneously representing and analyzing both structural and functional data and their relationships in various organs of the body. This paper provides a detailed description of this system, as well as some of the rationale, background, theoretical concepts, and practical considerations related to system implementation. ImagesFigure 5Figure 7Figure 8Figure 9Figure 10Figure 11Figure 12Figure 13Figure 14Figure 15Figure 16

  16. Quantitative structure-activity relationship study on BTK inhibitors by modified multivariate adaptive regression spline and CoMSIA methods.

    PubMed

    Xu, A; Zhang, Y; Ran, T; Liu, H; Lu, S; Xu, J; Xiong, X; Jiang, Y; Lu, T; Chen, Y

    2015-01-01

    Bruton's tyrosine kinase (BTK) plays a crucial role in B-cell activation and development, and has emerged as a new molecular target for the treatment of autoimmune diseases and B-cell malignancies. In this study, two- and three-dimensional quantitative structure-activity relationship (2D and 3D-QSAR) analyses were performed on a series of pyridine and pyrimidine-based BTK inhibitors by means of genetic algorithm optimized multivariate adaptive regression spline (GA-MARS) and comparative molecular similarity index analysis (CoMSIA) methods. Here, we propose a modified MARS algorithm to develop 2D-QSAR models. The top ranked models showed satisfactory statistical results (2D-QSAR: Q(2) = 0.884, r(2) = 0.929, r(2)pred = 0.878; 3D-QSAR: q(2) = 0.616, r(2) = 0.987, r(2)pred = 0.905). Key descriptors selected by 2D-QSAR were in good agreement with the conclusions of 3D-QSAR, and the 3D-CoMSIA contour maps facilitated interpretation of the structure-activity relationship. A new molecular database was generated by molecular fragment replacement (MFR) and further evaluated with GA-MARS and CoMSIA prediction. Twenty-five pyridine and pyrimidine derivatives as novel potential BTK inhibitors were finally selected for further study. These results also demonstrated that our method can be a very efficient tool for the discovery of novel potent BTK inhibitors.

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

    NASA Astrophysics Data System (ADS)

    He, Huanyu

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

  18. Patient-specific dosimetry based on quantitative SPECT imaging and 3D-DFT convolution

    SciTech Connect

    Akabani, G.; Hawkins, W.G.; Eckblade, M.B.; Leichner, P.K.

    1999-01-01

    The objective of this study was to validate the use of a 3-D discrete Fourier Transform (3D-DFT) convolution method to carry out the dosimetry for I-131 for soft tissues in radioimmunotherapy procedures. To validate this convolution method, mathematical and physical phantoms were used as a basis of comparison with Monte Carlo transport (MCT) calculations which were carried out using the EGS4 system code. The mathematical phantom consisted of a sphere containing uniform and nonuniform activity distributions. The physical phantom consisted of a cylinder containing uniform and nonuniform activity distributions. Quantitative SPECT reconstruction was carried out using the Circular Harmonic Transform (CHT) algorithm.

  19. PREDICTING TOXICOLOGICAL ENDPOINTS OF CHEMICALS USING QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSARS)

    EPA Science Inventory

    Quantitative structure-activity relationships (QSARs) are being developed to predict the toxicological endpoints for untested chemicals similar in structure to chemicals that have known experimental toxicological data. Based on a very large number of predetermined descriptors, a...

  20. Quantitative Structure--Activity Relationship Modeling of Rat Acute Toxicity by Oral Exposure

    EPA Science Inventory

    Background: Few Quantitative Structure-Activity Relationship (QSAR) studies have successfully modeled large, diverse rodent toxicity endpoints. Objective: In this study, a combinatorial QSAR approach has been employed for the creation of robust and predictive models of acute toxi...

  1. Quantitative structure-activity relationships and the prediction of MHC supermotifs.

    PubMed

    Doytchinova, Irini A; Guan, Pingping; Flower, Darren R

    2004-12-01

    The underlying assumption in quantitative structure-activity relationship (QSAR) methodology is that related chemical structures exhibit related biological activities. We review here two QSAR methods in terms of their applicability for human MHC supermotif definition. Supermotifs are motifs that characterise binding to more than one allele. Supermotif definition is the initial in silico step of epitope-based vaccine design. The first QSAR method we review here--the additive method--is based on the assumption that the binding affinity of a peptide depends on contributions from both amino acids and the interactions between them. The second method is a 3D-QSAR method: comparative molecular similarity indices analysis (CoMSIA). Both methods were applied to 771 peptides binding to 9 HLA alleles. Five of the alleles (A*0201, A*0202, A*0203, A*0206 and A*6802) belong to the HLA-A2 superfamily and the other four (A*0301, A*1101, A*3101 and A*6801) to the HLA-A3 superfamily. For each superfamily, supermotifs defined by the two QSAR methods agree closely and are supported by many experimental data. PMID:15542370

  2. Improving quantitative structure-activity relationship models using Artificial Neural Networks trained with dropout.

    PubMed

    Mendenhall, Jeffrey; Meiler, Jens

    2016-02-01

    Dropout is an Artificial Neural Network (ANN) training technique that has been shown to improve ANN performance across canonical machine learning (ML) datasets. Quantitative Structure Activity Relationship (QSAR) datasets used to relate chemical structure to biological activity in Ligand-Based Computer-Aided Drug Discovery pose unique challenges for ML techniques, such as heavily biased dataset composition, and relatively large number of descriptors relative to the number of actives. To test the hypothesis that dropout also improves QSAR ANNs, we conduct a benchmark on nine large QSAR datasets. Use of dropout improved both enrichment false positive rate and log-scaled area under the receiver-operating characteristic curve (logAUC) by 22-46 % over conventional ANN implementations. Optimal dropout rates are found to be a function of the signal-to-noise ratio of the descriptor set, and relatively independent of the dataset. Dropout ANNs with 2D and 3D autocorrelation descriptors outperform conventional ANNs as well as optimized fingerprint similarity search methods.

  3. Docking and quantitative structure-activity relationship of oxadiazole derivates as inhibitors of GSK3β.

    PubMed

    Quesada-Romero, Luisa; Caballero, Julio

    2014-02-01

    The binding modes of 42 oxadiazole derivates inside glycogen synthase kinase 3 beta (GSK3β were determined using docking experiments; thus, the preferred active conformations of these inhibitors are proposed. We found that these compounds adopt a scorpion-shaped conformation and they accept a hydrogen bond (HB) from the residue Val135 of the GSK3β ATP-binding site hinge region. In addition, quantitative structure-activity relationship (QSAR) models were constructed to explain the trend of the GSK3β inhibitory activities for the studied compounds. In a first approach, three-dimensional (3D) vectors were calculated using docking conformations and, by using multiple-linear regression, we assessed that GETAWAY vectors were able to describe the reported biological activities. In other QSAR approach, SMILES-based optimal descriptors were calculated. The best model included three-SMILES elements SSSβ leading to the identification of key molecular features that contribute to a high GSK3β inhibitory activity.

  4. Docking and quantitative structure-activity relationship of oxadiazole derivates as inhibitors of GSK3β.

    PubMed

    Quesada-Romero, Luisa; Caballero, Julio

    2014-02-01

    The binding modes of 42 oxadiazole derivates inside glycogen synthase kinase 3 beta (GSK3β were determined using docking experiments; thus, the preferred active conformations of these inhibitors are proposed. We found that these compounds adopt a scorpion-shaped conformation and they accept a hydrogen bond (HB) from the residue Val135 of the GSK3β ATP-binding site hinge region. In addition, quantitative structure-activity relationship (QSAR) models were constructed to explain the trend of the GSK3β inhibitory activities for the studied compounds. In a first approach, three-dimensional (3D) vectors were calculated using docking conformations and, by using multiple-linear regression, we assessed that GETAWAY vectors were able to describe the reported biological activities. In other QSAR approach, SMILES-based optimal descriptors were calculated. The best model included three-SMILES elements SSSβ leading to the identification of key molecular features that contribute to a high GSK3β inhibitory activity. PMID:24081608

  5. Quantitative model for the generic 3D shape of ICMEs at 1 AU

    NASA Astrophysics Data System (ADS)

    Démoulin, P.; Janvier, M.; Masías-Meza, J. J.; Dasso, S.

    2016-10-01

    Context. Interplanetary imagers provide 2D projected views of the densest plasma parts of interplanetary coronal mass ejections (ICMEs), while in situ measurements provide magnetic field and plasma parameter measurements along the spacecraft trajectory, that is, along a 1D cut. The data therefore only give a partial view of the 3D structures of ICMEs. Aims: By studying a large number of ICMEs, crossed at different distances from their apex, we develop statistical methods to obtain a quantitative generic 3D shape of ICMEs. Methods: In a first approach we theoretically obtained the expected statistical distribution of the shock-normal orientation from assuming simple models of 3D shock shapes, including distorted profiles, and compared their compatibility with observed distributions. In a second approach we used the shock normal and the flux rope axis orientations together with the impact parameter to provide statistical information across the spacecraft trajectory. Results: The study of different 3D shock models shows that the observations are compatible with a shock that is symmetric around the Sun-apex line as well as with an asymmetry up to an aspect ratio of around 3. Moreover, flat or dipped shock surfaces near their apex can only be rare cases. Next, the sheath thickness and the ICME velocity have no global trend along the ICME front. Finally, regrouping all these new results and those of our previous articles, we provide a quantitative ICME generic 3D shape, including the global shape of the shock, the sheath, and the flux rope. Conclusions: The obtained quantitative generic ICME shape will have implications for several aims. For example, it constrains the output of typical ICME numerical simulations. It is also a base for studying the transport of high-energy solar and cosmic particles during an ICME propagation as well as for modeling and forecasting space weather conditions near Earth.

  6. Qualitative and quantitative comparative analyses of 3D lidar landslide displacement field measurements

    NASA Astrophysics Data System (ADS)

    Haugen, Benjamin D.

    Landslide ground surface displacements vary at all spatial scales and are an essential component of kinematic and hazards analyses. Unfortunately, survey-based displacement measurements require personnel to enter unsafe terrain and have limited spatial resolution. And while recent advancements in LiDAR technology provide the ability remotely measure 3D landslide displacements at high spatial resolution, no single method is widely accepted. A series of qualitative metrics for comparing 3D landslide displacement field measurement methods were developed. The metrics were then applied to nine existing LiDAR techniques, and the top-ranking methods --Iterative Closest Point (ICP) matching and 3D Particle Image Velocimetry (3DPIV) -- were quantitatively compared using synthetic displacement and control survey data from a slow-moving translational landslide in north-central Colorado. 3DPIV was shown to be the most accurate and reliable point cloud-based 3D landslide displacement field measurement method, and the viability of LiDAR-based techniques for measuring 3D motion on landslides was demonstrated.

  7. 3D OCT imaging in clinical settings: toward quantitative measurements of retinal structures

    NASA Astrophysics Data System (ADS)

    Zawadzki, Robert J.; Fuller, Alfred R.; Zhao, Mingtao; Wiley, David F.; Choi, Stacey S.; Bower, Bradley A.; Hamann, Bernd; Izatt, Joseph A.; Werner, John S.

    2006-02-01

    The acquisition speed of current FD-OCT (Fourier Domain - Optical Coherence Tomography) instruments allows rapid screening of three-dimensional (3D) volumes of human retinas in clinical settings. To take advantage of this ability requires software used by physicians to be capable of displaying and accessing volumetric data as well as supporting post processing in order to access important quantitative information such as thickness maps and segmented volumes. We describe our clinical FD-OCT system used to acquire 3D data from the human retina over the macula and optic nerve head. B-scans are registered to remove motion artifacts and post-processed with customized 3D visualization and analysis software. Our analysis software includes standard 3D visualization techniques along with a machine learning support vector machine (SVM) algorithm that allows a user to semi-automatically segment different retinal structures and layers. Our program makes possible measurements of the retinal layer thickness as well as volumes of structures of interest, despite the presence of noise and structural deformations associated with retinal pathology. Our software has been tested successfully in clinical settings for its efficacy in assessing 3D retinal structures in healthy as well as diseased cases. Our tool facilitates diagnosis and treatment monitoring of retinal diseases.

  8. Structure-activity relationships of 6-(2,6-dichlorophenyl)-8-methyl-2-(phenylamino)pyrido[2,3-d]pyrimidin-7-ones: toward selective Abl inhibitors

    PubMed Central

    Antczak, Christophe; Veach, Darren R.; Ramirez, Christina N.; Minchenko, Maria A.; Shum, David; Calder, Paul A.; Frattini, Mark G.; Clarkson, Bayard; Djaballah, Hakim

    2013-01-01

    We report the design, synthesis and structure-activity relationship (SAR) of a series of novel pyrido[2,3-d]pyrimidin-7-one compounds as potent Abl kinase inhibitors. We evaluate their specificity profile against a panel of human recombinant kinases, as well as their biological profile toward a panel of well characterized cancer cell lines. Our study reveals that substitutions in the -3 and -4 positions of the phenylamino moiety lead to improved potency and improved selectivity both in target-based and cell based assays. Altogether, our results provide an insight into the SAR of pyrido[2,3-d]pyrimidin-7-ones for the development of drug candidates with improved potency and selectivity for the targeted treatment of CML. PMID:19889540

  9. Quantitative wound healing measurement and monitoring system based on an innovative 3D imaging system

    NASA Astrophysics Data System (ADS)

    Yi, Steven; Yang, Arthur; Yin, Gongjie; Wen, James

    2011-03-01

    In this paper, we report a novel three-dimensional (3D) wound imaging system (hardware and software) under development at Technest Inc. System design is aimed to perform accurate 3D measurement and modeling of a wound and track its healing status over time. Accurate measurement and tracking of wound healing enables physicians to assess, document, improve, and individualize the treatment plan given to each wound patient. In current wound care practices, physicians often visually inspect or roughly measure the wound to evaluate the healing status. This is not an optimal practice since human vision lacks precision and consistency. In addition, quantifying slow or subtle changes through perception is very difficult. As a result, an instrument that quantifies both skin color and geometric shape variations would be particularly useful in helping clinicians to assess healing status and judge the effect of hyperemia, hematoma, local inflammation, secondary infection, and tissue necrosis. Once fully developed, our 3D imaging system will have several unique advantages over traditional methods for monitoring wound care: (a) Non-contact measurement; (b) Fast and easy to use; (c) up to 50 micron measurement accuracy; (d) 2D/3D Quantitative measurements;(e) A handheld device; and (f) Reasonable cost (< $1,000).

  10. Changes in quantitative 3D shape features of the optic nerve head associated with age

    NASA Astrophysics Data System (ADS)

    Christopher, Mark; Tang, Li; Fingert, John H.; Scheetz, Todd E.; Abramoff, Michael D.

    2013-02-01

    Optic nerve head (ONH) structure is an important biological feature of the eye used by clinicians to diagnose and monitor progression of diseases such as glaucoma. ONH structure is commonly examined using stereo fundus imaging or optical coherence tomography. Stereo fundus imaging provides stereo views of the ONH that retain 3D information useful for characterizing structure. In order to quantify 3D ONH structure, we applied a stereo correspondence algorithm to a set of stereo fundus images. Using these quantitative 3D ONH structure measurements, eigen structures were derived using principal component analysis from stereo images of 565 subjects from the Ocular Hypertension Treatment Study (OHTS). To evaluate the usefulness of the eigen structures, we explored associations with the demographic variables age, gender, and race. Using regression analysis, the eigen structures were found to have significant (p < 0.05) associations with both age and race after Bonferroni correction. In addition, classifiers were constructed to predict the demographic variables based solely on the eigen structures. These classifiers achieved an area under receiver operating characteristic curve of 0.62 in predicting a binary age variable, 0.52 in predicting gender, and 0.67 in predicting race. The use of objective, quantitative features or eigen structures can reveal hidden relationships between ONH structure and demographics. The use of these features could similarly allow specific aspects of ONH structure to be isolated and associated with the diagnosis of glaucoma, disease progression and outcomes, and genetic factors.

  11. Segmentation of vascular structures and hematopoietic cells in 3D microscopy images and quantitative analysis

    NASA Astrophysics Data System (ADS)

    Mu, Jian; Yang, Lin; Kamocka, Malgorzata M.; Zollman, Amy L.; Carlesso, Nadia; Chen, Danny Z.

    2015-03-01

    In this paper, we present image processing methods for quantitative study of how the bone marrow microenvironment changes (characterized by altered vascular structure and hematopoietic cell distribution) caused by diseases or various factors. We develop algorithms that automatically segment vascular structures and hematopoietic cells in 3-D microscopy images, perform quantitative analysis of the properties of the segmented vascular structures and cells, and examine how such properties change. In processing images, we apply local thresholding to segment vessels, and add post-processing steps to deal with imaging artifacts. We propose an improved watershed algorithm that relies on both intensity and shape information and can separate multiple overlapping cells better than common watershed methods. We then quantitatively compute various features of the vascular structures and hematopoietic cells, such as the branches and sizes of vessels and the distribution of cells. In analyzing vascular properties, we provide algorithms for pruning fake vessel segments and branches based on vessel skeletons. Our algorithms can segment vascular structures and hematopoietic cells with good quality. We use our methods to quantitatively examine the changes in the bone marrow microenvironment caused by the deletion of Notch pathway. Our quantitative analysis reveals property changes in samples with deleted Notch pathway. Our tool is useful for biologists to quantitatively measure changes in the bone marrow microenvironment, for developing possible therapeutic strategies to help the bone marrow microenvironment recovery.

  12. High-throughput 3D whole-brain quantitative histopathology in rodents

    PubMed Central

    Vandenberghe, Michel E.; Hérard, Anne-Sophie; Souedet, Nicolas; Sadouni, Elmahdi; Santin, Mathieu D.; Briet, Dominique; Carré, Denis; Schulz, Jocelyne; Hantraye, Philippe; Chabrier, Pierre-Etienne; Rooney, Thomas; Debeir, Thomas; Blanchard, Véronique; Pradier, Laurent; Dhenain, Marc; Delzescaux, Thierry

    2016-01-01

    Histology is the gold standard to unveil microscopic brain structures and pathological alterations in humans and animal models of disease. However, due to tedious manual interventions, quantification of histopathological markers is classically performed on a few tissue sections, thus restricting measurements to limited portions of the brain. Recently developed 3D microscopic imaging techniques have allowed in-depth study of neuroanatomy. However, quantitative methods are still lacking for whole-brain analysis of cellular and pathological markers. Here, we propose a ready-to-use, automated, and scalable method to thoroughly quantify histopathological markers in 3D in rodent whole brains. It relies on block-face photography, serial histology and 3D-HAPi (Three Dimensional Histology Analysis Pipeline), an open source image analysis software. We illustrate our method in studies involving mouse models of Alzheimer’s disease and show that it can be broadly applied to characterize animal models of brain diseases, to evaluate therapeutic interventions, to anatomically correlate cellular and pathological markers throughout the entire brain and to validate in vivo imaging techniques. PMID:26876372

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

    PubMed

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

    2013-01-01

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

  14. 3D quantitative imaging of the microvasculature with the Texas Instruments Digital Micromirror Device

    NASA Astrophysics Data System (ADS)

    Fainman, Yeshaiahu; Botvinick, Elliott L.; Price, Jeffrey H.; Gough, David A.

    2001-11-01

    There is a growing need for developing 3D quantitative imaging tools that can operate at high speed enabling real-time visualization for the field of biology, material science, and the semiconductor industry. We will present our 3D quantitative imaging system based on a confocal microscope built with a Texas Instruments Digital Micromirror Device (DMD). By using the DMD as a spatial light modulator, confocal transverse surface (x, y) scanning can be performed in parallel at speeds faster than video rate without physical movement of the sample. The DMD allows us to programmably configure the source and the detection pinhole array in the lateral direction to achieve the best signal and to reduce the crosstalk noise. Investigations of the microcirculation were performed on 40 g to 45 g golden Syrian hamsters fit with dorsal skin fold window chambers. FITC-Dextran or Red blood cells from donor hamsters, stained with Celltracker CM-DiI, were injected into the circulation and imaged with the confocal microscope. We will present the measured results for the axial resolution, in vivo, as well as experimental results from imaging the window chamber.

  15. A Novel Qualitative and Quantitative Biofilm Assay Based on 3D Soft Tissue.

    PubMed

    Hakonen, Bodil; Lönnberg, Linnea K; Larkö, Eva; Blom, Kristina

    2014-01-01

    The lack of predictable in vitro methods to analyze antimicrobial activity could play a role in the development of resistance to antibiotics. Current used methods analyze planktonic cells but for the method to be clinically relevant, biofilm in in vivo like conditions ought to be studied. Hence, our group has developed a qualitative and quantitative method with in vivo like 3D tissue for prediction of antimicrobial activity in reality. Devices (wound dressings) were applied on top of Pseudomonas aeruginosa inoculated Muller-Hinton (MH) agar or 3D synthetic soft tissues (SST) and incubated for 24 hours. The antibacterial activity was then analyzed visually and by viable counts. On MH agar two out of three silver containing devices showed zone of inhibitions (ZOI) and on SST, ZOI were detected for all three. Corroborating results were found upon evaluating the bacterial load in SST and shown to be silver concentration dependent. In conclusion, a novel method was developed combining visual rapid screening and quantitative evaluation of the antimicrobial activity in both tissue and devices. It uses tissue allowing biofilm formation thus mimicking reality closely. These conditions are essential in order to predict antimicrobial activity of medical devices in the task to prevent device related infections.

  16. Whole-brain quantitative mapping of metabolites using short echo 3D-proton- MRSI

    PubMed Central

    Lecocq, Angèle; Le Fur, Yann; Maudsley, Andrew A; Le Troter, Arnaud; Sheriff, Sulaiman; Sabati, Mohamad; Donnadieu, Maxime; Confort-Gouny, Sylviane; Cozzone, Patrick J.; Guye, Maxime; Ranjeva, Jean-Philippe

    2014-01-01

    Purpose To improve the extent over which whole brain quantitative 3D-MRSI maps can be obtained and be used to explore brain metabolism in a population of healthy volunteers. Materials and Methods Two short TE (20 ms) acquisitions of 3D Echo Planar Spectroscopic Imaging at two orientations, one in the anterior commissure – posterior commissure (AC-PC) plane and the second tilted in the AC-PC +15° plane were obtained at 3T in a group of ten healthy volunteers. B1+, B1−, and B0 correction procedures and normalization of metabolite signals with quantitative water proton density measurements were performed. A combination of the two spatially normalized 3D-MRSI, using a weighted mean based on the pixel wise standard deviation metabolic maps of each orientation obtained from the whole group, provided metabolite maps for each subject allowing regional metabolic profiles of all parcels of the automated anatomical labeling (AAL) atlas to be obtained. Results The combined metabolite maps derived from the two acquisitions reduced the regional inter-subject variance. The numbers of AAL regions showing NAA SD/Mean ratios lower than 30% increased from 17 in the AC-PC orientation and 41 in the AC-PC+15° orientation, to a value of 76 regions out of 116 for the combined NAA maps. Quantitatively, regional differences in absolute metabolite concentrations (mM) over the whole brain were depicted such as in the GM of frontal lobes (cNAA=10.03+1.71, cCho=1.78±0.55, cCr=7.29±1.69; cmIns=5.30±2.67) and in cerebellum (cNAA=5.28±1.77, cCho=1.60±0.41, cCr=6.95±2.15; cmIns=3.60±0.74). Conclusion A double-angulation acquisition enables improved metabolic characterization over a wide volume of the brain. PMID:25431032

  17. Quantitative prediction of 3D solution shape and flexibility of nucleic acid nanostructures.

    PubMed

    Kim, Do-Nyun; Kilchherr, Fabian; Dietz, Hendrik; Bathe, Mark

    2012-04-01

    DNA nanotechnology enables the programmed synthesis of intricate nanometer-scale structures for diverse applications in materials and biological science. Precise control over the 3D solution shape and mechanical flexibility of target designs is important to achieve desired functionality. Because experimental validation of designed nanostructures is time-consuming and cost-intensive, predictive physical models of nanostructure shape and flexibility have the capacity to enhance dramatically the design process. Here, we significantly extend and experimentally validate a computational modeling framework for DNA origami previously presented as CanDo [Castro,C.E., Kilchherr,F., Kim,D.-N., Shiao,E.L., Wauer,T., Wortmann,P., Bathe,M., Dietz,H. (2011) A primer to scaffolded DNA origami. Nat. Meth., 8, 221-229.]. 3D solution shape and flexibility are predicted from basepair connectivity maps now accounting for nicks in the DNA double helix, entropic elasticity of single-stranded DNA, and distant crossovers required to model wireframe structures, in addition to previous modeling (Castro,C.E., et al.) that accounted only for the canonical twist, bend and stretch stiffness of double-helical DNA domains. Systematic experimental validation of nanostructure flexibility mediated by internal crossover density probed using a 32-helix DNA bundle demonstrates for the first time that our model not only predicts the 3D solution shape of complex DNA nanostructures but also their mechanical flexibility. Thus, our model represents an important advance in the quantitative understanding of DNA-based nanostructure shape and flexibility, and we anticipate that this model will increase significantly the number and variety of synthetic nanostructures designed using nucleic acids.

  18. Quantitative prediction of 3D solution shape and flexibility of nucleic acid nanostructures

    PubMed Central

    Kim, Do-Nyun; Kilchherr, Fabian; Dietz, Hendrik; Bathe, Mark

    2012-01-01

    DNA nanotechnology enables the programmed synthesis of intricate nanometer-scale structures for diverse applications in materials and biological science. Precise control over the 3D solution shape and mechanical flexibility of target designs is important to achieve desired functionality. Because experimental validation of designed nanostructures is time-consuming and cost-intensive, predictive physical models of nanostructure shape and flexibility have the capacity to enhance dramatically the design process. Here, we significantly extend and experimentally validate a computational modeling framework for DNA origami previously presented as CanDo [Castro,C.E., Kilchherr,F., Kim,D.-N., Shiao,E.L., Wauer,T., Wortmann,P., Bathe,M., Dietz,H. (2011) A primer to scaffolded DNA origami. Nat. Meth., 8, 221–229.]. 3D solution shape and flexibility are predicted from basepair connectivity maps now accounting for nicks in the DNA double helix, entropic elasticity of single-stranded DNA, and distant crossovers required to model wireframe structures, in addition to previous modeling (Castro,C.E., et al.) that accounted only for the canonical twist, bend and stretch stiffness of double-helical DNA domains. Systematic experimental validation of nanostructure flexibility mediated by internal crossover density probed using a 32-helix DNA bundle demonstrates for the first time that our model not only predicts the 3D solution shape of complex DNA nanostructures but also their mechanical flexibility. Thus, our model represents an important advance in the quantitative understanding of DNA-based nanostructure shape and flexibility, and we anticipate that this model will increase significantly the number and variety of synthetic nanostructures designed using nucleic acids. PMID:22156372

  19. Quantitative 3D molecular cutaneous absorption in human skin using label free nonlinear microscopy.

    PubMed

    Chen, Xueqin; Grégoire, Sébastien; Formanek, Florian; Galey, Jean-Baptiste; Rigneault, Hervé

    2015-02-28

    Understanding the penetration mechanisms of drugs into human skin is a key issue in pharmaceutical and cosmetics research. To date, the techniques available for percutaneous penetration of compounds fail to provide a quantitative 3D map of molecular concentration distribution in complex tissues as the detected microscopy images are an intricate combination of concentration distribution and laser beam attenuation upon deep penetration. Here we introduce and validate a novel framework for imaging and reconstructing molecular concentration within the depth of artificial and human skin samples. Our approach combines the use of deuterated molecular compounds together with coherent anti-Stokes Raman scattering spectroscopy and microscopy that permits targeted molecules to be unambiguously discriminated within skin layers. We demonstrate both intercellular and transcellular pathways for different active compounds, together with in-depth concentration profiles reflecting the detailed skin barrier architecture. This method provides an enabling platform for establishing functional activity of topically applied products. PMID:25550155

  20. Quantitative fully 3D PET via model-based scatter correction

    SciTech Connect

    Ollinger, J.M.

    1994-05-01

    We have investigated the quantitative accuracy of fully 3D PET using model-based scatter correction by measuring the half-life of Ga-68 in the presence of scatter from F-18. The inner chamber of a Data Spectrum cardiac phantom was filled with 18.5 MBq of Ga-68. The outer chamber was filled with an equivalent amount of F-18. The cardiac phantom was placed in a 22x30.5 cm elliptical phantom containing anthropomorphic lung inserts filled with a water-Styrofoam mixture. Ten frames of dynamic data were collected over 13.6 hours on Siemens-CTI 953B scanner with the septa retracted. The data were corrected using model-based scatter correction, which uses the emission images, transmission images and an accurate physical model to directly calculate the scatter distribution. Both uncorrected and corrected data were reconstructed using the Promis algorithm. The scatter correction required 4.3% of the total reconstruction time. The scatter fraction in a small volume of interest in the center of the inner chamber of the cardiac insert rose from 4.0% in the first interval to 46.4% in the last interval as the ratio of F-18 activity to Ga-68 activity rose from 1:1 to 33:1. Fitting a single exponential to the last three data points yields estimates of the half-life of Ga-68 of 77.01 minutes and 68.79 minutes for uncorrected and corrected data respectively. Thus, scatter correction reduces the error from 13.3% to 1.2%. This suggests that model-based scatter correction is accurate in the heterogeneous attenuating medium found in the chest, making possible quantitative, fully 3D PET in the body.

  1. The Quantitative Measurement Of Temperature Distribution In 3-D Thermal Field With High-Speed Real-Time Holographic Interferometry

    NASA Astrophysics Data System (ADS)

    Ji-zong, Wu; Wei-qiao, Fu; Qin, Wu

    1989-06-01

    The theory of using high-speed real-time holographic interferometry to measure quantitatively 3-D thermal field is discussed in thispaper. An experimental arrangement, and the holographic interference fringes of thermal field formed by the electrAc heating coil wires which were taken by the high-speed camera are given. With CONCEPT 32/2725 computer system and corresponding programms the distribution of 3-D thermal field is calculated and plotted Finally, the problems required to be improved and solved for the method of measuring quantitatively 3-D thermal field are discussed.

  2. MODIS volcanic ash retrievals vs FALL3D transport model: a quantitative comparison

    NASA Astrophysics Data System (ADS)

    Corradini, S.; Merucci, L.; Folch, A.

    2010-12-01

    Satellite retrievals and transport models represents the key tools to monitor the volcanic clouds evolution. Because of the harming effects of fine ash particles on aircrafts, the real-time tracking and forecasting of volcanic clouds is key for aviation safety. Together with the security reasons also the economical consequences of a disruption of airports must be taken into account. The airport closures due to the recent Icelandic Eyjafjöll eruption caused millions of passengers to be stranded not only in Europe, but across the world. IATA (the International Air Transport Association) estimates that the worldwide airline industry has lost a total of about 2.5 billion of Euro during the disruption. Both security and economical issues require reliable and robust ash cloud retrievals and trajectory forecasting. The intercomparison between remote sensing and modeling is required to assure precise and reliable volcanic ash products. In this work we perform a quantitative comparison between Moderate Resolution Imaging Spectroradiometer (MODIS) retrievals of volcanic ash cloud mass and Aerosol Optical Depth (AOD) with the FALL3D ash dispersal model. MODIS, aboard the NASA-Terra and NASA-Aqua polar satellites, is a multispectral instrument with 36 spectral bands operating in the VIS-TIR spectral range and spatial resolution varying between 250 and 1000 m at nadir. The MODIS channels centered around 11 and 12 micron have been used for the ash retrievals through the Brightness Temperature Difference algorithm and MODTRAN simulations. FALL3D is a 3-D time-dependent Eulerian model for the transport and deposition of volcanic particles that outputs, among other variables, cloud column mass and AOD. Three MODIS images collected the October 28, 29 and 30 on Mt. Etna volcano during the 2002 eruption have been considered as test cases. The results show a general good agreement between the retrieved and the modeled volcanic clouds in the first 300 km from the vents. Even if the

  3. Quantitative 3D analysis of shape dynamics of the left ventricle

    NASA Astrophysics Data System (ADS)

    Scowen, Barry C.; Smith, Stephen L.; Vannan, Mani A.; Arsenault, Marie

    1998-07-01

    There is an established link between Left Ventricular (LV) geometry and its performance. As a consequence of ischemic heart disease and the attempt to relieve myocardial tissue stress, ventricle shape begins to distort from a conical to spherical geometry with a reduction in pumping efficiency of the chamber. If untreated, premature heart failure will result. To increase the changes of successful treatment it is obviously important for the benefit of the patient to detect these abnormalities as soon as possible. It is the development of a technique to characterize and quantify the shape of the left ventricle that is described here. The system described in this paper uses a novel helix model which combines the advantages of current two dimensional (2D) quantitative measures which provide limited information, with 3D qualitative methods which provide accurate reconstructions of the LV using computationally expensive rendering schemes. A phantom object and dog ventricle (normal/abnormal) were imaged and helical models constructed. The result are encouraging with differences between normal and abnormal ventricles in both diastole and systole able to be determined. Further work entails building a library of subjects in order to determine the relationship between ventricle geometry and quantitative measurements.

  4. Improving organic tandem solar cells based on water-processed nanoparticles by quantitative 3D nanoimaging.

    PubMed

    Pedersen, E B L; Angmo, D; Dam, H F; Thydén, K T S; Andersen, T R; Skjønsfjell, E T B; Krebs, F C; Holler, M; Diaz, A; Guizar-Sicairos, M; Breiby, D W; Andreasen, J W

    2015-08-28

    Organic solar cells have great potential for upscaling due to roll-to-roll processing and a low energy payback time, making them an attractive sustainable energy source for the future. Active layers coated with water-dispersible Landfester particles enable greater control of the layer formation and easier access to the printing industry, which has reduced the use of organic solvents since the 1980s. Through ptychographic X-ray computed tomography (PXCT), we image quantitatively a roll-to-roll coated photovoltaic tandem stack consisting of one bulk heterojunction active layer and one Landfester particle active layer. We extract the layered morphology with structural and density information including the porosity present in the various layers and the silver electrode with high resolution in 3D. The Landfester particle layer is found to have an undesired morphology with negatively correlated top- and bottom interfaces, wide thickness distribution and only partial surface coverage causing electric short circuits through the layer. By top coating a polymer material onto the Landfester nanoparticles we eliminate the structural defects of the layer such as porosity and roughness, and achieve the increased performance larger than 1 V expected for a tandem cell. This study highlights that quantitative imaging of weakly scattering stacked layers of organic materials has become feasible by PXCT, and that this information cannot be obtained by other methods. In the present study, this technique specifically reveals the need to improve the coatability and layer formation of Landfester nanoparticles, thus allowing improved solar cells to be produced. PMID:26220159

  5. Quantitative structure-activity relationships and docking studies of calcitonin gene-related peptide antagonists.

    PubMed

    Kyani, Anahita; Mehrabian, Mohadeseh; Jenssen, Håvard

    2012-02-01

    Defining the role of calcitonin gene-related peptide in migraine pathogenesis could lead to the application of calcitonin gene-related peptide antagonists as novel migraine therapeutics. In this work, quantitative structure-activity relationship modeling of biological activities of a large range of calcitonin gene-related peptide antagonists was performed using a panel of physicochemical descriptors. The computational studies evaluated different variable selection techniques and demonstrated shuffling stepwise multiple linear regression to be superior over genetic algorithm-multiple linear regression. The linear quantitative structure-activity relationship model revealed better statistical parameters of cross-validation in comparison with the non-linear support vector regression technique. Implementing only five peptide descriptors into this linear quantitative structure-activity relationship model resulted in an extremely robust and highly predictive model with calibration, leave-one-out and leave-20-out validation R(2) of 0.9194, 0.9103, and 0.9214, respectively. We performed docking of the most potent calcitonin gene-related peptide antagonists with the calcitonin gene-related peptide receptor and demonstrated that peptide antagonists act by blocking access to the peptide-binding cleft. We also demonstrated the direct contact of residues 28-37 of the calcitonin gene-related peptide antagonists with the receptor. These results are in agreement with the conclusions drawn from the quantitative structure-activity relationship model, indicating that both electrostatic and steric factors should be taken into account when designing novel calcitonin gene-related peptide antagonists. PMID:21974743

  6. Quantitative 3D Determination of Radiosensitization by Bismuth-Based Nanoparticles.

    PubMed

    Alqathami, Mamdooh; Blencowe, Anton; Geso, Moshi; Ibbott, Geoffrey

    2016-03-01

    The nanoparticle-induced dose enhancement effect has been shown to improve the therapeutic efficacy of ionizing radiation in external beam radiotherapy. Whereas previous studies have focused on gold nanoparticles (AuNPs), no quantitative studies have been conducted to investigate the potential superiority of other high atomic number (Z) nanomaterials such as bismuth-based nanoparticles. The aims of this study were to experimentally validate and quantify the dose enhancement properties of commercially available bismuth-based nanoparticles (bismuth oxide (Bi2O3-NPs) and bismuth sulfide (Bi2S3-NPs)), and investigate their potential superiority over AuNPs in terms of radiation dose enhancement. Phantom cuvettes doped with and without nanoparticles where employed for measuring radiation dose enhancement produced from the interaction of radiation with metal nanoparticles. Novel 3D phantoms were employed to investigate the 3D spatial distribution of ionising radiation dose deposition. The phantoms were irradiated with kilovoltage and megavoltage X-ray beams and optical absorption changes were measured using a spectrophotometer and optical CT scanner. The radiation dose enhancement factors (DEFs) obtained for 50 nm diameter Bi2O3-NPs and AuNPs were 1.90 and 1.77, respectively, for 100 kV energy and a nanoparticle concentration of 0.5 mM. In addition, the DEFs of 5 nm diameter Bi2S3-NPs and AuNPs were determined to be 1.38 and 1.51, respectively, for 150 kV energy and a nanoparticle concentration of 0.25 mM. The results demonstrate that both bismuth-based nanoparticles can enhance the effects of radiation. For 6 MV energy the DEFs for all the investigated nanoparticles were lower (< 15%) than with kilovoltage energy. PMID:27280244

  7. An imaging-based platform for high-content, quantitative evaluation of therapeutic response in 3D tumour models

    NASA Astrophysics Data System (ADS)

    Celli, Jonathan P.; Rizvi, Imran; Blanden, Adam R.; Massodi, Iqbal; Glidden, Michael D.; Pogue, Brian W.; Hasan, Tayyaba

    2014-01-01

    While it is increasingly recognized that three-dimensional (3D) cell culture models recapitulate drug responses of human cancers with more fidelity than monolayer cultures, a lack of quantitative analysis methods limit their implementation for reliable and routine assessment of emerging therapies. Here, we introduce an approach based on computational analysis of fluorescence image data to provide high-content readouts of dose-dependent cytotoxicity, growth inhibition, treatment-induced architectural changes and size-dependent response in 3D tumour models. We demonstrate this approach in adherent 3D ovarian and pancreatic multiwell extracellular matrix tumour overlays subjected to a panel of clinically relevant cytotoxic modalities and appropriately designed controls for reliable quantification of fluorescence signal. This streamlined methodology reads out the high density of information embedded in 3D culture systems, while maintaining a level of speed and efficiency traditionally achieved with global colorimetric reporters in order to facilitate broader implementation of 3D tumour models in therapeutic screening.

  8. Improving organic tandem solar cells based on water-processed nanoparticles by quantitative 3D nanoimaging

    NASA Astrophysics Data System (ADS)

    Pedersen, E. B. L.; Angmo, D.; Dam, H. F.; Thydén, K. T. S.; Andersen, T. R.; Skjønsfjell, E. T. B.; Krebs, F. C.; Holler, M.; Diaz, A.; Guizar-Sicairos, M.; Breiby, D. W.; Andreasen, J. W.

    2015-08-01

    Organic solar cells have great potential for upscaling due to roll-to-roll processing and a low energy payback time, making them an attractive sustainable energy source for the future. Active layers coated with water-dispersible Landfester particles enable greater control of the layer formation and easier access to the printing industry, which has reduced the use of organic solvents since the 1980s. Through ptychographic X-ray computed tomography (PXCT), we image quantitatively a roll-to-roll coated photovoltaic tandem stack consisting of one bulk heterojunction active layer and one Landfester particle active layer. We extract the layered morphology with structural and density information including the porosity present in the various layers and the silver electrode with high resolution in 3D. The Landfester particle layer is found to have an undesired morphology with negatively correlated top- and bottom interfaces, wide thickness distribution and only partial surface coverage causing electric short circuits through the layer. By top coating a polymer material onto the Landfester nanoparticles we eliminate the structural defects of the layer such as porosity and roughness, and achieve the increased performance larger than 1 V expected for a tandem cell. This study highlights that quantitative imaging of weakly scattering stacked layers of organic materials has become feasible by PXCT, and that this information cannot be obtained by other methods. In the present study, this technique specifically reveals the need to improve the coatability and layer formation of Landfester nanoparticles, thus allowing improved solar cells to be produced.Organic solar cells have great potential for upscaling due to roll-to-roll processing and a low energy payback time, making them an attractive sustainable energy source for the future. Active layers coated with water-dispersible Landfester particles enable greater control of the layer formation and easier access to the printing

  9. 3D reconstruction and quantitative assessment method of mitral eccentric regurgitation from color Doppler echocardiography

    NASA Astrophysics Data System (ADS)

    Liu, Qi; Ge, Yi Nan; Wang, Tian Fu; Zheng, Chang Qiong; Zheng, Yi

    2005-10-01

    Based on the two-dimensional color Doppler image in this article, multilane transesophageal rotational scanning method is used to acquire original Doppler echocardiography while echocardiogram is recorded synchronously. After filtering and interpolation, the surface rendering and volume rendering methods are performed. Through analyzing the color-bar information and the color Doppler flow image's superposition principle, the grayscale mitral anatomical structure and color-coded regurgitation velocity parameter were separated from color Doppler flow images, three-dimensional reconstruction of mitral structure and regurgitation velocity distribution was implemented separately, fusion visualization of the reconstructed regurgitation velocity distribution parameter with its corresponding 3D mitral anatomical structures was realized, which can be used in observing the position, phase, direction and measuring the jet length, area, volume, space distribution and severity level of the mitral regurgitation. In addition, in patients with eccentric mitral regurgitation, this new modality overcomes the inherent limitations of two-dimensional color Doppler flow image by depicting the full extent of the jet trajectory, the area of eccentric regurgitation on three-dimensional image was much larger than that on two-dimensional image, the area variation tendency and volume variation tendency of regurgitation have been shown in figure at different angle and different systolic phase. The study shows that three-dimensional color Doppler provides quantitative measurements of eccentric mitral regurgitation that are more accurate and reproducible than conventional color Doppler.

  10. A Novel Multiparametric Approach to 3D Quantitative MRI of the Brain

    PubMed Central

    Palma, Giuseppe; Tedeschi, Enrico; Borrelli, Pasquale; Cocozza, Sirio; Russo, Carmela; Liu, Saifeng; Ye, Yongquan; Comerci, Marco; Alfano, Bruno; Salvatore, Marco; Haacke, E. Mark; Mancini, Marcello

    2015-01-01

    Magnetic Resonance properties of tissues can be quantified in several respects: relaxation processes, density of imaged nuclei, magnetism of environmental molecules, etc. In this paper, we propose a new comprehensive approach to obtain 3D high resolution quantitative maps of arbitrary body districts, mainly focusing on the brain. The theory presented makes it possible to map longitudinal (R1), pure transverse (R2) and free induction decay (R2*) rates, along with proton density (PD) and magnetic susceptibility (χ), from a set of fast acquisition sequences in steady-state that are highly insensitive to flow phenomena. A novel denoising scheme is described and applied to the acquired datasets to enhance the signal to noise ratio of the derived maps and an information theory approach compensates for biases from radio frequency (RF) inhomogeneities, if no direct measure of the RF field is available. Finally, the results obtained on sample brain scans of healthy controls and multiple sclerosis patients are presented and discussed. PMID:26284778

  11. Quantitative structure-activity relationships of antimicrobial fatty acids and derivatives against Staphylococcus aureus *

    PubMed Central

    Zhang, Hui; Zhang, Lu; Peng, Li-juan; Dong, Xiao-wu; Wu, Di; Wu, Vivian Chi-Hua; Feng, Feng-qin

    2012-01-01

    Fatty acids and derivatives (FADs) are resources for natural antimicrobials. In order to screen for additional potent antimicrobial agents, the antimicrobial activities of FADs against Staphylococcus aureus were examined using a microplate assay. Monoglycerides of fatty acids were the most potent class of fatty acids, among which monotridecanoin possessed the most potent antimicrobial activity. The conventional quantitative structure-activity relationship (QSAR) and comparative molecular field analysis (CoMFA) were performed to establish two statistically reliable models (conventional QSAR: R 2=0.942, Q 2 LOO=0.910; CoMFA: R 2=0.979, Q 2=0.588, respectively). Improved forecasting can be achieved by the combination of these two models that provide a good insight into the structure-activity relationships of the FADs and that may be useful to design new FADs as antimicrobial agents. PMID:22302421

  12. 3-D segmentation and quantitative analysis of inner and outer walls of thrombotic abdominal aortic aneurysms

    NASA Astrophysics Data System (ADS)

    Lee, Kyungmoo; Yin, Yin; Wahle, Andreas; Olszewski, Mark E.; Sonka, Milan

    2008-03-01

    An abdominal aortic aneurysm (AAA) is an area of a localized widening of the abdominal aorta, with a frequent presence of thrombus. A ruptured aneurysm can cause death due to severe internal bleeding. AAA thrombus segmentation and quantitative analysis are of paramount importance for diagnosis, risk assessment, and determination of treatment options. Until now, only a small number of methods for thrombus segmentation and analysis have been presented in the literature, either requiring substantial user interaction or exhibiting insufficient performance. We report a novel method offering minimal user interaction and high accuracy. Our thrombus segmentation method is composed of an initial automated luminal surface segmentation, followed by a cost function-based optimal segmentation of the inner and outer surfaces of the aortic wall. The approach utilizes the power and flexibility of the optimal triangle mesh-based 3-D graph search method, in which cost functions for thrombus inner and outer surfaces are based on gradient magnitudes. Sometimes local failures caused by image ambiguity occur, in which case several control points are used to guide the computer segmentation without the need to trace borders manually. Our method was tested in 9 MDCT image datasets (951 image slices). With the exception of a case in which the thrombus was highly eccentric, visually acceptable aortic lumen and thrombus segmentation results were achieved. No user interaction was used in 3 out of 8 datasets, and 7.80 +/- 2.71 mouse clicks per case / 0.083 +/- 0.035 mouse clicks per image slice were required in the remaining 5 datasets.

  13. A Combined Quantitative Structure-Activity Relationship Research of Quinolinone Derivatives as Androgen Receptor Antagonists.

    PubMed

    Wang, Yuwei; Bai, Fang; Cao, Hong; Li, Jiazhong; Liu, Huanxiang; Gramatica, Paola

    2015-01-01

    Antiandrogens bicalutamide, flutamide and enzalutamide etc. have been used in clinical trials to treat prostate cancer by binding to and antagonizing androgen receptor (AR). Although initially effective, the drug resistance problem will emerge eventually, which results in a high medical need for novel AR antagonist exploitation. Here in this work, to facilitate the rational design of novel AR antagonists, we studied the structure-activity relationships of a series of 2-quinolinone derivatives and investigated the structural requirements for their antiandrogenic activities. Different modeling methods, including 2D MLR, 3D CoMFA and CoMSIA, were implemented to evolve QSAR models. All these models, thoroughly validated, demonstrated satisfactory results especially for the good predictive abilities. The contour maps from 3D CoMFA and CoMSIA models provide visualized explanation of key structural characteristics relevant to the antiandrogenic activities, which is summarized to a position-specific conclusion at the end. The obtained results from this research are practically useful for rational design and screening of promising chemicals with high antiandrogenic activities.

  14. A computational quantitative structure-activity relationship study of carbamate anticonvulsants using quantum pharmacological methods.

    PubMed

    Knight, J L; Weaver, D F

    1998-10-01

    A pattern recognition quantitative structure-activity relationship (QSAR) study has been performed to determine the molecular features of carbamate anticonvulsants which influence biological activity. Although carbamates, such as felbamate, have been used to treat epilepsy, their mechanisms of efficacy and toxicity are not completely understood. Quantum and classical mechanics calculations have been exploited to describe 46 carbamate drugs. Employing a principal component analysis and multiple linear regression calculations, five crucial structural descriptors were identified which directly relate to the bioactivity of the carbamate family. With the resulting mathematical model, the biological activity of carbamate analogues can be predicted with 85-90% accuracy.

  15. Curating and Preparing High-Throughput Screening Data for Quantitative Structure-Activity Relationship Modeling.

    PubMed

    Kim, Marlene T; Wang, Wenyi; Sedykh, Alexander; Zhu, Hao

    2016-01-01

    Publicly available bioassay data often contains errors. Curating massive bioassay data, especially high-throughput screening (HTS) data, for Quantitative Structure-Activity Relationship (QSAR) modeling requires the assistance of automated data curation tools. Using automated data curation tools are beneficial to users, especially ones without prior computer skills, because many platforms have been developed and optimized based on standardized requirements. As a result, the users do not need to extensively configure the curation tool prior to the application procedure. In this chapter, a freely available automatic tool to curate and prepare HTS data for QSAR modeling purposes will be described.

  16. The current status and future applicability of quantitative structure-activity relationships (QSARs) in predicting toxicity.

    PubMed

    Cronin, Mark T D

    2002-12-01

    The current status of quantitative structure-activity relationships (QSARs) in predicting toxicity is assessed. Widespread use of these methods to predict toxicity from chemical structure is possible, both by industry to develop new compounds, and also by regulatory agencies. The current use of QSARs is restricted by the lack of suitable toxicity data available for modelling, the suitability of simplistic modelling approaches for the prediction of certain endpoints, and the poor definition and utilisation of the applicability domain of models. Suggestions to resolve these issues are made.

  17. Curating and Preparing High-Throughput Screening Data for Quantitative Structure-Activity Relationship Modeling.

    PubMed

    Kim, Marlene T; Wang, Wenyi; Sedykh, Alexander; Zhu, Hao

    2016-01-01

    Publicly available bioassay data often contains errors. Curating massive bioassay data, especially high-throughput screening (HTS) data, for Quantitative Structure-Activity Relationship (QSAR) modeling requires the assistance of automated data curation tools. Using automated data curation tools are beneficial to users, especially ones without prior computer skills, because many platforms have been developed and optimized based on standardized requirements. As a result, the users do not need to extensively configure the curation tool prior to the application procedure. In this chapter, a freely available automatic tool to curate and prepare HTS data for QSAR modeling purposes will be described. PMID:27518634

  18. Structure-activity relationships: quantitative techniques for predicting the behavior of chemicals in the ecosystem

    SciTech Connect

    Nirmalakhandan, N.; Speece, R.E.

    1988-06-01

    Quantitative Structure-Activity Relationships (QSARs) are used increasingly to screen and predict the toxicity and the fate of chemicals released into the environment. The impetus to use QSAR methods in this area has been the large number of synthetic chemicals introduced into the ecosystem via intensive agriculture and industrialization. Because of the costly and time-consuming nature of environmental fate testing, QSARs have been effectively used to screen large classes of chemical compounds and flag those that appear to warrant more thorough testing.

  19. 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...

  20. ESTIMATION OF MICROBIAL REDUCTIVE TRANSFORMATION RATES FOR CHLORINATED BENZENES AND PHENOLS USING A QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP APPROACH

    EPA Science Inventory

    A set of literature data was used to derive several quantitative structure-activity relationships (QSARs) to predict the rate constants for the microbial reductive dehalogenation of chlorinated aromatics. Dechlorination rate constants for 25 chloroaromatics were corrected for th...

  1. 3D Quantitative Confocal Laser Microscopy of Ilmenite Volume Distribution in Alpe Arami Olivine

    NASA Astrophysics Data System (ADS)

    Bozhilov, K. N.

    2001-12-01

    The deep origin of the Alpe Arami garnet lherzolite massif in the Swiss Alps proposed by Dobrzhinetskaya et al. (Science, 1996) has been a focus of heated debate. One of the lines of evidence supporting an exhumation from more than 200 km depth includes the abundance, distribution, and orientation of magnesian ilmenite rods in the oldest generation of olivine. This argument has been disputed in terms of the abundance of ilmenite and consequently the maximum TiO2 content in the discussed olivine. In order to address this issue, we have directly measured the volume fraction of ilmenite of the oldest generation of olivine by applying confocal laser scanning microscopy (CLSM). CLSM is a method which allows for three-dimensional imaging and quantitative volume determination by optical sectioning of the objects. The images for 3D reconstruction and measurements were acquired from petrographic thin sections in reflected laser light with 488 nm wavelength. Measurements of more than 80 olivine grains in six thin sections of our material yielded an average volume fraction of 0.31% ilmenite in the oldest generation of olivine from Alpe Arami. This translates into 0.23 wt.% TiO2 in olivine with error in determination of ±0.097 wt.%, a value significantly different from that of 0.02 to 0.03 wt.% TiO2 determined by Hacker et al. (Science, 1997) by a broad-beam microanalysis technique. During the complex geological history of the Alpe Arami massif, several events of metamorphism are recorded which all could have caused increased mobility of the mineral components. Evidence for loss of TiO2 from olivine is the tendency for high densities of ilmenite to be restricted to cores of old grains, the complete absence of ilmenite inclusions from the younger, recrystallized, generation of olivine, and reduction in ilmenite size and abundance in more serpentinized specimens. These observations suggest that only olivine grains with the highest concentrations of ilmenite are close to the

  2. Using quantitative structure-activity relationship modeling to quantitatively predict the developmental toxicity of halogenated azole compounds.

    PubMed

    Craig, Evisabel A; Wang, Nina Ching; Zhao, Q Jay

    2014-07-01

    Developmental toxicity is a relevant endpoint for the comprehensive assessment of human health risk from chemical exposure. However, animal developmental toxicity data remain unavailable for many environmental contaminants due to the complexity and cost of these types of analyses. Here we describe an approach that uses quantitative structure-activity relationship modeling as an alternative methodology to fill data gaps in the developmental toxicity profile of certain halogenated compounds. Chemical information was obtained and curated using the OECD Quantitative Structure-Activity Relationship Toolbox, version 3.0. Data from 35 curated compounds were analyzed via linear regression to build the predictive model, which has an R(2) of 0.79 and a Q(2) of 0.77. The applicability domain (AD) was defined by chemical category and structural similarity. Seven halogenated chemicals that fit the AD but are not part of the training set were employed for external validation purposes. Our model predicted lowest observed adverse effect level values with a maximal threefold deviation from the observed experimental values for all chemicals that fit the AD. The good predictability of our model suggests that this method may be applicable to the analysis of qualifying compounds whenever developmental toxicity information is lacking or incomplete for risk assessment considerations.

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

    PubMed

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

    2010-04-01

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

  4. Prediction of anticancer property of bowsellic acid derivatives by quantitative structure activity relationship analysis and molecular docking study

    PubMed Central

    Satpathy, Raghunath; Guru, R. K.; Behera, R.; Nayak, B.

    2015-01-01

    Context: Boswellic acid consists of a series of pentacyclic triterpene molecules that are produced by the plant Boswellia serrata. The potential applications of Bowsellic acid for treatment of cancer have been focused here. Aims: To predict the property of the bowsellic acid derivatives as anticancer compounds by various computational approaches. Materials and Methods: In this work, all total 65 derivatives of bowsellic acids from the PubChem database were considered for the study. After energy minimization of the ligands various types of molecular descriptors were computed and corresponding two-dimensional quantitative structure activity relationship (QSAR) models were obtained by taking Andrews coefficient as the dependent variable. Statistical Analysis Used: Different types of comparative analysis were used for QSAR study are multiple linear regression, partial least squares, support vector machines and artificial neural network. Results: From the study geometrical descriptors shows the highest correlation coefficient, which indicates the binding factor of the compound. To evaluate the anticancer property molecular docking study of six selected ligands based on Andrews affinity were performed with nuclear factor-kappa protein kinase (Protein Data Bank ID 4G3D), which is an established therapeutic target for cancers. Along with QSAR study and docking result, it was predicted that bowsellic acid can also be treated as a potential anticancer compound. Conclusions: Along with QSAR study and docking result, it was predicted that bowsellic acid can also be treated as a potential anticancer compound. PMID:25709332

  5. Quantitative analysis of 3D extracellular matrix remodelling by pancreatic stellate cells

    PubMed Central

    Robinson, Benjamin K.; Cortes, Ernesto; Rice, Alistair J.; Sarper, Muge

    2016-01-01

    ABSTRACT Extracellular matrix (ECM) remodelling is integral to numerous physiological and pathological processes in biology, such as embryogenesis, wound healing, fibrosis and cancer. Until recently, most cellular studies have been conducted on 2D environments where mechanical cues significantly differ from physiologically relevant 3D environments, impacting cellular behaviour and masking the interpretation of cellular function in health and disease. We present an integrated methodology where cell-ECM interactions can be investigated in 3D environments via ECM remodelling. Monitoring and quantification of collagen-I structure in remodelled matrices, through designated algorithms, show that 3D matrices can be used to correlate remodelling with increased ECM stiffness observed in fibrosis. Pancreatic stellate cells (PSCs) are the key effectors of the stromal fibrosis associated to pancreatic cancer. We use PSCs to implement our methodology and demonstrate that PSC matrix remodelling capabilities depend on their contractile machinery and β1 integrin-mediated cell-ECM attachment. PMID:27170254

  6. GeoCube: A 3D mineral resources quantitative prediction and assessment system

    NASA Astrophysics Data System (ADS)

    Li, Ruixi; Wang, Gongwen; Carranza, Emmanuel John Muico

    2016-04-01

    This paper introduces a software system (GeoCube) for three dimensional (3D) extraction and integration of exploration criteria from spatial data. The software system contains four key modules: (1) Import and Export, supporting many formats from commercial 3D geological modeling software and offering various export options; (2) pre-process, containing basic statistics and fractal/multi-fractal methods (concentration-volume (C-V) fractal method) for extraction of exploration criteria from spatial data (i.e., separation of geological, geochemical and geophysical anomalies from background values in 3D space); (3) assessment, supporting five data-driven integration methods (viz., information entropy, logistic regression, ordinary weights of evidence, weighted weights of evidence, boost weights of evidence) for integration of exploration criteria; and (4) post-process, for classifying integration outcomes into several levels based on mineralization potentiality. The Nanihu Mo (W) camp (5.0 km×4.0 km×2.7 km) of the Luanchuan region was used as a case study. The results show that GeoCube can enhance the use of 3D geological modeling to store, retrieve, process, display, analyze and integrate exploration criteria. Furthermore, it was found that the ordinary weights of evidence, boost weights of evidence and logistic regression methods showed superior performance as integration tools for exploration targeting in this case study.

  7. Alterations of filopodia by near infrared photoimmunotherapy: evaluation with 3D low-coherent quantitative phase microscopy

    PubMed Central

    Nakamura, Yuko; Nagaya, Tadanobu; Sato, Kazuhide; Harada, Toshiko; Okuyama, Shuhei; Choyke, Peter L.; Yamauchi, Toyohiko; Kobayashi, Hisataka

    2016-01-01

    Filopodia are highly organized cellular membrane structures that facilitate intercellular communication. Near infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that causes necrotic cell death. Three-dimensional low-coherent quantitative phase microscopy (3D LC-QPM) is based on a newly established low-coherent interference microscope designed to obtain serial topographic images of the cellular membrane. Herein, we report rapid involution of filopodia after NIR-PIT using 3D LC-QPM. For 3T3/HER2 cells, the number of filopodia decreased immediately after treatment with significant differences. Volume and relative height of 3T3/HER2 cells increased immediately after NIR light exposure, but significant differences were not observed. Thus, disappearance of filopodia, evaluated by 3D LC-QPM, is an early indicator of cell membrane damage after NIR-PIT. PMID:27446702

  8. Alterations of filopodia by near infrared photoimmunotherapy: evaluation with 3D low-coherent quantitative phase microscopy.

    PubMed

    Nakamura, Yuko; Nagaya, Tadanobu; Sato, Kazuhide; Harada, Toshiko; Okuyama, Shuhei; Choyke, Peter L; Yamauchi, Toyohiko; Kobayashi, Hisataka

    2016-07-01

    Filopodia are highly organized cellular membrane structures that facilitate intercellular communication. Near infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that causes necrotic cell death. Three-dimensional low-coherent quantitative phase microscopy (3D LC-QPM) is based on a newly established low-coherent interference microscope designed to obtain serial topographic images of the cellular membrane. Herein, we report rapid involution of filopodia after NIR-PIT using 3D LC-QPM. For 3T3/HER2 cells, the number of filopodia decreased immediately after treatment with significant differences. Volume and relative height of 3T3/HER2 cells increased immediately after NIR light exposure, but significant differences were not observed. Thus, disappearance of filopodia, evaluated by 3D LC-QPM, is an early indicator of cell membrane damage after NIR-PIT. PMID:27446702

  9. Automated quantitative analysis of 3D morphology and mean corpuscular hemoglobin in human red blood cells stored in different periods.

    PubMed

    Moon, Inkyu; Yi, Faliu; Lee, Yeon H; Javidi, Bahram; Boss, Daniel; Marquet, Pierre

    2013-12-16

    Quantitative phase (QP) images of red blood cells (RBCs), which are obtained by off-axis digital holographic microscopy, can provide quantitative information about three-dimensional (3D) morphology of human RBCs and the characteristic properties such as mean corpuscular hemoglobin (MCH) and MCH surface density (MCHSD). In this paper, we investigate modifications of the 3D morphology and MCH in RBCs induced by the period of storage time for the purpose of classification of RBCs with different periods of storage by using off-axis digital holographic microscopy. The classification of RBCs based on the duration of storage is highly relevant because a long storage of blood before transfusion may alter the functionality of RBCs and, therefore, cause complications in patients. To analyze any changes in the 3D morphology and MCH of RBCs due to storage, we use data sets from RBC samples stored for 8, 13, 16, 23, 27, 30, 34, 37, 40, 47, and 57 days, respectively. The data sets consist of more than 3,300 blood cells in eleven classes, with more than 300 blood cells per class. The classes indicate the storage period of RBCs and are listed in chronological order. Using the RBCs donated by healthy persons, the off-axis digital holographic microscopy reconstructs several quantitative phase images of RBC samples stored for eleven different periods. We employ marker-controlled watershed transform to remove the background in the RBC quantitative phase images obtained by the off-axis digital holographic microscopy. More than 300 single RBCs are extracted from the segmented quantitative phase images for each class. Such a large number of RBC samples enable us to obtain statistical distributions of the characteristic properties of RBCs after a specific period of storage. Experimental results show that the 3D morphology of the RBCs, in contrast to MCH, is essentially related to the aging of the RBCs.

  10. Proceedings of the third international workshop on quantitative structure-activity relationships in environmental toxicology

    SciTech Connect

    Turner, J.E.; England, M.W.; Schultz, T.W.; Kwaak, N.J.

    1988-06-01

    The 3rd International Workshop on Quantitative Structure-Activity Relationships (QSAR) in Environmental Toxicology (QSAR-88) was organized to facilitate the exchange of ideas between experts in different areas working in QSAR. Invited participants were selected to provide a mixture of representatives from biology, chemistry, and statistics as well as industry, government, and academia. The theme for QSAR-88 was ''Interrelationships of QSAR and Mechanisms of Toxic Actions.'' The program was divided into four sessions of invited talks on statistics, molecular descriptors, fish QSARs, and non-fish QSARs and a poster session. These Proceedings contain the text of the 16 invited technical papers and descriptions of the 16 contributed poster presentations. In addition, we include a summary of the Workshop prepared by Dr. Kaiser. The use of structure-activity relationships to elucidate trends in toxicology has been documented for more than a century. However, it is only over the past fifteen years that the modern tools, initially developed for experimental drug design, have been brought to bear on the problem of environmental contamination. The very nature of the field has, from the start, required the collaboration of experts from several scientific disciplines.

  11. Development and validation of a quantitative structure-activity relationship for chronic narcosis to fish.

    PubMed

    Claeys, Lieve; Iaccino, Federica; Janssen, Colin R; Van Sprang, Patrick; Verdonck, Frederik

    2013-10-01

    Vertebrate testing under the European Union's regulation on Registration, Evaluation, Authorisation and Restriction of Chemical substances (REACH) is discouraged, and the use of alternative nontesting approaches such as quantitative structure-activity relationships (QSARs) is encouraged. However, robust QSARs predicting chronic ecotoxicity of organic compounds to fish are not available. The Ecological Structure Activity Relationships (ECOSAR) Class Program is a computerized predictive system that estimates the acute and chronic toxicity of organic compounds for several chemical classes based on their log octanol-water partition coefficient (K(OW)). For those chemical classes for which chronic training data sets are lacking, acute to chronic ratios are used to predict chronic toxicity to aquatic organisms. Although ECOSAR reaches a high score against the Organisation for Economic Co-operation and Development (OECD) principles for QSAR validation, the chronic QSARs in ECOSAR are not fully compliant with OECD criteria in the framework of REACH or CLP (classification, labeling, and packaging) regulation. The objective of the present study was to develop a chronic ecotoxicity QSAR for fish for compounds acting via nonpolar and polar narcosis. These QSARs were built using a database of quality screened toxicity values, considering only chronic exposure durations and relevant end points. After statistical multivariate diagnostic analysis, literature-based, mechanistically relevant descriptors were selected to develop a multivariate regression model. Finally, these QSARs were tested for their acceptance for regulatory purposes and were found to be compliant with the OECD principles for the validation of a QSAR.

  12. Flavonoids promoting HaCaT migration: I. Hologram quantitative structure-activity relationships.

    PubMed

    Cho, Moonjae; Yoon, Hyuk; Park, Mijoo; Kim, Young Hwa; Lim, Yoongho

    2014-03-15

    Cell migration plays an important role in multicellular development and preservation. Because wound healing requires cell migration, compounds promoting cell migration can be used for wound repair therapy. Several plant-derived polyphenols are known to promote cell migration, which improves wound healing. Previous studies of flavonoids on cell lines have focused on their inhibitory effects and not on wound healing. In addition, studies of flavonoids on wound healing have been performed using mixtures. In this study, individual flavonoids were used for cellular migration measurements. Relationships between the cell migration effects of flavonoids and their structural properties have never been reported. Here, we investigated the migration of keratinocytes caused by 100 flavonoids and examined their relationships using hologram quantitative structure-activity relationships. The structural conditions responsible for efficient cell migration on keratinocyte cell lines determined from the current study will facilitate the design of flavonoids with improved activity.

  13. New Quantitative Structure-Activity Relationship Models Improve Predictability of Ames Mutagenicity for Aromatic Azo Compounds.

    PubMed

    Manganelli, Serena; Benfenati, Emilio; Manganaro, Alberto; Kulkarni, Sunil; Barton-Maclaren, Tara S; Honma, Masamitsu

    2016-10-01

    Existing Quantitative Structure-Activity Relationship (QSAR) models have limited predictive capabilities for aromatic azo compounds. In this study, 2 new models were built to predict Ames mutagenicity of this class of compounds. The first one made use of descriptors based on simplified molecular input-line entry system (SMILES), calculated with the CORAL software. The second model was based on the k-nearest neighbors algorithm. The statistical quality of the predictions from single models was satisfactory. The performance further improved when the predictions from these models were combined. The prediction results from other QSAR models for mutagenicity were also evaluated. Most of the existing models were found to be good at finding toxic compounds but resulted in many false positive predictions. The 2 new models specific for this class of compounds avoid this problem thanks to a larger set of related compounds as training set and improved algorithms.

  14. Quantitative structure-activity relationship of antifungal activity of rosin derivatives.

    PubMed

    Wang, Hui; Nguyen, Thi Thanh Hien; Li, Shujun; Liang, Tao; Zhang, Yuanyuan; Li, Jian

    2015-01-15

    To develop new rosin-based wood preservatives with good antifungal activity, 24 rosin derivatives were synthesized, bioassay tested with Trametes versicolor and Gloeophyllum trabeum, and subjected to analysis of their quantitative structure-activity relationships (QSAR). A QSAR analysis using Ampac 9.2.1 and Codessa 2.7.16 software built two QSAR models of antifungal ratio for T. versicolor and G. trabeum with values of R(2)=0.9740 and 0.9692, respectively. Based on the models, tri-N-(3-hydroabietoxy-2-hydroxy) propyl-triethyl ammonium chloride was designed and the bioassay test result proved its better inhibitory effect against the two selected fungi as expected.

  15. Design, synthesis and exploring the quantitative structure-activity relationship of some antioxidant flavonoid analogues.

    PubMed

    Das, Sreeparna; Mitra, Indrani; Batuta, Shaikh; Niharul Alam, Md; Roy, Kunal; Begum, Naznin Ara

    2014-11-01

    A series of flavonoid analogues were synthesized and screened for the in vitro antioxidant activity through their ability to quench 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical. The activity of these compounds, measured in comparison to the well-known standard antioxidants (29-32), their precursors (38-42) and other bioactive moieties (38-42) resembling partially the flavone skeleton was analyzed further to develop Quantitative Structure-Activity Relationship (QSAR) models using the Genetic Function Approximation (GFA) technique. Based on the essential structural requirements predicted by the QSAR models, some analogues were designed, synthesized and tested for activity. The predicted and experimental activities of these compounds were well correlated. Flavone analogue 20 was found to be the most potent antioxidant.

  16. Quantitative structure-activity relationships of imidazolium oximes as nerve agent antidotes

    SciTech Connect

    Musallam, H.A.; Foye, W.O.; Hansch, C.; Harris, R.N.; Engle, R.R.

    1993-05-13

    Organophosphorus-containing pesticides and chemical warfare agents are potent inhibitors of synaptic acetylcholinesterase, a key regulator of cholinergic neurotransmission. These nerve agents have for many years constituted a serious threat to military personnel. These threats stimulated considerable efforts to develop effective medical countermeasures. Several potential drugs have been found recently which are capable of protecting animals from lethal levels of nerve agents. A recent U. S. Army Medical Research and Development Command drug development project synthesized a large number of imidazolium oximes. These compounds were found to possess strong antidotal activity against one of the most lethal nerve agents, soman. The Army's approach, like most conventional drug discovery approaches, depended primarily on the trial and error method. This research was carried out to determine if these potential nerve agent antidotes could have been discovered through the use of Quantitative Structure Activity-Relationships (QSAR) technique.

  17. Simplifying complex QSAR's (quantitative structure-activity relationships) in toxicity studies with multivariate statistics

    SciTech Connect

    Niemi, G.J.; McKim, J.M.

    1988-07-01

    During the past several decades many quantitative structure-activity relationships (QSAR's) have been derived from relatively small data sets of chemicals in a homologous series and selected empirical observations. An alternative approach is to analyze large data sets consisting of heterogeneous groups of chemicals and to explore QSAR's among these chemicals for generalized patterns of chemical behavior. The use of exploratory multivariate statistical techniques for simplifying complex QSAR problems is demonstrated through the use of research data on biodegradation and mode of toxic action. In these examples, a large number of explanatory variables were examined to explore which variables might best explain whether a chemical biodegrades or whether a toxic response by an organism can be used to identify a mode of toxic action. In both cases, the procedures reduced the number of potential explanatory variables and generated hypotheses about biodegradation and mode of toxic action for future research without explicitly testing an existing hypothesis.

  18. A quantitative structure-activity relationship approach for assessing toxicity of mixture of organic compounds.

    PubMed

    Chang, C M; Ou, Y H; Liu, T-C; Lu, S-Y; Wang, M-K

    2016-06-01

    Four types of reactivity indices were employed to construct quantitative structure-activity relationships for the assessment of toxicity of organic chemical mixtures. Results of analysis indicated that the maximum positive charge of the hydrogen atom and the inverse of the apolar surface area are the most important descriptors for the toxicity of mixture of benzene and its derivatives to Vibrio fischeri. The toxicity of mixture of aromatic compounds to green alga Scenedesmus obliquus is mainly affected by the electron flow and electrostatic interactions. The electron-acceptance chemical potential and the maximum positive charge of the hydrogen atom are found to be the most important descriptors for the joint toxicity of aromatic compounds.

  19. Prediction of activated carbon adsorption capacities for organic vapors using quantitative structure-activity relationship methods

    SciTech Connect

    Nirmalakhandan, N.N. ); Speece, R.E. )

    1993-08-01

    Quantitative structure-activity relationship (QSAR) methods were used to develop models to estimate and predict activated carbon adsorption capacities for organic vapors. Literature isothermal data from two sources for 22 organic contaminants on six different carbons were merged to form a training set of 75 data points. Two different QSAR approaches were evaluated: the molecular connectivity approach and the linear solvation energy relationship approach. The QSAR model developed in this study using the molecular connectivity approach was able to fit the experimental data with r = 0.96 and standard error of 0.09. The utility of the model was demonstrated by using predicted k values to calculate adsorption capacities of 12 chemicals on two different carbons and comparing them with experimentally determined values. 9 refs., 1 fig., 3 tabs.

  20. Quantitative structure-activity relationships of selective antagonists of glucagon receptor using QuaSAR descriptors.

    PubMed

    Manoj Kumar, Palanivelu; Karthikeyan, Chandrabose; Hari Narayana Moorthy, Narayana Subbiah; Trivedi, Piyush

    2006-11-01

    In the present paper, quantitative structure activity relationship (QSAR) approach was applied to understand the affinity and selectivity of a novel series of triaryl imidazole derivatives towards glucagon receptor. Statistically significant and highly predictive QSARs were derived for glucagon receptor inhibition by triaryl imidazoles using QuaSAR descriptors of molecular operating environment (MOE) employing computer-assisted multiple regression procedure. The generated QSAR models revealed that factors related to hydrophobicity, molecular shape and geometry predominantly influences glucagon receptor binding affinity of the triaryl imidazoles indicating the relevance of shape specific steric interactions between the molecule and the receptor. Further, QSAR models formulated for selective inhibition of glucagon receptor over p38 mitogen activated protein (MAP) kinase of the compounds in the series highlights that the same structural features, which influence the glucagon receptor affinity, also contribute to their selective inhibition.

  1. Quantitative structure-activity relationship of antifungal activity of rosin derivatives.

    PubMed

    Wang, Hui; Nguyen, Thi Thanh Hien; Li, Shujun; Liang, Tao; Zhang, Yuanyuan; Li, Jian

    2015-01-15

    To develop new rosin-based wood preservatives with good antifungal activity, 24 rosin derivatives were synthesized, bioassay tested with Trametes versicolor and Gloeophyllum trabeum, and subjected to analysis of their quantitative structure-activity relationships (QSAR). A QSAR analysis using Ampac 9.2.1 and Codessa 2.7.16 software built two QSAR models of antifungal ratio for T. versicolor and G. trabeum with values of R(2)=0.9740 and 0.9692, respectively. Based on the models, tri-N-(3-hydroabietoxy-2-hydroxy) propyl-triethyl ammonium chloride was designed and the bioassay test result proved its better inhibitory effect against the two selected fungi as expected. PMID:25466709

  2. New Quantitative Structure-Activity Relationship Models Improve Predictability of Ames Mutagenicity for Aromatic Azo Compounds.

    PubMed

    Manganelli, Serena; Benfenati, Emilio; Manganaro, Alberto; Kulkarni, Sunil; Barton-Maclaren, Tara S; Honma, Masamitsu

    2016-10-01

    Existing Quantitative Structure-Activity Relationship (QSAR) models have limited predictive capabilities for aromatic azo compounds. In this study, 2 new models were built to predict Ames mutagenicity of this class of compounds. The first one made use of descriptors based on simplified molecular input-line entry system (SMILES), calculated with the CORAL software. The second model was based on the k-nearest neighbors algorithm. The statistical quality of the predictions from single models was satisfactory. The performance further improved when the predictions from these models were combined. The prediction results from other QSAR models for mutagenicity were also evaluated. Most of the existing models were found to be good at finding toxic compounds but resulted in many false positive predictions. The 2 new models specific for this class of compounds avoid this problem thanks to a larger set of related compounds as training set and improved algorithms. PMID:27413112

  3. The 18th European symposium on quantitative structure-activity relationships.

    PubMed

    Tsantili-Kakoulidou, Anna; Agrafiotis, Dimitris K

    2011-04-01

    The 18th European Symposium on Quantitative Structure-Activity Relationships (QSAR) took place in Rhodes, Greece, on 19 - 24 September 2010. It was organized by the Hellenic Society of Medicinal Chemistry and the Cheminformatics and QSAR Society, and co-sponsored by the European Federation of Medicinal Chemistry. The conference was thematically dedicated to discovery informatics and drug design and addressed the impact of informatics in all its variants (chemoinformatics, bioinformatics, pharmacoinformatics) on drug discovery in the broader context of biological complexity. The latest scientific and technological advances in QSAR as tools for the discovery of new, safer and more efficacious drugs were discussed during the meeting. This paper highlights the most important outcomes of the symposium, commenting briefly on some of the key presentations.

  4. Nondestructive 3D confocal laser imaging with deconvolution of seven whole stardust tracks with complementary XRF and quantitative analysis

    SciTech Connect

    Greenberg, M.; Ebel, D.S.

    2009-03-19

    We present a nondestructive 3D system for analysis of whole Stardust tracks, using a combination of Laser Confocal Scanning Microscopy and synchrotron XRF. 3D deconvolution is used for optical corrections, and results of quantitative analyses of several tracks are presented. The Stardust mission to comet Wild 2 trapped many cometary and ISM particles in aerogel, leaving behind 'tracks' of melted silica aerogel on both sides of the collector. Collected particles and their tracks range in size from submicron to millimeter scale. Interstellar dust collected on the obverse of the aerogel collector is thought to have an average track length of {approx}15 {micro}m. It has been our goal to perform a total non-destructive 3D textural and XRF chemical analysis on both types of tracks. To that end, we use a combination of Laser Confocal Scanning Microscopy (LCSM) and X Ray Florescence (XRF) spectrometry. Utilized properly, the combination of 3D optical data and chemical data provides total nondestructive characterization of full tracks, prior to flattening or other destructive analysis methods. Our LCSM techniques allow imaging at 0.075 {micro}m/pixel, without the use of oil-based lenses. A full textural analysis on track No.82 is presented here as well as analysis of 6 additional tracks contained within 3 keystones (No.128, No.129 and No.140). We present a method of removing the axial distortion inherent in LCSM images, by means of a computational 3D Deconvolution algorithm, and present some preliminary experiments with computed point spread functions. The combination of 3D LCSM data and XRF data provides invaluable information, while preserving the integrity of the samples for further analysis. It is imperative that these samples, the first extraterrestrial solids returned since the Apollo era, be fully mapped nondestructively in 3D, to preserve the maximum amount of information prior to other, destructive analysis.

  5. Quantitative Analysis of Vascular Heterogeneity in Breast Lesions Using Contrast-Enhanced 3-D Harmonic and Subharmonic Ultrasound Imaging

    PubMed Central

    Sridharan, Anush; Eisenbrey, John R.; Machado, Priscilla; Ojeda-Fournier, Haydee; Wilkes, Annina; Sevrukov, Alexander; Mattrey, Robert F.; Wallace, Kirk; Chalek, Carl L.; Thomenius, Kai E.; Forsberg, Flemming

    2015-01-01

    Ability to visualize breast lesion vascularity and quantify the vascular heterogeneity using contrast-enhanced 3-D harmonic (HI) and subharmonic (SHI) ultrasound imaging was investigated in a clinical population. Patients (n = 134) identified with breast lesions on mammography were scanned using power Doppler imaging, contrast-enhanced 3-D HI, and 3-D SHI on a modified Logiq 9 scanner (GE Healthcare). A region of interest corresponding to ultrasound contrast agent flow was identified in 4D View (GE Medical Systems) and mapped to raw slice data to generate a map of time-intensity curves for the lesion volume. Time points corresponding to baseline, peak intensity, and washout of ultrasound contrast agent were identified and used to generate and compare vascular heterogeneity plots for malignant and benign lesions. Vascularity was observed with power Doppler imaging in 84 lesions (63 benign and 21 malignant). The 3-D HI showed flow in 8 lesions (5 benign and 3 malignant), whereas 3-D SHI visualized flow in 68 lesions (49 benign and 19 malignant). Analysis of vascular heterogeneity in the 3-D SHI volumes found benign lesions having a significant difference in vascularity between central and peripheral sections (1.71 ± 0.96 vs. 1.13 ± 0.79 dB, p < 0.001, respectively), whereas malignant lesions showed no difference (1.66 ± 1.39 vs. 1.24 ± 1.14 dB, p = 0.24), indicative of more vascular coverage. These preliminary results suggest quantitative evaluation of vascular heterogeneity in breast lesions using contrast-enhanced 3-D SHI is feasible and able to detect variations in vascularity between central and peripheral sections for benign and malignant lesions. PMID:25935933

  6. 3-D Ultrafast Doppler Imaging Applied to the Noninvasive and Quantitative Imaging of Blood Vessels in Vivo

    PubMed Central

    Provost, J.; Papadacci, C.; Demene, C.; Gennisson, J-L.; Tanter, M.; Pernot, M.

    2016-01-01

    Ultrafast Doppler Imaging was introduced as a technique to quantify blood flow in an entire 2-D field of view, expanding the field of application of ultrasound imaging to the highly sensitive anatomical and functional mapping of blood vessels. We have recently developed 3-D Ultrafast Ultrasound Imaging, a technique that can produce thousands of ultrasound volumes per second, based on three-dimensional plane and diverging wave emissions, and demonstrated its clinical feasibility in human subjects in vivo. In this study, we show that non-invasive 3-D Ultrafast Power Doppler, Pulsed Doppler, and Color Doppler Imaging can be used to perform quantitative imaging of blood vessels in humans when using coherent compounding of three-dimensional tilted plane waves. A customized, programmable, 1024-channel ultrasound system was designed to perform 3-D Ultrafast Imaging. Using a 32X32, 3-MHz matrix phased array (Vermon, France), volumes were beamformed by coherently compounding successive tilted plane wave emissions. Doppler processing was then applied in a voxel-wise fashion. 3-D Ultrafast Power Doppler Imaging was first validated by imaging Tygon tubes of varying diameter and its in vivo feasibility was demonstrated by imaging small vessels in the human thyroid. Simultaneous 3-D Color and Pulsed Doppler Imaging using compounded emissions were also applied in the carotid artery and the jugular vein in one healthy volunteer. PMID:26276956

  7. A Quantitative 3D Motility Analysis of Trypanosoma brucei by Use of Digital In-line Holographic Microscopy

    PubMed Central

    Weiße, Sebastian; Heddergott, Niko; Heydt, Matthias; Pflästerer, Daniel; Maier, Timo; Haraszti, Tamás; Grunze, Michael; Engstler, Markus; Rosenhahn, Axel

    2012-01-01

    We present a quantitative 3D analysis of the motility of the blood parasite Trypanosoma brucei. Digital in-line holographic microscopy has been used to track single cells with high temporal and spatial accuracy to obtain quantitative data on their behavior. Comparing bloodstream form and insect form trypanosomes as well as mutant and wildtype cells under varying external conditions we were able to derive a general two-state-run-and-tumble-model for trypanosome motility. Differences in the motility of distinct strains indicate that adaption of the trypanosomes to their natural environments involves a change in their mode of swimming. PMID:22629379

  8. A review of state-of-the-art stereology for better quantitative 3D morphology in cardiac research.

    PubMed

    Mühlfeld, Christian; Nyengaard, Jens Randel; Mayhew, Terry M

    2010-01-01

    The aim of stereological methods in biomedical research is to obtain quantitative information about three-dimensional (3D) features of tissues, cells, or organelles from two-dimensional physical or optical sections. With immunogold labeling, stereology can even be used for the quantitative analysis of the distribution of molecules within tissues and cells. Nowadays, a large number of design-based stereological methods offer an efficient quantitative approach to intriguing questions in cardiac research, such as "Is there a significant loss of cardiomyocytes during progression from ventricular hypertrophy to heart failure?" or "Does a specific treatment reduce the degree of fibrosis in the heart?" Nevertheless, the use of stereological methods in cardiac research is rare. The present review article demonstrates how some of the potential pitfalls in quantitative microscopy may be avoided. To this end, we outline the concepts of design-based stereology and illustrate their practical applications to a wide range of biological questions in cardiac research. We hope that the present article will stimulate researchers in cardiac research to incorporate design-based stereology into their study designs, thus promoting an unbiased quantitative 3D microscopy.

  9. Applying quantitative structure-activity relationship approaches to nanotoxicology: current status and future potential.

    PubMed

    Winkler, David A; Mombelli, Enrico; Pietroiusti, Antonio; Tran, Lang; Worth, Andrew; Fadeel, Bengt; McCall, Maxine J

    2013-11-01

    The potential (eco)toxicological hazard posed by engineered nanoparticles is a major scientific and societal concern since several industrial sectors (e.g. electronics, biomedicine, and cosmetics) are exploiting the innovative properties of nanostructures resulting in their large-scale production. Many consumer products contain nanomaterials and, given their complex life-cycle, it is essential to anticipate their (eco)toxicological properties in a fast and inexpensive way in order to mitigate adverse effects on human health and the environment. In this context, the application of the structure-toxicity paradigm to nanomaterials represents a promising approach. Indeed, according to this paradigm, it is possible to predict toxicological effects induced by chemicals on the basis of their structural similarity with chemicals for which toxicological endpoints have been previously measured. These structure-toxicity relationships can be quantitative or qualitative in nature and they can predict toxicological effects directly from the physicochemical properties of the entities (e.g. nanoparticles) of interest. Therefore, this approach can aid in prioritizing resources in toxicological investigations while reducing the ethical and monetary costs that are related to animal testing. The purpose of this review is to provide a summary of recent key advances in the field of QSAR modelling of nanomaterial toxicity, to identify the major gaps in research required to accelerate the use of quantitative structure-activity relationship (QSAR) methods, and to provide a roadmap for future research needed to achieve QSAR models useful for regulatory purposes. PMID:23165187

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

    PubMed

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

    2009-07-01

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

  11. Quantitative structure-activity relationship for toxicity of ionic liquids to Daphnia magna: aromaticity vs. lipophilicity.

    PubMed

    Roy, Kunal; Das, Rudra Narayan; Popelier, Paul L A

    2014-10-01

    Water solubility of ionic liquids (ILs) allows their dispersion into aquatic systems and raises concerns on their pollutant potential. Again, lipophilicity can contribute to the toxicity of ILs due to increased ability of the compounds to cross lipoidal bio-membranes. In the present work, we have performed statistical model development for toxicity of a set of ionic liquids to Daphnia magna, a widely accepted model organism for toxicity testing, using computed lipophilicity, atom-type fragment, quantum topological molecular similarity (QTMS) and extended topochemical atom (ETA) descriptors. The models have been developed and validated in accordance with the Organization for Economic Co-operation and Development (OECD) guidelines for quantitative structure-activity relationships (QSARs). The best partial least squares (PLS) model outperforms the previously reported multiple linear regression (MLR) model in statistical quality and predictive ability (R(2)=0.955, Q(2)=0.917, Rpred(2)=0.848). In this work, the ETA descriptors show importance of branching and aromaticity while the QTMS descriptor ellipticity efficiently shows which compounds are influential in the data set, with reference to the model. While obvious importance of lipophilicity is evident from the models, the best model clearly shows the importance of aromaticity suggesting that more lipophilic ILs with less toxicity may be designed by avoiding aromaticity, nitrogen atoms and increasing branching in the cationic structure. The developed quantitative models are in consonance with the recent hypothesis of importance of aromaticity for toxicity of ILs.

  12. Applying quantitative structure-activity relationship approaches to nanotoxicology: current status and future potential.

    PubMed

    Winkler, David A; Mombelli, Enrico; Pietroiusti, Antonio; Tran, Lang; Worth, Andrew; Fadeel, Bengt; McCall, Maxine J

    2013-11-01

    The potential (eco)toxicological hazard posed by engineered nanoparticles is a major scientific and societal concern since several industrial sectors (e.g. electronics, biomedicine, and cosmetics) are exploiting the innovative properties of nanostructures resulting in their large-scale production. Many consumer products contain nanomaterials and, given their complex life-cycle, it is essential to anticipate their (eco)toxicological properties in a fast and inexpensive way in order to mitigate adverse effects on human health and the environment. In this context, the application of the structure-toxicity paradigm to nanomaterials represents a promising approach. Indeed, according to this paradigm, it is possible to predict toxicological effects induced by chemicals on the basis of their structural similarity with chemicals for which toxicological endpoints have been previously measured. These structure-toxicity relationships can be quantitative or qualitative in nature and they can predict toxicological effects directly from the physicochemical properties of the entities (e.g. nanoparticles) of interest. Therefore, this approach can aid in prioritizing resources in toxicological investigations while reducing the ethical and monetary costs that are related to animal testing. The purpose of this review is to provide a summary of recent key advances in the field of QSAR modelling of nanomaterial toxicity, to identify the major gaps in research required to accelerate the use of quantitative structure-activity relationship (QSAR) methods, and to provide a roadmap for future research needed to achieve QSAR models useful for regulatory purposes.

  13. Localized heuristic inverse quantitative structure activity relationship with bulk descriptors using numerical gradients.

    PubMed

    Stålring, Jonna; Almeida, Pedro R; Carlsson, Lars; Helgee Ahlberg, Ernst; Hasselgren, Catrin; Boyer, Scott

    2013-08-26

    State-of-the-art quantitative structure-activity relationship (QSAR) models are often based on nonlinear machine learning algorithms, which are difficult to interpret. From a pharmaceutical perspective, QSARs are used to enhance the chemical design process. Ultimately, they should not only provide a prediction but also contribute to a mechanistic understanding and guide modifications to the chemical structure, promoting compounds with desirable biological activity profiles. Global ranking of descriptor importance and inverse QSAR have been used for these purposes. This paper introduces localized heuristic inverse QSAR, which provides an assessment of the relative ability of the descriptors to influence the biological response in an area localized around the predicted compound. The method is based on numerical gradients with parameters optimized using data sets sampled from analytical functions. The heuristic character of the method reduces the computational requirements and makes it applicable not only to fragment based methods but also to QSARs based on bulk descriptors. The application of the method is illustrated on congeneric QSAR data sets, and it is shown that the predicted influential descriptors can be used to guide structural modifications that affect the biological response in the desired direction. The method is implemented into the AZOrange Open Source QSAR package. The current implementation of localized heuristic inverse QSAR is a step toward a generally applicable method for elucidating the structure activity relationship specifically for a congeneric region of chemical space when using QSARs based on bulk properties. Consequently, this method could contribute to accelerating the chemical design process in pharmaceutical projects, as well as provide information that could enhance the mechanistic understanding for individual scaffolds.

  14. A novel 3D absorption correction method for quantitative EDX-STEM tomography.

    PubMed

    Burdet, Pierre; Saghi, Z; Filippin, A N; Borrás, A; Midgley, P A

    2016-01-01

    This paper presents a novel 3D method to correct for absorption in energy dispersive X-ray (EDX) microanalysis of heterogeneous samples of unknown structure and composition. By using STEM-based tomography coupled with EDX, an initial 3D reconstruction is used to extract the location of generated X-rays as well as the X-ray path through the sample to the surface. The absorption correction needed to retrieve the generated X-ray intensity is then calculated voxel-by-voxel estimating the different compositions encountered by the X-ray. The method is applied to a core/shell nanowire containing carbon and oxygen, two elements generating highly absorbed low energy X-rays. Absorption is shown to cause major reconstruction artefacts, in the form of an incomplete recovery of the oxide and an erroneous presence of carbon in the shell. By applying the correction method, these artefacts are greatly reduced. The accuracy of the method is assessed using reference X-ray lines with low absorption.

  15. 3D quantitative visualization of altered LV wall thickening dynamics caused by coronary microembolization

    NASA Astrophysics Data System (ADS)

    Eusemann, Christian D.; Mohlenkamp, Stefan; Ritman, Erik L.; Robb, Richard A.

    2001-05-01

    Regional heart wall dynamics has been shown to be a sensitive indicator of LV wall ischemia. Rates of local LV wall thickening during a cardiac cycle can be measured and illustrated using functional parametric mappings. This display conveys the spatial distribution of dynamic strain in the myocardium and thereby provides a rapid qualitative appreciation of the severity and extent of the ischemic region. 3D reconstructions were obtained in an anesthetized pig from 8 adjacent, shortaxis, slices of the left ventricle imaged with an Electron Beam Computer Tomograph at 11 time points through one complete cardiac cycle. The 3D reconstructions were obtained before and after injection of 100 micrometer microspheres into the Left Anterior Descending (LAD) coronary artery. This injection causes microembolization of LAD artery branches within the heart wall. The image processing involved radially dividing the tomographic images of the myocardium into small subdivisions with color encoding of the local magnitude of regional thickness or regional velocities of LV wall thickening throughout the cardiac cycle. We compared the effectiveness of animation of wall thickness encoded in color versus a static image of computed rate of wall thickness change in color. The location, extent and severity of regional wall akinesis or dyskinesis, as determined from these displays, can then be compared to the region of embolization as indicated by the distribution of altered LV wall perfusion.

  16. A novel 3D absorption correction method for quantitative EDX-STEM tomography.

    PubMed

    Burdet, Pierre; Saghi, Z; Filippin, A N; Borrás, A; Midgley, P A

    2016-01-01

    This paper presents a novel 3D method to correct for absorption in energy dispersive X-ray (EDX) microanalysis of heterogeneous samples of unknown structure and composition. By using STEM-based tomography coupled with EDX, an initial 3D reconstruction is used to extract the location of generated X-rays as well as the X-ray path through the sample to the surface. The absorption correction needed to retrieve the generated X-ray intensity is then calculated voxel-by-voxel estimating the different compositions encountered by the X-ray. The method is applied to a core/shell nanowire containing carbon and oxygen, two elements generating highly absorbed low energy X-rays. Absorption is shown to cause major reconstruction artefacts, in the form of an incomplete recovery of the oxide and an erroneous presence of carbon in the shell. By applying the correction method, these artefacts are greatly reduced. The accuracy of the method is assessed using reference X-ray lines with low absorption. PMID:26484792

  17. Chemical graphs, molecular matrices and topological indices in chemoinformatics and quantitative structure-activity relationships.

    PubMed

    Ivanciuc, Ovidiu

    2013-06-01

    Chemical and molecular graphs have fundamental applications in chemoinformatics, quantitative structureproperty relationships (QSPR), quantitative structure-activity relationships (QSAR), virtual screening of chemical libraries, and computational drug design. Chemoinformatics applications of graphs include chemical structure representation and coding, database search and retrieval, and physicochemical property prediction. QSPR, QSAR and virtual screening are based on the structure-property principle, which states that the physicochemical and biological properties of chemical compounds can be predicted from their chemical structure. Such structure-property correlations are usually developed from topological indices and fingerprints computed from the molecular graph and from molecular descriptors computed from the three-dimensional chemical structure. We present here a selection of the most important graph descriptors and topological indices, including molecular matrices, graph spectra, spectral moments, graph polynomials, and vertex topological indices. These graph descriptors are used to define several topological indices based on molecular connectivity, graph distance, reciprocal distance, distance-degree, distance-valency, spectra, polynomials, and information theory concepts. The molecular descriptors and topological indices can be developed with a more general approach, based on molecular graph operators, which define a family of graph indices related by a common formula. Graph descriptors and topological indices for molecules containing heteroatoms and multiple bonds are computed with weighting schemes based on atomic properties, such as the atomic number, covalent radius, or electronegativity. The correlation in QSPR and QSAR models can be improved by optimizing some parameters in the formula of topological indices, as demonstrated for structural descriptors based on atomic connectivity and graph distance. PMID:23701000

  18. Deep neural nets as a method for quantitative structure-activity relationships.

    PubMed

    Ma, Junshui; Sheridan, Robert P; Liaw, Andy; Dahl, George E; Svetnik, Vladimir

    2015-02-23

    Neural networks were widely used for quantitative structure-activity relationships (QSAR) in the 1990s. Because of various practical issues (e.g., slow on large problems, difficult to train, prone to overfitting, etc.), they were superseded by more robust methods like support vector machine (SVM) and random forest (RF), which arose in the early 2000s. The last 10 years has witnessed a revival of neural networks in the machine learning community thanks to new methods for preventing overfitting, more efficient training algorithms, and advancements in computer hardware. In particular, deep neural nets (DNNs), i.e. neural nets with more than one hidden layer, have found great successes in many applications, such as computer vision and natural language processing. Here we show that DNNs can routinely make better prospective predictions than RF on a set of large diverse QSAR data sets that are taken from Merck's drug discovery effort. The number of adjustable parameters needed for DNNs is fairly large, but our results show that it is not necessary to optimize them for individual data sets, and a single set of recommended parameters can achieve better performance than RF for most of the data sets we studied. The usefulness of the parameters is demonstrated on additional data sets not used in the calibration. Although training DNNs is still computationally intensive, using graphical processing units (GPUs) can make this issue manageable.

  19. Deep neural nets as a method for quantitative structure-activity relationships.

    PubMed

    Ma, Junshui; Sheridan, Robert P; Liaw, Andy; Dahl, George E; Svetnik, Vladimir

    2015-02-23

    Neural networks were widely used for quantitative structure-activity relationships (QSAR) in the 1990s. Because of various practical issues (e.g., slow on large problems, difficult to train, prone to overfitting, etc.), they were superseded by more robust methods like support vector machine (SVM) and random forest (RF), which arose in the early 2000s. The last 10 years has witnessed a revival of neural networks in the machine learning community thanks to new methods for preventing overfitting, more efficient training algorithms, and advancements in computer hardware. In particular, deep neural nets (DNNs), i.e. neural nets with more than one hidden layer, have found great successes in many applications, such as computer vision and natural language processing. Here we show that DNNs can routinely make better prospective predictions than RF on a set of large diverse QSAR data sets that are taken from Merck's drug discovery effort. The number of adjustable parameters needed for DNNs is fairly large, but our results show that it is not necessary to optimize them for individual data sets, and a single set of recommended parameters can achieve better performance than RF for most of the data sets we studied. The usefulness of the parameters is demonstrated on additional data sets not used in the calibration. Although training DNNs is still computationally intensive, using graphical processing units (GPUs) can make this issue manageable. PMID:25635324

  20. Quantitative structure-activity relationships for toxicity of nonpolar narcotic chemicals to Pseudokirchneriella subcapitata.

    PubMed

    Hsieh, Shih-Hung; Hsu, Chih-Hsiung; Tsai, Din-Yu; Chen, Chung-Yuan

    2006-11-01

    This study presents data for 27 nonpolar narcotic compounds regarding toxicity to Pseudokirchneriella subcapitata as evaluated using a closed-system algal toxicity test with an exposure time of 48 h. Two test endpoints, dissolved oxygen production and algal growth rate, were used to assess the toxicity of nonpolar narcotic chemicals on algae. Hydrophobicity (1-octanol-water partition coefficient [K(OW)]) provided satisfactory descriptions for the toxicity of nonpolar narcotic compounds, and quantitative structure-activity relationships based on log K(OW) were established. The relative sensitivity of various aquatic organisms to nonpolar chemicals was as follows: P. subcapitata > Vibriofischeri > or = Nitrosomonas sp. > fathead minnow > Daphnia magna > polytox > activated sludge. In addition, linear relationships were found between the toxicity observed in P. subcapitata and other aquatic organisms, except in the case of Nitrosomonas sp. Therefore, for nonpolar toxicants, the closed-system technique applied in the present study can be an ideal surrogate for other tests, such as fathead minnow and D. magna, that are either time-consuming or labor-intensive. However, because the current toxicity database is based primarily on the conventional batch tests, it cannot provide adequate assessment regarding the effects of various organic toxicants. Therefore, more extensive research is needed to revise the database for the toxicity of organic compounds on phytoplankton using the closed-system technique.

  1. Antiproliferative Pt(IV) complexes: synthesis, biological activity, and quantitative structure-activity relationship modeling.

    PubMed

    Gramatica, Paola; Papa, Ester; Luini, Mara; Monti, Elena; Gariboldi, Marzia B; Ravera, Mauro; Gabano, Elisabetta; Gaviglio, Luca; Osella, Domenico

    2010-09-01

    Several Pt(IV) complexes of the general formula [Pt(L)2(L')2(L'')2] [axial ligands L are Cl-, RCOO-, or OH-; equatorial ligands L' are two am(m)ine or one diamine; and equatorial ligands L'' are Cl- or glycolato] were rationally designed and synthesized in the attempt to develop a predictive quantitative structure-activity relationship (QSAR) model. Numerous theoretical molecular descriptors were used alongside physicochemical data (i.e., reduction peak potential, Ep, and partition coefficient, log Po/w) to obtain a validated QSAR between in vitro cytotoxicity (half maximal inhibitory concentrations, IC50, on A2780 ovarian and HCT116 colon carcinoma cell lines) and some features of Pt(IV) complexes. In the resulting best models, a lipophilic descriptor (log Po/w or the number of secondary sp3 carbon atoms) plus an electronic descriptor (Ep, the number of oxygen atoms, or the topological polar surface area expressed as the N,O polar contribution) is necessary for modeling, supporting the general finding that the biological behavior of Pt(IV) complexes can be rationalized on the basis of their cellular uptake, the Pt(IV)-->Pt(II) reduction, and the structure of the corresponding Pt(II) metabolites. Novel compounds were synthesized on the basis of their predicted cytotoxicity in the preliminary QSAR model, and were experimentally tested. A final QSAR model, based solely on theoretical molecular descriptors to ensure its general applicability, is proposed.

  2. Quantitative structure-activity relationships and ecological risk assessment: an overview of predictive aquatic toxicology research.

    PubMed

    Bradbury, S P

    1995-09-01

    In the field of aquatic toxicology, quantitative structure-activity relationships (QSARs) have developed as scientifically credible tools for predicting the toxicity of chemicals when little or no empirical data are available. A fundamental understanding of toxicological principles has been considered an important component to the acceptance and application of QSAR approaches as biologically relevant in ecological risk assessments. As a consequence, there has been an evolution of QSAR development and application from that of a chemical-class perspective to one that is more consistent with assumptions regarding modes of toxic action. In this review, techniques to assess modes of toxic action from chemical structure are discussed, with consideration that toxicodynamic knowledge bases must be clearly defined with regard to exposure regimes, biological models/endpoints and compounds that adequately span the diversity of chemicals anticipated for future applications. With such knowledge bases, classification systems, including rule-based expert systems, have been established for use in predictive aquatic toxicology applications. The establishment of QSAR techniques that are based on an understanding of toxic mechanisms is needed to provide a link to physiologically based toxicokinetic and toxicodynamic models, which can provide the means to extrapolate adverse effects across species and exposure regimes. PMID:7570660

  3. Quantitative structure-activity relationships for chemical toxicity to environmental bacteria

    SciTech Connect

    Blum, D.J.; Speece, R.E. )

    1991-10-01

    Quantitative structure-activity relationships (QSARs) were developed for nonreactive chemical toxicity to each of four groups of bacteria of importance in environmental engineering: aerobic heterotrophs, methanogens, Nitrosomonas, and Microtox. The QSARs were based on chemicals covering a range of structures and including important environmental pollutants (i.e., chlorinated and other substituted benzenes, phenols, and aliphatic hydrocarbons). QSARs were developed for each chemical class and for combinations of chemical classes. Three QSAR methods (groups of chemical describing parameters) were evaluated for their accuracy and ease of use: log P, linear solvation energy relationships (LSER), and molecular connectivity. Successful QSARs were found for each group of bacteria and by each method, with correlation coefficients (adjusted r2) between 0.79 and 0.95. LSER QSARs incorporated the widest range of chemicals with the greatest accuracy. Log P and molecular connectivity QSARs are easier to use because their parameters are readily available. Outliers from the QSARs likely due to reactive toxicity included acryls, low pKa compounds, and aldehydes. Nitro compounds and chlorinated aliphatic hydrocarbons and alcohols showed enhanced toxicity to the methanogens only. Chemicals with low IC50 concentrations (log IC50 mumol/liter less than 1.5) were often outliers for Nitrosomonas. QSARs were validated statistically and with literature data. A suggested method is provided for use of the QSARs.

  4. Quantitative structure-activity relationship models of chemical transformations from matched pairs analyses.

    PubMed

    Beck, Jeremy M; Springer, Clayton

    2014-04-28

    The concepts of activity cliffs and matched molecular pairs (MMP) are recent paradigms for analysis of data sets to identify structural changes that may be used to modify the potency of lead molecules in drug discovery projects. Analysis of MMPs was recently demonstrated as a feasible technique for quantitative structure-activity relationship (QSAR) modeling of prospective compounds. Although within a small data set, the lack of matched pairs, and the lack of knowledge about specific chemical transformations limit prospective applications. Here we present an alternative technique that determines pairwise descriptors for each matched pair and then uses a QSAR model to estimate the activity change associated with a chemical transformation. The descriptors effectively group similar transformations and incorporate information about the transformation and its local environment. Use of a transformation QSAR model allows one to estimate the activity change for novel transformations and therefore returns predictions for a larger fraction of test set compounds. Application of the proposed methodology to four public data sets results in increased model performance over a benchmark random forest and direct application of chemical transformations using QSAR-by-matched molecular pairs analysis (QSAR-by-MMPA).

  5. Toxicity of ionic liquids: database and prediction via quantitative structure-activity relationship method.

    PubMed

    Zhao, Yongsheng; Zhao, Jihong; Huang, Ying; Zhou, Qing; Zhang, Xiangping; Zhang, Suojiang

    2014-08-15

    A comprehensive database on toxicity of ionic liquids (ILs) is established. The database includes over 4000 pieces of data. Based on the database, the relationship between IL's structure and its toxicity has been analyzed qualitatively. Furthermore, Quantitative Structure-Activity relationships (QSAR) model is conducted to predict the toxicities (EC50 values) of various ILs toward the Leukemia rat cell line IPC-81. Four parameters selected by the heuristic method (HM) are used to perform the studies of multiple linear regression (MLR) and support vector machine (SVM). The squared correlation coefficient (R(2)) and the root mean square error (RMSE) of training sets by two QSAR models are 0.918 and 0.959, 0.258 and 0.179, respectively. The prediction R(2) and RMSE of QSAR test sets by MLR model are 0.892 and 0.329, by SVM model are 0.958 and 0.234, respectively. The nonlinear model developed by SVM algorithm is much outperformed MLR, which indicates that SVM model is more reliable in the prediction of toxicity of ILs. This study shows that increasing the relative number of O atoms of molecules leads to decrease in the toxicity of ILs.

  6. Blood-brain barrier permeability mechanisms in view of quantitative structure-activity relationships (QSAR).

    PubMed

    Bujak, Renata; Struck-Lewicka, Wiktoria; Kaliszan, Michał; Kaliszan, Roman; Markuszewski, Michał J

    2015-04-10

    The goal of the present paper was to develop a quantitative structure-activity relationship (QSAR) method using a simple statistical approach, such as multiple linear regression (MLR) for predicting the blood-brain barrier (BBB) permeability of chemical compounds. The "best" MLR models, comprised logP and either molecular mass (M) or isolated atomic energy (E(isol)), tested on a structurally diverse set of 66 compounds, is characterized the by correlation coefficients (R) around 0.8. The obtained models were validated using leave-one-out (LOO) cross-validation technique and the correlation coefficient of leave-one-out- R(LOO)(2) (Q(2)) was at least 0.6. Analysis of a case from legal medicine demonstrated informative value of our QSAR model. To best authors' knowledge the present study is a first application of the developed QSAR models of BBB permeability to case from the legal medicine. Our data indicate that molecular energy-related descriptors, in combination with the well-known descriptors of lipophilicity may have a supportive value in predicting blood-brain distribution, which is of utmost importance in drug development and toxicological studies.

  7. Quantitative Structure--Activity Relationship (QSAR) for the Oxidation of Trace Organic Contaminants by Sulfate Radical.

    PubMed

    Xiao, Ruiyang; Ye, Tiantian; Wei, Zongsu; Luo, Shuang; Yang, Zhihui; Spinney, Richard

    2015-11-17

    The sulfate radical anion (SO4•–) based oxidation of trace organic contaminants (TrOCs) has recently received great attention due to its high reactivity and low selectivity. In this study, a meta-analysis was conducted to better understand the role of functional groups on the reactivity between SO4•– and TrOCs. The results indicate that compounds in which electron transfer and addition channels dominate tend to exhibit a faster second-order rate constants (kSO4•–) than that of H–atom abstraction, corroborating the SO4•– reactivity and mechanisms observed in the individual studies. Then, a quantitative structure activity relationship (QSAR) model was developed using a sequential approach with constitutional, geometrical, electrostatic, and quantum chemical descriptors. Two descriptors, ELUMO and EHOMO energy gap (ELUMO–EHOMO) and the ratio of oxygen atoms to carbon atoms (#O:C), were found to mechanistically and statistically affect kSO4•– to a great extent with the standardized QSAR model: ln kSO4•– = 26.8–3.97 × #O:C – 0.746 × (ELUMO–EHOMO). In addition, the correlation analysis indicates that there is no dominant reaction channel for SO4•– reactions with various structurally diverse compounds. Our QSAR model provides a robust predictive tool for estimating emerging micropollutants removal using SO4•– during wastewater treatment processes.

  8. Quantitative structure-activity relationship correlation between molecular structure and the Rayleigh enantiomeric enrichment factor.

    PubMed

    Jammer, S; Rizkov, D; Gelman, F; Lev, O

    2015-08-01

    It was recently demonstrated that under environmentally relevant conditions the Rayleigh equation is valid to describe the enantiomeric enrichment - conversion relationship, yielding a proportional constant called the enantiomeric enrichment factor, εER. In the present study we demonstrate a quantitative structure-activity relationship model (QSAR) that describes well the dependence of εER on molecular structure. The enantiomeric enrichment factor can be predicted by the linear Hansch model, which correlates biological activity with physicochemical properties. Enantioselective hydrolysis of sixteen derivatives of 2-(phenoxy)propionate (PPMs) have been analyzed during enzymatic degradation by lipases from Pseudomonas fluorescens (PFL), Pseudomonas cepacia (PCL), and Candida rugosa (CRL). In all cases the QSAR relationships were significant with R(2) values of 0.90-0.93, and showed high predictive abilities with internal and external validations providing QLOO(2) values of 0.85-0.87 and QExt(2) values of 0.8-0.91. Moreover, it is demonstrated that this model enables differentiation between enzymes with different binding site shapes. The enantioselectivity of PFL and PCL was dictated by electronic properties, whereas the enantioselectivity of CRL was determined by lipophilicity and steric factors. The predictive ability of the QSAR model demonstrated in the present study may serve as a helpful tool in environmental studies, assisting in source tracking of unstudied chiral compounds belonging to a well-studied homologous series.

  9. Quantitative structure-activity relationships for weak acid respiratory uncouplers to Vibrio fisheri

    SciTech Connect

    Schultz, T.W.; Cronin, M.T.D.

    1997-02-01

    Acute toxicity values of 16 organic compounds thought to elicit their response via the weak acid respiratory uncoupling mechanism of toxic action were secured from the literature. Regression analysis of toxicities revealed that a measured 5-min V. fisheri potency value can be used as a surrogate for the 30-min value. Regression analysis of toxicity versus hydrophobicity, measured as the 1-octanol/water partition coefficient (log K{sub ow}), was used to formulate a quantitative structure-activity relationship (QSAR). The equation log pT{sub 30}{sup {minus}1} = 0.489(log K{sub ow}) + 0.126 was found to be a highly predictive model. This V. fisheri QSAR is statistically similar to QSARs generated from weak acid uncoupler potency data for Pimephales promelas survivability and Tetrahymena pyriformis population growth impairment. This work, therefore, suggests that the weak acid respiratory uncoupling mechanism of toxic action is present in V. fisheri, and as such is not restricted to mitochondria-containing organisms.

  10. Some methods of obtaining quantitative structure-activity relationships for quantities of environmental interest

    SciTech Connect

    Charton, M.

    1985-09-01

    Methods are described for obtaining quantitative structure-activity relationships (QSAR) for the estimation of quantities of environmental interest. Toxicities of alkylamines and of alkyl alkanoates are well correlated by the alkyl bioactivity branching equation (ABB). Narcotic activities of 1,1-disubstituted ethylenes are correlated by the intermolecular forces bioactivity (IMF) equation. When the data set has a limited number of substituents in equivalent positions the group number (GN) equation, derivable from the IMF equation, can be used for correlation. It has been successfully applied to aqueous solubilities, 1-octanol-water partition coefficients, and bioaccumulation factors and ecological magnifications for organochlorine compounds. A combination of the omega method for combining data sets for different organisms with the GN equation has been used to correlate toxicities of organochlorine insecticides in two species of fish. Toxicities of carbamates have been correlated by a combination of the zeta method and the IMFB equation. The ABB and the GN equations are particularly useful in that they generally do not require parameter tables, and that the parameters they use are error-free. The methods presented here, as shown by the examples given, should make it possible to establish a collection of QSAR for toxicities, bioaccumulation factors, aqueous solubilities, partition coefficients, and other properties of sets of compounds of environmental interest. 29 references.

  11. Interpretable, probability-based confidence metric for continuous quantitative structure-activity relationship models.

    PubMed

    Keefer, Christopher E; Kauffman, Gregory W; Gupta, Rishi Raj

    2013-02-25

    A great deal of research has gone into the development of robust confidence in prediction and applicability domain (AD) measures for quantitative structure-activity relationship (QSAR) models in recent years. Much of the attention has historically focused on structural similarity, which can be defined in many forms and flavors. A concept that is frequently overlooked in the realm of the QSAR applicability domain is how the local activity landscape plays a role in how accurate a prediction is or is not. In this work, we describe an approach that pairs information about both the chemical similarity and activity landscape of a test compound's neighborhood into a single calculated confidence value. We also present an approach for converting this value into an interpretable confidence metric that has a simple and informative meaning across data sets. The approach will be introduced to the reader in the context of models built upon four diverse literature data sets. The steps we will outline include the definition of similarity used to determine nearest neighbors (NN), how we incorporate the NN activity landscape with a similarity-weighted root-mean-square distance (wRMSD) value, and how that value is then calibrated to generate an intuitive confidence metric for prospective application. Finally, we will illustrate the prospective performance of the approach on five proprietary models whose predictions and confidence metrics have been tracked for more than a year.

  12. Utilization of quantitative structure-activity relationships (QSARs) in risk assessment: Alkylphenols

    SciTech Connect

    Beck, B.D.; Toole, A.P.; Callahan, B.G.; Siddhanti, S.K. )

    1991-12-01

    Alkylphenols are a class of environmentally pervasive compounds, found both in natural (e.g., crude oils) and in anthropogenic (e.g., wood tar, coal gasification waste) materials. Despite the frequent environmental occurrence of these chemicals, there is a limited toxicity database on alkylphenols. The authors have therefore developed a 'toxicity equivalence approach' for alkylphenols which is based on their ability to inhibit, in a specific manner, the enzyme cyclooxygenase. Enzyme-inhibiting ability for individual alkylphenols can be estimated based on the quantitative structure-activity relationship developed by Dewhirst (1980) and is a function of the free hydroxyl group, electron-donating ring substituents, and hydrophobic aromatic ring substituents. The authors evaluated the toxicological significance of cyclooxygenase inhibition by comparison of the inhibitory capacity of alkylphenols with the inhibitory capacity of acetylsalicylic acid, or aspirin, a compound whose low-level effects are due to cyclooxygenase inhibition. Since nearly complete absorption for alkylphenols and aspirin is predicted, based on estimates of hydrophobicity and fraction of charged molecules at gastrointestinal pHs, risks from alkylphenols can be expressed directly in terms of 'milligram aspirin equivalence,' without correction for absorption differences. They recommend this method for assessing risks of mixtures of alkylphenols, especially for those compounds with no chronic toxicity data.38 references.

  13. Quantitative Structure Activity Relationship for Inhibition of Human Organic Cation/Carnitine Transporter (OCTN2)

    PubMed Central

    Diao, Lei; Ekins, Sean; Polli, James E.

    2010-01-01

    Organic cation/carnitine transporter (OCTN2; SLC22A5) is an important transporter for L-carnitine homeostasis, but can be inhibited by drugs, which may cause L-carnitine deficiency and possibly other OCTN2-mediated drug-drug interactions. One objective was to develop a quantitative structure–activity relationship (QSAR) of OCTN2 inhibitors, in order to predict and identify other potential OCTN2 inhibitors and infer potential clinical interactions. A second objective was to assess two high renal clearance drugs that interact with OCTN2 in vitro (cetirizine and cephaloridine) for possible OCTN2-mediated drug-drug interactions. Using previously generated in vitro data of 22 drugs, a 3D quantitative pharmacophore model and a Bayesian machine learning model were developed. The four pharmacophore features include two hydrophobic groups, one hydrogen-bond acceptor, and one positive ionizable center. The Bayesian machine learning model was developed using simple interpretable descriptors and function class fingerprints of maximum diameter 6 (FCFP_6). An external test set of 27 molecules, including 15 newly identified OCTN2 inhibitors, and a literature test set of 22 molecules were used to validate both models. The computational models afforded good capability to identify structurally diverse OCTN2 inhibitors, providing a valuable tool to predict new inhibitors efficiently. Inhibition results confirmed our previously observed association between rhabdomyolysis and Cmax/Ki ratio. The two high renal clearance drugs cetirizine and cephaloridine were found not to be OCTN2 substrates and their diminished elimination by other drugs is concluded not to be mediated by OCTN2. PMID:20831193

  14. Quantitative wake analysis of a freely swimming fish using 3D synthetic aperture PIV

    NASA Astrophysics Data System (ADS)

    Mendelson, Leah; Techet, Alexandra H.

    2015-07-01

    Synthetic aperture PIV (SAPIV) is used to quantitatively analyze the wake behind a giant danio ( Danio aequipinnatus) swimming freely in a seeded quiescent tank. The experiment is designed with minimal constraints on animal behavior to ensure that natural swimming occurs. The fish exhibits forward swimming and turning behaviors at speeds between 0.9 and 1.5 body lengths/second. Results show clearly isolated and linked vortex rings in the wake structure, as well as the thrust jet coming off of a visual hull reconstruction of the fish body. As a benchmark for quantitative analysis of volumetric PIV data, the vortex circulation and impulse are computed using methods consistent with those applied to planar PIV data. Volumetric momentum analysis frameworks are discussed for linked and asymmetric vortex structures, laying a foundation for further volumetric studies of swimming hydrodynamics with SAPIV. Additionally, a novel weighted refocusing method is presented as an improvement to SAPIV reconstruction.

  15. Static and dynamic crystalline lens accommodation evaluated using quantitative 3-D OCT

    PubMed Central

    Gambra, Enrique; Ortiz, Sergio; Perez-Merino, Pablo; Gora, Michalina; Wojtkowski, Maciej; Marcos, Susana

    2013-01-01

    Custom high-resolution high-speed anterior segment spectral domain Optical Coherence Tomography (OCT) provided with automatic quantification and distortion correction algorithms was used to characterize three-dimensionally (3-D) the human crystalline lens in vivo in four subjects, for accommodative demands between 0 to 6 D in 1 D steps. Anterior and posterior lens radii of curvature decreased with accommodative demand at rates of 0.73 and 0.20 mm/D, resulting in an increase of the estimated optical power of the eye of 0.62 D per diopter of accommodative demand. Dynamic fluctuations in crystalline lens radii of curvature, anterior chamber depth and lens thickness were also estimated from dynamic 2-D OCT images (14 Hz), acquired during 5-s of steady fixation, for different accommodative demands. Estimates of the eye power from dynamical geometrical measurements revealed an increase of the fluctuations of the accommodative response from 0.07 D to 0.47 D between 0 and 6 D (0.044 D per D of accommodative demand). A sensitivity analysis showed that the fluctuations of accommodation were driven by dynamic changes in the lens surfaces, particularly in the posterior lens surface. PMID:24049680

  16. Differential axial contrast of optical sections: laser microtomography and quantitative 3D reconstruction

    NASA Astrophysics Data System (ADS)

    Pogorelova, M. A.; Golichenkov, V. A.; Pogorelov, A. G.

    2014-03-01

    Specific features of the quantitative laser microtomography of biological samples are discussed. The method exhibits the main advantages of a confocal microscope (rapid measurement of a stack of parallel optical cross sections and accurate displacement of an object along the optical axis). A relatively high contrast is reached owing to the superposition of pairwise complementary images on neighboring cross sections. A simple and convenient algorithm for image processing does not require additional software and can be computerized using a conventional graphic editor. The applicability of the method is illustrated using volume measurements of a single cell of an early mouse embryo.

  17. Automated quantitative 3D analysis of aorta size, morphology, and mural calcification distributions

    PubMed Central

    Kurugol, Sila; Come, Carolyn E.; Diaz, Alejandro A.; Ross, James C.; Kinney, Greg L.; Black-Shinn, Jennifer L.; Hokanson, John E.; Budoff, Matthew J.; Washko, George R.; San Jose Estepar, Raul

    2015-01-01

    Purpose: The purpose of this work is to develop a fully automated pipeline to compute aorta morphology and calcification measures in large cohorts of CT scans that can be used to investigate the potential of these measures as imaging biomarkers of cardiovascular disease. Methods: The first step of the automated pipeline is aorta segmentation. The algorithm the authors propose first detects an initial aorta boundary by exploiting cross-sectional circularity of aorta in axial slices and aortic arch in reformatted oblique slices. This boundary is then refined by a 3D level-set segmentation that evolves the boundary to the location of nearby edges. The authors then detect the aortic calcifications with thresholding and filter out the false positive regions due to nearby high intensity structures based on their anatomical location. The authors extract the centerline and oblique cross sections of the segmented aortas and compute the aorta morphology and calcification measures of the first 2500 subjects from COPDGene study. These measures include volume and number of calcified plaques and measures of vessel morphology such as average cross-sectional area, tortuosity, and arch width. Results: The authors computed the agreement between the algorithm and expert segmentations on 45 CT scans and obtained a closest point mean error of 0.62 ± 0.09 mm and a Dice coefficient of 0.92 ± 0.01. The calcification detection algorithm resulted in an improved true positive detection rate of 0.96 compared to previous work. The measurements of aorta size agreed with the measurements reported in previous work. The initial results showed associations of aorta morphology with calcification and with aging. These results may indicate aorta stiffening and unwrapping with calcification and aging. Conclusions: The authors have developed an objective tool to assess aorta morphology and aortic calcium plaques on CT scans that may be used to provide information about the presence of cardiovascular

  18. Quantitative analysis of 3D stent reconstruction from a limited number of views in cardiac rotational angiography

    NASA Astrophysics Data System (ADS)

    Perrenot, Béatrice; Vaillant, Régis; Prost, Rémy; Finet, Gérard; Douek, Philippe; Peyrin, Françoise

    2007-03-01

    Percutaneous coronary angioplasty consists in conducting a guidewire carrying a balloon and a stent through the lesion and deploying the stent by balloon inflation. A stent is a small 3D complex mesh hardly visible in X-ray images : the control of stent deployment is difficult although it is important to avoid post intervention complications. In a previous work, we proposed a method to reconstruct 3D stent images from a set of 2D cone-beam projections acquired in rotational acquisition mode. The process involves a motion compensation procedure based on the position of two markers located on the guidewire in the 2D radiographic sequence. Under the hypothesis that the stent and markers motions are identical, the method was shown to generate a negligible error. If this hypothesis is not fulfilled, a solution could be to use only the images where motion is weakest, at the detriment of having a limiter number of views. In this paper, we propose a simulation based study of the impact of a limited number of views in our context. The chain image involved in the acquisition of X-ray sequences is first modeled to simulate realistic noisy projections of stent animated by a motion close to cardiac motion. Then, the 3D stent images are reconstructed using the proposed motion compensation method from gated projections. Two gating strategies are examined to select projection in the sequences. A quantitative analysis is carried out to assess reconstruction quality as a function of noise and acquisition strategy.

  19. Assessment of diffuse coronary artery disease by quantitative analysis of coronary morphology based upon 3-D reconstruction from biplane angiograms.

    PubMed

    Wahle, A; Wellnhofer, E; Mugaragu, I; Saner, H U; Oswald, H; Fleck, E

    1995-01-01

    Quantitative evaluations on coronary vessel systems are of increasing importance in cardiovascular diagnosis, therapy planning, and surgical verification. Whereas local evaluations, such as stenosis analysis, are already available with sufficient accuracy, global evaluations of vessel segments or vessel subsystems are not yet common. Especially for the diagnosis of diffuse coronary artery diseases, the authors combined a 3D reconstruction system operating on biplane angiograms with a length/volume calculation. The 3D reconstruction results in a 3D model of the coronary vessel system, consisting of the vessel skeleton and a discrete number of contours. To obtain an utmost accurate model, the authors focussed on exact geometry determination. Several algorithms for calculating missing geometric parameters and correcting remaining geometry errors were implemented and verified. The length/volume evaluation can be performed either on single vessel segments, on a set of segments, or on subtrees. A volume model based on generalized elliptical conic sections is created for the selected segments. Volumes and lengths (measured along the vessel course) of those elements are summed up. In this way, the morphological parameters of a vessel subsystem can be set in relation to the parameters of the proximal segment supplying it. These relations allow objective assessments of diffuse coronary artery diseases.

  20. Lossless 3-D reconstruction and registration of semi-quantitative gene expression data in the mouse brain

    PubMed Central

    Enlow, Matthew A.; Ju, Tao; Kakadiaris, Ioannis A.; Carson, James P.

    2012-01-01

    As imaging, computing, and data storage technologies improve, there is an increasing opportunity for multiscale analysis of three-dimensional datasets (3-D). Such analysis enables, for example, microscale elements of multiple macroscale specimens to be compared throughout the entire macroscale specimen. Spatial comparisons require bringing datasets into co-alignment. One approach for co-alignment involves elastic deformations of data in addition to rigid alignments. The elastic deformations distort space, and if not accounted for, can distort the information at the microscale. The algorithms developed in this work address this issue by allowing multiple data points to be encoded into a single image pixel, appropriately tracking each data point to ensure lossless data mapping during elastic spatial deformation. This approach was developed and implemented for both 2-D and 3-D registration of images. Lossless reconstruction and registration was applied to semi-quantitative cellular gene expression data in the mouse brain, enabling comparison of multiple spatially registered 3-D datasets without any augmentation of the cellular data. Standard reconstruction and registration without the lossless approach resulted in errors in cellular quantities of ~ 8%. PMID:22256218

  1. Lossless 3-D reconstruction and registration of semi-quantitative gene expression data in the mouse brain.

    PubMed

    Enlow, Matthew A; Ju, Tao; Kakadiaris, Ioannis A; Carson, James P

    2011-01-01

    As imaging, computing, and data storage technologies improve, there is an increasing opportunity for multiscale analysis of three-dimensional datasets (3-D). Such analysis enables, for example, microscale elements of multiple macroscale specimens to be compared throughout the entire macroscale specimen. Spatial comparisons require bringing datasets into co-alignment. One approach for co-alignment involves elastic deformations of data in addition to rigid alignments. The elastic deformations distort space, and if not accounted for, can distort the information at the microscale. The algorithms developed in this work address this issue by allowing multiple data points to be encoded into a single image pixel, appropriately tracking each data point to ensure lossless data mapping during elastic spatial deformation. This approach was developed and implemented for both 2-D and 3D registration of images. Lossless reconstruction and registration was applied to semi-quantitative cellular gene expression data in the mouse brain, enabling comparison of multiple spatially registered 3-D datasets without any augmentation of the cellular data. Standard reconstruction and registration without the lossless approach resulted in errors in cellular quantities of ∼ 8%.

  2. Segmentation and quantitative evaluation of brain MRI data with a multiphase 3D implicit deformable model

    NASA Astrophysics Data System (ADS)

    Angelini, Elsa D.; Song, Ting; Mensh, Brett D.; Laine, Andrew

    2004-05-01

    Segmentation of three-dimensional anatomical brain images into tissue classes has applications in both clinical and research settings. This paper presents the implementation and quantitative evaluation of a four-phase three-dimensional active contour implemented with a level set framework for automated segmentation of brain MRIs. The segmentation algorithm performs an optimal partitioning of three-dimensional data based on homogeneity measures that naturally evolves to the extraction of different tissue types in the brain. Random seed initialization was used to speed up numerical computation and avoid the need for a priori information. This random initialization ensures robustness of the method to variation of user expertise, biased a priori information and errors in input information that could be influenced by variations in image quality. Experimentation on three MRI brain data sets showed that an optimal partitioning successfully labeled regions that accurately identified white matter, gray matter and cerebrospinal fluid in the ventricles. Quantitative evaluation of the segmentation was performed with comparison to manually labeled data and computed false positive and false negative assignments of voxels for the three organs. We report high accuracy for the two comparison cases. These results demonstrate the efficiency and flexibility of this segmentation framework to perform the challenging task of automatically extracting brain tissue volume contours.

  3. Quantitative Structure Activity Relationship Models for the Antioxidant Activity of Polysaccharides

    PubMed Central

    Nie, Kaiying; Wang, Zhaojing

    2016-01-01

    In this study, quantitative structure activity relationship (QSAR) models for the antioxidant activity of polysaccharides were developed with 50% effective concentration (EC50) as the dependent variable. To establish optimum QSAR models, multiple linear regressions (MLR), support vector machines (SVM) and artificial neural networks (ANN) were used, and 11 molecular descriptors were selected. The optimum QSAR model for predicting EC50 of DPPH-scavenging activity consisted of four major descriptors. MLR model gave EC50 = 0.033Ara-0.041GalA-0.03GlcA-0.025PC+0.484, and MLR fitted the training set with R = 0.807. ANN model gave the improvement of training set (R = 0.96, RMSE = 0.018) and test set (R = 0.933, RMSE = 0.055) which indicated that it was more accurately than SVM and MLR models for predicting the DPPH-scavenging activity of polysaccharides. 67 compounds were used for predicting EC50 of the hydroxyl radicals scavenging activity of polysaccharides. MLR model gave EC50 = 0.12PC+0.083Fuc+0.013Rha-0.02UA+0.372. A comparison of results from models indicated that ANN model (R = 0.944, RMSE = 0.119) was also the best one for predicting the hydroxyl radicals scavenging activity of polysaccharides. MLR and ANN models showed that Ara and GalA appeared critical in determining EC50 of DPPH-scavenging activity, and Fuc, Rha, uronic acid and protein content had a great effect on the hydroxyl radicals scavenging activity of polysaccharides. The antioxidant activity of polysaccharide usually was high in MW range of 4000–100000, and the antioxidant activity could be affected simultaneously by other polysaccharide properties, such as uronic acid and Ara. PMID:27685320

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

    PubMed

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

    2016-11-01

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

  5. Quantitative structure-activity relationships for organophosphates binding to trypsin and chymotrypsin.

    PubMed

    Ruark, Christopher D; Hack, C Eric; Robinson, Peter J; Gearhart, Jeffery M

    2011-01-01

    Organophosphate (OP) nerve agents such as sarin, soman, tabun, and O-ethyl S-[2-(diisopropylamino) ethyl] methylphosphonothioate (VX) do not react solely with acetylcholinesterase (AChE). Evidence suggests that cholinergic-independent pathways over a wide range are also targeted, including serine proteases. These proteases comprise nearly one-third of all known proteases and play major roles in synaptic plasticity, learning, memory, neuroprotection, wound healing, cell signaling, inflammation, blood coagulation, and protein processing. Inhibition of these proteases by OP was found to exert a wide range of noncholinergic effects depending on the type of OP, the dose, and the duration of exposure. Consequently, in order to understand these differences, in silico biologically based dose-response and quantitative structure-activity relationship (QSAR) methodologies need to be integrated. Here, QSAR were used to predict OP bimolecular rate constants for trypsin and α-chymotrypsin. A heuristic regression of over 500 topological/constitutional, geometric, thermodynamic, electrostatic, and quantum mechanical descriptors, using the software Ampac 8.0 and Codessa 2.51 (SemiChem, Inc., Shawnee, KS), was developed to obtain statistically verified equations for the models. General models, using all data subsets, resulted in R(2) values of .94 and .92 and leave-one-out Q(2) values of 0.9 and 0.87 for trypsin and α-chymotrypsin. To validate the general model, training sets were split into independent subsets for test set evaluation. A y-randomization procedure, used to estimate chance correlation, was performed 10,000 times, resulting in mean R(2) values of .24 and .3 for trypsin and α-chymotrypsin. The results show that these models are highly predictive and capable of delineating the complex mechanism of action between OP and serine proteases, and ultimately, by applying this approach to other OP enzyme reactions such as AChE, facilitate the development of biologically based

  6. Polychlorinated biphenyls: correlation between in vivo and in vitro quantitative structure-activity relationships (QSARs)

    SciTech Connect

    Leece, B.; Denomme, M.A.; Towner, R.; Li, S.M.A.; Safe, S.

    1985-01-01

    The in vivo quantitative structure-activity relationships (QSARs) for several polychlorinated biphenyls (PCBs) were determined in the immature male Wistar rat. The ED25 and ED50 values for hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) induction as well as for body weight loss and for thymic atrophy were determined for nine PCB congeners and 4'-bromo-2,3,4,5-tetrachlorobiphenyl. The most active compounds were the coplanar PCB congeners, 3,3',4,4',5-penta- and 3,3',4,4',5,5'-hexachlorobiphenyl; for example, their ED50 values for body weight loss were 3.25 and 15.1 ..mu..mol/kg, respectively. The in vivo toxicity of the coplanar PCB, 3,3',4,4'-tetrachlorobiphenyl, was significantly lower (ED50 for body weight loss = 730 ..mu..mol/kg) than the values observed for the more highly chlorinated homologs, and this was consistent with the more rapid metabolism of the lower chlorinated congener. The dose-response biologic and toxic effects of several mono-ortho-chloro-substituted analogs of the coplanar PCBs, including 2,3,4,4',5-, 2,3,3',4,4'-, 2',3,4,4',5- and 2,3',4,4',5-penta-, 2,3,3',4,4',5- and 2,3,3',4,4',5-hexachlorobiphenyl were also determined, and members of this group of compounds were all less toxic than 3,3',4,4',5-penta and 3,3',4,4',5,5'-hexachlorobiphenyl. There was a good rank order correlation between the in vivo QSAR data and the in vitro QSAR data and the in vitro QSARs for PCBs that were developed from their relative receptor binding affinities and potencies as inducers of AHH and EROD in rat hepatoma H-4-II E cells in culture.

  7. Design and prediction of new acetylcholinesterase inhibitor via quantitative structure activity relationship of huprines derivatives.

    PubMed

    Zhang, Shuqun; Hou, Bo; Yang, Huaiyu; Zuo, Zhili

    2016-05-01

    Acetylcholinesterase (AChE) is an important enzyme in the pathogenesis of Alzheimer's disease (AD). Comparative quantitative structure-activity relationship (QSAR) analyses on some huprines inhibitors against AChE were carried out using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and hologram QSAR (HQSAR) methods. Three highly predictive QSAR models were constructed successfully based on the training set. The CoMFA, CoMSIA, and HQSAR models have values of r (2) = 0.988, q (2) = 0.757, ONC = 6; r (2) = 0.966, q (2) = 0.645, ONC = 5; and r (2) = 0.957, q (2) = 0.736, ONC = 6. The predictabilities were validated using an external test sets, and the predictive r (2) values obtained by the three models were 0.984, 0.973, and 0.783, respectively. The analysis was performed by combining the CoMFA and CoMSIA field distributions with the active sites of the AChE to further understand the vital interactions between huprines and the protease. On the basis of the QSAR study, 14 new potent molecules have been designed and six of them are predicted to be more active than the best active compound 24 described in the literature. The final QSAR models could be helpful in design and development of novel active AChE inhibitors.

  8. Quantitative structure-activity relationships (QSARs) for the transformation of organic micropollutants during oxidative water treatment.

    PubMed

    Lee, Yunho; von Gunten, Urs

    2012-12-01

    Various oxidants such as chlorine, chlorine dioxide, ferrate(VI), ozone, and hydroxyl radicals can be applied for eliminating organic micropollutant by oxidative transformation during water treatment in systems such as drinking water, wastewater, and water reuse. Over the last decades, many second-order rate constants (k) have been determined for the reaction of these oxidants with model compounds and micropollutants. Good correlations (quantitative structure-activity relationships or QSARs) are often found between the k-values for an oxidation reaction of closely related compounds (i.e. having a common organic functional group) and substituent descriptor variables such as Hammett or Taft sigma constants. In this study, we developed QSARs for the oxidation of organic and some inorganic compounds and organic micropollutants transformation during oxidative water treatment. A number of 18 QSARs were developed based on overall 412 k-values for the reaction of chlorine, chlorine dioxide, ferrate, and ozone with organic compounds containing electron-rich moieties such as phenols, anilines, olefins, and amines. On average, 303 out of 412 (74%) k-values were predicted by these QSARs within a factor of 1/3-3 compared to the measured values. For HO(·) reactions, some principles and estimation methods of k-values (e.g. the Group Contribution Method) are discussed. The developed QSARs and the Group Contribution Method could be used to predict the k-values for various emerging organic micropollutants. As a demonstration, 39 out of 45 (87%) predicted k-values were found within a factor 1/3-3 compared to the measured values for the selected emerging micropollutants. Finally, it is discussed how the uncertainty in the predicted k-values using the QSARs affects the accuracy of prediction for micropollutant elimination during oxidative water treatment. PMID:22939392

  9. Quantitative Structure--Activity Relationship (QSAR) for the Oxidation of Trace Organic Contaminants by Sulfate Radical.

    PubMed

    Xiao, Ruiyang; Ye, Tiantian; Wei, Zongsu; Luo, Shuang; Yang, Zhihui; Spinney, Richard

    2015-11-17

    The sulfate radical anion (SO4•–) based oxidation of trace organic contaminants (TrOCs) has recently received great attention due to its high reactivity and low selectivity. In this study, a meta-analysis was conducted to better understand the role of functional groups on the reactivity between SO4•– and TrOCs. The results indicate that compounds in which electron transfer and addition channels dominate tend to exhibit a faster second-order rate constants (kSO4•–) than that of H–atom abstraction, corroborating the SO4•– reactivity and mechanisms observed in the individual studies. Then, a quantitative structure activity relationship (QSAR) model was developed using a sequential approach with constitutional, geometrical, electrostatic, and quantum chemical descriptors. Two descriptors, ELUMO and EHOMO energy gap (ELUMO–EHOMO) and the ratio of oxygen atoms to carbon atoms (#O:C), were found to mechanistically and statistically affect kSO4•– to a great extent with the standardized QSAR model: ln kSO4•– = 26.8–3.97 × #O:C – 0.746 × (ELUMO–EHOMO). In addition, the correlation analysis indicates that there is no dominant reaction channel for SO4•– reactions with various structurally diverse compounds. Our QSAR model provides a robust predictive tool for estimating emerging micropollutants removal using SO4•– during wastewater treatment processes. PMID:26451961

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

    PubMed Central

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

    2011-01-01

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

  11. Quantitative characterization of 3D deformations of cell interactions with soft biomaterials

    NASA Astrophysics Data System (ADS)

    Franck, Christian

    In recent years, the importance of mechanical forces in directing cellular function has been recognized as a significant factor in biological and physiological processes. In fact, these physical forces are now viewed equally as important as biochemical stimuli in controlling cellular response. Not only do these cellular forces, or cell tractions, play an important role in cell migration, they are also significant to many other physiological and pathological processes, both at the tissue and organ level, including wound healing, inflammation, angiogenesis, and embryogenesis. A complete quantification of cell tractions during cell-material interactions can lead to a deeper understanding of the fundamental role these forces play in cell biology. Thus, understanding the function and role of a cell from a mechanical framework can have important implications towards the development of new implant materials and drug treatments. Previous research has contributed significant descriptions of cell-tissue interactions by quantifying cell tractions in two-dimensional environments; however, most physiological processes are three-dimensional in nature. Recent studies have shown morphological differences in cells cultured on two-dimensional substrates versus three-dimensional matrices, and that the intrinsic extracellular matrix interactions and migration behavior are different in three dimensions versus two dimensions. Hence, measurement techniques are needed to investigate cellular behavior in all three dimensions. This thesis presents a full-field imaging technique capable of quantitatively measuring cell traction forces in all three spatial dimensions, and hence addresses the need of a three-dimensional quantitative imaging technique to gain insight into the fundamental role of physical forces in biological processes. The technique combines laser scanning confocal microscopy (LSCM) with digital volume correlation (DVC) to track the motion of fluorescent particles during cell

  12. Quantitative 3D Analysis of Plant Roots Growing in Soil Using Magnetic Resonance Imaging.

    PubMed

    van Dusschoten, Dagmar; Metzner, Ralf; Kochs, Johannes; Postma, Johannes A; Pflugfelder, Daniel; Bühler, Jonas; Schurr, Ulrich; Jahnke, Siegfried

    2016-03-01

    Precise measurements of root system architecture traits are an important requirement for plant phenotyping. Most of the current methods for analyzing root growth require either artificial growing conditions (e.g. hydroponics), are severely restricted in the fraction of roots detectable (e.g. rhizotrons), or are destructive (e.g. soil coring). On the other hand, modalities such as magnetic resonance imaging (MRI) are noninvasive and allow high-quality three-dimensional imaging of roots in soil. Here, we present a plant root imaging and analysis pipeline using MRI together with an advanced image visualization and analysis software toolbox named NMRooting. Pots up to 117 mm in diameter and 800 mm in height can be measured with the 4.7 T MRI instrument used here. For 1.5 l pots (81 mm diameter, 300 mm high), a fully automated system was developed enabling measurement of up to 18 pots per day. The most important root traits that can be nondestructively monitored over time are root mass, length, diameter, tip number, and growth angles (in two-dimensional polar coordinates) and spatial distribution. Various validation measurements for these traits were performed, showing that roots down to a diameter range between 200 μm and 300 μm can be quantitatively measured. Root fresh weight correlates linearly with root mass determined by MRI. We demonstrate the capabilities of MRI and the dedicated imaging pipeline in experimental series performed on soil-grown maize (Zea mays) and barley (Hordeum vulgare) plants.

  13. Quantitative 3D Analysis of Plant Roots Growing in Soil Using Magnetic Resonance Imaging.

    PubMed

    van Dusschoten, Dagmar; Metzner, Ralf; Kochs, Johannes; Postma, Johannes A; Pflugfelder, Daniel; Bühler, Jonas; Schurr, Ulrich; Jahnke, Siegfried

    2016-03-01

    Precise measurements of root system architecture traits are an important requirement for plant phenotyping. Most of the current methods for analyzing root growth require either artificial growing conditions (e.g. hydroponics), are severely restricted in the fraction of roots detectable (e.g. rhizotrons), or are destructive (e.g. soil coring). On the other hand, modalities such as magnetic resonance imaging (MRI) are noninvasive and allow high-quality three-dimensional imaging of roots in soil. Here, we present a plant root imaging and analysis pipeline using MRI together with an advanced image visualization and analysis software toolbox named NMRooting. Pots up to 117 mm in diameter and 800 mm in height can be measured with the 4.7 T MRI instrument used here. For 1.5 l pots (81 mm diameter, 300 mm high), a fully automated system was developed enabling measurement of up to 18 pots per day. The most important root traits that can be nondestructively monitored over time are root mass, length, diameter, tip number, and growth angles (in two-dimensional polar coordinates) and spatial distribution. Various validation measurements for these traits were performed, showing that roots down to a diameter range between 200 μm and 300 μm can be quantitatively measured. Root fresh weight correlates linearly with root mass determined by MRI. We demonstrate the capabilities of MRI and the dedicated imaging pipeline in experimental series performed on soil-grown maize (Zea mays) and barley (Hordeum vulgare) plants. PMID:26729797

  14. Quantitative 3D Analysis of Plant Roots Growing in Soil Using Magnetic Resonance Imaging1[OPEN

    PubMed Central

    Kochs, Johannes; Pflugfelder, Daniel

    2016-01-01

    Precise measurements of root system architecture traits are an important requirement for plant phenotyping. Most of the current methods for analyzing root growth require either artificial growing conditions (e.g. hydroponics), are severely restricted in the fraction of roots detectable (e.g. rhizotrons), or are destructive (e.g. soil coring). On the other hand, modalities such as magnetic resonance imaging (MRI) are noninvasive and allow high-quality three-dimensional imaging of roots in soil. Here, we present a plant root imaging and analysis pipeline using MRI together with an advanced image visualization and analysis software toolbox named NMRooting. Pots up to 117 mm in diameter and 800 mm in height can be measured with the 4.7 T MRI instrument used here. For 1.5 l pots (81 mm diameter, 300 mm high), a fully automated system was developed enabling measurement of up to 18 pots per day. The most important root traits that can be nondestructively monitored over time are root mass, length, diameter, tip number, and growth angles (in two-dimensional polar coordinates) and spatial distribution. Various validation measurements for these traits were performed, showing that roots down to a diameter range between 200 μm and 300 μm can be quantitatively measured. Root fresh weight correlates linearly with root mass determined by MRI. We demonstrate the capabilities of MRI and the dedicated imaging pipeline in experimental series performed on soil-grown maize (Zea mays) and barley (Hordeum vulgare) plants. PMID:26729797

  15. Three-dimensional quantitative structure-activity relationship study on anti-cancer activity of 3,4-dihydroquinazoline derivatives against human lung cancer A549 cells

    NASA Astrophysics Data System (ADS)

    Cho, Sehyeon; Choi, Min Ji; Kim, Minju; Lee, Sunhoe; Lee, Jinsung; Lee, Seok Joon; Cho, Haelim; Lee, Kyung-Tae; Lee, Jae Yeol

    2015-03-01

    A series of 3,4-dihydroquinazoline derivatives with anti-cancer activities against human lung cancer A549 cells were subjected to three-dimensional quantitative structure-activity relationship (3D-QSAR) studies using the comparative molecular similarity indices analysis (CoMSIA) approaches. The most potent compound, 1 was used to align the molecules. As a result, the best prediction was obtained with CoMSIA combined the steric, electrostatic, hydrophobic, hydrogen bond donor, and hydrogen bond acceptor fields (q2 = 0.720, r2 = 0.897). This model was validated by an external test set of 6 compounds giving satisfactory predictive r2 value of 0.923 as well as the scrambling stability test. This model would guide the design of potent 3,4-dihydroquinazoline derivatives as anti-cancer agent for the treatment of human lung cancer.

  16. Quantitative structure-activity relationship of the curcumin-related compounds using various regression methods

    NASA Astrophysics Data System (ADS)

    Khazaei, Ardeshir; Sarmasti, Negin; Seyf, Jaber Yousefi

    2016-03-01

    Quantitative structure activity relationship were used to study a series of curcumin-related compounds with inhibitory effect on prostate cancer PC-3 cells, pancreas cancer Panc-1 cells, and colon cancer HT-29 cells. Sphere exclusion method was used to split data set in two categories of train and test set. Multiple linear regression, principal component regression and partial least squares were used as the regression methods. In other hand, to investigate the effect of feature selection methods, stepwise, Genetic algorithm, and simulated annealing were used. In two cases (PC-3 cells and Panc-1 cells), the best models were generated by a combination of multiple linear regression and stepwise (PC-3 cells: r2 = 0.86, q2 = 0.82, pred_r2 = 0.93, and r2m (test) = 0.43, Panc-1 cells: r2 = 0.85, q2 = 0.80, pred_r2 = 0.71, and r2m (test) = 0.68). For the HT-29 cells, principal component regression with stepwise (r2 = 0.69, q2 = 0.62, pred_r2 = 0.54, and r2m (test) = 0.41) is the best method. The QSAR study reveals descriptors which have crucial role in the inhibitory property of curcumin-like compounds. 6ChainCount, T_C_C_1, and T_O_O_7 are the most important descriptors that have the greatest effect. With a specific end goal to design and optimization of novel efficient curcumin-related compounds it is useful to introduce heteroatoms such as nitrogen, oxygen, and sulfur atoms in the chemical structure (reduce the contribution of T_C_C_1 descriptor) and increase the contribution of 6ChainCount and T_O_O_7 descriptors. Models can be useful in the better design of some novel curcumin-related compounds that can be used in the treatment of prostate, pancreas, and colon cancers.

  17. Quantitative structure-activity relationship of the curcumin-related compounds using various regression methods

    NASA Astrophysics Data System (ADS)

    Khazaei, Ardeshir; Sarmasti, Negin; Seyf, Jaber Yousefi

    2016-03-01

    Quantitative structure activity relationship were used to study a series of curcumin-related compounds with inhibitory effect on prostate cancer PC-3 cells, pancreas cancer Panc-1 cells, and colon cancer HT-29 cells. Sphere exclusion method was used to split data set in two categories of train and test set. Multiple linear regression, principal component regression and partial least squares were used as the regression methods. In other hand, to investigate the effect of feature selection methods, stepwise, Genetic algorithm, and simulated annealing were used. In two cases (PC-3 cells and Panc-1 cells), the best models were generated by a combination of multiple linear regression and stepwise (PC-3 cells: r2 = 0.86, q2 = 0.82, pred_r2 = 0.93, and r2m (test) = 0.43, Panc-1 cells: r2 = 0.85, q2 = 0.80, pred_r2 = 0.71, and r2m (test) = 0.68). For the HT-29 cells, principal component regression with stepwise (r2 = 0.69, q2 = 0.62, pred_r2 = 0.54, and r2m (test) = 0.41) is the best method. The QSAR study reveals descriptors which have crucial role in the inhibitory property of curcumin-like compounds. 6ChainCount, T_C_C_1, and T_O_O_7 are the most important descriptors that have the greatest effect. With a specific end goal to design and optimization of novel efficient curcumin-related compounds it is useful to introduce heteroatoms such as nitrogen, oxygen, and sulfur atoms in the chemical structure (reduce the contribution of T_C_C_1 descriptor) and increase the contribution of 6ChainCount and T_O_O_7 descriptors. Models can be useful in the better design of some novel curcumin-related compounds that can be used in the treatment of prostate, pancreas, and colon cancers.

  18. Structure-based approach to pharmacophore identification, in silico screening, and three-dimensional quantitative structure-activity relationship studies for inhibitors of Trypanosoma cruzi dihydrofolate reductase function

    SciTech Connect

    Schormann, N.; Senkovich, O.; Walker, K.; Wright, D.L.; Anderson, A.C.; Rosowsky, A.; Ananthan, S.; Shinkre, B.; Velu, S.; Chattopadhyay, D.

    2009-07-10

    We have employed a structure-based three-dimensional quantitative structure-activity relationship (3D-QSAR) approach to predict the biochemical activity for inhibitors of T. cruzi dihydrofolate reductase-thymidylate synthase (DHFR-TS). Crystal structures of complexes of the enzyme with eight different inhibitors of the DHFR activity together with the structure in the substrate-free state (DHFR domain) were used to validate and refine docking poses of ligands that constitute likely active conformations. Structural information from these complexes formed the basis for the structure-based alignment used as input for the QSAR study. Contrary to indirect ligand-based approaches the strategy described here employs a direct receptor-based approach. The goal is to generate a library of selective lead inhibitors for further development as antiparasitic agents. 3D-QSAR models were obtained for T. cruzi DHFR-TS (30 inhibitors in learning set) and human DHFR (36 inhibitors in learning set) that show a very good agreement between experimental and predicted enzyme inhibition data. For crossvalidation of the QSAR model(s), we have used the 10% leave-one-out method. The derived 3D-QSAR models were tested against a few selected compounds (a small test set of six inhibitors for each enzyme) with known activity, which were not part of the learning set, and the quality of prediction of the initial 3D-QSAR models demonstrated that such studies are feasible. Further refinement of the models through integration of additional activity data and optimization of reliable docking poses is expected to lead to an improved predictive ability.

  19. Proton HR-MAS spectroscopy and quantitative pathologic analysis of MRI/3D-MRSI-targeted postsurgical prostate tissues.

    PubMed

    Swanson, Mark G; Vigneron, Daniel B; Tabatabai, Z Laura; Males, Ryan G; Schmitt, Lars; Carroll, Peter R; James, Joyce K; Hurd, Ralph E; Kurhanewicz, John

    2003-11-01

    Proton high-resolution magic angle spinning ((1)H HR-MAS) NMR spectroscopy and quantitative histopathology were performed on the same 54 MRI/3D-MRSI-targeted postsurgical prostate tissue samples. Presurgical MRI/3D-MRSI targeted healthy and malignant prostate tissues with an accuracy of 81%. Even in the presence of substantial tissue heterogeneity, distinct (1)H HR-MAS spectral patterns were observed for different benign tissue types and prostate cancer. Specifically, healthy glandular tissue was discriminated from prostate cancer based on significantly higher levels of citrate (P = 0.04) and polyamines (P = 0.01), and lower (P = 0.02) levels of the choline-containing compounds choline, phosphocholine (PC), and glycerophosphocholine (GPC). Predominantly stromal tissue lacked both citrate and polyamines, but demonstrated significantly (P = 0.01) lower levels of choline compounds than cancer. In addition, taurine, myo-inositol, and scyllo-inositol were all higher in prostate cancer vs. healthy glandular and stromal tissues. Among cancer samples, larger increases in choline, and decreases in citrate and polyamines (P = 0.05) were observed with more aggressive cancers, and a MIB-1 labeling index correlated (r = 0.62, P = 0.01) with elevated choline. The elucidation of spectral patterns associated with mixtures of different prostate tissue types and cancer grades, and the inclusion of new metabolic markers for prostate cancer may significantly improve the clinical interpretation of in vivo prostate MRSI data.

  20. Knowledge-based 3D segmentation of the brain in MR images for quantitative multiple sclerosis lesion tracking

    NASA Astrophysics Data System (ADS)

    Fisher, Elizabeth; Cothren, Robert M., Jr.; Tkach, Jean A.; Masaryk, Thomas J.; Cornhill, J. Fredrick

    1997-04-01

    Brain segmentation in magnetic resonance (MR) images is an important step in quantitative analysis applications, including the characterization of multiple sclerosis (MS) lesions over time. Our approach is based on a priori knowledge of the intensity and three-dimensional (3D) spatial relationships of structures in MR images of the head. Optimal thresholding and connected-components analysis are used to generate a starting point for segmentation. A 3D radial search is then performed to locate probable locations of the intra-cranial cavity (ICC). Missing portions of the ICC surface are interpolated in order to exclude connected structures. Partial volume effects and inter-slice intensity variations in the image are accounted for automatically. Several studies were conducted to validate the segmentation. Accuracy was tested by calculating the segmented volume and comparing to known volumes of a standard MR phantom. Reliability was tested by comparing calculated volumes of individual segmentation results from multiple images of the same subject. The segmentation results were also compared to manual tracings. The average error in volume measurements for the phantom was 1.5% and the average coefficient of variation of brain volume measurements of the same subject was 1.2%. Since the new algorithm requires minimal user interaction, variability introduced by manual tracing and interactive threshold or region selection was eliminated. Overall, the new algorithm was shown to produce a more accurate and reliable brain segmentation than existing manual and semi-automated techniques.

  1. Quantitative Evaluation of Tissue Surface Adaption of CAD-Designed and 3D Printed Wax Pattern of Maxillary Complete Denture

    PubMed Central

    Chen, Hu; Wang, Han; Lv, Peijun; Wang, Yong; Sun, Yuchun

    2015-01-01

    Objective. To quantitatively evaluate the tissue surface adaption of a maxillary complete denture wax pattern produced by CAD and 3DP. Methods. A standard edentulous maxilla plaster cast model was used, for which a wax pattern of complete denture was designed using CAD software developed in our previous study and printed using a 3D wax printer, while another wax pattern was manufactured by the traditional manual method. The cast model and the two wax patterns were scanned in the 3D scanner as “DataModel,” “DataWaxRP,” and “DataWaxManual.” After setting each wax pattern on the plaster cast, the whole model was scanned for registration. After registration, the deviations of tissue surface between “DataModel” and “DataWaxRP” and between “DataModel” and “DataWaxManual” were measured. The data was analyzed by paired t-test. Results. For both wax patterns produced by the CAD&RP method and the manual method, scanning data of tissue surface and cast surface showed a good fit in the majority. No statistically significant (P > 0.05) difference was observed between the CAD&RP method and the manual method. Conclusions. Wax pattern of maxillary complete denture produced by the CAD&3DP method is comparable with traditional manual method in the adaption to the edentulous cast model. PMID:26583108

  2. 3D Quantitative Assessment of Lesion Response to MR-guided High-Intensity Focused Ultrasound Treatment of Uterine Fibroids

    PubMed Central

    Savic, Lynn J.; Lin, MingDe; Duran, Rafael; Schernthaner, Rüdiger E.; Hamm, Bernd; Geschwind, Jean-François; Hong, Kelvin; Chapiro, Julius

    2015-01-01

    Rationale and Objectives To investigate the response after MR-guided high-intensity focused ultrasound (MRgHIFU) treatment of uterine fibroids (UF) using a 3D quantification of total and enhancing lesion volume (TLV, ELV) on contrast-enhanced MRI (ceMRI) scans. Methods and Materials In a total of 24 patients, ceMRI scans were obtained at baseline and 24 hrs, 6, 12 and 24 months after MRgHIFU treatment. The dominant lesion was assessed using a semi-automatic quantitative 3D segmentation technique. Agreement between software-assisted and manual measurements was then analyzed using a linear regression model. Patients were classified as responders (R) or non-responders (NR) based on their symptom report after 6 months. Statistical analysis included the paired t-test and Mann-Whitney-test. Results Preprocedurally, the median TLV and ELV were 263.74cm3 (30.45–689.56cm3) and 210.13cm3 (14.43–689.53cm3), respectively. The 6-month follow-up demonstrated a reduction of TLV in 21 patients (87.5%) with a median TLV of 171.7cm3 (8.5–791.2cm3) (p<.0001). TLV remained stable with significant differences compared to baseline (p<.001 and p=.047 after 12 and 24 months). A reduction of ELV was apparent in 16 patients (66.6%) with a median ELV of 158.91cm3 (8.55–779.61cm3) after 6 months (p=.065). 3D quantification and manual measurements showed strong intermethod-agreement for fibroid volumes (R2=.889 and R2=.917) but greater discrepancy for enhancement calculations (R2=.659 and R2=.419) at baseline and 6 mo. No significant differences in TLV or ELV were observed between clinical R (n=15) and NR (n=3). Conclusion The 3D assessment has proven feasible and accurate in the quantification of fibroid response to MRgHIFU. Contrary to ELV, changes in TLV may be representative of the clinical outcome. PMID:26160057

  3. Polyphase basin evolution of the Vienna Basin inferred from 3D visualization of sedimentation setting and quantitative subsidence

    NASA Astrophysics Data System (ADS)

    Lee, Eun Young; Novotny, Johannes; Wagreich, Michael

    2016-04-01

    This study analyzed and visualized data from 210 wells using a MATLAB-based program (BasinVis 1.0) for 3D visualization of sediment distribution, thickness, and quantitative subsidence of the northern and central Vienna Basin. The sedimentation settings for selected horizons were visualized to 3D sediment distribution maps, isopach maps, and cross-sections. Subsidence of the study area resulted in 3D subsidence depth and rate maps of basement and tectonic subsidences. Due to the special position of the Vienna Basin, the basin evolution was influenced by the regional tectonics of surrounding units. The 2D/3D maps provided insights into the polyphase evolution of the Vienna Basin, which is closely related to changes in the changing regional stress field and the paleoenvironmental setting. In the Early Miocene, the sedimentation and subsidence were shallow and E-W/NE-SW trending, indicating the development of piggy-back basins. During the late Early Miocene, maps show wider sedimentation and abruptly increasing subsidence by sinistral strike-slip faults, which initiated the Vienna pull-apart basin system. The sediments of the Early Miocene were supplied through a small deltaic system entering from the south. After thin sedimentation and shallow subsidence of the early Middle Miocene, the development of the Vienna Basin was controlled and accelerated mainly by NE-SW trending synsedimentary normal faults, especially the Steinberg fault. From the Middle Miocene, the subsidence was decreasing overall, however the tectonic subsidence show regionally different patterns. This study suggests that a major tensional regime change, from transtension to E-W extension, caused laterally varying subsidence across the Vienna Basin. The Late Miocene was characterized by the slowing down of basement and tectonic subsidence. From the middle Middle to Late Miocene, enormous amount of sediments supplied by a broad paleo-Danube delta complex on the western flank of the basin. The latest

  4. Automated 3D quantitative assessment and measurement of alpha angles from the femoral head-neck junction using MR imaging

    NASA Astrophysics Data System (ADS)

    Xia, Ying; Fripp, Jurgen; Chandra, Shekhar S.; Walker, Duncan; Crozier, Stuart; Engstrom, Craig

    2015-10-01

    To develop an automated approach for 3D quantitative assessment and measurement of alpha angles from the femoral head-neck (FHN) junction using bone models derived from magnetic resonance (MR) images of the hip joint. Bilateral MR images of the hip joints were acquired from 30 male volunteers (healthy active individuals and high-performance athletes, aged 18-49 years) using a water-excited 3D dual echo steady state (DESS) sequence. In a subset of these subjects (18 water-polo players), additional True Fast Imaging with Steady-state Precession (TrueFISP) images were acquired from the right hip joint. For both MR image sets, an active shape model based algorithm was used to generate automated 3D bone reconstructions of the proximal femur. Subsequently, a local coordinate system of the femur was constructed to compute a 2D shape map to project femoral head sphericity for calculation of alpha angles around the FHN junction. To evaluate automated alpha angle measures, manual analyses were performed on anterosuperior and anterior radial MR slices from the FHN junction that were automatically reformatted using the constructed coordinate system. High intra- and inter-rater reliability (intra-class correlation coefficients  >  0.95) was found for manual alpha angle measurements from the auto-extracted anterosuperior and anterior radial slices. Strong correlations were observed between manual and automatic measures of alpha angles for anterosuperior (r  =  0.84) and anterior (r  =  0.92) FHN positions. For matched DESS and TrueFISP images, there were no significant differences between automated alpha angle measures obtained from the upper anterior quadrant of the FHN junction (two-way repeated measures ANOVA, F  <  0.01, p  =  0.98). Our automatic 3D method analysed MR images of the hip joints to generate alpha angle measures around the FHN junction circumference with very good reliability and reproducibility. This work has the

  5. Highly-accelerated quantitative 2D and 3D localized spectroscopy with linear algebraic modeling (SLAM) and sensitivity encoding

    PubMed Central

    Zhang, Yi; Gabr, Refaat E.; Zhou, Jinyuan; Weiss, Robert G.; Bottomley, Paul A.

    2013-01-01

    Noninvasive magnetic resonance spectroscopy (MRS) with chemical shift imaging (CSI) provides valuable metabolic information for research and clinical studies, but is often limited by long scan times. Recently, spectroscopy with linear algebraic modeling (SLAM) was shown to provide compartment-averaged spectra resolved in one spatial dimension with many-fold reductions in scan-time. This was achieved using a small subset of the CSI phase-encoding steps from central image k-space that maximized the signal-to-noise ratio. Here, SLAM is extended to two- and three-dimensions (2D, 3D). In addition, SLAM is combined with sensitivity-encoded (SENSE) parallel imaging techniques, enabling the replacement of even more CSI phase-encoding steps to further accelerate scan-speed. A modified SLAM reconstruction algorithm is introduced that significantly reduces the effects of signal nonuniformity within compartments. Finally, main-field inhomogeneity corrections are provided, analogous to CSI. These methods are all tested on brain proton MRS data from a total of 24 patients with brain tumors, and in a human cardiac phosphorus 3D SLAM study at 3T. Acceleration factors of up to 120-fold versus CSI are demonstrated, including speed-up factors of 5-fold relative to already-accelerated SENSE CSI. Brain metabolites are quantified in SLAM and SENSE SLAM spectra and found to be indistinguishable from CSI measures from the same compartments. The modified reconstruction algorithm demonstrated immunity to maladjusted segmentation and errors from signal heterogeneity in brain data. In conclusion, SLAM demonstrates the potential to supplant CSI in studies requiring compartment-average spectra or large volume coverage, by dramatically reducing scan-time while providing essentially the same quantitative results. PMID:24188921

  6. Highly-accelerated quantitative 2D and 3D localized spectroscopy with linear algebraic modeling (SLAM) and sensitivity encoding

    NASA Astrophysics Data System (ADS)

    Zhang, Yi; Gabr, Refaat E.; Zhou, Jinyuan; Weiss, Robert G.; Bottomley, Paul A.

    2013-12-01

    Noninvasive magnetic resonance spectroscopy (MRS) with chemical shift imaging (CSI) provides valuable metabolic information for research and clinical studies, but is often limited by long scan times. Recently, spectroscopy with linear algebraic modeling (SLAM) was shown to provide compartment-averaged spectra resolved in one spatial dimension with many-fold reductions in scan-time. This was achieved using a small subset of the CSI phase-encoding steps from central image k-space that maximized the signal-to-noise ratio. Here, SLAM is extended to two- and three-dimensions (2D, 3D). In addition, SLAM is combined with sensitivity-encoded (SENSE) parallel imaging techniques, enabling the replacement of even more CSI phase-encoding steps to further accelerate scan-speed. A modified SLAM reconstruction algorithm is introduced that significantly reduces the effects of signal nonuniformity within compartments. Finally, main-field inhomogeneity corrections are provided, analogous to CSI. These methods are all tested on brain proton MRS data from a total of 24 patients with brain tumors, and in a human cardiac phosphorus 3D SLAM study at 3T. Acceleration factors of up to 120-fold versus CSI are demonstrated, including speed-up factors of 5-fold relative to already-accelerated SENSE CSI. Brain metabolites are quantified in SLAM and SENSE SLAM spectra and found to be indistinguishable from CSI measures from the same compartments. The modified reconstruction algorithm demonstrated immunity to maladjusted segmentation and errors from signal heterogeneity in brain data. In conclusion, SLAM demonstrates the potential to supplant CSI in studies requiring compartment-average spectra or large volume coverage, by dramatically reducing scan-time while providing essentially the same quantitative results.

  7. SU-E-QI-17: Dependence of 3D/4D PET Quantitative Image Features On Noise

    SciTech Connect

    Oliver, J; Budzevich, M; Zhang, G; Latifi, K; Dilling, T; Balagurunathan, Y; Gu, Y; Grove, O; Feygelman, V; Gillies, R; Moros, E; Lee, H.

    2014-06-15

    Purpose: Quantitative imaging is a fast evolving discipline where a large number of features are extracted from images; i.e., radiomics. Some features have been shown to have diagnostic, prognostic and predictive value. However, they are sensitive to acquisition and processing factors; e.g., noise. In this study noise was added to positron emission tomography (PET) images to determine how features were affected by noise. Methods: Three levels of Gaussian noise were added to 8 lung cancer patients PET images acquired in 3D mode (static) and using respiratory tracking (4D); for the latter images from one of 10 phases were used. A total of 62 features: 14 shape, 19 intensity (1stO), 18 GLCM textures (2ndO; from grey level co-occurrence matrices) and 11 RLM textures (2ndO; from run-length matrices) features were extracted from segmented tumors. Dimensions of GLCM were 256×256, calculated using 3D images with a step size of 1 voxel in 13 directions. Grey levels were binned into 256 levels for RLM and features were calculated in all 13 directions. Results: Feature variation generally increased with noise. Shape features were the most stable while RLM were the most unstable. Intensity and GLCM features performed well; the latter being more robust. The most stable 1stO features were compactness, maximum and minimum length, standard deviation, root-mean-squared, I30, V10-V90, and entropy. The most stable 2ndO features were entropy, sum-average, sum-entropy, difference-average, difference-variance, difference-entropy, information-correlation-2, short-run-emphasis, long-run-emphasis, and run-percentage. In general, features computed from images from one of the phases of 4D scans were more stable than from 3D scans. Conclusion: This study shows the need to characterize image features carefully before they are used in research and medical applications. It also shows that the performance of features, and thereby feature selection, may be assessed in part by noise analysis.

  8. NEW 3D TECHNIQUES FOR RANKING AND PRIORITIZATION OF CHEMICAL INVENTORIES

    EPA Science Inventory

    New three-dimensional quantitative structure activity (3-D QSAR) techniques for prioritizing chemical inventories for endocrine activity will be presented. The Common Reactivity Pattern (COREPA) approach permits identification of common steric and/or electronic patterns associate...

  9. Benzimidazole-Based Quinazolines: In Vitro Evaluation, Quantitative Structure-Activity Relationship, and Molecular Modeling as Aurora Kinase Inhibitors.

    PubMed

    Sharma, Alka; Luxami, Vijay; Saxena, Sanjai; Paul, Kamaldeep

    2016-03-01

    A series of benzimidazole-based quinazoline derivatives with different substitutions of primary and secondary amines at the C2 position (1-12) were evaluated for their Aurora kinase inhibitory activities. All compounds except for 3 and 6 showed good activity against Aurora kinase inhibitors, with IC50 values in the range of 0.035-0.532 μM. The ligand efficiency (LE) of the compounds with Aurora A kinase was also determined. The structure-activity relationship and the quantitative structure-activity relationship revealed that the Aurora inhibitory activities of these derivatives primarily depend on the different substitutions of the amine present at the C2 position of the quinazoline core. Molecular docking studies in the active binding site also provided theoretical support for the experimental biological data acquired. The current study identifies a novel class of Aurora kinase inhibitors, which can further be used for the treatment of cancer.

  10. Aquatic toxicity of acrylates and methacrylates: quantitative structure-activity relationships based on Kow and LC50

    SciTech Connect

    Reinert, K.H.

    1987-12-01

    Recent EPA scrutiny of acrylate and methacrylate monomers has resulted in restrictive consent orders and Significant New Use Rules under the Toxic Substances Control Act, based on structure-activity relationships using mouse skin painting studies. The concern is centered on human health issues regarding worker and consumer exposure. Environmental issues, such as aquatic toxicity, are still of concern. Understanding the relationships and environmental risks to aquatic organisms may improve the understanding of the potential risks to human health. This study evaluates the quantitative structure-activity relationships from measured log Kow's and log LC50's for Pimephales promelas (fathead minnow) and Carassius auratus (goldfish). Scientific support of the current regulations is also addressed. Two monomer classes were designated: acrylates and methacrylates. Spearman rank correlation and linear regression were run. Based on this study, an ecotoxicological difference exists between acrylates and methacrylates. Regulatory activities and scientific study should reflect this difference.

  11. Structure-guided unravelling: Phenolic hydroxyls contribute to reduction of acrylamide using multiplex quantitative structure-activity relationship modelling.

    PubMed

    Zhang, Yu; Huang, Mengmeng; Wang, Qiao; Cheng, Jun

    2016-05-15

    We reported a structure-activity relationship study on unravelling phenolic hydroxyls instead of alcoholic hydroxyls contribute to the reduction of acrylamide formation by flavonoids. The dose-dependent study shows a close correlation between the number of phenolic hydroxyls of flavonoids and their reduction effects. In view of positions of hydroxyls, the 3',4'(ortho)-dihydroxyls in B cycle, 3-hydroxyl or hydroxyls of 3-gallate in C cycle, and 5,7(meta)-dihydroxyls in A cycle of flavonoid structures play an important role in the reduction of acrylamide. Flavone C-glycosides are more effective at reducing the formation of acrylamide than flavone O-glycosides when sharing the same aglycone. The current multiplex quantitative structure-activity relationship (QSAR) equations effectively predict the inhibitory rates of acrylamide using selected chemometric parameters (R(2): 0.835-0.938). This pioneer study opens a broad understanding on the chemoprevention of acrylamide contaminants on a structural basis.

  12. Hologram quantitative structure-activity relationship and comparative molecular field analysis studies within a series of tricyclic phthalimide HIV-1 integrase inhibitors.

    PubMed

    Magalhães, Uiaran de Oliveira; Souza, Alessandra Mendonça Teles de; Albuquerque, Magaly Girão; Brito, Monique Araújo de; Bello, Murilo Lamim; Cabral, Lucio Mendes; Rodrigues, Carlos Rangel

    2013-01-01

    Acquired immunodeficiency syndrome is a public health problem worldwide caused by the Human immunodeficiency virus (HIV). Treatment with antiretroviral drugs is the best option for viral suppression, reducing morbidity and mortality. However, viral resistance in HIV-1 therapy has been reported. HIV-1 integrase (IN) is an essential enzyme for effective viral replication and an attractive target for the development of new inhibitors. In the study reported here, two- and three-dimensional quantitative structure-activity relationship (2D/3D-QSAR) studies, applying hologram quantitative structure-activity relationship (HQSAR) and comparative molecular field analysis (CoMFA) methods, respectively, were performed on a series of tricyclic phthalimide HIV-1 IN inhibitors. The best HQSAR model (q (2) = 0.802, r (2) = 0.972) was obtained using atoms, bonds, and connectivity as the fragment distinction, a fragment size of 2-5 atoms, hologram length of 61 bins, and six components. The best CoMFA model (q (2) = 0.748, r (2) = 0.974) was obtained with alignment of all atoms of the tricyclic phthalimide moiety (alignment II). The HQSAR contribution map identified that the carbonyl-hydroxy-aromatic nitrogen motif made a positive contribution to the activity of the compounds. Furthermore, CoMFA contour maps suggested that bulky groups in meta and para positions in the phenyl ring would increase the biological activity of this class. The conclusions of this work may lead to a better understanding of HIV-1 IN inhibition and contribute to the design of new and more potent derivatives.

  13. A quantitative study of 3D-scanning frequency and Δd of tracking points on the tooth surface

    PubMed Central

    Li, Hong; Lyu, Peijun; Sun, Yuchun; Wang, Yong; Liang, Xiaoyue

    2015-01-01

    Micro-movement of human jaws in the resting state might influence the accuracy of direct three-dimensional (3D) measurement. Providing a reference for sampling frequency settings of intraoral scanning systems to overcome this influence is important. In this study, we measured micro-movement, or change in distance (∆d), as the change in position of a single tracking point from one sampling time point to another in five human subjects. ∆d of tracking points on incisors at 7 sampling frequencies was judged against the clinical accuracy requirement to select proper sampling frequency settings. The curve equation was then fit quantitatively between ∆d median and the sampling frequency to predict the trend of ∆d with increasing f. The difference of ∆d among the subjects and the difference between upper and lower incisor feature points of the same subject were analyzed by a non-parametric test (α = 0.05). Significant differences of incisor feature points were noted among different subjects and between upper and lower jaws of the same subject (P < 0.01). Overall, ∆d decreased with increasing frequency. When the frequency was 60 Hz, ∆d nearly reached the clinical accuracy requirement. Frequencies higher than 60 Hz did not significantly decrease Δd further. PMID:26400112

  14. Quantitative structure-activity relationship modeling on in vitro endocrine effects and metabolic stability involving 26 selected brominated flame retardants.

    PubMed

    Harju, Mikael; Hamers, Timo; Kamstra, Jorke H; Sonneveld, Edwin; Boon, Jan P; Tysklind, Mats; Andersson, Patrik L

    2007-04-01

    In this work, quantitative structure-activity relationships (QSARs) were developed to aid human and environmental risk assessment processes for brominated flame retardants (BFRs). Brominated flame retardants, such as the high-production-volume chemicals polybrominated diphenyl ethers (PBDEs), tetrabromobisphenol A, and hexabromocyclododecane, have been identified as potential endocrine disruptors. Quantitative structure-activity relationship models were built based on the in vitro potencies of 26 selected BFRs. The in vitro assays included interactions with, for example, androgen, progesterone, estrogen, and dioxin (aryl hydrocarbon) receptor, plus competition with thyroxine for its plasma carrier protein (transthyretin), inhibition of estradiol sulfation via sulfotransferase, and finally, rate of metabolization. The QSAR modeling, a number of physicochemical parameters were calculated describing the electronic, lipophilic, and structural characteristics of the molecules. These include frontier molecular orbitals, molecular charges, polarities, log octanol/water partitioning coefficient, and two- and three-dimensional molecularproperties. Experimental properties were included and measured for PBDEs, such as their individual ultraviolet spectra (200-320 nm) and retention times on three different high-performance liquid chromatography columns and one nonpolar gas chromatography column. Quantitative structure-activity relationship models based on androgen antagonism and metabolic degradation rates generally gave similar results, suggesting that lower-brominated PBDEs with bromine substitutions in ortho positions and bromine-free meta- and para positions had the highest potencies and metabolic degradation rates. Predictions made for the constituents of the technical flame retardant Bromkal 70-5DE found BDE 17 to be a potent androgen antagonist and BDE 66, which is a relevant PBDE in environmental samples, to be only a weak antagonist.

  15. Quantitative structure-activity relationship modeling of polycyclic aromatic hydrocarbon mutagenicity by classification methods based on holistic theoretical molecular descriptors.

    PubMed

    Gramatica, Paola; Papa, Ester; Marrocchi, Assunta; Minuti, Lucio; Taticchi, Aldo

    2007-03-01

    Various polycyclic aromatic hydrocarbons (PAHs), ubiquitous environmental pollutants, are recognized mutagens and carcinogens. A homogeneous set of mutagenicity data (TA98 and TA100,+S9) for 32 benzocyclopentaphenanthrenes/chrysenes was modeled by the quantitative structure-activity relationship classification methods k-nearest neighbor and classification and regression tree, using theoretical holistic molecular descriptors. Genetic algorithm provided the selection of the best subset of variables for modeling mutagenicity. The models were validated by leave-one-out and leave-50%-out approaches and have good performance, with sensitivity and specificity ranges of 90-100%. Mutagenicity assessment for these PAHs requires only a few theoretical descriptors of their molecular structure.

  16. Obscure phenomena in statistical analysis of quantitative structure-activity relationships. Part 1: Multicollinearity of physicochemical descriptors.

    PubMed

    Mager, P P; Rothe, H

    1990-10-01

    Multicollinearity of physicochemical descriptors leads to serious consequences in quantitative structure-activity relationship (QSAR) analysis, such as incorrect estimators and test statistics of regression coefficients of the ordinary least-squares (OLS) model applied usually to QSARs. Beside the diagnosis of the known simple collinearity, principal component regression analysis (PCRA) also allows the diagnosis of various types of multicollinearity. Only if the absolute values of PCRA estimators are order statistics that decrease monotonically, the effects of multicollinearity can be circumvented. Otherwise, obscure phenomena may be observed, such as good data recognition but low predictive model power of a QSAR model.

  17. Kinetics and quantitative structure-activity relationship study on the degradation reaction from perfluorooctanoic acid to trifluoroacetic acid.

    PubMed

    Gong, Chen; Sun, Xiaomin; Zhang, Chenxi; Zhang, Xue; Niu, Junfeng

    2014-08-14

    Investigation of the degradation kinetics of perfluorooctanoic acid (PFOA) has been carried out to calculate rate constants of the main elementary reactions using the multichannel Rice-Ramsperger-Kassel-Marcus theory and canonical variational transition state theory with small-curvature tunneling correction over a temperature range of 200~500 K. The Arrhenius equations of rate constants of elementary reactions are fitted. The decarboxylation is role step in the degradation mechanism of PFOA. For the perfluorinated carboxylic acids from perfluorooctanoic acid to trifluoroacetic acid, the quantitative structure-activity relationship of the decarboxylation was analyzed with the genetic function approximation method and the structure-activity model was constructed. The main parameters governing rate constants of the decarboxylation reaction from the eight-carbon chain to the two-carbon chain were obtained. As the structure-activity model shows, the bond length and energy of C1-C2 (RC1-C2 and EC1-C2) are positively correlated to rate constants, while the volume (V), the energy difference between EHOMO and ELUMO (ΔE), and the net atomic charges on atom C2 (QC2) are negatively correlated.

  18. Architectural analysis and chronology of an Alpine alluvial fan using 3D ground penetrating radar investigation and quantitative outcrop analysis

    NASA Astrophysics Data System (ADS)

    Franke, D.; Hornung, J.; Hinderer, M.

    2012-04-01

    Alluvial fans represent sediment sinks directly at the outlet of the source area in mountain landscapes. They contain multiple information on short-term as well as on long-term changes of sediment supply and of environmental parameters like climate and vegetation. However, most studies on alluvial fans are restricted to selective surface analysis and almost no studies exist which aim to clear the subsurface geometry of an alluvial fan in total. Our study is embedded in the SedyMONT research program within the TOPO-EUROPE framework and aims to clarify the subsurface structure of an alluvial fan by a time-controlled 3D architectural model. The Illgraben fan is located in the Central Alps of Switzerland within the Rhone valley and covers an area of about 6.5 km2. Currently construction works for a highway cuts through the fan exposing its deposits (mainly gravel and diamicton) up to 15 m depth and therefore offers the unique opportunity to link ground penetrating radar (GPR) investigations with quantitative outcrop analysis. GPR measurements on the Illgraben fan have been carried out at two different scales: (i) a fan-wide scale with about 80 km radar sections forming a half spiderweb pattern to identify the fundamental architecture of the fan (using 100 MHz and 40 MHz antenna), and (ii) four orthogonal grids of about 50 m x 100 m for detailed architectural analysis (using a 200 MHz antenna). Penetration depth was up to 15 m for high and low frequency antennas. The radargrams were processed, georeferenced and transferred into a 3D-modeling software (GOCAD®) to map radar facies units. By means of quantitative sedimentological analyses and precisely scaled photo panels we could translate radar facies pattern into sedimentary facies, and interpret reflectors and their properties in terms of sedimentary units. These geobodies can be characterized in terms of volume, shape, geometrical key parameters, their spatial distribution, as well as internal sedimentary structures

  19. Synthesis, biological activity, and quantitative structure-activity relationship study of azanaphthalimide and arylnaphthalimide derivatives.

    PubMed

    Braña, Miguel F; Gradillas, Ana; Gómez, Angel; Acero, Nuria; Llinares, Francisco; Muñoz-Mingarro, Dolores; Abradelo, Cristina; Rey-Stolle, Fernanda; Yuste, Mercedes; Campos, Joaquín; Gallo, Miguel A; Espinosa, Antonio

    2004-04-22

    A series of quinoline derivatives as aza analogues of the naphthalene chromophore and a series of "nonfused" tricyclic aromatic systems, in particular 5-arylquinolines and 5- or 6-aryl and heteroaryl naphthalene systems, were synthesized and evaluated for growth-inhibitory properties in several human cell lines. The analysis of quantitative structure-antitumor activity relationships for the growth-inhibitory properties is also reported. Findings suggest that these compounds may not express their cytotoxicity via interaction on DNA. PMID:15084122

  20. Hepatoprotection of sesquiterpenoids: a quantitative structure-activity relationship (QSAR) approach.

    PubMed

    Vinholes, Juliana; Rudnitskaya, Alisa; Gonçalves, Pedro; Martel, Fátima; Coimbra, Manuel A; Rocha, Sílvia M

    2014-03-01

    The relative hepatoprotection effect of fifteen sesquiterpenoids, commonly found in plants and plant-derived foods and beverages was assessed. Endogenous lipid peroxidation (assay A) and induced lipid peroxidation (assay B) were evaluated in liver homogenates from Wistar rats by the thiobarbituric acid reactive species test. Sesquiterpenoids with different chemical structures were tested: trans,trans-farnesol, cis-nerolidol, (-)-α-bisabolol, trans-β-farnesene, germacrene D, α-humulene, β-caryophyllene, isocaryophyllene, (+)-valencene, guaiazulene, (-)-α-cedrene, (+)-aromadendrene, (-)-α-neoclovene, (-)-α-copaene, and (+)-cyclosativene. Ascorbic acid was used as a positive antioxidant control. With the exception of α-humulene, all the sesquiterpenoids under study (1mM) were effective in reducing the malonaldehyde levels in both endogenous and induced lipid peroxidation up to 35% and 70%, respectively. The 3D-QSAR models developed, relating the hepatoprotection activity with molecular properties, showed good fit (Radj(2) 0.819 and 0.972 for the assays A and B, respectively) with good prediction power (Q(2)>0.950 and SDEP<2%, for both models A and B). A network of effects associated with structural and chemical features of sesquiterpenoids such as shape, branching, symmetry, and presence of electronegative fragments, can modulate the hepatoprotective activity observed for these compounds.

  1. A Fuzzy-Based Fusion Method of Multimodal Sensor-Based Measurements for the Quantitative Evaluation of Eye Fatigue on 3D Displays

    PubMed Central

    Bang, Jae Won; Choi, Jong-Suk; Heo, Hwan; Park, Kang Ryoung

    2015-01-01

    With the rapid increase of 3-dimensional (3D) content, considerable research related to the 3D human factor has been undertaken for quantitatively evaluating visual discomfort, including eye fatigue and dizziness, caused by viewing 3D content. Various modalities such as electroencephalograms (EEGs), biomedical signals, and eye responses have been investigated. However, the majority of the previous research has analyzed each modality separately to measure user eye fatigue. This cannot guarantee the credibility of the resulting eye fatigue evaluations. Therefore, we propose a new method for quantitatively evaluating eye fatigue related to 3D content by combining multimodal measurements. This research is novel for the following four reasons: first, for the evaluation of eye fatigue with high credibility on 3D displays, a fuzzy-based fusion method (FBFM) is proposed based on the multimodalities of EEG signals, eye blinking rate (BR), facial temperature (FT), and subjective evaluation (SE); second, to measure a more accurate variation of eye fatigue (before and after watching a 3D display), we obtain the quality scores of EEG signals, eye BR, FT and SE; third, for combining the values of the four modalities we obtain the optimal weights of the EEG signals BR, FT and SE using a fuzzy system based on quality scores; fourth, the quantitative level of the variation of eye fatigue is finally obtained using the weighted sum of the values measured by the four modalities. Experimental results confirm that the effectiveness of the proposed FBFM is greater than other conventional multimodal measurements. Moreover, the credibility of the variations of the eye fatigue using the FBFM before and after watching the 3D display is proven using a t-test and descriptive statistical analysis using effect size. PMID:25961382

  2. Quantitative Validation of the Presto Blue Metabolic Assay for Online Monitoring of Cell Proliferation in a 3D Perfusion Bioreactor System.

    PubMed

    Sonnaert, Maarten; Papantoniou, Ioannis; Luyten, Frank P; Schrooten, Jan Ir

    2015-06-01

    As the fields of tissue engineering and regenerative medicine mature toward clinical applications, the need for online monitoring both for quantitative and qualitative use becomes essential. Resazurin-based metabolic assays are frequently applied for determining cytotoxicity and have shown great potential for monitoring 3D bioreactor-facilitated cell culture. However, no quantitative correlation between the metabolic conversion rate of resazurin and cell number has been defined yet. In this work, we determined conversion rates of Presto Blue, a resazurin-based metabolic assay, for human periosteal cells during 2D and 3D static and 3D perfusion cultures. Our results showed that for the evaluated culture systems there is a quantitative correlation between the Presto Blue conversion rate and the cell number during the expansion phase with no influence of the perfusion-related parameters, that is, flow rate and shear stress. The correlation between the cell number and Presto Blue conversion subsequently enabled the definition of operating windows for optimal signal readouts. In conclusion, our data showed that the conversion of the resazurin-based Presto Blue metabolic assay can be used as a quantitative readout for online monitoring of cell proliferation in a 3D perfusion bioreactor system, although a system-specific validation is required.

  3. A quantitative comparison of the effects of stabilizing functionals in 3D regularized inversion of marine CSEM data

    NASA Astrophysics Data System (ADS)

    Wilson, G. A.; Cuma, M.; Zhdanov, M. S.; Gribenko, A.; Black, N.

    2010-12-01

    Three-dimensional (3D) inversion is required for defining 3D geoelectric structures associated with hydrocarbon (HC) deposits from marine controlled-source electromagnetic (CSEM) data. In 3D inversion, regularization is introduced to ensure uniqueness and stability in the inverse model. However, a common misconception is that regularization implies smoothing of the inverse model when in fact regularization and the stabilizing functionals are used to select the class of model from which an inverse solution is sought. Smooth stabilizers represent just one inverse model class from which the minimum norm or first or second derivatives of the 3D resistivity distribution are minimized. Smooth stabilizers have limited physical basis in geological interpretation aimed at exploration for HC reservoirs. Focusing stabilizers on the other hand make it possible to recover subsurface models with sharp resistivity contrasts which are typical for HC reservoirs. Using a synthetic example of the stacked anticlinal structures and reservoir units of the Shtokman gas field in the Barents Sea, we demonstrate that focusing stabilizers not only recover more geologically meaningful models than smooth stabilizers, but they provide better convergence for iterative inversion. This makes it practical to run multiple inversion scenarios based on the suite of a priori models, different data combinations, and various other parameters so as to build confidence in the recovered 3D resistivity model and to discriminate any artifacts that may arise from the interpretation of a single 3D inversion result.

  4. Qualitative and quantitative structure-activity relationship modelling for predicting blood-brain barrier permeability of structurally diverse chemicals.

    PubMed

    Gupta, S; Basant, N; Singh, K P

    2015-01-01

    In this study, structure-activity relationship (SAR) models have been established for qualitative and quantitative prediction of the blood-brain barrier (BBB) permeability of chemicals. The structural diversity of the chemicals and nonlinear structure in the data were tested. The predictive and generalization ability of the developed SAR models were tested through internal and external validation procedures. In complete data, the QSAR models rendered ternary classification accuracy of >98.15%, while the quantitative SAR models yielded correlation (r(2)) of >0.926 between the measured and the predicted BBB permeability values with the mean squared error (MSE) <0.045. The proposed models were also applied to an external new in vitro data and yielded classification accuracy of >82.7% and r(2) > 0.905 (MSE < 0.019). The sensitivity analysis revealed that topological polar surface area (TPSA) has the highest effect in qualitative and quantitative models for predicting the BBB permeability of chemicals. Moreover, these models showed predictive performance superior to those reported earlier in the literature. This demonstrates the appropriateness of the developed SAR models to reliably predict the BBB permeability of new chemicals, which can be used for initial screening of the molecules in the drug development process.

  5. Quantitative structure-activity relationships of insecticides and plant growth regulators: comparative studies toward understanding the molecular mechanism of action.

    PubMed Central

    Iwamura, H; Nishimura, K; Fujita, T

    1985-01-01

    Emphasis was put on the comparative quantitative structure-activity approaches to the exploration of action mechanisms of structurally different classes of compounds showing the same type of activity as well as those of the same type of compounds having different actions. Examples were selected from studies performed on insecticides and plant growth regulators, i.e., neurotoxic carbamates, phosphates, pyrethroids and DDT analogs, insect juvenile hormone mimics, and cytokinin agonistic and antagonistic compounds. Similarities and dissimilarities in structures required to elicit activity between compounds classes were revealed in terms of physicochemical parameters, provoking further exploration and evoking insights into the molecular mechanisms of action which may lead to the development of new structures having better qualities. PMID:3905379

  6. Quantitative structure-activity relationship studies of a series of sulfa drugs as inhibitors of Pneumocystis carinii dihydropteroate synthetase.

    PubMed

    Johnson, T; Khan, I A; Avery, M A; Grant, J; Meshnick, S R

    1998-06-01

    Sulfone and sulfanilamide sulfa drugs have been shown to inhibit dihydropteroate synthetase (DHPS) isolated from Pneumocystis carinii. In order to develop a pharmacophoric model for this inhibition, quantitative structure-activity relationships (QSAR) for sulfa drugs active against DHPS have been studied. Accurate 50% inhibitory concentrations were collected for 44 analogs, and other parameters, such as partition coefficients and molar refractivity, were calculated. Conventional multiple regression analysis of these data did not provide acceptable QSAR. However, three-dimensional QSAR provided by comparative molecular field analysis did give excellent results. Upon removal of poorly correlated analogs, a data set of 36 analogs, all having a common NHSO2 group, provided a cross-validated r2 value of 0.699 and conventional r2 value of 0.964. The resulting pharmacophore model should be useful for understanding and predicting the binding of DHPS by new sulfa drugs.

  7. Semisynthesis and quantitative structure-activity relationship (QSAR) study of some cholesterol-based hydrazone derivatives as insecticidal agents.

    PubMed

    Yang, Chun; Shao, Yonghua; Zhi, Xiaoyan; Huan, Qu; Yu, Xiang; Yao, Xiaojun; Xu, Hui

    2013-09-01

    In continuation of our program aimed at the discovery and development of natural-product-based insecticidal agents, four series of novel cholesterol-based hydrazone derivatives were synthesized, and their insecticidal activity was tested against the pre-third-instar larvae of oriental armyworm, Mythimna separata (Walker) in vivo at 1mg/mL. All the derivatives showed the better insecticidal activity than their precursor cholesterol. Quantitative structure-activity relationship (QSAR) model demonstrated that six descriptors such as RDF085v, Mor06u, Mor11u, Dv, HATS0v and H-046, are likely to influence the insecticidal activity of these compounds. Among them, two important ones are the Mor06u and RDF085v.

  8. Topological study on the toxicity of ionic liquids on Vibrio fischeri by the quantitative structure-activity relationship method.

    PubMed

    Yan, Fangyou; Shang, Qiaoyan; Xia, Shuqian; Wang, Qiang; Ma, Peisheng

    2015-04-01

    As environmentally friendly solvents, ionic liquids (ILs) are unlikely to act as air contaminants or inhalation toxins resulting from their negligible vapor pressure and excellent thermal stability. However, they can be potential water contaminants because of their considerable solubility in water; therefore, a proper toxicological assessment of ILs is essential. The environmental fate of ILs is studied by quantitative structure-activity relationship (QSAR) method. A multiple linear regression (MLR) model is obtained by topological method using toxicity data of 157 ILs on Vibrio fischeri, which are composed of 74 cations and 22 anions. The topological index developed in our research group is used for predicting the V. fischeri toxicity for the first time. The MLR model is precise for estimating LogEC50 of ILs on V. fischeri with square of correlation coefficient (R(2)) = 0.908 and the average absolute error (AAE) = 0.278.

  9. Chromanyl-isoxazolidines as Antibacterial agents: Synthesis, Biological Evaluation, Quantitative Structure Activity Relationship, and Molecular Docking Studies.

    PubMed

    Singh, Gagandeep; Sharma, Anuradha; Kaur, Harpreet; Ishar, Mohan Paul S

    2016-02-01

    Regio- and stereoselective 1,3-dipolar cycloadditions of C-(chrom-4-one-3-yl)-N-phenylnitrones (N) with different mono-substituted, disubstituted, and cyclic dipolarophiles were carried out to obtain substituted N-phenyl-3'-(chrom-4-one-3-yl)-isoxazolidines (1-40). All the synthesized compounds were assayed for their in vitro antibacterial activity and display significant inhibitory potential; in particular, compound 32 exhibited good inhibitory activity against Salmonella typhymurium-1 & Salmonella typhymurium-2 with minimum inhibitory concentration value of 1.56 μg/mL and also showed good potential against methicillin-resistant Staphylococcus aureus with minimum inhibitory concentration 3.12 μg/mL. Quantitative structure activity relationship investigations with stepwise multiple linear regression analysis and docking simulation studies have been performed for validation of the observed antibacterial potential of the investigated compounds for determination of the most important parameters regulating antibacterial activities.

  10. Quantitative structure-activity relationship (QSAR) study of a series of benzimidazole derivatives as inhibitors of Saccharomyces cerevisiae.

    PubMed

    Podunavac-Kuzmanović, Sonja O; Cvetković, Dragoljub D; Jevrić, Lidija R; Uzelac, Natasa J

    2013-01-01

    A quantitative structure activity relationship (QSAR) has been carried out on a series of benzimidazole derivatives to identify the structural requirements for their inhibitory activity against yeast Saccharomyces cerevisiae. A multiple linear regression (MLR) procedure was used to model the relationships between various physicochemical, steric, electronic, and structural molecular descriptors and antifungal activity of benzimidazole derivatives. The QSAR expressions were generated using a training set of 16 compounds and the predictive ability of the resulting models was evaluated against a test set of 8 compounds. The best QSAR models were further validated by leave one out technique as well as by the calculation of statistical parameters for the established theoretical models. Therefore, satisfactory relationships between antifungal activity and molecular descriptors were found. QSAR analysis reveals that lipophilicity descriptor (logP), dipole moment (DM) and surface area grid (SAG) govern the inhibitory activity of compounds studied against Saccharomyces cerevisiae.

  11. Non-linear quantitative structure-activity relationship for adenine derivatives as competitive inhibitors of adenosine deaminase

    SciTech Connect

    Sadat Hayatshahi, Sayyed Hamed; Khajeh, Khosro

    2005-12-16

    Logistic regression and artificial neural networks have been developed as two non-linear models to establish quantitative structure-activity relationships between structural descriptors and biochemical activity of adenosine based competitive inhibitors, toward adenosine deaminase. The training set included 24 compounds with known k {sub i} values. The models were trained to solve two-class problems. Unlike the previous work in which multiple linear regression was used, the highest of positive charge on the molecules was recognized to be in close relation with their inhibition activity, while the electric charge on atom N1 of adenosine was found to be a poor descriptor. Consequently, the previously developed equation was improved and the newly formed one could predict the class of 91.66% of compounds correctly. Also optimized 2-3-1 and 3-4-1 neural networks could increase this rate to 95.83%.

  12. Quantitative structure-activation barrier relationship modeling for Diels-Alder ligations utilizing quantum chemical structural descriptors

    PubMed Central

    2013-01-01

    Background In the present study, we show the correlation of quantum chemical structural descriptors with the activation barriers of the Diels-Alder ligations. A set of 72 non-catalysed Diels-Alder reactions were subjected to quantitative structure-activation barrier relationship (QSABR) under the framework of theoretical quantum chemical descriptors calculated solely from the structures of diene and dienophile reactants. Experimental activation barrier data were obtained from literature. Descriptors were computed using Hartree-Fock theory using 6-31G(d) basis set as implemented in Gaussian 09 software. Results Variable selection and model development were carried out by stepwise multiple linear regression methodology. Predictive performance of the quantitative structure-activation barrier relationship (QSABR) model was assessed by training and test set concept and by calculating leave-one-out cross-validated Q2 and predictive R2 values. The QSABR model can explain and predict 86.5% and 80% of the variances, respectively, in the activation energy barrier training data. Alternatively, a neural network model based on back propagation of errors was developed to assess the nonlinearity of the sought correlations between theoretical descriptors and experimental reaction barriers. Conclusions A reasonable predictability for the activation barrier of the test set reactions was obtained, which enabled an exploration and interpretation of the significant variables responsible for Diels-Alder interaction between dienes and dienophiles. Thus, studies in the direction of QSABR modelling that provide efficient and fast prediction of activation barriers of the Diels-Alder reactions turn out to be a meaningful alternative to transition state theory based computation. PMID:24171724

  13. Spherical blurred shape model for 3-D object and pose recognition: quantitative analysis and HCI applications in smart environments.

    PubMed

    Lopes, Oscar; Reyes, Miguel; Escalera, Sergio; Gonzàlez, Jordi

    2014-12-01

    The use of depth maps is of increasing interest after the advent of cheap multisensor devices based on structured light, such as Kinect. In this context, there is a strong need of powerful 3-D shape descriptors able to generate rich object representations. Although several 3-D descriptors have been already proposed in the literature, the research of discriminative and computationally efficient descriptors is still an open issue. In this paper, we propose a novel point cloud descriptor called spherical blurred shape model (SBSM) that successfully encodes the structure density and local variabilities of an object based on shape voxel distances and a neighborhood propagation strategy. The proposed SBSM is proven to be rotation and scale invariant, robust to noise and occlusions, highly discriminative for multiple categories of complex objects like the human hand, and computationally efficient since the SBSM complexity is linear to the number of object voxels. Experimental evaluation in public depth multiclass object data, 3-D facial expressions data, and a novel hand poses data sets show significant performance improvements in relation to state-of-the-art approaches. Moreover, the effectiveness of the proposal is also proved for object spotting in 3-D scenes and for real-time automatic hand pose recognition in human computer interaction scenarios. PMID:25415944

  14. 3D imaging and quantitative analysis of small solubilized membrane proteins and their complexes by transmission electron microscopy.

    PubMed

    Vahedi-Faridi, Ardeschir; Jastrzebska, Beata; Palczewski, Krzysztof; Engel, Andreas

    2013-02-01

    Inherently unstable, detergent-solubilized membrane protein complexes can often not be crystallized. For complexes that have a mass of >300 kDa, cryo-electron microscopy (EM) allows their three-dimensional (3D) structure to be assessed to a resolution that makes secondary structure elements visible in the best case. However, many interesting complexes exist whose mass is below 300 kDa and thus need alternative approaches. Two methods are reviewed: (i) Mass measurement in a scanning transmission electron microscope, which has provided important information on the stoichiometry of membrane protein complexes. This technique is applicable to particulate, filamentous and sheet-like structures. (ii) 3D-EM of negatively stained samples, which determines the molecular envelope of small membrane protein complexes. Staining and dehydration artifacts may corrupt the quality of the 3D map. Staining conditions thus need to be optimized. 3D maps of plant aquaporin SoPIP2;1 tetramers solubilized in different detergents illustrate that the flattening artifact can be partially prevented and that the detergent itself contributes significantly. Another example discussed is the complex of G protein-coupled receptor rhodopsin with its cognate G protein transducin.

  15. Designing quantitative structure activity relationships to predict specific toxic endpoints for polybrominated diphenyl ethers in mammalian cells.

    PubMed

    Rawat, S; Bruce, E D

    2014-01-01

    Polybrominated diphenyl ethers (PBDEs) are known as effective flame retardants and have vast industrial application in products like plastics, building materials and textiles. They are found to be structurally similar to thyroid hormones that are responsible for regulating metabolism in the body. Structural similarity with the hormones poses a threat to human health because, once in the system, PBDEs have the potential to affect thyroid hormone transport and metabolism. This study was aimed at designing quantitative structure-activity relationship (QSAR) models for predicting toxic endpoints, namely cell viability and apoptosis, elicited by PBDEs in mammalian cells. Cell viability was evaluated quantitatively using a general cytotoxicity bioassay using Janus Green dye and apoptosis was evaluated using a caspase assay. This study has thus modelled the overall cytotoxic influence of PBDEs at an early and a late endpoint by the Genetic Function Approximation method. This research was a twofold process including running in vitro bioassays to collect data on the toxic endpoints and modeling the evaluated endpoints using QSARs. Cell viability and apoptosis responses for Hep G2 cells exposed to PBDEs were successfully modelled with an r(2) of 0.97 and 0.94, respectively. PMID:24738916

  16. R2OBBIE-3D, a Fast Robotic High-Resolution System for Quantitative Phenotyping of Surface Geometry and Colour-Texture

    PubMed Central

    Manukyan, Liana; Milinkovitch, Michel C.

    2015-01-01

    While recent imaging techniques provide insights into biological processes from the molecular to the cellular scale, phenotypes at larger scales remain poorly amenable to quantitative analyses. For example, investigations of the biophysical mechanisms generating skin morphological complexity and diversity would greatly benefit from 3D geometry and colour-texture reconstructions. Here, we report on R2OBBIE-3D, an integrated system that combines a robotic arm, a high-resolution digital colour camera, an illumination basket of high-intensity light-emitting diodes and state-of-the-art 3D-reconstruction approaches. We demonstrate that R2OBBIE generates accurate 3D models of biological objects between 1 and 100 cm, makes multiview photometric stereo scanning possible in practical processing times, and enables the capture of colour-texture and geometric resolutions better than 15 μm without the use of magnifying lenses. R2OBBIE has the potential to greatly improve quantitative analyses of phenotypes in addition to providing multiple new applications in, e.g., biomedical science. PMID:26039509

  17. R(2)OBBIE-3D, a Fast Robotic High-Resolution System for Quantitative Phenotyping of Surface Geometry and Colour-Texture.

    PubMed

    Martins, António F; Bessant, Michel; Manukyan, Liana; Milinkovitch, Michel C

    2015-01-01

    While recent imaging techniques provide insights into biological processes from the molecular to the cellular scale, phenotypes at larger scales remain poorly amenable to quantitative analyses. For example, investigations of the biophysical mechanisms generating skin morphological complexity and diversity would greatly benefit from 3D geometry and colour-texture reconstructions. Here, we report on R(2)OBBIE-3D, an integrated system that combines a robotic arm, a high-resolution digital colour camera, an illumination basket of high-intensity light-emitting diodes and state-of-the-art 3D-reconstruction approaches. We demonstrate that R(2)OBBIE generates accurate 3D models of biological objects between 1 and 100 cm, makes multiview photometric stereo scanning possible in practical processing times, and enables the capture of colour-texture and geometric resolutions better than 15 μm without the use of magnifying lenses. R(2)OBBIE has the potential to greatly improve quantitative analyses of phenotypes in addition to providing multiple new applications in, e.g., biomedical science. PMID:26039509

  18. Mechanistic and quantitative studies of bystander response in 3D tissues for low-dose radiation risk estimations

    SciTech Connect

    Amundson, Sally A.

    2013-06-12

    We have used the MatTek 3-dimensional human skin model to study the gene expression response of a 3D model to low and high dose low LET radiation, and to study the radiation bystander effect as a function of distance from the site of irradiation with either alpha particles or low LET protons. We have found response pathways that appear to be specific for low dose exposures, that could not have been predicted from high dose studies. We also report the time and distance dependent expression of a large number of genes in bystander tissue. the bystander response in 3D tissues showed many similarities to that described previously in 2D cultured cells, but also showed some differences.

  19. Longitudinal, label-free, quantitative tracking of cell death and viability in a 3D tumor model with OCT

    NASA Astrophysics Data System (ADS)

    Jung, Yookyung; Klein, Oliver J.; Wang, Hequn; Evans, Conor L.

    2016-06-01

    Three-dimensional in vitro tumor models are highly useful tools for studying tumor growth and treatment response of malignancies such as ovarian cancer. Existing viability and treatment assessment assays, however, face shortcomings when applied to these large, complex, and heterogeneous culture systems. Optical coherence tomography (OCT) is a noninvasive, label-free, optical imaging technique that can visualize live cells and tissues over time with subcellular resolution and millimeters of optical penetration depth. Here, we show that OCT is capable of carrying out high-content, longitudinal assays of 3D culture treatment response. We demonstrate the usage and capability of OCT for the dynamic monitoring of individual and combination therapeutic regimens in vitro, including both chemotherapy drugs and photodynamic therapy (PDT) for ovarian cancer. OCT was validated against the standard LIVE/DEAD Viability/Cytotoxicity Assay in small tumor spheroid cultures, showing excellent correlation with existing standards. Importantly, OCT was shown to be capable of evaluating 3D spheroid treatment response even when traditional viability assays failed. OCT 3D viability imaging revealed synergy between PDT and the standard-of-care chemotherapeutic carboplatin that evolved over time. We believe the efficacy and accuracy of OCT in vitro drug screening will greatly contribute to the field of cancer treatment and therapy evaluation.

  20. Longitudinal, label-free, quantitative tracking of cell death and viability in a 3D tumor model with OCT

    PubMed Central

    Jung, Yookyung; Klein, Oliver J.; Wang, Hequn; Evans, Conor L.

    2016-01-01

    Three-dimensional in vitro tumor models are highly useful tools for studying tumor growth and treatment response of malignancies such as ovarian cancer. Existing viability and treatment assessment assays, however, face shortcomings when applied to these large, complex, and heterogeneous culture systems. Optical coherence tomography (OCT) is a noninvasive, label-free, optical imaging technique that can visualize live cells and tissues over time with subcellular resolution and millimeters of optical penetration depth. Here, we show that OCT is capable of carrying out high-content, longitudinal assays of 3D culture treatment response. We demonstrate the usage and capability of OCT for the dynamic monitoring of individual and combination therapeutic regimens in vitro, including both chemotherapy drugs and photodynamic therapy (PDT) for ovarian cancer. OCT was validated against the standard LIVE/DEAD Viability/Cytotoxicity Assay in small tumor spheroid cultures, showing excellent correlation with existing standards. Importantly, OCT was shown to be capable of evaluating 3D spheroid treatment response even when traditional viability assays failed. OCT 3D viability imaging revealed synergy between PDT and the standard-of-care chemotherapeutic carboplatin that evolved over time. We believe the efficacy and accuracy of OCT in vitro drug screening will greatly contribute to the field of cancer treatment and therapy evaluation. PMID:27248849

  1. 3D-Assisted Quantitative Assessment of Orbital Volume Using an Open-Source Software Platform in a Taiwanese Population

    PubMed Central

    Shyu, Victor Bong-Hang; Hsu, Chung-En; Chen, Chih-hao; Chen, Chien-Tzung

    2015-01-01

    Orbital volume evaluation is an important part of pre-operative assessments in orbital trauma and congenital deformity patients. The availability of the affordable, open-source software, OsiriX, as a tool for preoperative planning increased the popularity of radiological assessments by the surgeon. A volume calculation method based on 3D volume rendering-assisted region-of-interest computation was used to determine the normal orbital volume in Taiwanese patients after reorientation to the Frankfurt plane. Method one utilized 3D points for intuitive orbital rim outlining. The mean normal orbital volume for left and right orbits was 24.3±1.51 ml and 24.7±1.17 ml in male and 21.0±1.21 ml and 21.1±1.30 ml in female subjects. Another method (method two) based on the bilateral orbital lateral rim was also used to calculate orbital volume and compared with method one. The mean normal orbital volume for left and right orbits was 19.0±1.68 ml and 19.1±1.45 ml in male and 16.0±1.01 ml and 16.1±0.92 ml in female subjects. The inter-rater reliability and intra-rater measurement accuracy between users for both methods was found to be acceptable for orbital volume calculations. 3D-assisted quantification of orbital volume is a feasible technique for orbital volume assessment. The normal orbital volume can be used as controls in cases of unilateral orbital reconstruction with a mean size discrepancy of less than 3.1±2.03% in females and 2.7±1.32% in males. The OsiriX software can be used reliably by the individual surgeon as a comprehensive preoperative planning and imaging tool for orbital volume measurement and computed tomography reorientation. PMID:25774683

  2. Quantitative 3-d diagnostic ultrasound imaging using a modified transducer array and an automated image tracking technique.

    PubMed

    Hossack, John A; Sumanaweera, Thilaka S; Napel, Sandy; Ha, Jun S

    2002-08-01

    An approach for acquiring dimensionally accurate three-dimensional (3-D) ultrasound data from multiple 2-D image planes is presented. This is based on the use of a modified linear-phased array comprising a central imaging array that acquires multiple, essentially parallel, 2-D slices as the transducer is translated over the tissue of interest. Small, perpendicularly oriented, tracking arrays are integrally mounted on each end of the imaging transducer. As the transducer is translated in an elevational direction with respect to the central imaging array, the images obtained by the tracking arrays remain largely coplanar. The motion between successive tracking images is determined using a minimum sum of absolute difference (MSAD) image matching technique with subpixel matching resolution. An initial phantom scanning-based test of a prototype 8 MHz array indicates that linear dimensional accuracy of 4.6% (2 sigma) is achievable. This result compares favorably with those obtained using an assumed average velocity [31.5% (2 sigma) accuracy] and using an approach based on measuring image-to-image decorrelation [8.4% (2 sigma) accuracy]. The prototype array and imaging system were also tested in a clinical environment, and early results suggest that the approach has the potential to enable a low cost, rapid, screening method for detecting carotid artery stenosis. The average time for performing a screening test for carotid stenosis was reduced from an average of 45 minutes using 2-D duplex Doppler to 12 minutes using the new 3-D scanning approach.

  3. SU-E-T-624: Quantitative Evaluation of 2D Versus 3D Dosimetry for Stereotactic Volumetric Modulated Arc Delivery Using COMPASS

    SciTech Connect

    Vikraman, S; Karrthick, K; Rajesh, T; Sambasivaselli, R; Senniandanvar, V; Kataria, T; Manigandan, D; Karthikeyan, N; Muthukumaran, M

    2014-06-15

    Purpose: The purpose of this study was to evaluate quantitatively 2D versus 3D dosimetry for stereotactic volumetric modulated arc delivery using COMPASS with 2D array. Methods: Twenty-five patients CT images and RT structures of different sites like brain, head and neck, thorax, abdomen and spine were taken from Multiplan planning system for this study. All these patients underwent radical stereotactic treatment in Cyberknife. For each patient, linac based VMAT stereotactic plans were generated in Monaco TPS v 3.1 using Elekta Beam Modulator MLC. Dose prescription was in the range of 5-20Gy/fraction.TPS calculated VMAT plan delivery accuracy was quantitatively evaluated with COMPASS measured dose and calculated dose based on DVH metrics. In order to ascertain the potential of COMPASS 3D dosimetry for stereotactic plan delivery, 2D fluence verification was performed with MatriXX using Multicube. Results: For each site, D{sub 9} {sub 5} was achieved with 100% of prescription dose with maximum 0.05SD. Conformity index (CI) was observed closer to 1.15 in all cases. Maximum deviation of 2.62 % was observed for D{sub 9} {sub 5} when compared TPS versus COMPASS measured. Considerable deviations were observed in head and neck cases compare to other sites. The maximum mean and standard deviation for D{sub 9} {sub 5}, average target dose and average gamma were -0.78±1.72, -1.10±1.373 and 0.39±0.086 respectively. Numbers of pixels passing 2D fluence verification were observed as a mean of 99.36% ±0.455 SD with 3% dose difference and 3mm DTA. For critical organs in head and neck cases, significant dose differences were observed in 3D dosimetry while the target doses were matched well within limit in both 2D and 3D dosimetry. Conclusion: The quantitative evaluations of 2D versus 3D dosimetry for stereotactic volumetric modulated plans showed the potential of highlighting the delivery errors. This study reveals that COMPASS 3D dosimetry is an effective tool for patient

  4. A quantitative structure-activity relationship to predict efficacy of granular activated carbon adsorption to control emerging contaminants.

    PubMed

    Kennicutt, A R; Morkowchuk, L; Krein, M; Breneman, C M; Kilduff, J E

    2016-08-01

    A quantitative structure-activity relationship was developed to predict the efficacy of carbon adsorption as a control technology for endocrine-disrupting compounds, pharmaceuticals, and components of personal care products, as a tool for water quality professionals to protect public health. Here, we expand previous work to investigate a broad spectrum of molecular descriptors including subdivided surface areas, adjacency and distance matrix descriptors, electrostatic partial charges, potential energy descriptors, conformation-dependent charge descriptors, and Transferable Atom Equivalent (TAE) descriptors that characterize the regional electronic properties of molecules. We compare the efficacy of linear (Partial Least Squares) and non-linear (Support Vector Machine) machine learning methods to describe a broad chemical space and produce a user-friendly model. We employ cross-validation, y-scrambling, and external validation for quality control. The recommended Support Vector Machine model trained on 95 compounds having 23 descriptors offered a good balance between good performance statistics, low error, and low probability of over-fitting while describing a wide range of chemical features. The cross-validated model using a log-uptake (qe) response calculated at an aqueous equilibrium concentration (Ce) of 1 μM described the training dataset with an r(2) of 0.932, had a cross-validated r(2) of 0.833, and an average residual of 0.14 log units. PMID:27586364

  5. A Quantitative Structure Activity Relationship for acute oral toxicity of pesticides on rats: Validation, domain of application and prediction.

    PubMed

    Hamadache, Mabrouk; Benkortbi, Othmane; Hanini, Salah; Amrane, Abdeltif; Khaouane, Latifa; Si Moussa, Cherif

    2016-02-13

    Quantitative Structure Activity Relationship (QSAR) models are expected to play an important role in the risk assessment of chemicals on humans and the environment. In this study, we developed a validated QSAR model to predict acute oral toxicity of 329 pesticides to rats because a few QSAR models have been devoted to predict the Lethal Dose 50 (LD50) of pesticides on rats. This QSAR model is based on 17 molecular descriptors, and is robust, externally predictive and characterized by a good applicability domain. The best results were obtained with a 17/9/1 Artificial Neural Network model trained with the Quasi Newton back propagation (BFGS) algorithm. The prediction accuracy for the external validation set was estimated by the Q(2)ext and the root mean square error (RMS) which are equal to 0.948 and 0.201, respectively. 98.6% of external validation set is correctly predicted and the present model proved to be superior to models previously published. Accordingly, the model developed in this study provides excellent predictions and can be used to predict the acute oral toxicity of pesticides, particularly for those that have not been tested as well as new pesticides.

  6. Estimating the Potential Toxicity of Chemicals Associated with Hydraulic Fracturing Operations Using Quantitative Structure-Activity Relationship Modeling.

    PubMed

    Yost, Erin E; Stanek, John; DeWoskin, Robert S; Burgoon, Lyle D

    2016-07-19

    The United States Environmental Protection Agency (EPA) identified 1173 chemicals associated with hydraulic fracturing fluids, flowback, or produced water, of which 1026 (87%) lack chronic oral toxicity values for human health assessments. To facilitate the ranking and prioritization of chemicals that lack toxicity values, it may be useful to employ toxicity estimates from quantitative structure-activity relationship (QSAR) models. Here we describe an approach for applying the results of a QSAR model from the TOPKAT program suite, which provides estimates of the rat chronic oral lowest-observed-adverse-effect level (LOAEL). Of the 1173 chemicals, TOPKAT was able to generate LOAEL estimates for 515 (44%). To address the uncertainty associated with these estimates, we assigned qualitative confidence scores (high, medium, or low) to each TOPKAT LOAEL estimate, and found 481 to be high-confidence. For 48 chemicals that had both a high-confidence TOPKAT LOAEL estimate and a chronic oral reference dose from EPA's Integrated Risk Information System (IRIS) database, Spearman rank correlation identified 68% agreement between the two values (permutation p-value =1 × 10(-11)). These results provide support for the use of TOPKAT LOAEL estimates in identifying and prioritizing potentially hazardous chemicals. High-confidence TOPKAT LOAEL estimates were available for 389 of 1026 hydraulic fracturing-related chemicals that lack chronic oral RfVs and OSFs from EPA-identified sources, including a subset of chemicals that are frequently used in hydraulic fracturing fluids. PMID:27172125

  7. 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.

  8. Quantitative structure-activity relationship modelling of oral acute toxicity and cytotoxic activity of fragrance materials in rodents.

    PubMed

    Papa, E; Luini, M; Gramatica, P

    2009-10-01

    Fragrance materials are used as ingredients in many consumer and personal care products. The wide and daily use of these substances, as well as their mainly uncontrolled discharge through domestic sewage, make fragrance materials both potential indoor and outdoor air pollutants which are also connected to possible toxic effects on humans (asthma, allergies, headaches). Unfortunately, little is known about the environmental fate and toxicity of these substances. However, the use of alternative, predictive approaches, such as quantitative structure-activity relationships (QSARs), can help in filling the data gap and in the characterization of the environmental and toxicological profile of these substances. In the proposed study, ordinary least squares regression-based QSAR models were developed for three toxicological endpoints: mouse oral LD(50), inhibition of NADH-oxidase (EC(50) NADH-Ox) and the effect on mitochondrial membrane potential (EC(50) DeltaPsim). Theoretical molecular descriptors were calculated by using DRAGON software, and the best QSAR models were developed according to the principles defined by the Organization for Economic Co-operation and Development.

  9. Quantitative structure-activity relationships and mixture toxicity of organic chemicals in Photobacterium phosphoreum: the Microtox test

    SciTech Connect

    Hermens, J.; Busser, F.; Leeuwangh, P.; Musch, A.

    1985-02-01

    Quantitative structure-activity relationships were calculated for the inhibition of bioluminescence of Photobacterium phosphoreum by 22 nonreactive organic chemicals. The inhibition was measured using the Microtox test and correlated with the partition coefficient between n-octanol and water (Poct), molar refractivity (MR), and molar volume (MW/d). At log Poct less than 1 and greater than 3, deviations from linearity were observed. Introduction of MR and MW/d improved the quality of the relationships. The influences of MR or MW/d may be related with an interaction of the tested chemicals to the enzyme system which produces the light emission. The sensitivity of the Microtox test to the 22 tested compounds is comparable to a 14-day acute mortality test with guppies for chemicals with log Poct less than 4. The inhibition of bioluminescence by a mixture of the tested compounds was slightly less than was expected in case of concentration addition. The Microtox test can give a good estimate of the total aspecific minimum toxicity of polluted waters. When rather lipophilic compounds or pollutants with more specific modes of action are present, this test will underestimate the toxicity to other aquatic life.

  10. Overview of data and conceptual approaches for derivation of quantitative structure-activity relationships for ecotoxicological effects of organic chemicals.

    PubMed

    Bradbury, Steven P; Russom, Christine L; Ankley, Gerald T; Schultz, T Wayne; Walker, John D

    2003-08-01

    The use of quantitative structure-activity relationships (QSARs) in assessing potential toxic effects of organic chemicals on aquatic organisms continues to evolve as computational efficiency and toxicological understanding advance. With the ever-increasing production of new chemicals, and the need to optimize resources to assess thousands of existing chemicals in commerce, regulatory agencies have turned to QSARs as essential tools to help prioritize tiered risk assessments when empirical data are not available to evaluate toxicological effects. Progress in designing scientifically credible QSARs is intimately associated with the development of empirically derived databases of well-defined and quantified toxicity endpoints, which are based on a strategic evaluation of diverse sets of chemical structures, modes of toxic action, and species. This review provides a brief overview of four databases created for the purpose of developing QSARs for estimating toxicity of chemicals to aquatic organisms. The evolution of QSARs based initially on general chemical classification schemes, to models founded on modes of toxic action that range from nonspecific partitioning into hydrophobic cellular membranes to receptor-mediated mechanisms is summarized. Finally, an overview of expert systems that integrate chemical-specific mode of action classification and associated QSAR selection for estimating potential toxicological effects of organic chemicals is presented. PMID:12924578

  11. Chemical toxicity to environmental bacteria: Quantitative structure activity relationships and interspecies correlations and comparisons (Volumes I and II)

    SciTech Connect

    Blum, D.J.W.

    1989-01-01

    Toxicity data were collected for four groups of bacteria and a fish. These data were collected for four groups of bacteria and a fish. These data were used to compare and correlate the toxicities to different organisms, and to develop Quantitative Structure Activity Relationships (QSARs) correlating chemical structure with toxicity. Chemical toxicity to aerobic heterotrophic bacteria, Nitrosomonas, and methanogens were measured using serum bottle techniques in order to determine the concentration of chemical which caused 50% inhibition in microorganism's activity. Toxicity to Photobacteria phosphoreum (Microtox bacteria) and fathead minnows was also tested or data collected from the literature. Toxicants included chlorinated and other substituted benzenes and phenols, chlorinated alkanes, and a variety of additional compounds covering a range of chemical structures. Data were obtained for 50 to 130 chemicals per species. The sensitivity of the organism fell into two groups with Microtox bacteria, Nitrosomonas, and fathead minnows showing significantly greater sensitivity than aerobic heterotrophs and methanogens. Highly successful interspecies correlations were found between Microtox and each of the other species.

  12. Estimating the Potential Toxicity of Chemicals Associated with Hydraulic Fracturing Operations Using Quantitative Structure-Activity Relationship Modeling.

    PubMed

    Yost, Erin E; Stanek, John; DeWoskin, Robert S; Burgoon, Lyle D

    2016-07-19

    The United States Environmental Protection Agency (EPA) identified 1173 chemicals associated with hydraulic fracturing fluids, flowback, or produced water, of which 1026 (87%) lack chronic oral toxicity values for human health assessments. To facilitate the ranking and prioritization of chemicals that lack toxicity values, it may be useful to employ toxicity estimates from quantitative structure-activity relationship (QSAR) models. Here we describe an approach for applying the results of a QSAR model from the TOPKAT program suite, which provides estimates of the rat chronic oral lowest-observed-adverse-effect level (LOAEL). Of the 1173 chemicals, TOPKAT was able to generate LOAEL estimates for 515 (44%). To address the uncertainty associated with these estimates, we assigned qualitative confidence scores (high, medium, or low) to each TOPKAT LOAEL estimate, and found 481 to be high-confidence. For 48 chemicals that had both a high-confidence TOPKAT LOAEL estimate and a chronic oral reference dose from EPA's Integrated Risk Information System (IRIS) database, Spearman rank correlation identified 68% agreement between the two values (permutation p-value =1 × 10(-11)). These results provide support for the use of TOPKAT LOAEL estimates in identifying and prioritizing potentially hazardous chemicals. High-confidence TOPKAT LOAEL estimates were available for 389 of 1026 hydraulic fracturing-related chemicals that lack chronic oral RfVs and OSFs from EPA-identified sources, including a subset of chemicals that are frequently used in hydraulic fracturing fluids.

  13. Quantitative structure-activity relationships for polychlorinated hydroxybiphenyl estrogen receptor binding affinity: An assessment of conformer flexibility

    SciTech Connect

    Bradbury, S.P.; Ankley, G.T.; Mekenyan, O.G.

    1996-11-01

    A diverse group of xenobiotics has a high binding affinity to the estrogen receptor (ER), suggesting that it can accommodate large variability in ligand structure. Relationships between xenobiotic surface, binding affinity, and estrogenic response have been suggested to be dependent on the conformational structures of the ligands. To explore the influence of conformational flexibility on ER binding affinity, a quantitative structure-activity relationship (QSAR) study was undertaken with estradiol, diethylstilbestrol, and a set of polychlorinated hydroxybiphenyls (PCHBs) of environmental concern. Although the low-energy minima of the PCHB congeners suggested that interconversions among conformers were likely, the electronic parameters associated with the conformer geometries for a specific PCHB congener could vary significantly. The results of the QSAR analysis suggested that among the PCHBs studied, the most polarizable conformers (lower absolute volume polarizability values) were most closely associated with ER binding affinity. Across the set of polarizable conformers, which did not include the low-energy gas-phase conformers, the electron donating properties of the hydroxy moiety and the aromatic component of the estradiol A ring analogue in the PCHBs were found to be correlated with higher ER binding affinity.

  14. Quantitative structure-activity relationships for evaluating the influence of sorbate structure on sorption of organic compounds by soil

    SciTech Connect

    Hu, Q.; Wang, X.; Brusseau, M.L.

    1995-07-01

    The purpose of this work was to investigate the effect of sorbate structure, by using the quantitative structure-activity relationship (QSAR) approach, on sorption of organic compounds by two soils with different amounts of organic matter. Miscible displacement experiments were performed with several organic contaminants representing six classes of nonpolar, nonionizable organic chemicals, including chlorinated aliphatics, chlorobenzenes, polycyclic aromatic hydrocarbons (PAHs), n-alkylbenzenes, methylated benzenes, and polychlorinated biphenyls (PCBs). The breakthrough curves were analyzed by using a bicontinuum model where in sorption is assumed to be instantaneous for a fraction of the sorbent and rate limited for the remainder. The QSAR approach was used to investigate the dependency of both equilibrium and nonequilibrium sorption coefficients on topological descriptor representing structural properties of the solutes. For both equilibrium and nonequilibrium parameters, the first-order valence molecular connectivity ({sup 1}{chi}{sup v}) was found to be the best topological descriptor. Most of the rate-limited sorption behavior could be explained by accounting for the size and structure of the solute molecule, as indicated by the good correlation between the rate coefficient and {sup 1}{chi}{sup v}. This supports the contention that rate-limited sorption in these systems is controlled by a physical diffusion mechanism, consistent with the polymer diffusion model. Based on this model, the calculated diffusion-length ratios for the Borden and Mt. Lemmon soils, which have a large difference in organic-matter contents, compare favorably to the values determined from the measured rate data.

  15. Synthetic cannabinoids: In silico prediction of the cannabinoid receptor 1 affinity by a quantitative structure-activity relationship model.

    PubMed

    Paulke, Alexander; Proschak, Ewgenij; Sommer, Kai; Achenbach, Janosch; Wunder, Cora; Toennes, Stefan W

    2016-03-14

    The number of new synthetic psychoactive compounds increase steadily. Among the group of these psychoactive compounds, the synthetic cannabinoids (SCBs) are most popular and serve as a substitute of herbal cannabis. More than 600 of these substances already exist. For some SCBs the in vitro cannabinoid receptor 1 (CB1) affinity is known, but for the majority it is unknown. A quantitative structure-activity relationship (QSAR) model was developed, which allows the determination of the SCBs affinity to CB1 (expressed as binding constant (Ki)) without reference substances. The chemically advance template search descriptor was used for vector representation of the compound structures. The similarity between two molecules was calculated using the Feature-Pair Distribution Similarity. The Ki values were calculated using the Inverse Distance Weighting method. The prediction model was validated using a cross validation procedure. The predicted Ki values of some new SCBs were in a range between 20 (considerably higher affinity to CB1 than THC) to 468 (considerably lower affinity to CB1 than THC). The present QSAR model can serve as a simple, fast and cheap tool to get a first hint of the biological activity of new synthetic cannabinoids or of other new psychoactive compounds.

  16. Quantitative structure-activity relationship analysis of substituted arylazo pyridone dyes in photocatalytic system: Experimental and theoretical study.

    PubMed

    Dostanić, J; Lončarević, D; Zlatar, M; Vlahović, F; Jovanović, D M

    2016-10-01

    A series of arylazo pyridone dyes was synthesized by changing the type of the substituent group in the diazo moiety, ranging from strong electron-donating to strong electron-withdrawing groups. The structural and electronic properties of the investigated dyes was calculated at the M062X/6-31+G(d,p) level of theory. The observed good linear correlations between atomic charges and Hammett σp constants provided a basis to discuss the transmission of electronic substituent effects through a dye framework. The reactivity of synthesized dyes was tested through their decolorization efficiency in TiO2 photocatalytic system (Degussa P-25). Quantitative structure-activity relationship analysis revealed a strong correlation between reactivity of investigated dyes and Hammett substituent constants. The reaction was facilitated by electron-withdrawing groups, and retarded by electron-donating ones. Quantum mechanical calculations was used in order to describe the mechanism of the photocatalytic oxidation reactions of investigated dyes and interpret their reactivities within the framework of the Density Functional Theory (DFT). According to DFT based reactivity descriptors, i.e. Fukui functions and local softness, the active site moves from azo nitrogen atom linked to benzene ring to pyridone carbon atom linked to azo bond, going from dyes with electron-donating groups to dyes with electron-withdrawing groups.

  17. A quantitative structure-activity relationship to predict efficacy of granular activated carbon adsorption to control emerging contaminants.

    PubMed

    Kennicutt, A R; Morkowchuk, L; Krein, M; Breneman, C M; Kilduff, J E

    2016-08-01

    A quantitative structure-activity relationship was developed to predict the efficacy of carbon adsorption as a control technology for endocrine-disrupting compounds, pharmaceuticals, and components of personal care products, as a tool for water quality professionals to protect public health. Here, we expand previous work to investigate a broad spectrum of molecular descriptors including subdivided surface areas, adjacency and distance matrix descriptors, electrostatic partial charges, potential energy descriptors, conformation-dependent charge descriptors, and Transferable Atom Equivalent (TAE) descriptors that characterize the regional electronic properties of molecules. We compare the efficacy of linear (Partial Least Squares) and non-linear (Support Vector Machine) machine learning methods to describe a broad chemical space and produce a user-friendly model. We employ cross-validation, y-scrambling, and external validation for quality control. The recommended Support Vector Machine model trained on 95 compounds having 23 descriptors offered a good balance between good performance statistics, low error, and low probability of over-fitting while describing a wide range of chemical features. The cross-validated model using a log-uptake (qe) response calculated at an aqueous equilibrium concentration (Ce) of 1 μM described the training dataset with an r(2) of 0.932, had a cross-validated r(2) of 0.833, and an average residual of 0.14 log units.

  18. Using three-dimensional quantitative structure-activity relationships to examine estrogen receptor binding affinities of polychlorinated hydroxybiphenyls

    SciTech Connect

    Waller, C.L.; Minor, D.L.; McKinney, J.D.

    1995-07-01

    Certain phenyl-substituted hydrocarbons of environmental concern have the potential to disrupt the endocrine system of animals, apparently in association with their estrogenic properties. Competition with natural estrogens for the estrogen receptor is a possible mechanism by which such effects could occur. We used comparative molecular field analysis (CoMFA), a three-dimensional quantitative structure-activity relationship (QSAR) paradigm, to examine the underlying structural properties of ortho-chlorinated hydroxybiphenyl analogs known to bind to the estrogen receptor. The cross-validated and conventional statistical results indicate a high degree of internal predictability for the molecules included in the training data set. In addition to the phenolic (A) ring system, conformational restriction of the overall structure appears to play an important role in estrogen receptor binding affinity. Hydrophobic character as assessed using hydropathic interaction fields also contributes in a positive way to binding affinity. The CoMFA-derived QSARs may be useful in examining the estrogenic activity of a wider range of phenyl-substituted hydrocarbons of environmental concern. 37 refs., 2 figs., 2 tabs.

  19. Applying quantitative structure-activity relationship (QSAR) methodology for modeling postmortem redistribution of benzodiazepines and tricyclic antidepressants.

    PubMed

    Giaginis, Constantinos; Tsantili-Kakoulidou, Anna; Theocharis, Stamatios

    2014-06-01

    Postmortem redistribution (PMR) constitutes a multifaceted process, which complicates the interpretation of drug concentrations by forensic toxicologists. The present study aimed to apply quantitative structure-activity relationship (QSAR) analysis for modeling PMR data of structurally related drugs, 10 benzodiazepines and 10 tricyclic antidepressants. For benzodiazepines, an adequate QSAR model was obtained (R(2) = 0.98, Q(2) = 0.88, RMSEE = 0.12), in which energy, ionization and molecular size exerted significant impact. For tricyclic antidepressants, an adequate QSAR model with slightly inferior statistics (R(2) = 0.95, Q(2) = 0.87, RMSEE = 0.29) was established after exclusion of maprotiline, in which energy parameters, basicity character and lipophilicity exerted significant contribution. Thus, QSAR analysis could be used as a complementary tool to provide an informative illustration of the contributing molecular, physicochemical and structural properties in PMR process. However, the complexity, non-static and time-dependent nature of PMR endpoints raises serious concerns whether QSAR methodology could predict the degree of redistribution, highlighting the need for animal-derived PMR data.

  20. Quantitative structure-activity relationship model for the fetal-maternal blood concentration ratio of chemicals in humans.

    PubMed

    Takaku, Tomoyuki; Nagahori, Hirohisa; Sogame, Yoshihisa; Takagi, Tatsuya

    2015-01-01

    A quantitative structure-activity relationship (QSAR) model of the fetal-maternal blood concentration ratio (F/M ratio) of chemicals was developed to predict the placental transfer in humans. Data on F/M ratio of 55 compounds found in the literature were separated into training (75%, 41 compounds) and testing sets (25%, 14 compounds). The training sets were then subjected to multiple linear regression analysis using the descriptors of molecular weight (MW), topological polar surface area (TopoPSA), and maximum E-state of hydrogen atom (Hmax). Multiple linear regression analysis and a cross-validation showed a relatively high adjusted coefficient of determination (Ra(2)) (0.73) and cross-validated coefficient of determination (Q(2)) (0.71), after removing three outliers. In the external validation, R(2) for external validation (R(2)pred) was calculated to be 0.51. These results suggested that the QSAR model developed in this study can be considered reliable in terms of its robustness and predictive performance. Since it is difficult to examine the F/M ratio in humans experimentally, this QSAR model for prediction of the placental transfer of chemicals in humans could be useful in risk assessment of chemicals in humans.

  1. Ecotoxicity quantitative structure-activity relationships for alcohol ethoxylate mixtures based on substance-specific toxicity predictions.

    PubMed

    Boeije, G M; Cano, M L; Marshall, S J; Belanger, S E; Van Compernolle, R; Dorn, P B; Gümbel, H; Toy, R; Wind, T

    2006-05-01

    Traditionally, ecotoxicity quantitative structure-activity relationships (QSARs) for alcohol ethoxylate (AE) surfactants have been developed by assigning the measured ecotoxicity for commercial products to the average structures (alkyl chain length and ethoxylate chain length) of these materials. Acute Daphnia magna toxicity tests for binary mixtures indicate that mixtures are more toxic than the individual AE substances corresponding with their average structures (due to the nonlinear relation of toxicity with structure). Consequently, the ecotoxicity value (expressed as effects concentration) attributed to the average structures that are used to develop the existing QSARs is expected to be too low. A new QSAR technique for complex substances, which interprets the mixture toxicity with regard to the "ethoxymers" distribution (i.e., the individual AE components) rather than the average structure, was developed. This new technique was then applied to develop new AE ecotoxicity QSARs for invertebrates, fish, and mesocosms. Despite the higher complexity, the fit and accuracy of the new QSARs are at least as good as those for the existing QSARs based on the same data set. As expected from typical ethoxymer distributions of commercial AEs, the new QSAR generally predicts less toxicity than the QSARs based on average structure. PMID:16256196

  2. Quantitative Structure-Activity Relationships Study on the Rate Constants of Polychlorinated Dibenzo-p-Dioxins with OH Radical

    PubMed Central

    Qi, Chuansong; Zhang, Chenxi; Sun, Xiaomin

    2015-01-01

    The OH-initiated reaction rate constants (kOH) are of great importance to measure atmospheric behaviors of polychlorinated dibenzo-p-dioxins (PCDDs) in the environment. The rate constants of 75 PCDDs with the OH radical at 298.15 K have been calculated using high level molecular orbital theory, and the rate constants (kα, kβ, kγ and kOH) were further analyzed by the quantitative structure-activity relationships (QSAR) study. According to the QSAR models, the relations between rate constants and the numbers and positions of Cl atoms, the energy of the highest occupied molecular orbital (EHOMO), the energy of the lowest unoccupied molecular orbital (ELUMO), the difference ΔEHOMO-LUMO between EHOMO and ELUMO, and the dipole of oxidizing agents (D) were discussed. It was found that EHOMO is the main factor in the kOH. The number of Cl atoms is more effective than the number of relative position of these Cl atoms in the kOH. The kOH decreases with the increase of the substitute number of Cl atoms. PMID:26274950

  3. Investigation of the quantitative accuracy of 3D iterative reconstruction algorithms in comparison to filtered back projection method: a phantom study

    NASA Astrophysics Data System (ADS)

    Abuhadi, Nouf; Bradley, David; Katarey, Dev; Podolyak, Zsolt; Sassi, Salem

    2014-03-01

    Introduction: Single-Photon Emission Computed Tomography (SPECT) is used to measure and quantify radiopharmaceutical distribution within the body. The accuracy of quantification depends on acquisition parameters and reconstruction algorithms. Until recently, most SPECT images were constructed using Filtered Back Projection techniques with no attenuation or scatter corrections. The introduction of 3-D Iterative Reconstruction algorithms with the availability of both computed tomography (CT)-based attenuation correction and scatter correction may provide for more accurate measurement of radiotracer bio-distribution. The effect of attenuation and scatter corrections on accuracy of SPECT measurements is well researched. It has been suggested that the combination of CT-based attenuation correction and scatter correction can allow for more accurate quantification of radiopharmaceutical distribution in SPECT studies (Bushberg et al., 2012). However, The effect of respiratory induced cardiac motion on SPECT images acquired using higher resolution algorithms such 3-D iterative reconstruction with attenuation and scatter corrections has not been investigated. Aims: To investigate the quantitative accuracy of 3D iterative reconstruction algorithms in comparison to filtered back projection (FBP) methods implemented on cardiac SPECT/CT imaging with and without CT-attenuation and scatter corrections. Also to investigate the effects of respiratory induced cardiac motion on myocardium perfusion quantification. Lastly, to present a comparison of spatial resolution for FBP and ordered subset expectation maximization (OSEM) Flash 3D together with and without respiratory induced motion, and with and without attenuation and scatter correction. Methods: This study was performed on a Siemens Symbia T16 SPECT/CT system using clinical acquisition protocols. Respiratory induced cardiac motion was simulated by imaging a cardiac phantom insert whilst moving it using a respiratory motion motor

  4. Taming supersymmetric defects in 3d-3d correspondence

    NASA Astrophysics Data System (ADS)

    Gang, Dongmin; Kim, Nakwoo; Romo, Mauricio; Yamazaki, Masahito

    2016-07-01

    We study knots in 3d Chern-Simons theory with complex gauge group {SL}(N,{{C}}), in the context of its relation with 3d { N }=2 theory (the so-called 3d-3d correspondence). The defect has either co-dimension 2 or co-dimension 4 inside the 6d (2,0) theory, which is compactified on a 3-manifold \\hat{M}. We identify such defects in various corners of the 3d-3d correspondence, namely in 3d {SL}(N,{{C}}) CS theory, in 3d { N }=2 theory, in 5d { N }=2 super Yang-Mills theory, and in the M-theory holographic dual. We can make quantitative checks of the 3d-3d correspondence by computing partition functions at each of these theories. This Letter is a companion to a longer paper [1], which contains more details and more results.

  5. A comparison of three SPRITE techniques for the quantitative 3D imaging of the 23Na spin density on a 4T whole-body machine.

    PubMed

    Romanzetti, S; Halse, M; Kaffanke, J; Zilles, K; Balcom, B J; Shah, N J

    2006-03-01

    Sodium density maps acquired with three SPRITE-based methods have been compared in terms of the resulting quantitative information as well as image quality and acquisition times. Consideration of factors relevant for the clinical implementation of SPRITE shows that the Conical-SPRITE variant is preferred because of a 20-fold reduction in acquisition time, slightly improved image quality, and no loss of quantitative information. The acquisition of a 3D data set (32x32x16; FOV=256x256x160 mm) for the quantitative determination of sodium density is demonstrated. In vivo Conical-SPRITE 23Na images of the brain of a healthy volunteer were acquired in 30 min with a resolution of 7.5x7.5x7.5 mm and a signal-to-noise ratio of 23 in cerebrospinal fluid and 17 in brain tissue. PMID:16325438

  6. Parabolic quantitative structure-activity relationships and photodynamic therapy: application of a three-compartment model with clearance to the in vivo quantitative structure-activity relationships of a congeneric series of pyropheophorbide derivatives used as photosensitizers for photodynamic therapy.

    PubMed

    Potter, W R; Henderson, B W; Bellnier, D A; Pandey, R K; Vaughan, L A; Weishaupt, K R; Dougherty, T J

    1999-11-01

    An open three-compartment pharmacokinetic model was applied to the in vivo quantitative structure-activity relationship (QSAR) data of a homologous series of pyropheophorbide photosensitizers for photodynamic therapy (PDT). The physical model was a lipid compartment sandwiched between two identical aqueous compartments. The first compartment was assumed to clear irreversibly at a rate K0. The measured octanol-water partition coefficients, P(i) (where i is the number of carbons in the alkyl chain) and the clearance rate K0 determined the clearance kinetics of the drugs. Solving the coupled differential equations of the three-compartment model produced clearance kinetics for each of the sensitizers in each of the compartments. The third compartment was found to contain the target of PDT. This series of compounds is quite lipophilic. Therefore these drugs are found mainly in the second compartment. The drug level in the third compartment represents a small fraction of the tissue level and is thus not accessible to direct measurement by extraction. The second compartment of the model accurately predicted the clearance from the serum of mice of the hexyl ether of pyropheophorbide a, one member of this series of compounds. The diffusion and clearance rate constants were those found by fitting the pharmacokinetics of the third compartment to the QSAR data. This result validated the magnitude and mechanistic significance of the rate constants used to model the QSAR data. The PDT response to dose theory was applied to the kinetic behavior of the target compartment drug concentration. This produced a pharmacokinetic-based function connecting PDT response to dose as a function of time postinjection. This mechanistic dose-response function was fitted to published, single time point QSAR data for the pheophorbides. As a result, the PDT target threshold dose together with the predicted QSAR as a function of time postinjection was found.

  7. Designing Anti-Influenza Aptamers: Novel Quantitative Structure Activity Relationship Approach Gives Insights into Aptamer – Virus Interaction

    PubMed Central

    Musafia, Boaz; Oren-Banaroya, Rony; Noiman, Silvia

    2014-01-01

    This study describes the development of aptamers as a therapy against influenza virus infection. Aptamers are oligonucleotides (like ssDNA or RNA) that are capable of binding to a variety of molecular targets with high affinity and specificity. We have studied the ssDNA aptamer BV02, which was designed to inhibit influenza infection by targeting the hemagglutinin viral protein, a protein that facilitates the first stage of the virus’ infection. While testing other aptamers and during lead optimization, we realized that the dominant characteristics that determine the aptamer’s binding to the influenza virus may not necessarily be sequence-specific, as with other known aptamers, but rather depend on general 2D structural motifs. We adopted QSAR (quantitative structure activity relationship) tool and developed computational algorithm that correlate six calculated structural and physicochemical properties to the aptamers’ binding affinity to the virus. The QSAR study provided us with a predictive tool of the binding potential of an aptamer to the influenza virus. The correlation between the calculated and actual binding was R2 = 0.702 for the training set, and R2 = 0.66 for the independent test set. Moreover, in the test set the model’s sensitivity was 89%, and the specificity was 87%, in selecting aptamers with enhanced viral binding. The most important properties that positively correlated with the aptamer’s binding were the aptamer length, 2D-loops and repeating sequences of C nucleotides. Based on the structure-activity study, we have managed to produce aptamers having viral affinity that was more than 20 times higher than that of the original BV02 aptamer. Further testing of influenza infection in cell culture and animal models yielded aptamers with 10 to 15 times greater anti-viral activity than the BV02 aptamer. Our insights concerning the mechanism of action and the structural and physicochemical properties that govern the interaction with the

  8. Issues involved in the quantitative 3D imaging of proton doses using optical CT and chemical dosimeters.

    PubMed

    Doran, Simon; Gorjiara, Tina; Kacperek, Andrzej; Adamovics, John; Kuncic, Zdenka; Baldock, Clive

    2015-01-21

    Dosimetry of proton beams using 3D imaging of chemical dosimeters is complicated by a variation with proton linear energy transfer (LET) of the dose-response (the so-called 'quenching effect'). Simple theoretical arguments lead to the conclusion that the total absorbed dose from multiple irradiations with different LETs cannot be uniquely determined from post-irradiation imaging measurements on the dosimeter. Thus, a direct inversion of the imaging data is not possible and the proposition is made to use a forward model based on appropriate output from a planning system to predict the 3D response of the dosimeter. In addition to the quenching effect, it is well known that chemical dosimeters have a non-linear response at high doses. To the best of our knowledge it has not yet been determined how this phenomenon is affected by LET. The implications for dosimetry of a number of potential scenarios are examined.Dosimeter response as a function of depth (and hence LET) was measured for four samples of the radiochromic plastic PRESAGE(®), using an optical computed tomography readout and entrance doses of 2.0 Gy, 4.0 Gy, 7.8 Gy and 14.7 Gy, respectively. The dosimeter response was separated into two components, a single-exponential low-LET response and a LET-dependent quenching. For the particular formulation of PRESAGE(®) used, deviations from linearity of the dosimeter response became significant for doses above approximately 16 Gy. In a second experiment, three samples were each irradiated with two separate beams of 4 Gy in various different configurations. On the basis of the previous characterizations, two different models were tested for the calculation of the combined quenching effect from two contributions with different LETs. It was concluded that a linear superposition model with separate calculation of the quenching for each irradiation did not match the measured result where two beams overlapped. A second model, which used the concept of an

  9. Structural development of benzhydrol-type 1'-acetoxychavicol acetate (ACA) analogs as human leukemia cell-growth inhibitors based on quantitative structure-activity relationship (QSAR) analysis.

    PubMed

    Misawa, Takashi; Aoyama, Hiroshi; Furuyama, Taniyuki; Dodo, Kosuke; Sagawa, Morihiko; Miyachi, Hiroyuki; Kizaki, Masahiro; Hashimoto, Yuichi

    2008-10-01

    Benzhydrol-type analogs of 1'-acetoxychavicol acetate (ACA) were developed as inhibitors of human leukemia HL-60 cell growth based on quantitative structure-activity relationship (QSAR) analysis. An analog containing an anthracenyl moiety (8) was a potent inhibitor with the IC(50) value of 0.12 microM.

  10. Quantitative description of the 3D regional mechanics of the left atrium using cardiac magnetic resonance imaging.

    PubMed

    Kuklik, P; Molaee, P; Podziemski, P; Ganesan, A N; Brooks, A G; Worthley, S G; Sanders, P

    2014-05-01

    The left atrium (LA) plays an important role in the maintenance of hemodynamic and electrical stability of the heart. One of the conditions altering the atrial mechanical function is atrial fibrillation (AF), leading to an increased thromboembolic risk due to impaired mechanical function. Preserving the regions of the LA that contribute the greatest to atrial mechanical function during curative strategies for AF is important. The purpose of this study is to introduce a novel method of regional assessment of mechanical function of the LA. We used cardiac MRI to reconstruct the 3D geometry of the LA in nine control and nine patients with paroxysmal atrial fibrillation (PAF). Regional mechanical function of the LA in pre-defined segments of the atrium was calculated using regional ejection fraction and wall velocity. We found significantly greater mechanical function in anterior, septal and lateral segments as opposed to roof and posterior segments, as well as a significant decrease of mechanical function in the PAF group. We suggest that in order to minimize the impact of the AF treatment on global atrial mechanical function, damage related to therapeutic intervention, such as catheter ablation, in those areas should be minimized.

  11. Orientation-weighted local Minkowski functionals in 3D for quantitative assessment of trabecular bone structure in the hip

    NASA Astrophysics Data System (ADS)

    Boehm, H. F.; Bitterling, H.; Weber, C.; Kuhn, V.; Eckstein, F.; Reiser, M.

    2007-03-01

    Fragility fractures or pathologic fractures of the hip, i.e. fractures with no apparent trauma, represent the worst complication in osteoporosis with a mortality close to 25% during the first post-traumatic year. Over 90% of hip fractures result from falls from standing height. A substantial number of femoral fractures are initiated in the femoral neck or the trochanteric regions which contain an internal architecture of trabeculae that are functionally highly specialized to withstand the complex pattern of external and internal forces associated with human gait. Prediction of the mechanical strength of bone tissue can be achieved by dedicated texture analysis of data obtained by high resolution imaging modalities, e.g. computed tomography (CT) or magnetic resonance tomography (MRI). Since in the case of the proximal femur, the connectivity, regional distribution and - most of all - the preferred orientation of individual trabeculae change considerably within narrow spatial limits, it seems most reasonable to evaluate the femoral bone structure on an orientation-weighted, local scale. In past studies, we could demonstrate the advantages of topological analysis of bone structure using the Minkowski Functionals in 3D on a global and on a local scale. The current study was designed to test the hypothesis that the prediction of the mechanical competence of the proximal femur by a new algorithm considering orientational changes of topological properties in the trabecular architecture is feasible and better suited than conventional methods based on the measurement of the mineral density of bone tissue (BMD).

  12. High density resolution synchrotron radiation based x-ray microtomography (SR μCT) for quantitative 3D-morphometrics in zoological sciences

    NASA Astrophysics Data System (ADS)

    Nickel, Michael; Hammel, Jörg U.; Herzen, Julia; Bullinger, Eric; Beckmann, Felix

    2008-08-01

    Zoological sciences widely rely on morphological data to reconstruct and understand body structures of animals. The best suitable methods like tomography allow for a direct representation of 3D-structures. In recent years, synchrotron radiation based x-ray microtomography (SR μCT) placed high resolutions to the disposal of morphologists. With the development of highly brilliant and collimated third generation synchrotron sources, phase contrast SR μCT became widely available. A number of scientific contributions stressed the superiority of phase contrast over absorption contrast. However, here we demonstrate the power of high density resolution methods based on absorption-contrast SRμCT for quantitative 3D-measurements of tissues and other delicate bio-structures in zoological sciences. We used beamline BW2 at DORIS III (DESY, Hamburg, Germany) to perform microtomography on tissue and mineral skeletons of marine sponges (Porifera) which were shock frozen and/or fixed in a glutamate osmium tetroxide solution, followed by critical point drying. High density resolution tomographic reconstructions allowed running quantitative 3D-image analyses in Matlab and ImageJ. By applying contrast and shape rule based algorithms we semi-automatically extracted and measured sponge body structures like mineral spicules, elements of the canal system or tissue structures. This lead to a better understanding of sponge biology: from skeleton functional morphology and internal water flow regimes to body contractility. Our high density resolution based quantitative approach can be applied to a wide variety of biological structures. However, two prerequisites apply: (1) maximum density resolution is necessary; (2) edge effects as seen for example in phase outline contrast SR μCT must not be present. As a consequence, to allow biological sciences to fully exploit the power of SR μCT further increase of density resolution in absorption contrast methods is desirable.

  13. Toxicity of substituted anilines to Pseudokirchneriella subcapitata and quantitative structure-activity relationship analysis for polar narcotics.

    PubMed

    Chen, Chung-Yuan; Ko, Chia-Wen; Lee, Po-I

    2007-06-01

    This study evaluated the toxic effects of substituted anilines on Pseudokirchneriella subcapitata with the use of a closed algal toxicity testing technique with no headspace. Two response endpoints (i.e., dissolved oxygen production [DO] and algal growth rate) were used to evaluate the toxicity of anilines. Both DO and growth rate endpoints revealed similar sensitivity to the effects of anilines. However, trichloroanilines showed stronger inhibitory effects on microalgal photosynthetic reactions than that on algal growth. For various aquatic organisms, the relative sensitivity relationship for anilines is Daphnia magna > luminescent bacteria (Microtox) > or = Pocelia reticulata > or = Pseudokirchneriella subcapitata > or = fathead minnow > Tetrahymena pyriformis. The susceptibility of P. subcapitata to anilines is similar to fish, but P. subcapitata is apparently less sensitive than the water flea. The lack of correlation between the toxicity revealed by different aquatic organisms (microalgae, D. magna, luminescent bacteria, and P. reticulata) suggests that anilines might have different metabolic routes in these organisms. Both hydrogen bonding donor capacity (the lowest unoccupied molecular orbital energy, Elumo) and hydrophobicity (1-octanol:water partition coefficient, Kow) were found to provide satisfactory descriptions for the toxicity of polar narcotics (substituted anilines and chlorophenols). Quantitative structure-activity relationships (QSARs) based on Elumo, log Kow, or both values were established with r2 values varying from 0.75 to 0.92. The predictive power for the QSAR models were found to be satisfactory through leave-one-out cross-validation. Such relationships could provide useful information for the estimation of toxicity for other polar narcotic compounds.

  14. Development of acute toxicity quantitative structure activity relationships (QSAR) and their use in linear alkylbenzene sulfonate species sensitivity distributions.

    PubMed

    Belanger, Scott E; Brill, Jessica L; Rawlings, Jane M; Price, Brad B

    2016-07-01

    Linear Alkylbenzene Sulfonate (LAS) is high tonnage and widely dispersed anionic surfactant used by the consumer products sector. A range of homologous structures are used in laundry applications that differ primarily on the length of the hydrophobic alkyl chain. This research summarizes the development of a set of acute toxicity QSARs (Quantitative Structure Activity Relationships) for fathead minnows (Pimephales promelas) and daphnids (Daphnia magna, Ceriodaphnia dubia) using accepted test guideline approaches. A series of studies on pure chain length LAS from C10 to C14 were used to develop the QSARs and the robustness of the QSARs was tested by evaluation of two technical mixtures of differing compositions. All QSARs were high quality (R(2) were 0.965-0.997, p < 0.0001). Toxicity normalization employing QSARs is used to interpret a broader array of tests on LAS chain length materials to a diverse group of test organisms with the objective of developing Species Sensitivity Distributions (SSDs) for various chain lengths of interest. Mixtures include environmental distributions measured from exposure monitoring surveys of wastewater effluents, various commercial mixtures, or specific chain lengths. SSD 5th percentile hazardous concentrations (HC5s) ranged from 0.129 to 0.254 mg/L for wastewater effluents containing an average of 11.26-12 alkyl carbons. The SSDs are considered highly robust given the breadth of species (n = 19), use of most sensitive endpoints from true chronic studies and the quality of the underlying statistical properties of the SSD itself. The data continue to indicate a low hazard to the environment relative to expected environmental concentrations.

  15. Assessment of quantitative structure-activity relationship of toxicity prediction models for Korean chemical substance control legislation

    PubMed Central

    Kim, Kwang-Yon; Shin, Seong Eun; No, Kyoung Tai

    2015-01-01

    Objectives For successful adoption of legislation controlling registration and assessment of chemical substances, it is important to obtain sufficient toxicological experimental evidence and other related information. It is also essential to obtain a sufficient number of predicted risk and toxicity results. Particularly, methods used in predicting toxicities of chemical substances during acquisition of required data, ultimately become an economic method for future dealings with new substances. Although the need for such methods is gradually increasing, the-required information about reliability and applicability range has not been systematically provided. Methods There are various representative environmental and human toxicity models based on quantitative structure-activity relationships (QSAR). Here, we secured the 10 representative QSAR-based prediction models and its information that can make predictions about substances that are expected to be regulated. We used models that predict and confirm usability of the information expected to be collected and submitted according to the legislation. After collecting and evaluating each predictive model and relevant data, we prepared methods quantifying the scientific validity and reliability, which are essential conditions for using predictive models. Results We calculated predicted values for the models. Furthermore, we deduced and compared adequacies of the models using the Alternative non-testing method assessed for Registration, Evaluation, Authorization, and Restriction of Chemicals Substances scoring system, and deduced the applicability domains for each model. Additionally, we calculated and compared inclusion rates of substances expected to be regulated, to confirm the applicability. Conclusions We evaluated and compared the data, adequacy, and applicability of our selected QSAR-based toxicity prediction models, and included them in a database. Based on this data, we aimed to construct a system that can be used

  16. Synthesis and quantitative structure activity relationship (QSAR) of arylidene (benzimidazol-1-yl)acetohydrazones as potential antibacterial agents.

    PubMed

    El-Kilany, Yeldez; Nahas, Nariman M; Al-Ghamdi, Mariam A; Badawy, Mohamed E I; El Ashry, El Sayed H

    2015-01-01

    Ethyl (benzimidazol-1-yl)acetate was subjected to hydrazinolysis with hydrazine hydrate to give (benzimidazol-1-yl)acetohydrazide. The latter was reacted with various aromatic aldehydes to give the respective arylidene (1H-benzimidazol-1-yl)acetohydrazones. Solutions of the prepared hydrazones were found to contain two geometric isomers. Similarly (2-methyl-benzimidazol-1-yl)acetohydrazide was reacted with various aldehydes to give the corresponding hydrazones. The antibacterial activity was evaluated in vitro by minimum inhibitory concentration (MIC) against Agrobacterium tumefaciens (A. tumefaciens), Erwinia carotovora (E. carotovora), Corynebacterium fascians (C. fascians) and Pseudomonas solanacearum (P. solanacearum). MIC result demonstrated that salicylaldehyde(1H-benzimidazol-1-yl)acetohydrazone (4) was the most active compound (MIC = 20, 35, 25 and 30 mg/L against A. tumefaciens, C. fascians, E. carotovora and P. solanacearum, respectively). Quantitative structure activity relationship (QSAR) investigation using Hansch analysis was applied to find out the correlation between antibacterial activity and physicochemical properties. Various physicochemical descriptors and experimentally determined MIC values for different microorganisms were used as independent and dependent variables, respectively. pMICs of the compounds exhibited good correlation (r = 0.983, 0.914, 0.960 and 0.958 for A. tumefaciens, C. fascians, E. carotovora and P. solanacearum, respectively) with the prediction made by the model. QSAR study revealed that the hydrophobic parameter (ClogP), the aqueous solubility (LogS), calculated molar refractivity, topological polar surface area and hydrogen bond acceptor were found to have overall significant correlation with antibacterial activity. The statistical results of training set, correlation coefficient (r and r (2)), the ratio between regression and residual variances (f, Fisher's statistic), the standard error of estimates and

  17. Oxidative toxicity of perfluorinated chemicals in green mussel and bioaccumulation factor dependent quantitative structure-activity relationship.

    PubMed

    Liu, Changhui; Chang, Victor W C; Gin, Karina Y H

    2014-10-01

    Concerns regarding perfluorinated chemicals (PFCs) have risen in recent years because of their ubiquitous presence and high persistency. However, data on the environmental impacts of PFCs on marine organisms are very limited. Oxidative toxicity has been suggested to be one of the major toxic pathways for PFCs to induce adverse effects on organisms. To investigate PFC-induced oxidative stress and oxidative toxicity, a series of antioxidant enzyme activities and oxidative damage biomarkers were examined to assess the adverse effects of the following 4 commonly detected compounds: perfluoro-octanesulfonate, perfluoro-ocanoic acid, perfluorononanoic acid, and perfluorodecanoic acid, on green mussel (Perna viridis). Quantitative structure-activity relationship (QSAR) models were also established. The results showed that all the tested PFCs are able to induce antioxidant response and oxidative damage on green mussels in a dose-dependent manner. At low exposure levels (0 µg/L-100 µg/L), activation of antioxidant enzymes (catalase [CAT] and superoxide dismutase [SOD]) was observed, which is an adaptive response to the excessive reactive oxygen species induced by PFCs, while at high exposure levels (100 µg/L-10 000 µg/L), PFCs were found to inhibit some enzyme activity (glutathione S-transferase and SOD) where the organism's ability to respond in an adaptive manner was compromised. The oxidative stress under high PFC exposure concentration also led to lipid and DNA damage. PFC-induced oxidative toxicity was found to be correlated with the bioaccumulation potential of PFCs. Based on this relationship, QSAR models were established using the bioaccumulation factor (BAF) as the molecular descriptor for the first time. Compared with previous octanol-water partition coefficient-dependent QSAR models, the BAF-dependent QSAR model is more suitable for the impact assessment of PFCs and thus provides a more accurate description of the toxic behavior of these compounds.

  18. Comparison of the applicability domain of a quantitative structure-activity relationship for estrogenicity with a large chemical inventory.

    PubMed

    Netzeva, Tatiana I; Gallegos Saliner, Ana; Worth, Andrew P

    2006-05-01

    The aim of the present study was to illustrate that it is possible and relatively straightforward to compare the domain of applicability of a quantitative structure-activity relationship (QSAR) model in terms of its physicochemical descriptors with a large inventory of chemicals. A training set of 105 chemicals with data for relative estrogenic gene activation, obtained in a recombinant yeast assay, was used to develop the QSAR. A binary classification model for predicting active versus inactive chemicals was developed using classification tree analysis and two descriptors with a clear physicochemical meaning (octanol-water partition coefficient, or log Kow, and the number of hydrogen bond donors, or n(Hdon)). The model demonstrated a high overall accuracy (90.5%), with a sensitivity of 95.9% and a specificity of 78.1%. The robustness of the model was evaluated using the leave-many-out cross-validation technique, whereas the predictivity was assessed using an artificial external test set composed of 12 compounds. The domain of the QSAR training set was compared with the chemical space covered by the European Inventory of Existing Commercial Chemical Substances (EINECS), as incorporated in the CDB-EC software, in the log Kow / n(Hdon) plane. The results showed that the training set and, therefore, the applicability domain of the QSAR model covers a small part of the physicochemical domain of the inventory, even though a simple method for defining the applicability domain (ranges in the descriptor space) was used. However, a large number of compounds are located within the narrow descriptor window.

  19. Development of acute toxicity quantitative structure activity relationships (QSAR) and their use in linear alkylbenzene sulfonate species sensitivity distributions.

    PubMed

    Belanger, Scott E; Brill, Jessica L; Rawlings, Jane M; Price, Brad B

    2016-07-01

    Linear Alkylbenzene Sulfonate (LAS) is high tonnage and widely dispersed anionic surfactant used by the consumer products sector. A range of homologous structures are used in laundry applications that differ primarily on the length of the hydrophobic alkyl chain. This research summarizes the development of a set of acute toxicity QSARs (Quantitative Structure Activity Relationships) for fathead minnows (Pimephales promelas) and daphnids (Daphnia magna, Ceriodaphnia dubia) using accepted test guideline approaches. A series of studies on pure chain length LAS from C10 to C14 were used to develop the QSARs and the robustness of the QSARs was tested by evaluation of two technical mixtures of differing compositions. All QSARs were high quality (R(2) were 0.965-0.997, p < 0.0001). Toxicity normalization employing QSARs is used to interpret a broader array of tests on LAS chain length materials to a diverse group of test organisms with the objective of developing Species Sensitivity Distributions (SSDs) for various chain lengths of interest. Mixtures include environmental distributions measured from exposure monitoring surveys of wastewater effluents, various commercial mixtures, or specific chain lengths. SSD 5th percentile hazardous concentrations (HC5s) ranged from 0.129 to 0.254 mg/L for wastewater effluents containing an average of 11.26-12 alkyl carbons. The SSDs are considered highly robust given the breadth of species (n = 19), use of most sensitive endpoints from true chronic studies and the quality of the underlying statistical properties of the SSD itself. The data continue to indicate a low hazard to the environment relative to expected environmental concentrations. PMID:27105149

  20. A novel quantitative structure-activity relationship model for prediction of biomagnification factor of some organochlorine pollutants.

    PubMed

    Fatemi, Mohammad Hossein; Baher, Elham

    2009-08-01

    The biomagnification factor (BMF) is an important property for toxicology and environmental chemistry. In this work, quantitative structure-activity relationship (QSAR) models were used for the prediction of BMF for a data set including 30 polychlorinated biphenyls and 12 organochlorine pollutants. This set was divided into training and prediction sets. The result of diversity test reveals that the structure of the training and test sets can represent those of the whole ones. After calculation and screening of a large number of molecular descriptors, the methods of stepwise multiple linear regression and genetic algorithm (GA) were used for the selection of most important and significant descriptors which were related to BMF. Then multiple linear regression and artificial neural network (ANN) techniques were applied as linear and non-linear feature mapping techniques, respectively. By comparison between statistical parameters of these methods it was concluded that an ANN model, which used GA selected descriptors, was superior over constructed models. Descriptors which were used by this model are: topographic electronic index, complementary information content, XY shadow/XY rectangle and difference between partial positively and negatively charge surface area. The standard errors for training and test sets of this model are 0.03 and 0.20, respectively. The degree of importance of each descriptor was evaluated by sensitivity analysis approach for the nonlinear model. A good results (Q (2) = 0.97 and SPRESS = 0.084) is obtained by applying cross-validation test that indicating the validation of descriptors in the obtained model in prediction of BMF for these compounds. PMID:19219557

  1. Modeling liver-related adverse effects of drugs using knearest neighbor quantitative structure-activity relationship method.

    PubMed

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

    2010-04-19

    Adverse effects of drugs (AEDs) continue to be a major cause of drug withdrawals in both development and postmarketing. 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 ratios 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 data sets. Models with high sensitivity (>73%) and specificity (>94%) for the 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 preclinical screening of drug candidates for potential hepatotoxicity in humans. PMID:20192250

  2. Rational Quantitative Structure-Activity Relationship (RQSAR) Screen for PXR and CAR Isoform-Specific Nuclear Receptor Ligands

    PubMed Central

    Dring, Ann M.; Anderson, Linnea E.; Qamar, Saima; Stoner, Matthew A.

    2010-01-01

    Constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are closely related orphan nuclear receptor proteins that share several ligands and target overlapping sets of genes involved in homeostasis and all phases of drug metabolism. CAR and PXR are involved in the development of certain diseases, including diabetes, metabolic syndrome and obesity. Ligand screens for these receptors so far have typically focused on steroid hormone analogs with pharmacophore-based approaches, only to find relatively few new hits. Multiple CAR isoforms have been detected in human liver, with the most abundant being the constitutively active reference, CAR1, and the ligand-dependent isoform CAR3. It has been assumed that any compound that binds CAR1 should also activate CAR3, and so CAR3 can be used as a ligand-activated surrogate for CAR1 studies. The possibility of CAR3-specific ligands has not, so far, been addressed. To investigate the differences between CAR1, CAR3 and PXR, and to look for more CAR ligands that may be of use in quantitative structure-activity relationship (QSAR) studies, we performed a luciferase transactivation assay screen of 60 mostly non-steroid compounds. Known active compounds with different core chemistries were chosen as starting points and structural variants were rationally selected for screening. Distinct differences in agonist versus inverse agonist/antagonist effects were seen in 49 compounds that had some ligand effect on at least one receptor and 18 that had effects on all three receptors; eight were CAR1 ligands only, three were CAR3 only ligands and four affected PXR only. This work provides evidence for new CAR ligands, some of which have CAR3-specific effects, and provides observational data on CAR and PXR ligands with which to inform in silico strategies. Compounds that demonstrated unique activity on any one receptor are potentially valuable diagnostic tools for the investigation of in vivo molecular targets. PMID:20869355

  3. RGB Color Calibration for Quantitative Image Analysis: The “3D Thin-Plate Spline” Warping Approach

    PubMed Central

    Menesatti, Paolo; Angelini, Claudio; Pallottino, Federico; Antonucci, Francesca; Aguzzi, Jacopo; Costa, Corrado

    2012-01-01

    In the last years the need to numerically define color by its coordinates in n-dimensional space has increased strongly. Colorimetric calibration is fundamental in food processing and other biological disciplines to quantitatively compare samples' color during workflow with many devices. Several software programmes are available to perform standardized colorimetric procedures, but they are often too imprecise for scientific purposes. In this study, we applied the Thin-Plate Spline interpolation algorithm to calibrate colours in sRGB space (the corresponding Matlab code is reported in the Appendix). This was compared with other two approaches. The first is based on a commercial calibration system (ProfileMaker) and the second on a Partial Least Square analysis. Moreover, to explore device variability and resolution two different cameras were adopted and for each sensor, three consecutive pictures were acquired under four different light conditions. According to our results, the Thin-Plate Spline approach reported a very high efficiency of calibration allowing the possibility to create a revolution in the in-field applicative context of colour quantification not only in food sciences, but also in other biological disciplines. These results are of great importance for scientific color evaluation when lighting conditions are not controlled. Moreover, it allows the use of low cost instruments while still returning scientifically sound quantitative data. PMID:22969337

  4. A versatile pipeline for the multi-scale digital reconstruction and quantitative analysis of 3D tissue architecture

    PubMed Central

    Morales-Navarrete, Hernán; Segovia-Miranda, Fabián; Klukowski, Piotr; Meyer, Kirstin; Nonaka, Hidenori; Marsico, Giovanni; Chernykh, Mikhail; Kalaidzidis, Alexander; Zerial, Marino; Kalaidzidis, Yannis

    2015-01-01

    A prerequisite for the systems biology analysis of tissues is an accurate digital three-dimensional reconstruction of tissue structure based on images of markers covering multiple scales. Here, we designed a flexible pipeline for the multi-scale reconstruction and quantitative morphological analysis of tissue architecture from microscopy images. Our pipeline includes newly developed algorithms that address specific challenges of thick dense tissue reconstruction. Our implementation allows for a flexible workflow, scalable to high-throughput analysis and applicable to various mammalian tissues. We applied it to the analysis of liver tissue and extracted quantitative parameters of sinusoids, bile canaliculi and cell shapes, recognizing different liver cell types with high accuracy. Using our platform, we uncovered an unexpected zonation pattern of hepatocytes with different size, nuclei and DNA content, thus revealing new features of liver tissue organization. The pipeline also proved effective to analyse lung and kidney tissue, demonstrating its generality and robustness. DOI: http://dx.doi.org/10.7554/eLife.11214.001 PMID:26673893

  5. Quantitative, 3D Visualization of the Initiation and Progression of Vertebral Fractures Under Compression and Anterior Flexion.

    PubMed

    Jackman, Timothy M; Hussein, Amira I; Curtiss, Cameron; Fein, Paul M; Camp, Anderson; De Barros, Lidia; Morgan, Elise F

    2016-04-01

    The biomechanical mechanisms leading to vertebral fractures are not well understood. Clinical and laboratory evidence suggests that the vertebral endplate plays a key role in failure of the vertebra as a whole, but how this role differs for different types of vertebral loading is not known. Mechanical testing of human thoracic spine segments, in conjunction with time-lapsed micro-computed tomography, enabled quantitative assessment of deformations occurring throughout the entire vertebral body under axial compression combined with anterior flexion ("combined loading") and under axial compression only ("compression loading"). The resulting deformation maps indicated that endplate deflection was a principal feature of vertebral failure for both loading modes. Specifically, the onset of endplate deflection was temporally coincident with a pronounced drop in the vertebra's ability to support loads. The location of endplate deflection, and also vertebral strength, were associated with the porosity of the endplate and the microstructure of the underlying trabecular bone. However, the location of endplate deflection and the involvement of the cortex differed between the two types of loading. Under the combined loading, deflection initiated, and remained the largest, at the anterior central endplate or the anterior ring apophysis, depending in part on health of the adjacent intervertebral disc. This deflection was accompanied by outward bulging of the anterior cortex. In contrast, the location of endplate deflection was more varied in compression loading. For both loading types, the earliest progression to a mild fracture according to a quantitative morphometric criterion occurred only after much of the failure process had occurred. The outcomes of this work indicate that for two physiological loading modes, the vertebral endplate and underlying trabecular bone are critically involved in vertebral fracture. These outcomes provide a strong biomechanical rationale for

  6. Quantitative structure-activity relationship study of antioxidative peptide by using different sets of amino acids descriptors

    NASA Astrophysics Data System (ADS)

    Li, Yao-Wang; Li, Bo; He, Jiguo; Qian, Ping

    2011-07-01

    A database consisting of 214 tripeptides which contain either His or Tyr residue was applied to study quantitative structure-activity relationships (QSAR) of antioxidative tripeptides. Partial Least-Squares Regression analysis (PLSR) was conducted using parameters individually of each amino acid descriptor, including Divided Physico-chemical Property Scores (DPPS), Hydrophobic, Electronic, Steric, and Hydrogen (HESH), Vectors of Hydrophobic, Steric, and Electronic properties (VHSE), Molecular Surface-Weighted Holistic Invariant Molecular (MS-WHIM), isotropic surface area-electronic charge index (ISA-ECI) and Z-scale, to describe antioxidative tripeptides as X-variables and antioxidant activities measured with ferric thiocyanate methods were as Y-variable. After elimination of outliers by Hotelling's T 2 method and residual analysis, six significant models were obtained describing the entire data set. According to cumulative squared multiple correlation coefficients ( R2), cumulative cross-validation coefficients ( Q2) and relative standard deviation for calibration set (RSD c), the qualities of models using DPPS, HESH, ISA-ECI, and VHSE descriptors are better ( R2 > 0.6, Q2 > 0.5, RSD c < 0.39) than that of models using MS-WHIM and Z-scale descriptors ( R2 < 0.6, Q2 < 0.5, RSD c > 0.44). Furthermore, the predictive ability of models using DPPS descriptor is best among the six descriptors systems (cumulative multiple correlation coefficient for predict set ( Rext2) > 0.7). It was concluded that the DPPS is better to describe the amino acid of antioxidative tripeptides. The results of DPPS descriptor reveal that the importance of the center amino acid and the N-terminal amino acid are far more than the importance of the C-terminal amino acid for antioxidative tripeptides. The hydrophobic (positively to activity) and electronic (negatively to activity) properties of the N-terminal amino acid are suggested to play the most important significance to activity, followed

  7. An in vivo quantitative structure-activity relationship for a congeneric series of pyropheophorbide derivatives as photosensitizers for photodynamic therapy.

    PubMed

    Henderson, B W; Bellnier, D A; Greco, W R; Sharma, A; Pandey, R K; Vaughan, L A; Weishaupt, K R; Dougherty, T J

    1997-09-15

    An in vivo quantitative structure-activity relationship (QSAR) study was carried out on a congeneric series of pyropheophorbide photosensitizers to identify structural features critical for their antitumor activity in photodynamic therapy (PDT). The structural elements evaluated in this study include the length and shape (alkyl, alkenyl, cyclic, and secondary analogs) of the ether side chain. C3H mice, harboring the radiation-induced fibrosarcoma tumor model, were used to study three biological response endpoints: tumor growth delay, tumor cell lethality, and vascular perfusion. All three endpoints revealed highly similar QSAR patterns that constituted a function of the alkyl ether chain length and drug lipophilicity, which is defined as the log of the octanol:water partition coefficient (log P). When the illumination of tumor, tumor cells, or cutaneous vasculature occurred 24 h after sensitizer administration, activities were minimal with analogs of log P < or = 5, increased dramatically between log P of 5-6, and peaked between log P of 5.6-6.6. Activities declined gradually with higher log P. The lack of activity of the least-lipophilic analogs was explained in large part by their poor biodistribution characteristics, which yielded negligible tumor and plasma drug levels at the time of treatment with light. The progressively lower potencies of the most lipophilic analogs cannot be explained through the overall tumor and plasma pharmacokinetics of photosensitizer because tumor and plasma concentrations progressively increased with lipophilicity. When compensated for differences in tumor photosensitizer concentration, the 1-hexyl derivative (optimal lipophilicity) was 5-fold more potent than the 1-dodecyl derivative (more lipophilic) and 3-fold more potent than the 1-pentyl analog (less lipophilic), indicating that, in addition to the overall tumor pharmacokinetics, pharmacodynamic factors may influence PDT activity. Drug lipophilicity was highly predictive for

  8. QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP MODELS FOR PREDICTION OF ESTROGEN RECEPTOR BINDING AFFINITY OF STRUCTURALLY DIVERSE CHEMICALS

    EPA Science Inventory

    The demonstrated ability of a variety of structurally diverse chemicals to bind to the estrogen receptor has raised the concern that chemicals in the environment may be causing adverse effects through interference with nuclear receptor pathways. Many structure-activity relationsh...

  9. Longitudinal, Quantitative Monitoring of Therapeutic Response in 3D In Vitro Tumor Models with OCT for High-Content Therapeutic Screening

    PubMed Central

    Klein, O. J.; Jung, Y. K.; Evans, C. L.

    2013-01-01

    In vitro three-dimensional models of cancer have the ability to recapitulate many features of tumors found in vivo, including cell-cell and cell-matrix interactions, microenvironments that become hypoxic and acidic, and other barriers to effective therapy. These model tumors can be large, highly complex, heterogeneous, and undergo time-dependent growth and treatment response processes that are difficult to track and quantify using standard imaging tools. Optical coherence tomography is an optical ranging technique that is ideally suited for visualizing, monitoring, and quantifying the growth and treatment response dynamics occurring in these informative model systems. By optimizing both optical coherence tomography and 3D culture systems, it is possible to continuously and non-perturbatively monitor advanced in vitro models without the use of labels over the course of hours and days. In this article, we describe approaches and methods for creating and carrying out quantitative therapeutic screens with in vitro 3D cultures using optical coherence tomography to gain insights into therapeutic mechanisms and build more effective treatment regimens. PMID:24013042

  10. Three-dimensional quantitative structure-activity relationship analysis for human pregnane X receptor for the prediction of CYP3A4 induction in human hepatocytes: structure-based comparative molecular field analysis.

    PubMed

    Handa, Koichi; Nakagome, Izumi; Yamaotsu, Noriyuki; Gouda, Hiroaki; Hirono, Shuichi

    2015-01-01

    The pregnane X receptor [PXR (NR1I2)] induces the expression of xenobiotic metabolic genes and transporter genes. In this study, we aimed to establish a computational method for quantifying the enzyme-inducing potencies of different compounds via their ability to activate PXR, for the application in drug discovery and development. To achieve this purpose, we developed a three-dimensional quantitative structure-activity relationship (3D-QSAR) model using comparative molecular field analysis (CoMFA) for predicting enzyme-inducing potencies, based on computer-ligand docking to multiple PXR protein structures sampled from the trajectory of a molecular dynamics simulation. Molecular mechanics-generalized born/surface area scores representing the ligand-protein-binding free energies were calculated for each ligand. As a result, the predicted enzyme-inducing potencies for compounds generated by the CoMFA model were in good agreement with the experimental values. Finally, we concluded that this 3D-QSAR model has the potential to predict the enzyme-inducing potencies of novel compounds with high precision and therefore has valuable applications in the early stages of the drug discovery process.

  11. Evaluating quantitative 3-D image analysis as a design tool for low enriched uranium fuel compacts for the transient reactor test facility: A preliminary study

    DOE PAGES

    Kane, J. J.; van Rooyen, I. J.; Craft, A. E.; Roney, T. J.; Morrell, S. R.

    2016-02-05

    In this study, 3-D image analysis when combined with a non-destructive examination technique such as X-ray computed tomography (CT) provides a highly quantitative tool for the investigation of a material’s structure. In this investigation 3-D image analysis and X-ray CT were combined to analyze the microstructure of a preliminary subsized fuel compact for the Transient Reactor Test Facility’s low enriched uranium conversion program to assess the feasibility of the combined techniques for use in the optimization of the fuel compact fabrication process. The quantitative image analysis focused on determining the size and spatial distribution of the surrogate fuel particles andmore » the size, shape, and orientation of voids within the compact. Additionally, the maximum effect of microstructural features on heat transfer through the carbonaceous matrix of the preliminary compact was estimated. The surrogate fuel particles occupied 0.8% of the compact by volume with a log-normal distribution of particle sizes with a mean diameter of 39 μm and a standard deviation of 16 μm. Roughly 39% of the particles had a diameter greater than the specified maximum particle size of 44 μm suggesting that the particles agglomerate during fabrication. The local volume fraction of particles also varies significantly within the compact although uniformities appear to be evenly dispersed throughout the analysed volume. The voids produced during fabrication were on average plate-like in nature with their major axis oriented perpendicular to the compaction direction of the compact. Finally, the microstructure, mainly the large preferentially oriented voids, may cause a small degree of anisotropy in the thermal diffusivity within the compact. α∥/α⊥, the ratio of thermal diffusivities parallel to and perpendicular to the compaction direction are expected to be no less than 0.95 with an upper bound of 1.« less

  12. Evaluation of the Quantitative Accuracy of 3D Reconstruction of Edentulous Jaw Models with Jaw Relation Based on Reference Point System Alignment

    PubMed Central

    Li, Weiwei; Yuan, Fusong; Lv, Peijun; Wang, Yong; Sun, Yuchun

    2015-01-01

    Objectives To apply contact measurement and reference point system (RPS) alignment techniques to establish a method for 3D reconstruction of the edentulous jaw models with centric relation and to quantitatively evaluate its accuracy. Methods Upper and lower edentulous jaw models were clinically prepared, 10 pairs of resin cylinders with same size were adhered to axial surfaces of upper and lower models. The occlusal bases and the upper and lower jaw models were installed in the centric relation position. Faro Edge 1.8m was used to directly obtain center points of the base surface of the cylinders (contact method). Activity 880 dental scanner was used to obtain 3D data of the cylinders and the center points were fitted (fitting method). 3 pairs of center points were used to align the virtual model to centric relation. An observation coordinate system was interactively established. The straight-line distances in the X (horizontal left/right), Y (horizontal anterior/posterior), and Z (vertical) between the remaining 7 pairs of center points derived from contact method and fitting method were measured respectively and analyzed using a paired t-test. Results The differences of the straight-line distances of the remaining 7 pairs of center points between the two methods were X: 0.074 ± 0.107 mm, Y: 0.168 ± 0.176 mm, and Z: −0.003± 0.155 mm. The results of paired t-test were X and Z: p >0.05, Y: p <0.05. Conclusion By using contact measurement and the reference point system alignment technique, highly accurate reconstruction of the vertical distance and centric relation of a digital edentulous jaw model can be achieved, which meets the design and manufacturing requirements of the complete dentures. The error of horizontal anterior/posterior jaw relation was relatively large. PMID:25659133

  13. SU-C-201-06: Utility of Quantitative 3D SPECT/CT Imaging in Patient Specific Internal Dosimetry of 153-Samarium with GATE Monte Carlo Package

    SciTech Connect

    Fallahpoor, M; Abbasi, M; Sen, A; Parach, A; Kalantari, F

    2015-06-15

    Purpose: Patient-specific 3-dimensional (3D) internal dosimetry in targeted radionuclide therapy is essential for efficient treatment. Two major steps to achieve reliable results are: 1) generating quantitative 3D images of radionuclide distribution and attenuation coefficients and 2) using a reliable method for dose calculation based on activity and attenuation map. In this research, internal dosimetry for 153-Samarium (153-Sm) was done by SPECT-CT images coupled GATE Monte Carlo package for internal dosimetry. Methods: A 50 years old woman with bone metastases from breast cancer was prescribed 153-Sm treatment (Gamma: 103keV and beta: 0.81MeV). A SPECT/CT scan was performed with the Siemens Simbia-T scanner. SPECT and CT images were registered using default registration software. SPECT quantification was achieved by compensating for all image degrading factors including body attenuation, Compton scattering and collimator-detector response (CDR). Triple energy window method was used to estimate and eliminate the scattered photons. Iterative ordered-subsets expectation maximization (OSEM) with correction for attenuation and distance-dependent CDR was used for image reconstruction. Bilinear energy mapping is used to convert Hounsfield units in CT image to attenuation map. Organ borders were defined by the itk-SNAP toolkit segmentation on CT image. GATE was then used for internal dose calculation. The Specific Absorbed Fractions (SAFs) and S-values were reported as MIRD schema. Results: The results showed that the largest SAFs and S-values are in osseous organs as expected. S-value for lung is the highest after spine that can be important in 153-Sm therapy. Conclusion: We presented the utility of SPECT-CT images and Monte Carlo for patient-specific dosimetry as a reliable and accurate method. It has several advantages over template-based methods or simplified dose estimation methods. With advent of high speed computers, Monte Carlo can be used for treatment planning

  14. Augmented multivariate image analysis applied to quantitative structure-activity relationship modeling of the phytotoxicities of benzoxazinone herbicides and related compounds on problematic weeds.

    PubMed

    Freitas, Mirlaine R; Matias, Stella V B G; Macedo, Renato L G; Freitas, Matheus P; Venturin, Nelson

    2013-09-11

    Two of major weeds affecting cereal crops worldwide are Avena fatua L. (wild oat) and Lolium rigidum Gaud. (rigid ryegrass). Thus, development of new herbicides against these weeds is required; in line with this, benzoxazinones, their degradation products, and analogues have been shown to be important allelochemicals and natural herbicides. Despite earlier structure-activity studies demonstrating that hydrophobicity (log P) of aminophenoxazines correlates to phytotoxicity, our findings for a series of benzoxazinone derivatives do not show any relationship between phytotoxicity and log P nor with other two usual molecular descriptors. On the other hand, a quantitative structure-activity relationship (QSAR) analysis based on molecular graphs representing structural shape, atomic sizes, and colors to encode other atomic properties performed very accurately for the prediction of phytotoxicities of these compounds against wild oat and rigid ryegrass. Therefore, these QSAR models can be used to estimate the phytotoxicity of new congeners of benzoxazinone herbicides toward A. fatua L. and L. rigidum Gaud.

  15. Quantitative structure activity relationship model for predicting the depletion percentage of skin allergic chemical substances of glutathione.

    PubMed

    Si, Hongzong; Wang, Tao; Zhang, Kejun; Duan, Yun-Bo; Yuan, Shuping; Fu, Aiping; Hu, Zhide

    2007-05-22

    A quantitative model was developed to predict the depletion percentage of glutathione (DPG) compounds by gene expression programming (GEP). Each kind of compound was represented by several calculated structural descriptors involving constitutional, topological, geometrical, electrostatic and quantum-chemical features of compounds. The GEP method produced a nonlinear and five-descriptor quantitative model with a mean error and a correlation coefficient of 10.52 and 0.94 for the training set, 22.80 and 0.85 for the test set, respectively. It is shown that the GEP predicted results are in good agreement with experimental ones, better than those of the heuristic method.

  16. Quantitative anatomical analysis of facial expression using a 3D motion capture system: Application to cosmetic surgery and facial recognition technology.

    PubMed

    Lee, Jae-Gi; Jung, Su-Jin; Lee, Hyung-Jin; Seo, Jung-Hyuk; Choi, You-Jin; Bae, Hyun-Sook; Park, Jong-Tae; Kim, Hee-Jin

    2015-09-01

    The topography of the facial muscles differs between males and females and among individuals of the same gender. To explain the unique expressions that people can make, it is important to define the shapes of the muscle, their associations with the skin, and their relative functions. Three-dimensional (3D) motion-capture analysis, often used to study facial expression, was used in this study to identify characteristic skin movements in males and females when they made six representative basic expressions. The movements of 44 reflective markers (RMs) positioned on anatomical landmarks were measured. Their mean displacement was large in males [ranging from 14.31 mm (fear) to 41.15 mm (anger)], and 3.35-4.76 mm smaller in females [ranging from 9.55 mm (fear) to 37.80 mm (anger)]. The percentages of RMs involved in the ten highest mean maximum displacement values in making at least one expression were 47.6% in males and 61.9% in females. The movements of the RMs were larger in males than females but were more limited. Expanding our understanding of facial expression requires morphological studies of facial muscles and studies of related complex functionality. Conducting these together with quantitative analyses, as in the present study, will yield data valuable for medicine, dentistry, and engineering, for example, for surgical operations on facial regions, software for predicting changes in facial features and expressions after corrective surgery, and the development of face-mimicking robots. PMID:25872024

  17. Quantitative anatomical analysis of facial expression using a 3D motion capture system: Application to cosmetic surgery and facial recognition technology.

    PubMed

    Lee, Jae-Gi; Jung, Su-Jin; Lee, Hyung-Jin; Seo, Jung-Hyuk; Choi, You-Jin; Bae, Hyun-Sook; Park, Jong-Tae; Kim, Hee-Jin

    2015-09-01

    The topography of the facial muscles differs between males and females and among individuals of the same gender. To explain the unique expressions that people can make, it is important to define the shapes of the muscle, their associations with the skin, and their relative functions. Three-dimensional (3D) motion-capture analysis, often used to study facial expression, was used in this study to identify characteristic skin movements in males and females when they made six representative basic expressions. The movements of 44 reflective markers (RMs) positioned on anatomical landmarks were measured. Their mean displacement was large in males [ranging from 14.31 mm (fear) to 41.15 mm (anger)], and 3.35-4.76 mm smaller in females [ranging from 9.55 mm (fear) to 37.80 mm (anger)]. The percentages of RMs involved in the ten highest mean maximum displacement values in making at least one expression were 47.6% in males and 61.9% in females. The movements of the RMs were larger in males than females but were more limited. Expanding our understanding of facial expression requires morphological studies of facial muscles and studies of related complex functionality. Conducting these together with quantitative analyses, as in the present study, will yield data valuable for medicine, dentistry, and engineering, for example, for surgical operations on facial regions, software for predicting changes in facial features and expressions after corrective surgery, and the development of face-mimicking robots.

  18. Can anti-migratory drugs be screened in vitro? A review of 2D and 3D assays for the quantitative analysis of cell migration.

    PubMed

    Decaestecker, Christine; Debeir, Olivier; Van Ham, Philippe; Kiss, Robert

    2007-03-01

    The aim of the present review is to detail and analyze the pros and cons of in vitro tests available to quantify the anti-migratory effects of anti-cancer drugs for their eventual use in combating the dispersal of tumor cells, a clinical need which currently remains unsatisfied. We therefore briefly sum up why anti-migratory drugs constitute a promising approach in oncology while at the same time emphasizing that migrating cancer cells are resistant to apoptosis. To analyze the pros and cons of the various in vitro tests under review we also briefly sum up the molecular and cellular stages of cancer cell migration, an approach that enables us to argue both that no single in vitro test is sufficient to characterize the anti-migratory potential of a drug and that standardization is needed for the efficient quantitative analysis of cell locomotion in a 3D environment. Before concluding our review we devote the final two parts (i) to the description of new prototypes which, in the near future, could enter the screening process with a view to identifying novel anti-migratory compounds, and (ii) to the anti-migratory compounds currently developed against cancer, with particular emphasis on how these compounds were selected before entering the clinical trial phase.

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

    PubMed

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

    2016-04-01

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

  20. A quantitative structure activity/dose response relationship for contact allergic potential of alkyl group transfer agents.

    PubMed

    Roberts, D W; Basketter, D A

    1990-11-01

    As part of the investigation of structure activity relationships in contact allergy, it has been shown that methyl transfer agents are capable of acting as skin sensitizers. This work has now been extended to a more general examination of alkyl transfer reactions. The modified single injection adjuvant test has been used to investigate the sensitization potential of C12, C16 and unsaturated C18 alkyl transfer agents. Dose responses to challenge and the patterns of cross-reactivity between these materials and methyl transfer agents have been studied. All alkyl transfer agents examined were potent sensitizers in the guinea pig. There was evidence of mutual cross-reactivity between all alkyl transfer agents examined (including methyl transfer agents). Analysis of the data in terms of a modified relative alkylation index showed evidence of an overload effect. The sensitization data has been accurately modelled using a mathematical equation. These results emphasize the possibilities for relating physicochemical parameters and skin sensitization potential. Further studies with alkyl transfer agents are in progress of amplify the observations and conclusions presented in this report. No in vitro model is available for the prediction of skin sensitization potential. Therefore an approach based on a model using physicochemical criteria is the most likely route to a reduced requirement for animal testing. PMID:1965716

  1. A predictive quantitative structure-activity relationship model for the photoinduced toxicity of polycyclic aromatic hydrocarbons to Daphnia magna with the use of factors for photosensitization and photomodification.

    PubMed

    Lampi, Mark A; Gurska, Jolanta; Huang, Xiao-Dong; Dixon, D George; Greenberg, Bruce M

    2007-03-01

    Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants that readily absorb environmentally relevant solar ultraviolet radiation. On absorption of a photon, photoinduced toxicity of PAHs is manifested through photosensitization and photomodification. Both of these processes occur under environmentally relevant levels of actinic radiation. An empirical quantitative structure-activity relationship model previously developed was explanatory of photoinduced toxicity of 16 PAHs in Lemna gibba (duckweed). This model was found to be predictive of toxicity to Vibrio fischeri. The L. gibba quantitative structure-activity relationship showed that a photosensitization factor and a photomodification factor could be combined to describe photoinduced toxicity. To further examine this model, we assessed whether it could be applied to Daphnia magna (water flea), a key bioindicator species in aquatic ecosystems. Toxicity was assessed as median effective concentration and median effective time for immobility. As with L. gibba and V. fischeri, neither the photosensitization factor nor the photomodification factor alone correlated to toxicity in D. magna. However, a photosensitization factor modified for D. magna exhibited a correlation to toxicity (r2 = 0.86), which was modestly improved when summed with a modified photomodification factor (r2 = 0.92). The greatest correlation was observed with median effective concentration data. This research provides evidence that models incorporating factors for photosensitization and photomodification have interspecies applicability. PMID:17373503

  2. A predictive quantitative structure-activity relationship model for the photoinduced toxicity of polycyclic aromatic hydrocarbons to Daphnia magna with the use of factors for photosensitization and photomodification.

    PubMed

    Lampi, Mark A; Gurska, Jolanta; Huang, Xiao-Dong; Dixon, D George; Greenberg, Bruce M

    2007-03-01

    Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants that readily absorb environmentally relevant solar ultraviolet radiation. On absorption of a photon, photoinduced toxicity of PAHs is manifested through photosensitization and photomodification. Both of these processes occur under environmentally relevant levels of actinic radiation. An empirical quantitative structure-activity relationship model previously developed was explanatory of photoinduced toxicity of 16 PAHs in Lemna gibba (duckweed). This model was found to be predictive of toxicity to Vibrio fischeri. The L. gibba quantitative structure-activity relationship showed that a photosensitization factor and a photomodification factor could be combined to describe photoinduced toxicity. To further examine this model, we assessed whether it could be applied to Daphnia magna (water flea), a key bioindicator species in aquatic ecosystems. Toxicity was assessed as median effective concentration and median effective time for immobility. As with L. gibba and V. fischeri, neither the photosensitization factor nor the photomodification factor alone correlated to toxicity in D. magna. However, a photosensitization factor modified for D. magna exhibited a correlation to toxicity (r2 = 0.86), which was modestly improved when summed with a modified photomodification factor (r2 = 0.92). The greatest correlation was observed with median effective concentration data. This research provides evidence that models incorporating factors for photosensitization and photomodification have interspecies applicability.

  3. Tyrosine kinase inhibitors. 13. Structure-activity relationships for soluble 7-substituted 4-[(3-bromophenyl)amino]pyrido[4,3-d]pyrimidines designed as inhibitors of the tyrosine kinase activity of the epidermal growth factor receptor.

    PubMed

    Thompson, A M; Murray, D K; Elliott, W L; Fry, D W; Nelson, J A; Showalter, H D; Roberts, B J; Vincent, P W; Denny, W A

    1997-11-21

    The general class of 4-(phenylamino)quinazolines are potent (some members with IC50 values < 1 nM) and selective inhibitors of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR), via competitive binding at the ATP site of the enzyme, but many of the early analogues had poor aqueous solubility (< 1 mM). A series of 7-substituted 4-[(3-bromophenyl)-amino]pyrido[4,3-d]pyrimidines, together with selected (3-methylphenyl)amino analogues, were prepared by reaction of the analogous 7-fluoro derivatives with appropriate amine nucleophiles in 2-BuOH or aqueous 1-PrOH. All of the compounds were evaluated for their ability to inhibit the tyrosine-phosphorylating action of EGF-stimulated full-length EGFR enzyme. Selected analogues were also evaluated for their inhibition of autophosphorylation of the EGF receptor in A431 human epidermoid carcinoma cells in culture and against A431 tumor xenografts in mice. Analogues bearing a wide variety of polyol, cationic, and anionic solubilizing substituents retained activity, but the most effective in terms of both increased aqueous solubility (> 40 mM) and retention of overall inhibitory activity (IC50's of 0.5-10 nM against isolated enzyme and 8-40 nM for inhibition of EGFR autophosphorylation in A431 cells) were weakly basic amine derivatives. These results are broadly consistent with a proposed model for the binding of these compounds to EGFR, in which the 6- and 7-positions of the pyridopyrimidine ring are in a largely hydrophobic binding region of considerable steric freedom, at the entrance of the adenine binding cleft. The most active cationic analogues have a weakly basic side chain where the amine moiety is three or more carbon atoms away from the nucleus. Two of the compounds (bearing weakly basic morpholinopropyl and strongly basic (dimethylamino)butyl solubilizing groups) produced in vivo tumor growth delays of 13-21 days against advanced stage A431 epidermoid xenografts in nude mice, when

  4. 3D-QSAR - Applications, Recent Advances, and Limitations

    NASA Astrophysics Data System (ADS)

    Sippl, Wolfgang

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

  5. 3D rapid mapping

    NASA Astrophysics Data System (ADS)

    Isaksson, Folke; Borg, Johan; Haglund, Leif

    2008-04-01

    In this paper the performance of passive range measurement imaging using stereo technique in real time applications is described. Stereo vision uses multiple images to get depth resolution in a similar way as Synthetic Aperture Radar (SAR) uses multiple measurements to obtain better spatial resolution. This technique has been used in photogrammetry for a long time but it will be shown that it is now possible to do the calculations, with carefully designed image processing algorithms, in e.g. a PC in real time. In order to get high resolution and quantitative data in the stereo estimation a mathematical camera model is used. The parameters to the camera model are settled in a calibration rig or in the case of a moving camera the scene itself can be used for calibration of most of the parameters. After calibration an ordinary TV camera has an angular resolution like a theodolite, but to a much lower price. The paper will present results from high resolution 3D imagery from air to ground. The 3D-results from stereo calculation of image pairs are stitched together into a large database to form a 3D-model of the area covered.

  6. Quantitative Evaluation of 3D Mouse Behaviors and Motor Function in the Open-Field after Spinal Cord Injury Using Markerless Motion Tracking

    PubMed Central

    Sheets, Alison L.; Lai, Po-Lun; Fisher, Lesley C.; Basso, D. Michele

    2013-01-01

    Thousands of scientists strive to identify cellular mechanisms that could lead to breakthroughs in developing ameliorative treatments for debilitating neural and muscular conditions such as spinal cord injury (SCI). Most studies use rodent models to test hypotheses, and these are all limited by the methods available to evaluate animal motor function. This study’s goal was to develop a behavioral and locomotor assessment system in a murine model of SCI that enables quantitative kinematic measurements to be made automatically in the open-field by applying markerless motion tracking approaches. Three-dimensional movements of eight naïve, five mild, five moderate, and four severe SCI mice were recorded using 10 cameras (100 Hz). Background subtraction was used in each video frame to identify the animal’s silhouette, and the 3D shape at each time was reconstructed using shape-from-silhouette. The reconstructed volume was divided into front and back halves using k-means clustering. The animal’s front Center of Volume (CoV) height and whole-body CoV speed were calculated and used to automatically classify animal behaviors including directed locomotion, exploratory locomotion, meandering, standing, and rearing. More detailed analyses of CoV height, speed, and lateral deviation during directed locomotion revealed behavioral differences and functional impairments in animals with mild, moderate, and severe SCI when compared with naïve animals. Naïve animals displayed the widest variety of behaviors including rearing and crossing the center of the open-field, the fastest speeds, and tallest rear CoV heights. SCI reduced the range of behaviors, and decreased speed (r = .70 p<.005) and rear CoV height (r = .65 p<.01) were significantly correlated with greater lesion size. This markerless tracking approach is a first step toward fundamentally changing how rodent movement studies are conducted. By providing scientists with sensitive, quantitative measurement

  7. Investigation of an Immunoassay with Broad Specificity to Quinolone Drugs by Genetic Algorithm with Linear Assignment of Hypermolecular Alignment of Data Sets and Advanced Quantitative Structure-Activity Relationship Analysis.

    PubMed

    Chen, Jiahong; Lu, Ning; Shen, Xing; Tang, Qiushi; Zhang, Chijian; Xu, Jun; Sun, Yuanming; Huang, Xin-An; Xu, Zhenlin; Lei, Hongtao

    2016-04-01

    A polyclonal antibody against the quinolone drug pazufloxacin (PAZ) but with surprisingly broad specificity was raised to simultaneously detect 24 quinolones (QNs). The developed competitive indirect enzyme-linked immunosorbent assay (ciELISA) exhibited limits of detection (LODs) for the 24 QNs ranging from 0.45 to 15.16 ng/mL, below the maximum residue levels (MRLs). To better understand the obtained broad specificity, a genetic algorithm with linear assignment of hypermolecular alignment of data sets (GALAHAD) was used to generate the desired pharmacophore model and superimpose the QNs, and then advanced comparative molecular field analysis (CoMFA) and advanced comparative molecular similarity indices analysis (CoMSIA) models were employed to study the three-dimensional quantitative structure-activity relationship (3D QSAR) between QNs and the antibody. It was found that the QNs could interact with the antibody with different binding poses, and cross-reactivity was mainly positively correlated with the bulky substructure containing electronegative atom at the 7-position, while it was negatively associated with the large bulky substructure at the 1-position of QNs.

  8. Quantitative structure-activity relationship study of P2X7 receptor inhibitors using combination of principal component analysis and artificial intelligence methods.

    PubMed

    Ahmadi, Mehdi; Shahlaei, Mohsen

    2015-01-01

    P2X7 antagonist activity for a set of 49 molecules of the P2X7 receptor antagonists, derivatives of purine, was modeled with the aid of chemometric and artificial intelligence techniques. The activity of these compounds was estimated by means of combination of principal component analysis (PCA), as a well-known data reduction method, genetic algorithm (GA), as a variable selection technique, and artificial neural network (ANN), as a non-linear modeling method. First, a linear regression, combined with PCA, (principal component regression) was operated to model the structure-activity relationships, and afterwards a combination of PCA and ANN algorithm was employed to accurately predict the biological activity of the P2X7 antagonist. PCA preserves as much of the information as possible contained in the original data set. Seven most important PC's to the studied activity were selected as the inputs of ANN box by an efficient variable selection method, GA. The best computational neural network model was a fully-connected, feed-forward model with 7-7-1 architecture. The developed ANN model was fully evaluated by different validation techniques, including internal and external validation, and chemical applicability domain. All validations showed that the constructed quantitative structure-activity relationship model suggested is robust and satisfactory. PMID:26600858

  9. Further evaluation of quantitative structure--activity relationship models for the prediction of the skin sensitization potency of selected fragrance allergens.

    PubMed

    Patlewicz, Grace Y; Basketter, David A; Pease, Camilla K Smith; Wilson, Karen; Wright, Zoe M; Roberts, David W; Bernard, Guillaume; Arnau, Elena Giménez; Lepoittevin, Jean-Pierre

    2004-02-01

    Fragrance substances represent a very diverse group of chemicals; a proportion of them are associated with the ability to cause allergic reactions in the skin. Efforts to find substitute materials are hindered by the need to undertake animal testing for determining both skin sensitization hazard and potency. One strategy to avoid such testing is through an understanding of the relationships between chemical structure and skin sensitization, so-called structure-activity relationships. In recent work, we evaluated 2 groups of fragrance chemicals -- saturated aldehydes and alpha,beta-unsaturated aldehydes. Simple quantitative structure-activity relationship (QSAR) models relating the EC3 values [derived from the local lymph node assay (LLNA)] to physicochemical properties were developed for both sets of aldehydes. In the current study, we evaluated an additional group of carbonyl-containing compounds to test the predictive power of the developed QSARs and to extend their scope. The QSAR models were used to predict EC3 values of 10 newly selected compounds. Local lymph node assay data generated for these compounds demonstrated that the original QSARs were fairly accurate, but still required improvement. Development of these QSAR models has provided us with a better understanding of the potential mechanisms of action for aldehydes, and hence how to avoid or limit allergy. Knowledge generated from this work is being incorporated into new/improved rules for sensitization in the expert toxicity prediction system, deductive estimation of risk from existing knowledge (DEREK).

  10. Quantitative structure-activity relationship study of P2X7 receptor inhibitors using combination of principal component analysis and artificial intelligence methods.

    PubMed

    Ahmadi, Mehdi; Shahlaei, Mohsen

    2015-01-01

    P2X7 antagonist activity for a set of 49 molecules of the P2X7 receptor antagonists, derivatives of purine, was modeled with the aid of chemometric and artificial intelligence techniques. The activity of these compounds was estimated by means of combination of principal component analysis (PCA), as a well-known data reduction method, genetic algorithm (GA), as a variable selection technique, and artificial neural network (ANN), as a non-linear modeling method. First, a linear regression, combined with PCA, (principal component regression) was operated to model the structure-activity relationships, and afterwards a combination of PCA and ANN algorithm was employed to accurately predict the biological activity of the P2X7 antagonist. PCA preserves as much of the information as possible contained in the original data set. Seven most important PC's to the studied activity were selected as the inputs of ANN box by an efficient variable selection method, GA. The best computational neural network model was a fully-connected, feed-forward model with 7-7-1 architecture. The developed ANN model was fully evaluated by different validation techniques, including internal and external validation, and chemical applicability domain. All validations showed that the constructed quantitative structure-activity relationship model suggested is robust and satisfactory.

  11. Degradation mechanism of PCDDs initiated by OH radical in Photo-Fenton oxidation technology: quantum chemistry and quantitative structure-activity relationship.

    PubMed

    Sun, Xiaomin; Sun, Tingli; Zhang, Qingzhu; Wang, Wenxing

    2008-08-25

    A detailed understanding of the degradation mechanism of polychlorinated dibenzo-p-dioxins (PCDDs) is of great necessity. In wastewater treatment, an important degradation process of PCDDs ascribes to its reaction with the photo-Fenton reagent. In this paper, the reaction of 2,3,7,8-TeCDD with OH radicals has been studied using high level molecular orbital theory. The profile of the potential energy surface is constructed. A complete description of the possible degradation mechanism in solution is provided. Two degradation mechanisms are proposed: ring-opening and adducting mechanism, adducting and ring-opening mechanism. The main products obtained are 4,5-dichlorinate-o-dihydroxybenzene and 4,5-dichlorinate-o-quinone. The study on the quantitative structure-activity relationship of these PCDDs is performed. The structure-activity model has been constructed, in which three structural parameters, RO5-C12, RO5-C13 and QC14, are found to be positively correlated to the degradation activities. PMID:18554686

  12. QSAR for cholinesterase inhibition by organophosphorus esters and CNDO/2 calculations for organophosphorus ester hydrolysis. [quantitative structure-activity relationship, complete neglect of differential overlap

    NASA Technical Reports Server (NTRS)

    Johnson, H.; Kenley, R. A.; Rynard, C.; Golub, M. A.

    1985-01-01

    Quantitative structure-activity relationships were derived for acetyl- and butyrylcholinesterase inhibition by various organophosphorus esters. Bimolecular inhibition rate constants correlate well with hydrophobic substituent constants, and with the presence or absence of cationic groups on the inhibitor, but not with steric substituent constants. CNDO/2 calculations were performed on a separate set of organophosphorus esters, RR-primeP(O)X, where R and R-prime are alkyl and/or alkoxy groups and X is fluorine, chlorine or a phenoxy group. For each subset with the same X, the CNDO-derived net atomic charge at the central phosphorus atom in the ester correlates well with the alkaline hydrolysis rate constant. For the whole set of esters with different X, two equations were derived that relate either charge and leaving group steric bulk, or orbital energy and bond order to the hydrolysis rate constant.

  13. Comparison between 5,10,15,20-tetraaryl- and 5,15-diarylporphyrins as photosensitizers: synthesis, photodynamic activity, and quantitative structure-activity relationship modeling.

    PubMed

    Banfi, Stefano; Caruso, Enrico; Buccafurni, Loredana; Murano, Roberto; Monti, Elena; Gariboldi, Marzia; Papa, Ester; Gramatica, Paola

    2006-06-01

    The synthesis of a panel of seven nonsymmetric 5,10,15,20-tetraarylporphyrins, 13 symmetric and nonsymmetric 5,15-diarylporphyrins, and one 5,15-diarylchlorin is described. In vitro photodynamic activities on HCT116 human colon adenocarcinoma cells were evaluated by standard cytotoxicity assays. A predictive quantitative structure-activity relationship (QSAR) regression model, based on theoretical holistic molecular descriptors, of a series of 34 tetrapyrrolic photosensitizers (PSs), including the 24 compounds synthesized in this work, was developed to describe the relationship between structural features and photodynamic activity. The present study demonstrates that structural features significantly influence the photodynamic activity of tetrapyrrolic derivatives: diaryl compounds were more active with respect to the tetraarylporphyrins, and among the diaryl derivatives, hydroxy-substituted compounds were more effective than the corresponding methoxy-substituted ones. Furthermore, three monoarylporphyrins, isolated as byproducts during diarylporphyrin synthesis, were considered for both photodynamic and QSAR studies; surprisingly they were found to be particularly active photosensitizers.

  14. Using quantitative structure activity relationship models to predict an appropriate solvent system from a common solvent system family for countercurrent chromatography separation.

    PubMed

    Marsden-Jones, Siân; Colclough, Nicola; Garrard, Ian; Sumner, Neil; Ignatova, Svetlana

    2015-06-12

    Countercurrent chromatography (CCC) is a form of liquid-liquid chromatography. It works by running one immiscible solvent (mobile phase) over another solvent (stationary phase) being held in a CCC column using centrifugal force. The concentration of compound in each phase is characterised by the partition coefficient (Kd), which is the concentration in the stationary phase divided by the concentration in the mobile phase. When Kd is between approximately 0.2 and 2, it is most likely that optimal separation will be achieved. Having the Kd in this range allows the compound enough time in the column to be separated without resulting in a broad peak and long run time. In this paper we report the development of quantitative structure activity relationship (QSAR) models to predict logKd. The QSAR models use only the molecule's 2D structure to predict the molecular property logKd.

  15. Synthesis and quantitative structure-activity relationship (QSAR) analysis of some novel oxadiazolo[3,4-d]pyrimidine nucleosides derivatives as antiviral agents.

    PubMed

    Xu, Xiaojuan; Wang, Jun; Yao, Qizheng

    2015-01-15

    We have synthesized a series of 4H,6H-[1,2,5]oxadiazolo[3,4-d]pyrimidine-5,7-dione 1-oxide nucleoside and their anti-vesicular stomatitis virus (VSV) activities in Wish cell were also investigated in vitro. It was found that most compounds showed obvious anti-VSV activities and compound 9 with ribofuranoside improved the anti-VSV activity by approximately 10 times and 18 times compared to didanosine (DDI) and acyclovir, respectively. A quantitative structure-activity relationship (QSAR) study of these compounds as well as previous reported oxadiazolo[3,4-d]pyrimidine nucleoside derivatives indicated that compounds with high activity should have small values of logP(o/w), vsurf_G and a large logS value. These findings and results provide a base for further investigations.

  16. Novel phenolic inhibitors of the sarco/endoplasmic reticulum calcium ATPase: identification and characterization by quantitative structure-activity relationship modeling and virtual screening.

    PubMed

    Paula, Stefan; Hofmann, Emily; Burden, John; Stanton, David T

    2015-02-01

    Inhibitors of the sarco/endoplasmic reticulum calcium ATPase (SERCA) are valuable research tools and hold promise as a new generation of anti-prostate cancer agents. Based on previously determined potencies of phenolic SERCA inhibitors, we created quantitative structure-activity relationship (QSAR) models using three independent development strategies. The obtained QSAR models facilitated virtual screens of several commercial compound collections for novel inhibitors. Sixteen compounds were subsequently evaluated in SERCA activity inhibition assays and 11 showed detectable potencies in the micro- to millimolar range. The experimental results were then incorporated into a comprehensive master QSAR model, whose physical interpretation by partial least squares analysis revealed that properly positioned substituents at the central phenyl ring capable of forming hydrogen bonds and of undergoing hydrophobic interactions were prerequisites for effective SERCA inhibition. The established SAR was in good agreement with findings from previous structural studies, even though it was obtained independently using standard QSAR methodologies.

  17. Inhibition of /sup 125/I-labeled ristocetin binding to Micrococcus luteus cells by the peptides related to bacterial cell wall mucopeptide precursors: quantitative structure-activity relationships

    SciTech Connect

    Kim, K.H.; Martin, Y.; Otis, E.; Mao, J.

    1989-01-01

    Quantitative structure-activity relationships (QSAR) of N-Ac amino acids, N-Ac dipeptides, and N-Ac tripeptides in inhibition of /sup 125/I-labeled ristocetin binding to Micrococcus luteus cell wall have been developed to probe the details of the binding between ristocetin and N-acetylated peptides. The correlation equations indicate that (1) the binding is stronger for peptides in which the side chain of the C-terminal amino acid has a large molar refractivity (MR) value, (2) the binding is weaker for peptides with polar than for those with nonpolar C-terminal side chains, (3) the N-terminal amino acid in N-Ac dipeptides contributes 12 times that of the C-terminal amino acid to binding affinity, and (4) the interactions between ristocetin and the N-terminal amino acid of N-acetyl tripeptides appear to be much weaker than those with the first two amino acids.

  18. Synthesis, quantitative structure-activity relationship and biological evaluation of 1,3,4-oxadiazole derivatives possessing diphenylamine moiety as potential anticancer agents.

    PubMed

    Abdel Rahman, Doaa Ezzat

    2013-01-01

    Synthesis of 2,5-disubstituted-1,3,4-oxadiazole (2a-c), 3-substituted aminomethyl-5-substituted-1,3,4-oxadiazole-2(3H)-thione (4a-m) and 2-substituted thio-5-substituted-1,3,4-oxadiazole (5a, b) had been described. All the synthesized derivatives were screened for anticancer activity against HT29 and MCF7 cancer cell lines using Sulfo-Rodamine B (SRB) standard method. Most of the tested compounds exploited potent antiproliferative activity against HT29 cancer cell line rather than MCF7 cancer cell line. Compounds 2a-c, 4f and 5a exhibited potent cytotoxicity (IC(50) 1.3-2.0 µM) and selectivity against HT29 cancer cell line. Quantitative structure-activity relationship (QSAR) study was applied to find a correlation between the experimental antiproliferative activities of the newly synthesized oxadiazole derivatives with their physicochemical parameter and topological index.

  19. Quantitative analysis of tomotherapy, linear-accelerator-based 3D conformal radiation therapy, intensity-modulated radiation therapy, and 4D conformal radiation therapy

    NASA Astrophysics Data System (ADS)

    Cho, Jae-Hwan; Lee, Hae-Kag; Dong, Kyung-Rae; Chung, Woon-Kwan; Lee, Jong-Woong; Park, Hoon-Hee

    2012-04-01

    This study quantified, evaluated and analyzed the radiation dose to which tumors and normal tissues were exposed in 3D conformal radiation therapy (CRT), intensity-modulated radiation therapy (IMRT) and tomotherapy by using a dose volume histogram (DVH) that represented the volume dose and the dose distribution of anatomical structures in the evaluation of treatment planning. Furthermore, a comparison was made for the dose to the gross tumor volume (GTV) and the planning target volume (PTV) of organ to be treated based on the change in field size for three- and four-dimensional computed tomography (3D-CT and 4D-CT) (gating based) and in the histogram with a view to proving the usefulness of 4D-CT therapy, which corresponds to respiration-gated radiation therapy. According to the study results, a comparison of 3D CRT, IMRT with a linear accelerator (LINAC), and tomotherapy demonstrated that the GTV of the cranium was higher for tomotherapy than for 3D CRT and IMRT with a LINAC by 5.2% and 4.6%, respectively. The GTV of the neck was higher for tomotherapy than for 3D CRT and IMRT with a LINAC by 6.5% and 2.0%, respectively. The GTV of the pelvis was higher for tomotherapy than for 3D CRT and IMRT with a LINAC by 8.6% and 3.7%, respectively. When the comparison was made for the 3D-CT and the 4D-CT (gating based) treatment equipment, the GTV and the PTV became smaller for 4D-CT treatment planning than for 3D-CT, which could reduce the area in which normal tissues in the surroundings are exposed to an unnecessary radiation dose. In addition, when 4D-CT treatment planning (gating based) was used, the radiation dose could be concentrated on the GTV, CTV or PTV, which meant that the treatment area exceeded that when 3D-CT's treatment planning was used. Moreover, the radiation dose on nearby normal tissues could be reduced. When 4D-CT treatment planning (gating based) was utilized, unnecessary areas that were exposed to a radiation dose could be reduced more than they could

  20. The impact of 3D volume of interest definition on accuracy and precision of activity estimation in quantitative SPECT and planar processing methods

    NASA Astrophysics Data System (ADS)

    He, Bin; Frey, Eric C.

    2010-06-01

    Accurate and precise estimation of organ activities is essential for treatment planning in targeted radionuclide therapy. We have previously evaluated the impact of processing methodology, statistical noise and variability in activity distribution and anatomy on the accuracy and precision of organ activity estimates obtained with quantitative SPECT (QSPECT) and planar (QPlanar) processing. Another important factor impacting the accuracy and precision of organ activity estimates is accuracy of and variability in the definition of organ regions of interest (ROI) or volumes of interest (VOI). The goal of this work was thus to systematically study the effects of VOI definition on the reliability of activity estimates. To this end, we performed Monte Carlo simulation studies using randomly perturbed and shifted VOIs to assess the impact on organ activity estimates. The 3D NCAT phantom was used with activities that modeled clinically observed 111In ibritumomab tiuxetan distributions. In order to study the errors resulting from misdefinitions due to manual segmentation errors, VOIs of the liver and left kidney were first manually defined. Each control point was then randomly perturbed to one of the nearest or next-nearest voxels in three ways: with no, inward or outward directional bias, resulting in random perturbation, erosion or dilation, respectively, of the VOIs. In order to study the errors resulting from the misregistration of VOIs, as would happen, e.g. in the case where the VOIs were defined using a misregistered anatomical image, the reconstructed SPECT images or projections were shifted by amounts ranging from -1 to 1 voxels in increments of with 0.1 voxels in both the transaxial and axial directions. The activity estimates from the shifted reconstructions or projections were compared to those from the originals, and average errors were computed for the QSPECT and QPlanar methods, respectively. For misregistration, errors in organ activity estimations were

  1. The impact of 3D volume of interest definition on accuracy and precision of activity estimation in quantitative SPECT and planar processing methods.

    PubMed

    He, Bin; Frey, Eric C

    2010-06-21

    Accurate and precise estimation of organ activities is essential for treatment planning in targeted radionuclide therapy. We have previously evaluated the impact of processing methodology, statistical noise and variability in activity distribution and anatomy on the accuracy and precision of organ activity estimates obtained with quantitative SPECT (QSPECT) and planar (QPlanar) processing. Another important factor impacting the accuracy and precision of organ activity estimates is accuracy of and variability in the definition of organ regions of interest (ROI) or volumes of interest (VOI). The goal of this work was thus to systematically study the effects of VOI definition on the reliability of activity estimates. To this end, we performed Monte Carlo simulation studies using randomly perturbed and shifted VOIs to assess the impact on organ activity estimates. The 3D NCAT phantom was used with activities that modeled clinically observed (111)In ibritumomab tiuxetan distributions. In order to study the errors resulting from misdefinitions due to manual segmentation errors, VOIs of the liver and left kidney were first manually defined. Each control point was then randomly perturbed to one of the nearest or next-nearest voxels in three ways: with no, inward or outward directional bias, resulting in random perturbation, erosion or dilation, respectively, of the VOIs. In order to study the errors resulting from the misregistration of VOIs, as would happen, e.g. in the case where the VOIs were defined using a misregistered anatomical image, the reconstructed SPECT images or projections were shifted by amounts ranging from -1 to 1 voxels in increments of with 0.1 voxels in both the transaxial and axial directions. The activity estimates from the shifted reconstructions or projections were compared to those from the originals, and average errors were computed for the QSPECT and QPlanar methods, respectively. For misregistration, errors in organ activity estimations were

  2. Quantitative description of the temporal behavior of the internal Mn3d5 luminescence in ensembles of Zn0.99Mn0.01S quantum dots

    NASA Astrophysics Data System (ADS)

    Chen, L.; Brieler, F. J.; Fröba, M.; Klar, P. J.; Heimbrodt, W.

    2007-06-01

    We present an important step in resolving a long-standing controversy regarding the lifetime of the internal Mn2+ 3d5 emission in ZnS nanoparticles. Transients of the luminescence have been measured over more than five orders of magnitude in intensity, and in the time slot from 50ns to 20ms . We show that the nonexponential decay behavior of the internal 3d5 luminescence of ensembles of Zn0.99Mn0.01S quantum dots is a result of the killer center statistics within the dot ensemble, and thus an intrinsic effect of the Mn-doped II-VI nanoparticles.

  3. Europeana and 3D

    NASA Astrophysics Data System (ADS)

    Pletinckx, D.

    2011-09-01

    The current 3D hype creates a lot of interest in 3D. People go to 3D movies, but are we ready to use 3D in our homes, in our offices, in our communication? Are we ready to deliver real 3D to a general public and use interactive 3D in a meaningful way to enjoy, learn, communicate? The CARARE project is realising this for the moment in the domain of monuments and archaeology, so that real 3D of archaeological sites and European monuments will be available to the general public by 2012. There are several aspects to this endeavour. First of all is the technical aspect of flawlessly delivering 3D content over all platforms and operating systems, without installing software. We have currently a working solution in PDF, but HTML5 will probably be the future. Secondly, there is still little knowledge on how to create 3D learning objects, 3D tourist information or 3D scholarly communication. We are still in a prototype phase when it comes to integrate 3D objects in physical or virtual museums. Nevertheless, Europeana has a tremendous potential as a multi-facetted virtual museum. Finally, 3D has a large potential to act as a hub of information, linking to related 2D imagery, texts, video, sound. We describe how to create such rich, explorable 3D objects that can be used intuitively by the generic Europeana user and what metadata is needed to support the semantic linking.

  4. Quantitative assessment of cancer vascular architecture by skeletonization of high-resolution 3-D contrast-enhanced ultrasound images: role of liposomes and microbubbles.

    PubMed

    Molinari, F; Meiburger, K M; Giustetto, P; Rizzitelli, S; Boffa, C; Castano, M; Terreno, E

    2014-12-01

    The accurate characterization and description of the vascular network of a cancer lesion is of paramount importance in clinical practice and cancer research in order to improve diagnostic accuracy or to assess the effectiveness of a treatment. The aim of this study was to show the effectiveness of liposomes as an ultrasound contrast agent to describe the 3-D vascular architecture of a tumor. Eight C57BL/6 mice grafted with syngeneic B16-F10 murine melanoma cells were injected with a bolus of 1,2-Distearoyl-sn-glycero-3-phosphocoline (DSPC)-based non-targeted liposomes and with a bolus of microbubbles. 3-D contrast-enhanced images of the tumor lesions were acquired in three conditions: pre-contrast, after the injection of microbubbles, and after the injection of liposomes. By using a previously developed reconstruction and characterization image processing technique, we obtained the 3-D representation of the vascular architecture in these three conditions. Six descriptive parameters of these networks were also computed: the number of vascular trees (NT), the vascular density (VD), the number of branches, the 2-D curvature measure, the number of vascular flexes of the vessels, and the 3-D curvature. Results showed that all the vascular descriptors obtained by liposome-based images were statistically equal to those obtained by using microbubbles, except the VD which was found to be lower for liposome images. All the six descriptors computed in pre-contrast conditions had values that were statistically lower than those computed in presence of contrast, both for liposomes and microbubbles. Liposomes have already been used in cancer therapy for the selective ultrasound-mediated delivery of drugs. This work demonstrated their effectiveness also as vascular diagnostic contrast agents, therefore proving that liposomes can be used as efficient "theranostic" (i.e. therapeutic 1 diagnostic) ultrasound probes.

  5. Quantitative assessment of cancer vascular architecture by skeletonization of high-resolution 3-D contrast-enhanced ultrasound images: role of liposomes and microbubbles.

    PubMed

    Molinari, F; Meiburger, K M; Giustetto, P; Rizzitelli, S; Boffa, C; Castano, M; Terreno, E

    2014-12-01

    The accurate characterization and description of the vascular network of a cancer lesion is of paramount importance in clinical practice and cancer research in order to improve diagnostic accuracy or to assess the effectiveness of a treatment. The aim of this study was to show the effectiveness of liposomes as an ultrasound contrast agent to describe the 3-D vascular architecture of a tumor. Eight C57BL/6 mice grafted with syngeneic B16-F10 murine melanoma cells were injected with a bolus of 1,2-Distearoyl-sn-glycero-3-phosphocoline (DSPC)-based non-targeted liposomes and with a bolus of microbubbles. 3-D contrast-enhanced images of the tumor lesions were acquired in three conditions: pre-contrast, after the injection of microbubbles, and after the injection of liposomes. By using a previously developed reconstruction and characterization image processing technique, we obtained the 3-D representation of the vascular architecture in these three conditions. Six descriptive parameters of these networks were also computed: the number of vascular trees (NT), the vascular density (VD), the number of branches, the 2-D curvature measure, the number of vascular flexes of the vessels, and the 3-D curvature. Results showed that all the vascular descriptors obtained by liposome-based images were statistically equal to those obtained by using microbubbles, except the VD which was found to be lower for liposome images. All the six descriptors computed in pre-contrast conditions had values that were statistically lower than those computed in presence of contrast, both for liposomes and microbubbles. Liposomes have already been used in cancer therapy for the selective ultrasound-mediated delivery of drugs. This work demonstrated their effectiveness also as vascular diagnostic contrast agents, therefore proving that liposomes can be used as efficient "theranostic" (i.e. therapeutic 1 diagnostic) ultrasound probes. PMID:24206210

  6. Drug interaction study of natural steroids from herbs specifically toward human UDP-glucuronosyltransferase (UGT) 1A4 and their quantitative structure activity relationship (QSAR) analysis for prediction.

    PubMed

    Xu, Min; Dong, Peipei; Tian, Xiangge; Wang, Chao; Huo, Xiaokui; Zhang, Baojing; Wu, Lijun; Deng, Sa; Ma, Xiaochi

    2016-08-01

    The wide application of herbal medicines and foods containing steroids has resulted in the high risk of herb-drug interactions (HDIs). The present study aims to evaluate the inhibition potential of 43 natural steroids from herb medicines toward human UDP- glucuronosyltransferases (UGTs). A remarkable structure-dependent inhibition toward UGT1A4 was observed in vitro. Some natural steroids such as gitogenin, tigogenin, and solasodine were found to be the novel selective inhibitors of UGT1A4, and did not inhibit the activities of major human CYP isoforms. To clarify the possibility of the in vivo interaction of common steroids and clinical drugs, the kinetic inhibition type and related kinetic parameters (Ki) were measured. The target compounds 2-6 and 15, competitively inhibited the UGT1A4-catalyzed trifluoperazine glucuronidation reaction, with Ki values of 0.6, 0.18, 1.1, 0.7, 0.8, and 12.3μM, respectively. And this inhibition of steroids towards UGT1A4 was also verified in human primary hepatocytes. Furthermore, a quantitative structure-activity relationship (QSAR) of steroids with inhibitory effects toward human UGT1A4 isoform was established using the computational methods. Our findings elucidate the potential for in vivo HDI effects of steroids in herbal medicine and foods, with the clinical dr ugs eliminated by UGT1A4, and reveal the vital pharamcophoric requirement of natural steroids for UGT1A4 inhibition activity. PMID:27208893

  7. Physicochemical explanation of peptide binding to HLA-A*0201 major histocompatibility complex: a three-dimensional quantitative structure-activity relationship study.

    PubMed

    Doytchinova, Irini A; Flower, Darren R

    2002-08-15

    A three-dimensional quantitative structure-activity relationship method for the prediction of peptide binding affinities to the MHC class I molecule HLA-A*0201 was developed by applying the CoMSIA technique on a set of 266 peptides. To increase the self consistency of the initial CoMSIA model, the poorly predicted peptides were excluded from the training set in a stepwise manner and then included in the study as a test set. The final model, based on 236 peptides and considering the steric, electrostatic, hydrophobic, hydrogen bond donor, and hydrogen bond acceptor fields, had q2 = 0.683 and r2 = 0.891. The stability of this model was proven by cross-validations in two and five groups and by a bootstrap analysis of the non-cross-validated model. The residuals between the experimental pIC50 (-logIC50) values and those calculated by "leave-one-out" cross-validation were analyzed. According to the best model, 63.2% of the peptides were predicted with /residuals/ < or = 0.5 log unit; 29.3% with 1.0 < or = /residuals/ < 0.5; and 7.5% with /residuals/ > 1.0 log unit. The mean /residual/ value was 0.489. The coefficient contour maps identify the physicochemical property requirements at each position in the peptide molecule and suggest amino acid sequences for high-affinity binding to the HLA-A*0201 molecule. PMID:12112675

  8. Oxidation of substituted phenols in the environment: A QSAR analysis of rate constants for reaction with singlet oxygen. [Quantitative Structure-Activity Relationship

    SciTech Connect

    Tratnyek, P.G.; Holgne, J. , Duebendorf )

    1991-09-01

    Substituted phenols can be oxidized by singlet oxygen ({sup 1}O{sub 2}), which is formed in sunlit surface waters, and it has been suggested that this reaction may contribute to the environmental fate of phenolic substances. In aqueous solution, the observed rate of phenol disappearance is due to reaction of both the phenolate anion and the undissociated phenol. In order to quantify the effect of substituents on the rates of these reactions, second-order rate constants have been measured for both species for 22 substituted phenols by use of a model system containing the sensitizer rose bengal. Correlation analysis based on half-wave oxidation potentials, E{sub 1/2}, and on {sigma} constants reveals significant quantitative structure-activity relationships (QSARs) for both the undissociated phenols and the phenolate anions. Ortho- and multisubstituted phenols have been included in the correlations. These QSARs are consistent with the rate-limiting formation of a precursor complex with a small amount of charge-transfer character and can be used to predict additional rate constants for a wide range of environmentally significant substituted phenols.

  9. Quantitative Structure-Activity Relationship Analysis of the Effect of Metoclopramide and Related Compounds on the Surface Ionization of Fumed Silica.

    PubMed

    Buyuktimkin, Tuba; Wurster, Dale Eric

    2015-08-01

    Potentiometric titration curves were generated for fumed silica with various concentrations of dissolved metoclopramide. The effects of various benzamide analogs of metoclopramide, which are positively charged in the titration medium and differ solely by their aromatic substituents, as well as lidocaine, which is also structurally analogous but is mainly in the unionized form, were also studied. At sufficiently high pH, pH 7.0 and above, the silica surface charge was independent of the metoclopramide concentration. A reasonable linear relationship with a positive slope was found between the logarithmic octanol-water partition coefficient (log P) values of the compounds and the negative surface charge determined at pH 7.0 and 7.2. These results can be attributed to specific adsorbate-surface interactions rather than concentration effects. The carbonyl oxygens of the benzamide structures most likely form hydrogen bonds with the neutral silanols. The use of positively charged triethylamine and ephedrine resulted in surface charge values that were the least negative in the aforementioned quantitative structure-activity relationship analyses. These results are consistent with ionic interactions between the positively charged aliphatic amine groups and the negatively charged surface silanols occurring simultaneously with the nonionic interactions.

  10. Nano-quantitative structure-activity relationship modeling using easily computable and interpretable descriptors for uptake of magnetofluorescent engineered nanoparticles in pancreatic cancer cells.

    PubMed

    Kar, Supratik; Gajewicz, Agnieszka; Puzyn, Tomasz; Roy, Kunal

    2014-06-01

    As experimental evaluation of the safety of nanoparticles (NPs) is expensive and time-consuming, computational approaches have been found to be an efficient alternative for predicting the potential toxicity of new NPs before mass production. In this background, we have developed here a regression-based nano quantitative structure-activity relationship (nano-QSAR) model to establish statistically significant relationships between the measured cellular uptakes of 109 magnetofluorescent NPs in pancreatic cancer cells with their physical, chemical, and structural properties encoded within easily computable, interpretable and reproducible descriptors. The developed model was rigorously validated internally as well as externally with the application of the principles of Organization for Economic Cooperation and Development (OECD). The test for domain of applicability was also carried out for checking reliability of the predictions. Important fragments contributing to higher/lower cellular uptake of NPs were identified through critical analysis and interpretation of the developed model. Considering all these identified structural attributes, one can choose or design safe, economical and suitable surface modifiers for NPs. The presented approach provides rich information in the context of virtual screening of relevant NP libraries.

  11. Toxicity in relation to mode of action for the nematode Caenorhabditis elegans: Acute-to-chronic ratios and quantitative structure-activity relationships.

    PubMed

    Ristau, Kai; Akgül, Yeliz; Bartel, Anna Sophie; Fremming, Jana; Müller, Marie-Theres; Reiher, Luise; Stapela, Frederike; Splett, Jan-Paul; Spann, Nicole

    2015-10-01

    Acute-to-chronic ratios (ACRs) and quantitative structure-activity relationships (QSARs) are of particular interest in chemical risk assessment. Previous studies focusing on the relationship between the size or variation of ACRs to substance classes and QSAR models were often based on data for standard test organisms, such as daphnids and fish. In the present study, acute and chronic toxicity tests were performed with the nematode Caenorhabditis elegans for a total of 11 chemicals covering 3 substance classes (nonpolar narcotics: 1-propanol, ethanol, methanol, 2-butoxyethanol; metals: copper, cadmium, zinc; and carbamates: methomyl, oxamyl, aldicarb, dioxacarb). The ACRs were variable, especially for the carbamates and metals, although there was a trend toward small and less variable ACRs for nonpolar narcotic substances. The octanol-water partition coefficient was a good predictor for explaining acute and chronic toxicity of nonpolar narcotic substances to C. elegans, but not for carbamates. Metal toxicity could be related to the covalent index χm2r. Overall, the results support earlier results from ACR and QSAR studies with standard freshwater test animals. As such C. elegans as a representative of small soil/sediment invertebrates would probably be protected by risk assessment strategies already in use. To increase the predictive power of ACRs and QSARs, further research should be expanded to other species and compounds and should also consider the target sites and toxicokinetics of chemicals.

  12. Drug interaction study of natural steroids from herbs specifically toward human UDP-glucuronosyltransferase (UGT) 1A4 and their quantitative structure activity relationship (QSAR) analysis for prediction.

    PubMed

    Xu, Min; Dong, Peipei; Tian, Xiangge; Wang, Chao; Huo, Xiaokui; Zhang, Baojing; Wu, Lijun; Deng, Sa; Ma, Xiaochi

    2016-08-01

    The wide application of herbal medicines and foods containing steroids has resulted in the high risk of herb-drug interactions (HDIs). The present study aims to evaluate the inhibition potential of 43 natural steroids from herb medicines toward human UDP- glucuronosyltransferases (UGTs). A remarkable structure-dependent inhibition toward UGT1A4 was observed in vitro. Some natural steroids such as gitogenin, tigogenin, and solasodine were found to be the novel selective inhibitors of UGT1A4, and did not inhibit the activities of major human CYP isoforms. To clarify the possibility of the in vivo interaction of common steroids and clinical drugs, the kinetic inhibition type and related kinetic parameters (Ki) were measured. The target compounds 2-6 and 15, competitively inhibited the UGT1A4-catalyzed trifluoperazine glucuronidation reaction, with Ki values of 0.6, 0.18, 1.1, 0.7, 0.8, and 12.3μM, respectively. And this inhibition of steroids towards UGT1A4 was also verified in human primary hepatocytes. Furthermore, a quantitative structure-activity relationship (QSAR) of steroids with inhibitory effects toward human UGT1A4 isoform was established using the computational methods. Our findings elucidate the potential for in vivo HDI effects of steroids in herbal medicine and foods, with the clinical dr ugs eliminated by UGT1A4, and reveal the vital pharamcophoric requirement of natural steroids for UGT1A4 inhibition activity.

  13. The use of quantitative structure-activity relationship models to develop optimized processes for the removal of tobacco host cell proteins during biopharmaceutical production.

    PubMed

    Buyel, J F; Woo, J A; Cramer, S M; Fischer, R

    2013-12-27

    The production of recombinant pharmaceutical proteins in plants benefits from the low cost of upstream production and the greater scalability of plants compared to fermenter-based systems. Now that manufacturing processes that comply with current good manufacturing practices have been developed, plants can compete with established platforms on equal terms. However, the costs of downstream processing remain high, in part because of the dedicated process steps required to remove plant-specific process-related impurities. We therefore investigated whether the ideal strategy for the chromatographic removal of tobacco host cell proteins can be predicted by quantitative structure-activity relationship (QSAR) modeling to reduce the process development time and overall costs. We identified more than 100 tobacco proteins by mass spectrometry and their structures were reconstructed from X-ray crystallography, nuclear magnetic resonance spectroscopy and/or homology modeling data. The resulting three-dimensional models were used to calculate protein descriptors, and significant descriptors were selected based on recently-published retention data for model proteins to develop QSAR models for protein retention on anion, cation and mixed-mode resins. The predicted protein retention profiles were compared with experimental results using crude tobacco protein extracts. Because of the generic nature of the method, it can easily be transferred to other expression systems such as mammalian cells. The quality of the models and potential improvements are discussed.

  14. Synthesis and quantitative structure-activity relationship (QSAR) study of novel 4-acyloxypodophyllotoxin derivatives modified in the A and C rings as insecticidal agents.

    PubMed

    He, Shuzhen; Shao, Yonghua; Fan, Lingling; Che, Zhiping; Xu, Hui; Zhi, Xiaoyan; Wang, Juanjuan; Yao, Xiaojun; Qu, Huan

    2013-01-23

    In continuation of our program aimed at the discovery and development of natural-product-based insecticidal agents, we have synthesized three series of novel 4-acyloxy compounds derived from podophyllotoxin modified in the A and C rings, which is isolated as the main secondary metabolite from the roots and rhizomes of Podophyllum hexandrum . Their insecticidal activity was preliminarily evaluated against the pre-third-instar larvae of Mythimna separata in vivo. Compound 9g displayed the best promising insecticidal activity. It revealed that cleavage of the 6,7-methylenedioxy group of podophyllotoxin will lead to a less active compound and that the C-4 position of podophyllotoxin was the important modification location. A quantitative structure-activity relationship (QSAR) model was developed by genetic algorithm combined with multiple linear regression (GA-MLR). For this model, the squared correlation coefficient (R(2)) is 0.914, the leave-one-out cross-validation correlation coefficient (Q(2)(LOO)) is 0.881, and the root-mean-square error (RMSE) is 0.024. Five descriptors, BEHm2, Mor14v, Wap, G1v, and RDF020e, are likely to influence the biological activity of these compounds. Among them, two important ones are BEHm2 and Mor14v. This study will pave the way for further design, structural modification, and development of podophyllotoxin derivatives as insecticidal agents.

  15. Application of quantitative structure-activity relationship models of 5-HT1A receptor binding to virtual screening identifies novel and potent 5-HT1A ligands.

    PubMed

    Luo, Man; Wang, Xiang Simon; Roth, Bryan L; Golbraikh, Alexander; Tropsha, Alexander

    2014-02-24

    The 5-hydroxytryptamine 1A (5-HT1A) serotonin receptor has been an attractive target for treating mood and anxiety disorders such as schizophrenia. We have developed binary classification quantitative structure-activity relationship (QSAR) models of 5-HT1A receptor binding activity using data retrieved from the PDSP Ki database. The prediction accuracy of these models was estimated by external 5-fold cross-validation as well as using an additional validation set comprising 66 structurally distinct compounds from the World of Molecular Bioactivity database. These validated models were then used to mine three major types of chemical screening libraries, i.e., drug-like libraries, GPCR targeted libraries, and diversity libraries, to identify novel computational hits. The five best hits from each class of libraries were chosen for further experimental testing in radioligand binding assays, and nine of the 15 hits were confirmed to be active experimentally with binding affinity better than 10 μM. The most active compound, Lysergol, from the diversity library showed very high binding affinity (Ki) of 2.3 nM against 5-HT1A receptor. The novel 5-HT1A actives identified with the QSAR-based virtual screening approach could be potentially developed as novel anxiolytics or potential antischizophrenic drugs.

  16. A systematic investigation of quaternary ammonium ions as asymmetric phase-transfer catalysts. Application of quantitative structure activity/selectivity relationships.

    PubMed

    Denmark, Scott E; Gould, Nathan D; Wolf, Larry M

    2011-06-01

    Although the synthetic utility of asymmetric phase-transfer catalysis continues to expand, the number of proven catalyst types and design criteria remains limited. At the origin of this scarcity is a lack in understanding of how catalyst structural features affect the rate and enantioselectivity of phase transfer catalyzed reactions. Described in this paper is the development of quantitative structure-activity relationships (QSAR) and -selectivity relationships (QSSR) for the alkylation of a protected glycine imine with libraries of quaternary ammonium ion catalysts. Catalyst descriptors including ammonium ion accessibility, interfacial adsorption affinity, and partition coefficient were found to correlate meaningfully with catalyst activity. The physical nature of the descriptors was rationalized through differing contributions of the interfacial and extraction mechanisms to the reaction under study. The variation in the observed enantioselectivity was rationalized employing a comparative molecular field analysis (CoMFA) using both the steric and electrostatic fields of the catalysts. A qualitative analysis of the developed model reveals preferred regions for catalyst binding to afford both configurations of the alkylated product.

  17. The use of quantitative structure-activity relationship models to develop optimized processes for the removal of tobacco host cell proteins during biopharmaceutical production.

    PubMed

    Buyel, J F; Woo, J A; Cramer, S M; Fischer, R

    2013-12-27

    The production of recombinant pharmaceutical proteins in plants benefits from the low cost of upstream production and the greater scalability of plants compared to fermenter-based systems. Now that manufacturing processes that comply with current good manufacturing practices have been developed, plants can compete with established platforms on equal terms. However, the costs of downstream processing remain high, in part because of the dedicated process steps required to remove plant-specific process-related impurities. We therefore investigated whether the ideal strategy for the chromatographic removal of tobacco host cell proteins can be predicted by quantitative structure-activity relationship (QSAR) modeling to reduce the process development time and overall costs. We identified more than 100 tobacco proteins by mass spectrometry and their structures were reconstructed from X-ray crystallography, nuclear magnetic resonance spectroscopy and/or homology modeling data. The resulting three-dimensional models were used to calculate protein descriptors, and significant descriptors were selected based on recently-published retention data for model proteins to develop QSAR models for protein retention on anion, cation and mixed-mode resins. The predicted protein retention profiles were compared with experimental results using crude tobacco protein extracts. Because of the generic nature of the method, it can easily be transferred to other expression systems such as mammalian cells. The quality of the models and potential improvements are discussed. PMID:24268820

  18. A cellular system for quantitation of vitamin K cycle activity: structure-activity effects on vitamin K antagonism by warfarin metabolites

    PubMed Central

    Haque, Jamil A.; McDonald, Matthew G.; Kulman, John D.

    2014-01-01

    Warfarin and other 4-hydroxycoumarins inhibit vitamin K epoxide reductase (VKOR) by depleting reduced vitamin K that is required for posttranslational modification of vitamin K–dependent clotting factors. In vitro prediction of the in vivo potency of vitamin K antagonists is complicated by the complex multicomponent nature of the vitamin K cycle. Here we describe a sensitive assay that enables quantitative analysis of γ-glutamyl carboxylation and its antagonism in live cells. We engineered a human embryonic kidney (HEK) 293–derived cell line (HEK 293-C3) to express a chimeric protein (F9CH) comprising the Gla domain of factor IX fused to the transmembrane and cytoplasmic regions of proline-rich Gla protein 2. Maximal γ-glutamyl carboxylation of F9CH required vitamin K supplementation, and was dose-dependently inhibited by racemic warfarin at a physiologically relevant concentration. Cellular γ-glutamyl carboxylation also exhibited differential VKOR inhibition by warfarin enantiomers (S > R) consistent with their in vivo potencies. We further analyzed the structure-activity relationship for inhibition of γ-glutamyl carboxylation by warfarin metabolites, observing tolerance to phenolic substitution at the C-5 and especially C-6, but not C-7 or C-8, positions on the 4-hydroxycoumarin nucleus. After correction for in vivo concentration and protein binding, 10-hydroxywarfarin and warfarin alcohols were predicted to be the most potent inhibitory metabolites in vivo. PMID:24297869

  19. Quantitative Structure-Activity Relationship Analysis and a Combined Ligand-Based/Structure-Based Virtual Screening Study for Glycogen Synthase Kinase-3.

    PubMed

    Fu, Gang; Liu, Sheng; Nan, Xiaofei; Dale, Olivia R; Zhao, Zhendong; Chen, Yixin; Wilkins, Dawn E; Manly, Susan P; Cutler, Stephen J; Doerksen, Robert J

    2014-09-01

    Glycogen synthase kinase-3 (GSK-3) is a multifunctional serine/threonine protein kinase which regulates a wide range of cellular processes, involving various signalling pathways. GSK-3β has emerged as an important therapeutic target for diabetes and Alzheimer's disease. To identify structurally novel GSK-3β inhibitors, we performed virtual screening by implementing a combined ligand-based/structure-based approach, which included quantitative structure-activity relationship (QSAR) analysis and docking prediction. To integrate and analyze complex data sets from multiple experimental sources, we drafted and validated a hierarchical QSAR method, which adopts a two-level structure to take data heterogeneity into account. A collection of 728 GSK-3 inhibitors with diverse structural scaffolds was obtained from published papers that used different experimental assay protocols. Support vector machines and random forests were implemented with wrapper-based feature selection algorithms to construct predictive learning models. The best models for each single group of compounds were then used to build the final hierarchical QSAR model, with an overall R(2) of 0.752 for the 141 compounds in the test set. The compounds obtained from the virtual screening experiment were tested for GSK-3β inhibition. The bioassay results confirmed that 2 hit compounds are indeed GSK-3β inhibitors exhibiting sub-micromolar inhibitory activity, and therefore validated our combined ligand-based/structure-based approach as effective for virtual screening experiments. PMID:27486081

  20. Nano-quantitative structure-activity relationship modeling using easily computable and interpretable descriptors for uptake of magnetofluorescent engineered nanoparticles in pancreatic cancer cells.

    PubMed

    Kar, Supratik; Gajewicz, Agnieszka; Puzyn, Tomasz; Roy, Kunal

    2014-06-01

    As experimental evaluation of the safety of nanoparticles (NPs) is expensive and time-consuming, computational approaches have been found to be an efficient alternative for predicting the potential toxicity of new NPs before mass production. In this background, we have developed here a regression-based nano quantitative structure-activity relationship (nano-QSAR) model to establish statistically significant relationships between the measured cellular uptakes of 109 magnetofluorescent NPs in pancreatic cancer cells with their physical, chemical, and structural properties encoded within easily computable, interpretable and reproducible descriptors. The developed model was rigorously validated internally as well as externally with the application of the principles of Organization for Economic Cooperation and Development (OECD). The test for domain of applicability was also carried out for checking reliability of the predictions. Important fragments contributing to higher/lower cellular uptake of NPs were identified through critical analysis and interpretation of the developed model. Considering all these identified structural attributes, one can choose or design safe, economical and suitable surface modifiers for NPs. The presented approach provides rich information in the context of virtual screening of relevant NP libraries. PMID:24412539

  1. 3d-3d correspondence revisited

    NASA Astrophysics Data System (ADS)

    Chung, Hee-Joong; Dimofte, Tudor; Gukov, Sergei; Sułkowski, Piotr

    2016-04-01

    In fivebrane compactifications on 3-manifolds, we point out the importance of all flat connections in the proper definition of the effective 3d {N}=2 theory. The Lagrangians of some theories with the desired properties can be constructed with the help of homological knot invariants that categorify colored Jones polynomials. Higgsing the full 3d theories constructed this way recovers theories found previously by Dimofte-Gaiotto-Gukov. We also consider the cutting and gluing of 3-manifolds along smooth boundaries and the role played by all flat connections in this operation.

  2. 3d-3d correspondence revisited

    DOE PAGES

    Chung, Hee -Joong; Dimofte, Tudor; Gukov, Sergei; Sułkowski, Piotr

    2016-04-21

    In fivebrane compactifications on 3-manifolds, we point out the importance of all flat connections in the proper definition of the effective 3d N = 2 theory. The Lagrangians of some theories with the desired properties can be constructed with the help of homological knot invariants that categorify colored Jones polynomials. Higgsing the full 3d theories constructed this way recovers theories found previously by Dimofte-Gaiotto-Gukov. As a result, we also consider the cutting and gluing of 3-manifolds along smooth boundaries and the role played by all flat connections in this operation.

  3. Quantitative trait loci affecting the 3D skull shape and size in mouse and prioritization of candidate genes in-silico

    PubMed Central

    Maga, A. Murat; Navarro, Nicolas; Cunningham, Michael L.; Cox, Timothy C.

    2015-01-01

    We describe the first application of high-resolution 3D micro-computed tomography, together with 3D landmarks and geometric morphometrics, to map QTL responsible for variation in skull shape and size using a backcross between C57BL/6J and A/J inbred strains. Using 433 animals, 53 3D landmarks, and 882 SNPs from autosomes, we identified seven QTL responsible for the skull size (SCS.qtl) and 30 QTL responsible for the skull shape (SSH.qtl). Size, sex, and direction-of-cross were all significant factors and included in the analysis as covariates. All autosomes harbored at least one SSH.qtl, sometimes up to three. Effect sizes of SSH.qtl appeared to be small, rarely exceeding 1% of the overall shape variation. However, they account for significant amount of variation in some specific directions of the shape space. Many QTL have stronger effect on the neurocranium than expected from a random vector that will parcellate uniformly across the four cranial regions. On the contrary, most of QTL have an effect on the palate weaker than expected. Combined interval length of 30 SSH.qtl was about 315 MB and contained 2476 known protein coding genes. We used a bioinformatics approach to filter these candidate genes and identified 16 high-priority candidates that are likely to play a role in the craniofacial development and disorders. Thus, coupling the QTL mapping approach in model organisms with candidate gene enrichment approaches appears to be a feasible way to identify high-priority candidates genes related to the structure or tissue of interest. PMID:25859222

  4. Quantitative trait loci affecting the 3D skull shape and size in mouse and prioritization of candidate genes in-silico.

    PubMed

    Maga, A Murat; Navarro, Nicolas; Cunningham, Michael L; Cox, Timothy C

    2015-01-01

    We describe the first application of high-resolution 3D micro-computed tomography, together with 3D landmarks and geometric morphometrics, to map QTL responsible for variation in skull shape and size using a backcross between C57BL/6J and A/J inbred strains. Using 433 animals, 53 3D landmarks, and 882 SNPs from autosomes, we identified seven QTL responsible for the skull size (SCS.qtl) and 30 QTL responsible for the skull shape (SSH.qtl). Size, sex, and direction-of-cross were all significant factors and included in the analysis as covariates. All autosomes harbored at least one SSH.qtl, sometimes up to three. Effect sizes of SSH.qtl appeared to be small, rarely exceeding 1% of the overall shape variation. However, they account for significant amount of variation in some specific directions of the shape space. Many QTL have stronger effect on the neurocranium than expected from a random vector that will parcellate uniformly across the four cranial regions. On the contrary, most of QTL have an effect on the palate weaker than expected. Combined interval length of 30 SSH.qtl was about 315 MB and contained 2476 known protein coding genes. We used a bioinformatics approach to filter these candidate genes and identified 16 high-priority candidates that are likely to play a role in the craniofacial development and disorders. Thus, coupling the QTL mapping approach in model organisms with candidate gene enrichment approaches appears to be a feasible way to identify high-priority candidates genes related to the structure or tissue of interest.

  5. New opportunities for quantitative and time efficient 3D MRI of liquid and solid electrochemical cell components: Sectoral Fast Spin Echo and SPRITE.

    PubMed

    Romanenko, Konstantin; Forsyth, Maria; O'Dell, Luke A

    2014-11-01

    The ability to image electrochemical processes in situ using nuclear magnetic resonance imaging (MRI) offers exciting possibilities for understanding and optimizing materials in batteries, fuel cells and supercapacitors. In these applications, however, the quality of the MRI measurement is inherently limited by the presence of conductive elements in the cell or device. To overcome related difficulties, optimal methodologies have to be employed. We show that time-efficient three dimensional (3D) imaging of liquid and solid lithium battery components can be performed by Sectoral Fast Spin Echo and Single Point Imaging with T1 Enhancement (SPRITE), respectively. The former method is based on the generalized phase encoding concept employed in clinical MRI, which we have adapted and optimized for materials science and electrochemistry applications. Hard radio frequency pulses, short echo spacing and centrically ordered sectoral phase encoding ensure accurate and time-efficient full volume imaging. Mapping of density, diffusivity and relaxation time constants in metal-containing liquid electrolytes is demonstrated. 1, 2 and 3D SPRITE approaches show strong potential for rapid high resolution (7)Li MRI of lithium electrode components.

  6. New opportunities for quantitative and time efficient 3D MRI of liquid and solid electrochemical cell components: Sectoral Fast Spin Echo and SPRITE

    NASA Astrophysics Data System (ADS)

    Romanenko, Konstantin; Forsyth, Maria; O'Dell, Luke A.

    2014-11-01

    The ability to image electrochemical processes in situ using nuclear magnetic resonance imaging (MRI) offers exciting possibilities for understanding and optimizing materials in batteries, fuel cells and supercapacitors. In these applications, however, the quality of the MRI measurement is inherently limited by the presence of conductive elements in the cell or device. To overcome related difficulties, optimal methodologies have to be employed. We show that time-efficient three dimensional (3D) imaging of liquid and solid lithium battery components can be performed by Sectoral Fast Spin Echo and Single Point Imaging with T1 Enhancement (SPRITE), respectively. The former method is based on the generalized phase encoding concept employed in clinical MRI, which we have adapted and optimized for materials science and electrochemistry applications. Hard radio frequency pulses, short echo spacing and centrically ordered sectoral phase encoding ensure accurate and time-efficient full volume imaging. Mapping of density, diffusivity and relaxation time constants in metal-containing liquid electrolytes is demonstrated. 1, 2 and 3D SPRITE approaches show strong potential for rapid high resolution 7Li MRI of lithium electrode components.

  7. New opportunities for quantitative and time efficient 3D MRI of liquid and solid electrochemical cell components: Sectoral Fast Spin Echo and SPRITE.

    PubMed

    Romanenko, Konstantin; Forsyth, Maria; O'Dell, Luke A

    2014-11-01

    The ability to image electrochemical processes in situ using nuclear magnetic resonance imaging (MRI) offers exciting possibilities for understanding and optimizing materials in batteries, fuel cells and supercapacitors. In these applications, however, the quality of the MRI measurement is inherently limited by the presence of conductive elements in the cell or device. To overcome related difficulties, optimal methodologies have to be employed. We show that time-efficient three dimensional (3D) imaging of liquid and solid lithium battery components can be performed by Sectoral Fast Spin Echo and Single Point Imaging with T1 Enhancement (SPRITE), respectively. The former method is based on the generalized phase encoding concept employed in clinical MRI, which we have adapted and optimized for materials science and electrochemistry applications. Hard radio frequency pulses, short echo spacing and centrically ordered sectoral phase encoding ensure accurate and time-efficient full volume imaging. Mapping of density, diffusivity and relaxation time constants in metal-containing liquid electrolytes is demonstrated. 1, 2 and 3D SPRITE approaches show strong potential for rapid high resolution (7)Li MRI of lithium electrode components. PMID:25442778

  8. 3D numerical analyses for the quantitative risk assessment of subsidence and water flood due to the partial collapse of an abandoned gypsum mine.

    NASA Astrophysics Data System (ADS)

    Castellanza, R.; Orlandi, G. M.; di Prisco, C.; Frigerio, G.; Flessati, L.; Fernandez Merodo, J. A.; Agliardi, F.; Grisi, S.; Crosta, G. B.

    2015-09-01

    After the abandonment occurred in the '70s, the mining system (rooms and pillars) located in S. Lazzaro di Savena (BO, Italy), grown on three levels with the method rooms and pillars, has been progressively more and more affected by degradation processes due to water infiltration. The mine is located underneath a residential area causing significant concern to the local municipality. On the basis of in situ surveys, laboratory and in situ geomechanical tests, some critical scenarios were adopted in the analyses to simulate the progressive collapse of pillars and of roofs in the most critical sectors of the mine. A first set of numerical analyses using 3D geotechnical FEM codes were performed to predict the extension of the subsidence area and its interaction with buildings. Secondly 3D CFD analyses were used to evaluated the amount of water that could be eventually ejected outside the mine and eventually flooding the downstream village. The predicted extension of the subsidence area together with the predicted amount of the ejected water have been used to design possible remedial measurements.

  9. Quantitative Analysis of Porosity and Transport Properties by FIB-SEM 3D Imaging of a Solder Based Sintered Silver for a New Microelectronic Component

    NASA Astrophysics Data System (ADS)

    Rmili, W.; Vivet, N.; Chupin, S.; Le Bihan, T.; Le Quilliec, G.; Richard, C.

    2016-04-01

    As part of development of a new assembly technology to achieve bonding for an innovative silicon carbide (SiC) power device used in harsh environments, the aim of this study is to compare two silver sintering profiles and then to define the best candidate for die attach material for this new component. To achieve this goal, the solder joints have been characterized in terms of porosity by determination of the morphological characteristics of the material heterogeneities and estimating their thermal and electrical transport properties. The three dimensional (3D) microstructure of sintered silver samples has been reconstructed using a focused ion beam scanning electron microscope (FIB-SEM) tomography technique. The sample preparation and the experimental milling and imaging parameters have been optimized in order to obtain a high quality of 3D reconstruction. Volume fractions and volumetric connectivity of the individual phases (silver and voids) have been determined. Effective thermal and electrical conductivities of the samples and the tortuosity of the silver phase have been also evaluated by solving the diffusive transport equation.

  10. 3D and Education

    NASA Astrophysics Data System (ADS)

    Meulien Ohlmann, Odile

    2013-02-01

    Today the industry offers a chain of 3D products. Learning to "read" and to "create in 3D" becomes an issue of education of primary importance. 25 years professional experience in France, the United States and Germany, Odile Meulien set up a personal method of initiation to 3D creation that entails the spatial/temporal experience of the holographic visual. She will present some different tools and techniques used for this learning, their advantages and disadvantages, programs and issues of educational policies, constraints and expectations related to the development of new techniques for 3D imaging. Although the creation of display holograms is very much reduced compared to the creation of the 90ies, the holographic concept is spreading in all scientific, social, and artistic activities of our present time. She will also raise many questions: What means 3D? Is it communication? Is it perception? How the seeing and none seeing is interferes? What else has to be taken in consideration to communicate in 3D? How to handle the non visible relations of moving objects with subjects? Does this transform our model of exchange with others? What kind of interaction this has with our everyday life? Then come more practical questions: How to learn creating 3D visualization, to learn 3D grammar, 3D language, 3D thinking? What for? At what level? In which matter? for whom?

  11. Robust patella motion tracking using intensity-based 2D-3D registration on dynamic bi-plane fluoroscopy: towards quantitative assessment in MPFL reconstruction surgery

    NASA Astrophysics Data System (ADS)

    Otake, Yoshito; Esnault, Matthieu; Grupp, Robert; Kosugi, Shinichi; Sato, Yoshinobu

    2016-03-01

    The determination of in vivo motion of multiple-bones using dynamic fluoroscopic images and computed tomography (CT) is useful for post-operative assessment of orthopaedic surgeries such as medial patellofemoral ligament reconstruction. We propose a robust method to measure the 3D motion of multiple rigid objects with high accuracy using a series of bi-plane fluoroscopic images and a multi-resolution, intensity-based, 2D-3D registration. A Covariance Matrix Adaptation Evolution Strategy (CMA-ES) optimizer was used with a gradient correlation similarity metric. Four approaches to register three rigid objects (femur, tibia-fibula and patella) were implemented: 1) an individual bone approach registering one bone at a time, each with optimization of a six degrees of freedom (6DOF) parameter, 2) a sequential approach registering one bone at a time but using the previous bone results as the background in DRR generation, 3) a simultaneous approach registering all the bones together (18DOF) and 4) a combination of the sequential and the simultaneous approaches. These approaches were compared in experiments using simulated images generated from the CT of a healthy volunteer and measured fluoroscopic images. Over the 120 simulated frames of motion, the simultaneous approach showed improved registration accuracy compared to the individual approach: with less than 0.68mm root-mean-square error (RMSE) for translation and less than 1.12° RMSE for rotation. A robustness evaluation was conducted with 45 trials of a randomly perturbed initialization showed that the sequential approach improved robustness significantly (74% success rate) compared to the individual bone approach (34% success) for patella registration (femur and tibia-fibula registration had a 100% success rate with each approach).

  12. Quantitative 3D Fluorescence Imaging of Single Catalytic Turnovers Reveals Spatiotemporal Gradients in Reactivity of Zeolite H-ZSM-5 Crystals upon Steaming

    PubMed Central

    2015-01-01

    Optimizing the number, distribution, and accessibility of Brønsted acid sites in zeolite-based catalysts is of a paramount importance to further improve their catalytic performance. However, it remains challenging to measure real-time changes in reactivity of single zeolite catalyst particles by ensemble-averaging characterization methods. In this work, a detailed 3D single molecule, single turnover sensitive fluorescence microscopy study is presented to quantify the reactivity of Brønsted acid sites in zeolite H-ZSM-5 crystals upon steaming. This approach, in combination with the oligomerization of furfuryl alcohol as a probe reaction, allowed the stochastic behavior of single catalytic turnovers and temporally resolved turnover frequencies of zeolite domains smaller than the diffraction limited resolution to be investigated with great precision. It was found that the single turnover kinetics of the parent zeolite crystal proceeds with significant spatial differences in turnover frequencies on the nanoscale and noncorrelated temporal fluctuations. Mild steaming of zeolite H-ZSM-5 crystals at 500 °C led to an enhanced surface reactivity, with up to 4 times higher local turnover rates than those of the parent H-ZSM-5 crystals, and revealed remarkable heterogeneities in surface reactivity. In strong contrast, severe steaming at 700 °C significantly dealuminated the zeolite H-ZSM-5 material, leading to a 460 times lower turnover rate. The differences in measured turnover activities are explained by changes in the 3D aluminum distribution due to migration of extraframework Al-species and their subsequent effect on pore accessibility, as corroborated by time-of-flight secondary ion mass spectrometry (TOF-SIMS) sputter depth profiling data. PMID:25867455

  13. Support vector regression-guided unravelling: antioxidant capacity and quantitative structure-activity relationship predict reduction and promotion effects of flavonoids on acrylamide formation

    NASA Astrophysics Data System (ADS)

    Huang, Mengmeng; Wei, Yan; Wang, Jun; Zhang, Yu

    2016-09-01

    We used the support vector regression (SVR) approach to predict and unravel reduction/promotion effect of characteristic flavonoids on the acrylamide formation under a low-moisture Maillard reaction system. Results demonstrated the reduction/promotion effects by flavonoids at addition levels of 1–10000 μmol/L. The maximal inhibition rates (51.7%, 68.8% and 26.1%) and promote rates (57.7%, 178.8% and 27.5%) caused by flavones, flavonols and isoflavones were observed at addition levels of 100 μmol/L and 10000 μmol/L, respectively. The reduction/promotion effects were closely related to the change of trolox equivalent antioxidant capacity (ΔTEAC) and well predicted by triple ΔTEAC measurements via SVR models (R: 0.633–0.900). Flavonols exhibit stronger effects on the acrylamide formation than flavones and isoflavones as well as their O-glycosides derivatives, which may be attributed to the number and position of phenolic and 3-enolic hydroxyls. The reduction/promotion effects were well predicted by using optimized quantitative structure-activity relationship (QSAR) descriptors and SVR models (R: 0.926–0.994). Compared to artificial neural network and multi-linear regression models, SVR models exhibited better fitting performance for both TEAC-dependent and QSAR descriptor-dependent predicting work. These observations demonstrated that the SVR models are competent for predicting our understanding on the future use of natural antioxidants for decreasing the acrylamide formation.

  14. Global quantitative structure-activity relationship models vs selected local models as predictors of off-target activities for project compounds.

    PubMed

    Sheridan, Robert P

    2014-04-28

    In the pharmaceutical industry, it is common for large numbers of compounds to be tested for off-target activities. Given a compound synthesized for an on-target project P, what is the best way to predict its off-target activity X? Is it better to use a global quantitative structure-activity relationship (QSAR) model calibrated against all compounds tested for X, or is it better to use a local model for X calibrated against only the set of compounds in project P? The literature is not consistent on this topic, and strong claims have been made for either. One particular idea is that local models will be superior to global models in prospective prediction if one generates many local models and chooses the type of local model that best predicts recent data. We tested this idea via simulated prospective prediction using in-house data involving compounds in 11 projects tested for 9 off-target activities. In our hands, the local model that best predicts the recent past is seldom the local model that is best at predicting the immediate future. Also, the local model that best predicts the recent past is not systematically better than the global model. This means the complexity of having project- or series-specific models for X can be avoided; a single global model for X is sufficient. We suggest that the relative predictivity of global vs local models may depend on the type of chemical descriptor used. Finally, we speculate why, contrary to observation, intuition suggests local models should be superior to global models.

  15. Support vector regression-guided unravelling: antioxidant capacity and quantitative structure-activity relationship predict reduction and promotion effects of flavonoids on acrylamide formation

    PubMed Central

    Huang, Mengmeng; Wei, Yan; Wang, Jun; Zhang, Yu

    2016-01-01

    We used the support vector regression (SVR) approach to predict and unravel reduction/promotion effect of characteristic flavonoids on the acrylamide formation under a low-moisture Maillard reaction system. Results demonstrated the reduction/promotion effects by flavonoids at addition levels of 1–10000 μmol/L. The maximal inhibition rates (51.7%, 68.8% and 26.1%) and promote rates (57.7%, 178.8% and 27.5%) caused by flavones, flavonols and isoflavones were observed at addition levels of 100 μmol/L and 10000 μmol/L, respectively. The reduction/promotion effects were closely related to the change of trolox equivalent antioxidant capacity (ΔTEAC) and well predicted by triple ΔTEAC measurements via SVR models (R: 0.633–0.900). Flavonols exhibit stronger effects on the acrylamide formation than flavones and isoflavones as well as their O-glycosides derivatives, which may be attributed to the number and position of phenolic and 3-enolic hydroxyls. The reduction/promotion effects were well predicted by using optimized quantitative structure-activity relationship (QSAR) descriptors and SVR models (R: 0.926–0.994). Compared to artificial neural network and multi-linear regression models, SVR models exhibited better fitting performance for both TEAC-dependent and QSAR descriptor-dependent predicting work. These observations demonstrated that the SVR models are competent for predicting our understanding on the future use of natural antioxidants for decreasing the acrylamide formation. PMID:27586851

  16. Mechanistic quantitative structure-activity relationship model for the photoinduced toxicity of polycyclic aromatic hydrocarbons. 1: Physical model based on chemical kinetics in a two-compartment system

    SciTech Connect

    Krylov, S.N.; Huang, X.D.; Zeiler, L.F.; Dixon, D.G.; Greenberg, B.M.

    1997-11-01

    A quantitative structure-activity relationship model for the photoinduced toxicity of 16 polycyclic aromatic hydrocarbons (PAHs) to duckweed (Lemna gibba) in simulated solar radiation (SSR) was developed. Lemna gibba was chosen for this study because toxicity could be considered in two compartments: water column and leaf tissue. Modeling of photoinduced toxicity was described by photochemical reactions between PAHs and a hypothetical group of endogenous biomolecules (G) required for normal growth, with damage to G by PAHs and/or photomodified PAHs in SSR resulting in impaired growth. The reaction scheme includes photomodification of PAHs, uptake of PAHs into leaves, triplet-state formation of intact PAHs, photosensitization reactions that damage G, and reactions between photomodified PAHs and G. The assumptions used were: the PAH photomodification rate is slower than uptake of chemicals into leaves, the PAH concentration in aqueous solution is nearly constant during a toxicity test, the fluence rate of actinic radiation is lower within leaves than in the aqueous phase, and the toxicity of intact PAHs in the dark is negligible. A series of differential equations describing the reaction kinetics of intact and photomodifed PAHs with G was derived. The resulting equation for PAH toxicity was a function of treatment period, initial PAH concentration, relative absorbance of SSR by each PAH, quantum yield for formation of triplet-state PAH, and rate of PAH photomodification. Data for growth in the presence of intact and photomodified PAHs were used to empirically solve for a photosensitization constant (PSC) and a photomodification constant (PMC) for each of the 16 PAHs tested. For 9 PAHs the PMC dominates and for 7 PAHs the PSC dominates.

  17. Toxicity of aryl- and benzylhalides to Daphnia magna and classification of their mode of action based on quantitative structure-activity relationship

    SciTech Connect

    Marchini, S.; Passerini, L.; Hoglund, M.D.; Pino, A.; Nendza, M.

    1999-12-01

    The acute toxicity of aryl- and benzylhalides to Daphnia magna was investigated to test the validity of existing classification schemes for chemicals by mode of action, mainly based on fish studies, and the applicability of predictive quantitative structure-activity relationship (QSAR) models. Halobenzenes and halotoluenes are generally agreed to be unambiguous baseline toxicants (class 1) with the major exception of the benzylic structures, which are reactive in fish tests (class 3). Eighty-nine percent of the arylhalides tested in this study match a log P{sub ow}-dependent QSAR, including fluorinated, chlorinated, brominated, and iodinated derivatives, thereby confirming the validity of the baseline models also for variously halogenated compounds (other than only-chloro compounds). The toxicities of the benzylhalides relative to baseline QSARs clearly indicate that these compounds belong to two classes of mode of action, i.e., they either act as narcotic toxicants (class 1) or reveal excess toxicity due to unspecific reactivity (class 3). On some occasions, the assignment to the two classes of F. magna deviates from the structural rules derived from fish, i.e., iodinated compounds as well as {alpha},{alpha}-Cl{sub 2}-toluene's lack reactive excess toxicity but behave as nonpolar nonspecific toxicants. The QSARs derived during this study reveal lower slopes and higher intercepts than typical baseline models and, together with the analysis of mixture toxicity studies, behavioral studies, and critical body burden, advocate the hypothesis that there are several different ways to produce baseline toxicity. Most halobenzenes and halotoluenes are actually baseline chemicals with some extra reactivity and as such form a subgroup, whose limits still have to be defined. Different primary sites of action could explain why the chemicals are discriminated by different classification systems, but still they must have some rate-limiting interaction in common as they fit the

  18. Support vector regression-guided unravelling: antioxidant capacity and quantitative structure-activity relationship predict reduction and promotion effects of flavonoids on acrylamide formation.

    PubMed

    Huang, Mengmeng; Wei, Yan; Wang, Jun; Zhang, Yu

    2016-01-01

    We used the support vector regression (SVR) approach to predict and unravel reduction/promotion effect of characteristic flavonoids on the acrylamide formation under a low-moisture Maillard reaction system. Results demonstrated the reduction/promotion effects by flavonoids at addition levels of 1-10000 μmol/L. The maximal inhibition rates (51.7%, 68.8% and 26.1%) and promote rates (57.7%, 178.8% and 27.5%) caused by flavones, flavonols and isoflavones were observed at addition levels of 100 μmol/L and 10000 μmol/L, respectively. The reduction/promotion effects were closely related to the change of trolox equivalent antioxidant capacity (ΔTEAC) and well predicted by triple ΔTEAC measurements via SVR models (R: 0.633-0.900). Flavonols exhibit stronger effects on the acrylamide formation than flavones and isoflavones as well as their O-glycosides derivatives, which may be attributed to the number and position of phenolic and 3-enolic hydroxyls. The reduction/promotion effects were well predicted by using optimized quantitative structure-activity relationship (QSAR) descriptors and SVR models (R: 0.926-0.994). Compared to artificial neural network and multi-linear regression models, SVR models exhibited better fitting performance for both TEAC-dependent and QSAR descriptor-dependent predicting work. These observations demonstrated that the SVR models are competent for predicting our understanding on the future use of natural antioxidants for decreasing the acrylamide formation. PMID:27586851

  19. Quantitative structure-activity relationship models for predicting drug-induced liver injury based on FDA-approved drug labeling annotation and using a large collection of drugs.

    PubMed

    Chen, Minjun; Hong, Huixiao; Fang, Hong; Kelly, Reagan; Zhou, Guangxu; Borlak, Jürgen; Tong, Weida

    2013-11-01

    Drug-induced liver injury (DILI) is one of the leading causes of the termination of drug development programs. Consequently, identifying the risk of DILI in humans for drug candidates during the early stages of the development process would greatly reduce the drug attrition rate in the pharmaceutical industry but would require the implementation of new research and development strategies. In this regard, several in silico models have been proposed as alternative means in prioritizing drug candidates. Because the accuracy and utility of a predictive model rests largely on how to annotate the potential of a drug to cause DILI in a reliable and consistent way, the Food and Drug Administration-approved drug labeling was given prominence. Out of 387 drugs annotated, 197 drugs were used to develop a quantitative structure-activity relationship (QSAR) model and the model was subsequently challenged by the left of drugs serving as an external validation set with an overall prediction accuracy of 68.9%. The performance of the model was further assessed by the use of 2 additional independent validation sets, and the 3 validation data sets have a total of 483 unique drugs. We observed that the QSAR model's performance varied for drugs with different therapeutic uses; however, it achieved a better estimated accuracy (73.6%) as well as negative predictive value (77.0%) when focusing only on these therapeutic categories with high prediction confidence. Thus, the model's applicability domain was defined. Taken collectively, the developed QSAR model has the potential utility to prioritize compound's risk for DILI in humans, particularly for the high-confidence therapeutic subgroups like analgesics, antibacterial agents, and antihistamines.

  20. Support vector regression-guided unravelling: antioxidant capacity and quantitative structure-activity relationship predict reduction and promotion effects of flavonoids on acrylamide formation.

    PubMed

    Huang, Mengmeng; Wei, Yan; Wang, Jun; Zhang, Yu

    2016-09-02

    We used the support vector regression (SVR) approach to predict and unravel reduction/promotion effect of characteristic flavonoids on the acrylamide formation under a low-moisture Maillard reaction system. Results demonstrated the reduction/promotion effects by flavonoids at addition levels of 1-10000 μmol/L. The maximal inhibition rates (51.7%, 68.8% and 26.1%) and promote rates (57.7%, 178.8% and 27.5%) caused by flavones, flavonols and isoflavones were observed at addition levels of 100 μmol/L and 10000 μmol/L, respectively. The reduction/promotion effects were closely related to the change of trolox equivalent antioxidant capacity (ΔTEAC) and well predicted by triple ΔTEAC measurements via SVR models (R: 0.633-0.900). Flavonols exhibit stronger effects on the acrylamide formation than flavones and isoflavones as well as their O-glycosides derivatives, which may be attributed to the number and position of phenolic and 3-enolic hydroxyls. The reduction/promotion effects were well predicted by using optimized quantitative structure-activity relationship (QSAR) descriptors and SVR models (R: 0.926-0.994). Compared to artificial neural network and multi-linear regression models, SVR models exhibited better fitting performance for both TEAC-dependent and QSAR descriptor-dependent predicting work. These observations demonstrated that the SVR models are competent for predicting our understanding on the future use of natural antioxidants for decreasing the acrylamide formation.

  1. Synthesis and quantitative structure-activity relationship (QSAR) study of novel N-arylsulfonyl-3-acylindole arylcarbonyl hydrazone derivatives as nematicidal agents.

    PubMed

    Che, Zhiping; Zhang, Shaoyong; Shao, Yonghua; Fan, Lingling; Xu, Hui; Yu, Xiang; Zhi, Xiaoyan; Yao, Xiaojun; Zhang, Rui

    2013-06-19

    In continuation of our program aimed at the discovery and development of natural-product-based pesticidal agents, 54 novel N-arylsulfonyl-3-acylindole arylcarbonyl hydrazone derivatives were prepared, and their structures were well characterized by ¹H NMR, ¹³C NMR, HRMS, ESI-MS, and mp. Their nematicidal activity was evaluated against that of the pine wood nematode, Bursaphelenchus xylophilus in vivo. Among all of the derivatives, especially V-12 and V-39 displayed the best promising nematicidal activity with LC₅₀ values of 1.0969 and 1.2632 mg/L, respectively. This suggested that introduction of R¹ and R² together as the electron-withdrawing substituents, R³ as the methyl group, and R⁴ as the phenyl with the electron-donating substituents could be taken into account for further preparation of these kinds of compounds as nematicidal agents. Six selected descriptors are a WHIM descriptor (E1m), two GETAWAY descriptors (R1m+ and R3m+), a Burden eigenvalues descriptor (BEHm8), and two edge-adjacency index descriptors (EEig05x and EEig13d). Quantitative structure-activity relationship (QSAR) studies demonstrated that the structural factors, such as molecular mass (a negative correlation with the bioactivity) and molecular polarity (a positive correlation with bioactivity), are likely to govern the nematicidal activities of these compounds. For this model, the correlation coefficient (R²(training set)), the leave-one-out cross-validation correlation coefficient (Q²(LOO)), and the 7-fold cross-validation correlation coefficient (Q²(7-fold)) were 0.791, 0.701, and 0.715, respectively. The external cross-validation correlation coefficient (Q²ext) and the root-mean-square error for the test set (RMSE(test set)) were 0.774 and 3.412, respectively. This study will pave the way for future design, structural modification, and development of indole derivatives as nematicidal agents.

  2. Quantitative structure-activity relationship modeling of juvenile hormone mimetic compounds for Culex pipiens larvae, with a discussion of descriptor-thinning methods.

    PubMed

    Basak, Subhash C; Natarajan, Ramanathan; Mills, Denise; Hawkins, Douglas M; Kraker, Jessica J

    2006-01-01

    Quantitative structure-activity relationship (QSAR) modelers often encounter the problem of multicollinearity owing to the availability of large numbers of computable molecular descriptors. Sparsity of the variables while using descriptors such as atom pairs increases the complexity. Three different predictor-thinning methods, namely, a modified Gram-Schmidt algorithm, a marginal soft thresholding algorithm, and LASSO (least absolute shrinkage and selection operator), were utilized to reduce the number of descriptors prior to developing linear models. Juvenile hormone (JH) activity of 304 compounds on Culex pipiens larvae was taken as the model data set, and predictor trimming of a large number of diverse descriptors comprising 268 global molecular descriptors (topostructural, topochemical, and geometrical), 13 quantum chemical descriptors, and 915 atom pairs (substructural counts) was applied prior to linear regression by the ridge regression method. The data set (N = 304) was split into five calibration data sets of random samples of sizes 60/110/160/210/260, and the remaining 244/194/144/94/44 compounds were used for validations. LASSO was not found to be a very effective method in handling a large set of descriptors because the number of predictors retained could not exceed the number of observations. The results indicated that the modified Gram-Schmidt algorithm could be used to trim the number of predictors in the global molecular descriptor set where collinearity of the descriptors was the major concern. On the contrary, the soft thresholding approach was found to be an effective tool in subset selection from a diverse set of descriptors having both sparsity and multicollinearity, as in the case of the combined set of atom pairs and global molecular descriptors. The final model developed after variable selection was dominated more by atom pairs, which indicated the important structural moieties that affect JH activity of the compounds. The success of the

  3. Predictions of Cleavability of Calpain Proteolysis by Quantitative Structure-Activity Relationship Analysis Using Newly Determined Cleavage Sites and Catalytic Efficiencies of an Oligopeptide Array*

    PubMed Central

    Shinkai-Ouchi, Fumiko; Koyama, Suguru; Ono, Yasuko; Hata, Shoji; Ojima, Koichi; Shindo, Mayumi; duVerle, David; Ueno, Mika; Kitamura, Fujiko; Doi, Naoko; Takigawa, Ichigaku; Mamitsuka, Hiroshi; Sorimachi, Hiroyuki

    2016-01-01

    Calpains are intracellular Ca2+-regulated cysteine proteases that are essential for various cellular functions. Mammalian conventional calpains (calpain-1 and calpain-2) modulate the structure and function of their substrates by limited proteolysis. Thus, it is critically important to determine the site(s) in proteins at which calpains cleave. However, the calpains' substrate specificity remains unclear, because the amino acid (aa) sequences around their cleavage sites are very diverse. To clarify calpains' substrate specificities, 84 20-mer oligopeptides, corresponding to P10-P10′ of reported cleavage site sequences, were proteolyzed by calpains, and the catalytic efficiencies (kcat/Km) were globally determined by LC/MS. This analysis revealed 483 cleavage site sequences, including 360 novel ones. The kcat/Kms for 119 sites ranged from 12.5–1,710 M−1s−1. Although most sites were cleaved by both calpain-1 and −2 with a similar kcat/Km, sequence comparisons revealed distinct aa preferences at P9-P7/P2/P5′. The aa compositions of the novel sites were not statistically different from those of previously reported sites as a whole, suggesting calpains have a strict implicit rule for sequence specificity, and that the limited proteolysis of intact substrates is because of substrates' higher-order structures. Cleavage position frequencies indicated that longer sequences N-terminal to the cleavage site (P-sites) were preferred for proteolysis over C-terminal (P′-sites). Quantitative structure-activity relationship (QSAR) analyses using partial least-squares regression and >1,300 aa descriptors achieved kcat/Km prediction with r = 0.834, and binary-QSAR modeling attained an 87.5% positive prediction value for 132 reported calpain cleavage sites independent of our model construction. These results outperformed previous calpain cleavage predictors, and revealed the importance of the P2, P3′, and P4′ sites, and P1-P2 cooperativity. Furthermore, using our

  4. Predictions of Cleavability of Calpain Proteolysis by Quantitative Structure-Activity Relationship Analysis Using Newly Determined Cleavage Sites and Catalytic Efficiencies of an Oligopeptide Array.

    PubMed

    Shinkai-Ouchi, Fumiko; Koyama, Suguru; Ono, Yasuko; Hata, Shoji; Ojima, Koichi; Shindo, Mayumi; duVerle, David; Ueno, Mika; Kitamura, Fujiko; Doi, Naoko; Takigawa, Ichigaku; Mamitsuka, Hiroshi; Sorimachi, Hiroyuki

    2016-04-01

    Calpains are intracellular Ca(2+)-regulated cysteine proteases that are essential for various cellular functions. Mammalian conventional calpains (calpain-1 and calpain-2) modulate the structure and function of their substrates by limited proteolysis. Thus, it is critically important to determine the site(s) in proteins at which calpains cleave. However, the calpains' substrate specificity remains unclear, because the amino acid (aa) sequences around their cleavage sites are very diverse. To clarify calpains' substrate specificities, 84 20-mer oligopeptides, corresponding to P10-P10' of reported cleavage site sequences, were proteolyzed by calpains, and the catalytic efficiencies (kcat/Km) were globally determined by LC/MS. This analysis revealed 483 cleavage site sequences, including 360 novel ones. Thekcat/Kms for 119 sites ranged from 12.5-1,710 M(-1)s(-1) Although most sites were cleaved by both calpain-1 and -2 with a similarkcat/Km, sequence comparisons revealed distinct aa preferences at P9-P7/P2/P5'. The aa compositions of the novel sites were not statistically different from those of previously reported sites as a whole, suggesting calpains have a strict implicit rule for sequence specificity, and that the limited proteolysis of intact substrates is because of substrates' higher-order structures. Cleavage position frequencies indicated that longer sequences N-terminal to the cleavage site (P-sites) were preferred for proteolysis over C-terminal (P'-sites). Quantitative structure-activity relationship (QSAR) analyses using partial least-squares regression and >1,300 aa descriptors achievedkcat/Kmprediction withr= 0.834, and binary-QSAR modeling attained an 87.5% positive prediction value for 132 reported calpain cleavage sites independent of our model construction. These results outperformed previous calpain cleavage predictors, and revealed the importance of the P2, P3', and P4' sites, and P1-P2 cooperativity. Furthermore, using our binary-QSAR model

  5. Metal artifacts from titanium and steel screws in CT, 1.5T and 3T MR images of the tibial Pilon: a quantitative assessment in 3D

    PubMed Central

    Radzi, Shairah; Cowin, Gary; Robinson, Mark; Pratap, Jit; Volp, Andrew; Schuetz, Michael A.

    2014-01-01

    Radiographs are commonly used to assess articular reduction of the distal tibia (pilon) fractures postoperatively, but may reveal malreductions inaccurately. While magnetic resonance imaging (MRI) and computed tomography (CT) are potential three-dimensional (3D) alternatives they generate metal-related artifacts. This study aims to quantify the artifact size from orthopaedic screws using CT, 1.5T and 3T MRI data. Three screws were inserted into one intact human cadaver ankle specimen proximal to and along the distal articular surface, then CT, 1.5T and 3T MRI scanned. Four types of screws were investigated: titanium alloy (TA), stainless steel (SS) (Ø =3.5 mm), cannulated TA (CTA) and cannulated SS (CSS) (Ø =4.0 mm, Ø empty core =2.6 mm). 3D artifact models were reconstructed using adaptive thresholding. The artifact size was measured by calculating the perpendicular distance from the central screw axis to the boundary of the artifact in four anatomical directions with respect to the distal tibia. The artifact sizes (in the order of TA, SS, CTA and CSS) from CT were 2.0, 2.6, 1.6 and 2.0 mm; from 1.5T MRI they were 3.7, 10.9, 2.9, and 9 mm; and 3T MRI they were 4.4, 15.3, 3.8, and 11.6 mm respectively. Therefore, CT can be used as long as the screws are at a safe distance of about 2 mm from the articular surface. MRI can be used if the screws are at least 3 mm away from the articular surface except for SS and CSS. Artifacts from steel screws were too large thus obstructed the pilon from being visualised in MRI. Significant differences (P<0.05) were found in the size of artifacts between all imaging modalities, screw types and material types, except 1.5T versus 3T MRI for the SS screws (P=0.063). CTA screws near the joint surface can improve postoperative assessment in CT and MRI. MRI presents a favourable non-ionising alternative when using titanium hardware. Since these factors may influence the quality of postoperative assessment, potential improvements in

  6. Metal artifacts from titanium and steel screws in CT, 1.5T and 3T MR images of the tibial Pilon: a quantitative assessment in 3D.

    PubMed

    Radzi, Shairah; Cowin, Gary; Robinson, Mark; Pratap, Jit; Volp, Andrew; Schuetz, Michael A; Schmutz, Beat

    2014-06-01

    Radiographs are commonly used to assess articular reduction of the distal tibia (pilon) fractures postoperatively, but may reveal malreductions inaccurately. While magnetic resonance imaging (MRI) and computed tomography (CT) are potential three-dimensional (3D) alternatives they generate metal-related artifacts. This study aims to quantify the artifact size from orthopaedic screws using CT, 1.5T and 3T MRI data. Three screws were inserted into one intact human cadaver ankle specimen proximal to and along the distal articular surface, then CT, 1.5T and 3T MRI scanned. Four types of screws were investigated: titanium alloy (TA), stainless steel (SS) (Ø =3.5 mm), cannulated TA (CTA) and cannulated SS (CSS) (Ø =4.0 mm, Ø empty core =2.6 mm). 3D artifact models were reconstructed using adaptive thresholding. The artifact size was measured by calculating the perpendicular distance from the central screw axis to the boundary of the artifact in four anatomical directions with respect to the distal tibia. The artifact sizes (in the order of TA, SS, CTA and CSS) from CT were 2.0, 2.6, 1.6 and 2.0 mm; from 1.5T MRI they were 3.7, 10.9, 2.9, and 9 mm; and 3T MRI they were 4.4, 15.3, 3.8, and 11.6 mm respectively. Therefore, CT can be used as long as the screws are at a safe distance of about 2 mm from the articular surface. MRI can be used if the screws are at least 3 mm away from the articular surface except for SS and CSS. Artifacts from steel screws were too large thus obstructed the pilon from being visualised in MRI. Significant differences (P<0.05) were found in the size of artifacts between all imaging modalities, screw types and material types, except 1.5T versus 3T MRI for the SS screws (P=0.063). CTA screws near the joint surface can improve postoperative assessment in CT and MRI. MRI presents a favourable non-ionising alternative when using titanium hardware. Since these factors may influence the quality of postoperative assessment, potential improvements in

  7. Fabrication of type I collagen microcarrier using a microfluidic 3D T-junction device and its application for the quantitative analysis of cell-ECM interactions.

    PubMed

    Yoon, Junghyo; Kim, Jaehoon; Jeong, Hyo Eun; Sudo, Ryo; Park, Myung-Jin; Chung, Seok

    2016-01-01

    We presented a new quantitative analysis for cell and extracellular matrix (ECM) interactions, using cell-coated ECM hydrogel microbeads (hydrobeads) made of type I collagen. The hydrobeads can carry cells as three-dimensional spheroidal forms with an ECM inside, facilitating a direct interaction between the cells and ECM. The cells on hydrobeads do not have a hypoxic core, which opens the possibility for using as a cell microcarrier for bottom-up tissue reconstitution. This technique can utilize various types of cells, even MDA-MB-231 cells, which have weak cell-cell interactions and do not form spheroids in conventional spheroid culture methods. Morphological indices of the cell-coated hydrobead visually present cell-ECM interactions in a quantitative manner. PMID:27563029

  8. Quantitative 3-D colocalization analysis as a tool to study the intracellular trafficking and dissociation of pDNA-chitosan polyplexes

    NASA Astrophysics Data System (ADS)

    Reitan, Nina Kristine; Sporsheim, Bjørnar; Bjørkøy, Astrid; Strand, Sabina; Davies, Catharina de Lange

    2012-02-01

    Multichannel microscopy is frequently used to study intermolecular interactions and spatial relationships between biomolecules and organelles or vesicles in cells. Based on multichannel images, quantitative colocalization analysis can provide valuable information about cellular internalization, vesicular transport, and the intracellular kinetics and location of biomolecules. However, such analyses should be performed carefully, because quantitative colocalization parameters have different interpretations and can be highly affected by image quality. We use quantitative three-dimensional colocalization analysis of deconvolved and chromatic-registered confocal images to study the dissociation of double-labeled pDNA-chitosan polyplexes in HeLa cells and their colocalization with early endosomes. Two chitosans that form polyplexes with highly different transfection efficacies are compared. Pearson's correlation coefficient, Manders' colocalization coefficients, and the intensity correlation quotient are estimated to determine the intracellular localization of polyplexes, free pDNA, and free chitosans. Differences are observed in the amount of uptake, and in the intracellular pathways and rates of dissociation for the two chitosans. The results support previous findings that polyplexes formed by self-branched, glycosylated chitosan oligomers are more favorable for cellular uptake and intracellular trafficking to the nucleus compared with polyplexes formed by linear chitosans.

  9. Commissioning and Implementation of an EPID Based IMRT QA System "Dosimetry Check" for 3D Absolute Dose Measurements and Quantitative Comparisons to MapCheck

    NASA Astrophysics Data System (ADS)

    Patel, Jalpa A.

    The software package "Dosimetry Check" by MathResolutions, LLC, provides an absolute 3D volumetric dose measurement for IMRT QA using the existing Electronic Portal Imaging Device (EPID) mounted on most linear accelerators. This package provides a feedback loop using the patient's treatment planning CT data as the phantom for dose reconstruction. The aim of this work is to study the difference between point, planar and volumetric doses with MapCheck and Dosimetry Check via the use of the EPID and the diode array respectively. Evaluating tools such as point doses at isocenter, 1-D profiles, gamma volume histograms, and dose volume histograms are used for IMRT dose comparison in three types of cases: head and neck, prostate, and lung. Dosimetry Check can be a valuable tool for IMRT QA as it uses patient specific attenuation corrections and the superiority of the EPID as compared to the MapCheck diode array. This helps reduce the uncertainty in dose for less variability in delivery and a more realistic measured vs computed dose verification system as compared to MapCheck.

  10. 3D Imaging.

    ERIC Educational Resources Information Center

    Hastings, S. K.

    2002-01-01

    Discusses 3 D imaging as it relates to digital representations in virtual library collections. Highlights include X-ray computed tomography (X-ray CT); the National Science Foundation (NSF) Digital Library Initiatives; output peripherals; image retrieval systems, including metadata; and applications of 3 D imaging for libraries and museums. (LRW)

  11. Correlative 3D-imaging of Pipistrellus penis micromorphology: Validating quantitative microCT images with undecalcified serial ground section histomorphology.

    PubMed

    Herdina, Anna Nele; Plenk, Hanns; Benda, Petr; Lina, Peter H C; Herzig-Straschil, Barbara; Hilgers, Helge; Metscher, Brian D

    2015-06-01

    Detailed knowledge of histomorphology is a prerequisite for the understanding of function, variation, and development. In bats, as in other mammals, penis and baculum morphology are important in species discrimination and phylogenetic studies. In this study, nondestructive 3D-microtomographic (microCT, µCT) images of bacula and iodine-stained penes of Pipistrellus pipistrellus were correlated with light microscopic images from undecalcified surface-stained ground sections of three of these penes of P. pipistrellus (1 juvenile). The results were then compared with µCT-images of bacula of P. pygmaeus, P. hanaki, and P. nathusii. The Y-shaped baculum in all studied Pipistrellus species has a proximal base with two club-shaped branches, a long slender shaft, and a forked distal tip. The branches contain a medullary cavity of variable size, which tapers into a central canal of variable length in the proximal baculum shaft. Both are surrounded by a lamellar and a woven bone layer and contain fatty marrow and blood vessels. The distal shaft consists of woven bone only, without a vascular canal. The proximal ends of the branches are connected with the tunica albuginea of the corpora cavernosa via entheses. In the penis shaft, the corpus spongiosum-surrounded urethra lies in a ventral grove of the corpora cavernosa, and continues in the glans under the baculum. The glans penis predominantly comprises an enlarged corpus spongiosum, which surrounds urethra and baculum. In the 12 studied juvenile and subadult P. pipistrellus specimens the proximal branches of the baculum were shorter and without marrow cavity, while shaft and distal tip appeared already fully developed. The present combination with light microscopic images from one species enabled a more reliable interpretation of histomorphological structures in the µCT-images from all four Pipistrellus species. PMID:25703625

  12. Correlative 3D-imaging of Pipistrellus penis micromorphology: Validating quantitative microCT images with undecalcified serial ground section histomorphology.

    PubMed

    Herdina, Anna Nele; Plenk, Hanns; Benda, Petr; Lina, Peter H C; Herzig-Straschil, Barbara; Hilgers, Helge; Metscher, Brian D

    2015-06-01

    Detailed knowledge of histomorphology is a prerequisite for the understanding of function, variation, and development. In bats, as in other mammals, penis and baculum morphology are important in species discrimination and phylogenetic studies. In this study, nondestructive 3D-microtomographic (microCT, µCT) images of bacula and iodine-stained penes of Pipistrellus pipistrellus were correlated with light microscopic images from undecalcified surface-stained ground sections of three of these penes of P. pipistrellus (1 juvenile). The results were then compared with µCT-images of bacula of P. pygmaeus, P. hanaki, and P. nathusii. The Y-shaped baculum in all studied Pipistrellus species has a proximal base with two club-shaped branches, a long slender shaft, and a forked distal tip. The branches contain a medullary cavity of variable size, which tapers into a central canal of variable length in the proximal baculum shaft. Both are surrounded by a lamellar and a woven bone layer and contain fatty marrow and blood vessels. The distal shaft consists of woven bone only, without a vascular canal. The proximal ends of the branches are connected with the tunica albuginea of the corpora cavernosa via entheses. In the penis shaft, the corpus spongiosum-surrounded urethra lies in a ventral grove of the corpora cavernosa, and continues in the glans under the baculum. The glans penis predominantly comprises an enlarged corpus spongiosum, which surrounds urethra and baculum. In the 12 studied juvenile and subadult P. pipistrellus specimens the proximal branches of the baculum were shorter and without marrow cavity, while shaft and distal tip appeared already fully developed. The present combination with light microscopic images from one species enabled a more reliable interpretation of histomorphological structures in the µCT-images from all four Pipistrellus species.

  13. Binary classification of a large collection of environmental chemicals from estrogen receptor assays by quantitative structure-activity relationship and machine learning methods.

    PubMed

    Zang, Qingda; Rotroff, Daniel M; Judson, Richard S

    2013-12-23

    There are thousands of environmental chemicals subject to regulatory decisions for endocrine disrupting potential. The ToxCast and Tox21 programs have tested ∼8200 chemicals in a broad screening panel of in vitro high-throughput screening (HTS) assays for estrogen receptor (ER) agonist and antagonist activity. The present work uses this large data set to develop in silico quantitative structure-activity relationship (QSAR) models using machine learning (ML) methods and a novel approach to manage the imbalanced data distribution. Training compounds from the ToxCast project were categorized as active or inactive (binding or nonbinding) classes based on a composite ER Interaction Score derived from a collection of 13 ER in vitro assays. A total of 1537 chemicals from ToxCast were used to derive and optimize the binary classification models while 5073 additional chemicals from the Tox21 project, evaluated in 2 of the 13 in vitro assays, were used to externally validate the model performance. In order to handle the imbalanced distribution of active and inactive chemicals, we developed a cluster-selection strategy to minimize information loss and increase predictive performance and compared this strategy to three currently popular techniques: cost-sensitive learning, oversampling of the minority class, and undersampling of the majority class. QSAR classification models were built to relate the molecular structures of chemicals to their ER activities using linear discriminant analysis (LDA), classification and regression trees (CART), and support vector machines (SVM) with 51 molecular descriptors from QikProp and 4328 bits of structural fingerprints as explanatory variables. A random forest (RF) feature selection method was employed to extract the structural features most relevant to the ER activity. The best model was obtained using SVM in combination with a subset of descriptors identified from a large set via the RF algorithm, which recognized the active and

  14. Binary classification of a large collection of environmental chemicals from estrogen receptor assays by quantitative structure-activity relationship and machine learning methods.

    PubMed

    Zang, Qingda; Rotroff, Daniel M; Judson, Richard S

    2013-12-23

    There are thousands of environmental chemicals subject to regulatory decisions for endocrine disrupting potential. The ToxCast and Tox21 programs have tested ∼8200 chemicals in a broad screening panel of in vitro high-throughput screening (HTS) assays for estrogen receptor (ER) agonist and antagonist activity. The present work uses this large data set to develop in silico quantitative structure-activity relationship (QSAR) models using machine learning (ML) methods and a novel approach to manage the imbalanced data distribution. Training compounds from the ToxCast project were categorized as active or inactive (binding or nonbinding) classes based on a composite ER Interaction Score derived from a collection of 13 ER in vitro assays. A total of 1537 chemicals from ToxCast were used to derive and optimize the binary classification models while 5073 additional chemicals from the Tox21 project, evaluated in 2 of the 13 in vitro assays, were used to externally validate the model performance. In order to handle the imbalanced distribution of active and inactive chemicals, we developed a cluster-selection strategy to minimize information loss and increase predictive performance and compared this strategy to three currently popular techniques: cost-sensitive learning, oversampling of the minority class, and undersampling of the majority class. QSAR classification models were built to relate the molecular structures of chemicals to their ER activities using linear discriminant analysis (LDA), classification and regression trees (CART), and support vector machines (SVM) with 51 molecular descriptors from QikProp and 4328 bits of structural fingerprints as explanatory variables. A random forest (RF) feature selection method was employed to extract the structural features most relevant to the ER activity. The best model was obtained using SVM in combination with a subset of descriptors identified from a large set via the RF algorithm, which recognized the active and

  15. An open source image processing method to quantitatively assess tissue growth after non-invasive magnetic resonance imaging in human bone marrow stromal cell seeded 3D polymeric scaffolds.

    PubMed

    Leferink, Anne M; Fratila, Raluca M; Koenrades, Maaike A; van Blitterswijk, Clemens A; Velders, Aldrik; Moroni, Lorenzo

    2014-01-01

    Monitoring extracellular matrix (ECM) components is one of the key methods used to determine tissue quality in three-dimensional (3D) scaffolds for regenerative medicine and clinical purposes. This is even more important when multipotent human bone marrow stromal cells (hMSCs) are used, as it could offer a method to understand in real time the dynamics of stromal cell differentiation and eventually steer it into the desired lineage. Magnetic Resonance Imaging (MRI) is a promising tool to overcome the challenge of a limited transparency in opaque 3D scaffolds. Technical limitations of MRI involve non-uniform background intensity leading to fluctuating background signals and therewith complicating quantifications on the retrieved images. We present a post-imaging processing sequence that is able to correct for this non-uniform background intensity. To test the processing sequence we investigated the use of MRI for in vitro monitoring of tissue growth in three-dimensional poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT) scaffolds. Results showed that MRI, without the need to use contrast agents, is a promising non-invasive tool to quantitatively monitor ECM production and cell distribution during in vitro culture in 3D porous tissue engineered constructs. PMID:25502022

  16. An Open Source Image Processing Method to Quantitatively Assess Tissue Growth after Non-Invasive Magnetic Resonance Imaging in Human Bone Marrow Stromal Cell Seeded 3D Polymeric Scaffolds

    PubMed Central

    Leferink, Anne M.; Fratila, Raluca M.; Koenrades, Maaike A.; van Blitterswijk, Clemens A.; Velders, Aldrik; Moroni, Lorenzo

    2014-01-01

    Monitoring extracellular matrix (ECM) components is one of the key methods used to determine tissue quality in three-dimensional (3D) scaffolds for regenerative medicine and clinical purposes. This is even more important when multipotent human bone marrow stromal cells (hMSCs) are used, as it could offer a method to understand in real time the dynamics of stromal cell differentiation and eventually steer it into the desired lineage. Magnetic Resonance Imaging (MRI) is a promising tool to overcome the challenge of a limited transparency in opaque 3D scaffolds. Technical limitations of MRI involve non-uniform background intensity leading to fluctuating background signals and therewith complicating quantifications on the retrieved images. We present a post-imaging processing sequence that is able to correct for this non-uniform background intensity. To test the processing sequence we investigated the use of MRI for in vitro monitoring of tissue growth in three-dimensional poly(ethylene oxide terephthalate)–poly(butylene terephthalate) (PEOT/PBT) scaffolds. Results showed that MRI, without the need to use contrast agents, is a promising non-invasive tool to quantitatively monitor ECM production and cell distribution during in vitro culture in 3D porous tissue engineered constructs. PMID:25502022

  17. 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

  18. 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...

  19. Forensic 3D scene reconstruction

    NASA Astrophysics Data System (ADS)

    Little, Charles Q.; Small, Daniel E.; Peters, Ralph R.; Rigdon, J. B.

    2000-05-01

    Traditionally law enforcement agencies have relied on basic measurement and imaging tools, such as tape measures and cameras, in recording a crime scene. A disadvantage of these methods is that they are slow and cumbersome. The development of a portable system that can rapidly record a crime scene with current camera imaging, 3D geometric surface maps, and contribute quantitative measurements such as accurate relative positioning of crime scene objects, would be an asset to law enforcement agents in collecting and recording significant forensic data. The purpose of this project is to develop a fieldable prototype of a fast, accurate, 3D measurement and imaging system that would support law enforcement agents to quickly document and accurately record a crime scene.

  20. Forensic 3D Scene Reconstruction

    SciTech Connect

    LITTLE,CHARLES Q.; PETERS,RALPH R.; RIGDON,J. BRIAN; SMALL,DANIEL E.

    1999-10-12

    Traditionally law enforcement agencies have relied on basic measurement and imaging tools, such as tape measures and cameras, in recording a crime scene. A disadvantage of these methods is that they are slow and cumbersome. The development of a portable system that can rapidly record a crime scene with current camera imaging, 3D geometric surface maps, and contribute quantitative measurements such as accurate relative positioning of crime scene objects, would be an asset to law enforcement agents in collecting and recording significant forensic data. The purpose of this project is to develop a feasible prototype of a fast, accurate, 3D measurement and imaging system that would support law enforcement agents to quickly document and accurately record a crime scene.

  1. 3D light scanning macrography.

    PubMed

    Huber, D; Keller, M; Robert, D

    2001-08-01

    The technique of 3D light scanning macrography permits the non-invasive surface scanning of small specimens at magnifications up to 200x. Obviating both the problem of limited depth of field inherent to conventional close-up macrophotography and the metallic coating required by scanning electron microscopy, 3D light scanning macrography provides three-dimensional digital images of intact specimens without the loss of colour, texture and transparency information. This newly developed technique offers a versatile, portable and cost-efficient method for the non-invasive digital and photographic documentation of small objects. Computer controlled device operation and digital image acquisition facilitate fast and accurate quantitative morphometric investigations, and the technique offers a broad field of research and educational applications in biological, medical and materials sciences. PMID:11489078

  2. Radiochromic 3D Detectors

    NASA Astrophysics Data System (ADS)

    Oldham, Mark

    2015-01-01

    Radiochromic materials exhibit a colour change when exposed to ionising radiation. Radiochromic film has been used for clinical dosimetry for many years and increasingly so recently, as films of higher sensitivities have become available. The two principle advantages of radiochromic dosimetry include greater tissue equivalence (radiologically) and the lack of requirement for development of the colour change. In a radiochromic material, the colour change arises direct from ionising interactions affecting dye molecules, without requiring any latent chemical, optical or thermal development, with important implications for increased accuracy and convenience. It is only relatively recently however, that 3D radiochromic dosimetry has become possible. In this article we review recent developments and the current state-of-the-art of 3D radiochromic dosimetry, and the potential for a more comprehensive solution for the verification of complex radiation therapy treatments, and 3D dose measurement in general.

  3. 3-D Seismic Interpretation

    NASA Astrophysics Data System (ADS)

    Moore, Gregory F.

    2009-05-01

    This volume is a brief introduction aimed at those who wish to gain a basic and relatively quick understanding of the interpretation of three-dimensional (3-D) seismic reflection data. The book is well written, clearly illustrated, and easy to follow. Enough elementary mathematics are presented for a basic understanding of seismic methods, but more complex mathematical derivations are avoided. References are listed for readers interested in more advanced explanations. After a brief introduction, the book logically begins with a succinct chapter on modern 3-D seismic data acquisition and processing. Standard 3-D acquisition methods are presented, and an appendix expands on more recent acquisition techniques, such as multiple-azimuth and wide-azimuth acquisition. Although this chapter covers the basics of standard time processing quite well, there is only a single sentence about prestack depth imaging, and anisotropic processing is not mentioned at all, even though both techniques are now becoming standard.

  4. Bootstrapping 3D fermions

    DOE PAGES

    Iliesiu, Luca; Kos, Filip; Poland, David; Pufu, Silviu S.; Simmons-Duffin, David; Yacoby, Ran

    2016-03-17

    We study the conformal bootstrap for a 4-point function of fermions <ψψψψ> in 3D. We first introduce an embedding formalism for 3D spinors and compute the conformal blocks appearing in fermion 4-point functions. Using these results, we find general bounds on the dimensions of operators appearing in the ψ × ψ OPE, and also on the central charge CT. We observe features in our bounds that coincide with scaling dimensions in the GrossNeveu models at large N. Finally, we also speculate that other features could coincide with a fermionic CFT containing no relevant scalar operators.

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

    NASA Astrophysics Data System (ADS)

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

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

  6. [Real time 3D echocardiography

    NASA Technical Reports Server (NTRS)

    Bauer, F.; Shiota, T.; Thomas, J. D.

    2001-01-01

    Three-dimensional representation of the heart is an old concern. Usually, 3D reconstruction of the cardiac mass is made by successive acquisition of 2D sections, the spatial localisation and orientation of which require complex guiding systems. More recently, the concept of volumetric acquisition has been introduced. A matricial emitter-receiver probe complex with parallel data processing provides instantaneous of a pyramidal 64 degrees x 64 degrees volume. The image is restituted in real time and is composed of 3 planes (planes B and C) which can be displaced in all spatial directions at any time during acquisition. The flexibility of this system of acquisition allows volume and mass measurement with greater accuracy and reproducibility, limiting inter-observer variability. Free navigation of the planes of investigation allows reconstruction for qualitative and quantitative analysis of valvular heart disease and other pathologies. Although real time 3D echocardiography is ready for clinical usage, some improvements are still necessary to improve its conviviality. Then real time 3D echocardiography could be the essential tool for understanding, diagnosis and management of patients.

  7. [Real time 3D echocardiography].

    PubMed

    Bauer, F; Shiota, T; Thomas, J D

    2001-07-01

    Three-dimensional representation of the heart is an old concern. Usually, 3D reconstruction of the cardiac mass is made by successive acquisition of 2D sections, the spatial localisation and orientation of which require complex guiding systems. More recently, the concept of volumetric acquisition has been introduced. A matricial emitter-receiver probe complex with parallel data processing provides instantaneous of a pyramidal 64 degrees x 64 degrees volume. The image is restituted in real time and is composed of 3 planes (planes B and C) which can be displaced in all spatial directions at any time during acquisition. The flexibility of this system of acquisition allows volume and mass measurement with greater accuracy and reproducibility, limiting inter-observer variability. Free navigation of the planes of investigation allows reconstruction for qualitative and quantitative analysis of valvular heart disease and other pathologies. Although real time 3D echocardiography is ready for clinical usage, some improvements are still necessary to improve its conviviality. Then real time 3D echocardiography could be the essential tool for understanding, diagnosis and management of patients. PMID:11494630

  8. Venus in 3D

    NASA Astrophysics Data System (ADS)

    Plaut, J. J.

    1993-08-01

    Stereographic images of the surface of Venus which enable geologists to reconstruct the details of the planet's evolution are discussed. The 120-meter resolution of these 3D images make it possible to construct digital topographic maps from which precise measurements can be made of the heights, depths, slopes, and volumes of geologic structures.

  9. 3D reservoir visualization

    SciTech Connect

    Van, B.T.; Pajon, J.L.; Joseph, P. )

    1991-11-01

    This paper shows how some simple 3D computer graphics tools can be combined to provide efficient software for visualizing and analyzing data obtained from reservoir simulators and geological simulations. The animation and interactive capabilities of the software quickly provide a deep understanding of the fluid-flow behavior and an accurate idea of the internal architecture of a reservoir.

  10. Complementary three-dimensional quantitative structure-activity relationship modeling of binding affinity and functional potency: a study on alpha4beta2 nicotinic ligands.

    PubMed

    Tosco, Paolo; Ahring, Philip K; Dyhring, Tino; Peters, Dan; Harpsøe, Kasper; Liljefors, Tommy; Balle, Thomas

    2009-04-23

    Complementary 3D-QSAR modeling of binding affinity and functional potency is proposed as a tool to pinpoint the molecular features of the ligands, and the corresponding amino acids in the receptor, responsible for high affinity binding vs those driving agonist behavior and receptor activation. This approach proved successful on a series of nicotinic alpha(4)beta(2) ligands, whose partial/full agonist profile could be linked to the size of the scaffold as well as to the nature of the substituents.

  11. Novel computer vision algorithm for the reliable analysis of organelle morphology in whole cell 3D images--A pilot study for the quantitative evaluation of mitochondrial fragmentation in amyotrophic lateral sclerosis.

    PubMed

    Lautenschläger, Janin; Lautenschläger, Christian; Tadic, Vedrana; Süße, Herbert; Ortmann, Wolfgang; Denzler, Joachim; Stallmach, Andreas; Witte, Otto W; Grosskreutz, Julian

    2015-11-01

    The function of intact organelles, whether mitochondria, Golgi apparatus or endoplasmic reticulum (ER), relies on their proper morphological organization. It is recognized that disturbances of organelle morphology are early events in disease manifestation, but reliable and quantitative detection of organelle morphology is difficult and time-consuming. Here we present a novel computer vision algorithm for the assessment of organelle morphology in whole cell 3D images. The algorithm allows the numerical and quantitative description of organelle structures, including total number and length of segments, cell and nucleus area/volume as well as novel texture parameters like lacunarity and fractal dimension. Applying the algorithm we performed a pilot study in cultured motor neurons from transgenic G93A hSOD1 mice, a model of human familial amyotrophic lateral sclerosis. In the presence of the mutated SOD1 and upon excitotoxic treatment with kainate we demonstrate a clear fragmentation of the mitochondrial network, with an increase in the number of mitochondrial segments and a reduction in the length of mitochondria. Histogram analyses show a reduced number of tubular mitochondria and an increased number of small mitochondrial segments. The computer vision algorithm for the evaluation of organelle morphology allows an objective assessment of disease-related organelle phenotypes with greatly reduced examiner bias and will aid the evaluation of novel therapeutic strategies on a cellular level. PMID:26440825

  12. Novel computer vision algorithm for the reliable analysis of organelle morphology in whole cell 3D images--A pilot study for the quantitative evaluation of mitochondrial fragmentation in amyotrophic lateral sclerosis.

    PubMed

    Lautenschläger, Janin; Lautenschläger, Christian; Tadic, Vedrana; Süße, Herbert; Ortmann, Wolfgang; Denzler, Joachim; Stallmach, Andreas; Witte, Otto W; Grosskreutz, Julian

    2015-11-01

    The function of intact organelles, whether mitochondria, Golgi apparatus or endoplasmic reticulum (ER), relies on their proper morphological organization. It is recognized that disturbances of organelle morphology are early events in disease manifestation, but reliable and quantitative detection of organelle morphology is difficult and time-consuming. Here we present a novel computer vision algorithm for the assessment of organelle morphology in whole cell 3D images. The algorithm allows the numerical and quantitative description of organelle structures, including total number and length of segments, cell and nucleus area/volume as well as novel texture parameters like lacunarity and fractal dimension. Applying the algorithm we performed a pilot study in cultured motor neurons from transgenic G93A hSOD1 mice, a model of human familial amyotrophic lateral sclerosis. In the presence of the mutated SOD1 and upon excitotoxic treatment with kainate we demonstrate a clear fragmentation of the mitochondrial network, with an increase in the number of mitochondrial segments and a reduction in the length of mitochondria. Histogram analyses show a reduced number of tubular mitochondria and an increased number of small mitochondrial segments. The computer vision algorithm for the evaluation of organelle morphology allows an objective assessment of disease-related organelle phenotypes with greatly reduced examiner bias and will aid the evaluation of novel therapeutic strategies on a cellular level.

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

    PubMed

    Fang, Cheng; Xiao, Zhiyan

    2016-01-01

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

  14. 3D ultrafast ultrasound imaging in vivo.

    PubMed

    Provost, Jean; Papadacci, Clement; Arango, Juan Esteban; Imbault, Marion; Fink, Mathias; Gennisson, Jean-Luc; Tanter, Mickael; Pernot, Mathieu

    2014-10-01

    Very high frame rate ultrasound imaging has recently allowed for the extension of the applications of echography to new fields of study such as the functional imaging of the brain, cardiac electrophysiology, and the quantitative imaging of the intrinsic mechanical properties of tumors, to name a few, non-invasively and in real time. In this study, we present the first implementation of Ultrafast Ultrasound Imaging in 3D based on the use of either diverging or plane waves emanating from a sparse virtual array located behind the probe. It achieves high contrast and resolution while maintaining imaging rates of thousands of volumes per second. A customized portable ultrasound system was developed to sample 1024 independent channels and to drive a 32  ×  32 matrix-array probe. Its ability to track in 3D transient phenomena occurring in the millisecond range within a single ultrafast acquisition was demonstrated for 3D Shear-Wave Imaging, 3D Ultrafast Doppler Imaging, and, finally, 3D Ultrafast combined Tissue and Flow Doppler Imaging. The propagation of shear waves was tracked in a phantom and used to characterize its stiffness. 3D Ultrafast Doppler was used to obtain 3D maps of Pulsed Doppler, Color Doppler, and Power Doppler quantities in a single acquisition and revealed, at thousands of volumes per second, the complex 3D flow patterns occurring in the ventricles of the human heart during an entire cardiac cycle, as well as the 3D in vivo interaction of blood flow and wall motion during the pulse wave in the carotid at the bifurcation. This study demonstrates the potential of 3D Ultrafast Ultrasound Imaging for the 3D mapping of stiffness, tissue motion, and flow in humans in vivo and promises new clinical applications of ultrasound with reduced intra--and inter-observer variability.

  15. 3D ultrafast ultrasound imaging in vivo

    NASA Astrophysics Data System (ADS)

    Provost, Jean; Papadacci, Clement; Esteban Arango, Juan; Imbault, Marion; Fink, Mathias; Gennisson, Jean-Luc; Tanter, Mickael; Pernot, Mathieu

    2014-10-01

    Very high frame rate ultrasound imaging has recently allowed for the extension of the applications of echography to new fields of study such as the functional imaging of the brain, cardiac electrophysiology, and the quantitative imaging of the intrinsic mechanical properties of tumors, to name a few, non-invasively and in real time. In this study, we present the first implementation of Ultrafast Ultrasound Imaging in 3D based on the use of either diverging or plane waves emanating from a sparse virtual array located behind the probe. It achieves high contrast and resolution while maintaining imaging rates of thousands of volumes per second. A customized portable ultrasound system was developed to sample 1024 independent channels and to drive a 32  ×  32 matrix-array probe. Its ability to track in 3D transient phenomena occurring in the millisecond range within a single ultrafast acquisition was demonstrated for 3D Shear-Wave Imaging, 3D Ultrafast Doppler Imaging, and, finally, 3D Ultrafast combined Tissue and Flow Doppler Imaging. The propagation of shear waves was tracked in a phantom and used to characterize its stiffness. 3D Ultrafast Doppler was used to obtain 3D maps of Pulsed Doppler, Color Doppler, and Power Doppler quantities in a single acquisition and revealed, at thousands of volumes per second, the complex 3D flow patterns occurring in the ventricles of the human heart during an entire cardiac cycle, as well as the 3D in vivo interaction of blood flow and wall motion during the pulse wave in the carotid at the bifurcation. This study demonstrates the potential of 3D Ultrafast Ultrasound Imaging for the 3D mapping of stiffness, tissue motion, and flow in humans in vivo and promises new clinical applications of ultrasound with reduced intra—and inter-observer variability.

  16. 3D ultrafast ultrasound imaging in vivo.

    PubMed

    Provost, Jean; Papadacci, Clement; Arango, Juan Esteban; Imbault, Marion; Fink, Mathias; Gennisson, Jean-Luc; Tanter, Mickael; Pernot, Mathieu

    2014-10-01

    Very high frame rate ultrasound imaging has recently allowed for the extension of the applications of echography to new fields of study such as the functional imaging of the brain, cardiac electrophysiology, and the quantitative imaging of the intrinsic mechanical properties of tumors, to name a few, non-invasively and in real time. In this study, we present the first implementation of Ultrafast Ultrasound Imaging in 3D based on the use of either diverging or plane waves emanating from a sparse virtual array located behind the probe. It achieves high contrast and resolution while maintaining imaging rates of thousands of volumes per second. A customized portable ultrasound system was developed to sample 1024 independent channels and to drive a 32  ×  32 matrix-array probe. Its ability to track in 3D transient phenomena occurring in the millisecond range within a single ultrafast acquisition was demonstrated for 3D Shear-Wave Imaging, 3D Ultrafast Doppler Imaging, and, finally, 3D Ultrafast combined Tissue and Flow Doppler Imaging. The propagation of shear waves was tracked in a phantom and used to characterize its stiffness. 3D Ultrafast Doppler was used to obtain 3D maps of Pulsed Doppler, Color Doppler, and Power Doppler quantities in a single acquisition and revealed, at thousands of volumes per second, the complex 3D flow patterns occurring in the ventricles of the human heart during an entire cardiac cycle, as well as the 3D in vivo interaction of blood flow and wall motion during the pulse wave in the carotid at the bifurcation. This study demonstrates the potential of 3D Ultrafast Ultrasound Imaging for the 3D mapping of stiffness, tissue motion, and flow in humans in vivo and promises new clinical applications of ultrasound with reduced intra--and inter-observer variability. PMID:25207828

  17. 3D Audio System

    NASA Technical Reports Server (NTRS)

    1992-01-01

    Ames Research Center research into virtual reality led to the development of the Convolvotron, a high speed digital audio processing system that delivers three-dimensional sound over headphones. It consists of a two-card set designed for use with a personal computer. The Convolvotron's primary application is presentation of 3D audio signals over headphones. Four independent sound sources are filtered with large time-varying filters that compensate for motion. The perceived location of the sound remains constant. Possible applications are in air traffic control towers or airplane cockpits, hearing and perception research and virtual reality development.

  18. 3D Ultrafast Ultrasound Imaging In Vivo

    PubMed Central

    Provost, Jean; Papadacci, Clement; Arango, Juan Esteban; Imbault, Marion; Gennisson, Jean-Luc; Tanter, Mickael; Pernot, Mathieu

    2014-01-01

    Very high frame rate ultrasound imaging has recently allowed for the extension of the applications of echography to new fields of study such as the functional imaging of the brain, cardiac electrophysiology, and the quantitative real-time imaging of the intrinsic mechanical properties of tumors, to name a few, non-invasively and in real time. In this study, we present the first implementation of Ultrafast Ultrasound Imaging in three dimensions based on the use of either diverging or plane waves emanating from a sparse virtual array located behind the probe. It achieves high contrast and resolution while maintaining imaging rates of thousands of volumes per second. A customized portable ultrasound system was developed to sample 1024 independent channels and to drive a 32×32 matrix-array probe. Its capability to track in 3D transient phenomena occurring in the millisecond range within a single ultrafast acquisition was demonstrated for 3-D Shear-Wave Imaging, 3-D Ultrafast Doppler Imaging and finally 3D Ultrafast combined Tissue and Flow Doppler. The propagation of shear waves was tracked in a phantom and used to characterize its stiffness. 3-D Ultrafast Doppler was used to obtain 3-D maps of Pulsed Doppler, Color Doppler, and Power Doppler quantities in a single acquisition and revealed, for the first time, the complex 3-D flow patterns occurring in the ventricles of the human heart during an entire cardiac cycle, and the 3-D in vivo interaction of blood flow and wall motion during the pulse wave in the carotid at the bifurcation. This study demonstrates the potential of 3-D Ultrafast Ultrasound Imaging for the 3-D real-time mapping of stiffness, tissue motion, and flow in humans in vivo and promises new clinical applications of ultrasound with reduced intra- and inter-observer variability. PMID:25207828

  19. 3DSEM: A 3D microscopy dataset.

    PubMed

    Tafti, Ahmad P; Kirkpatrick, Andrew B; Holz, Jessica D; Owen, Heather A; Yu, Zeyun

    2016-03-01

    The Scanning Electron Microscope (SEM) as a 2D imaging instrument has been widely used in many scientific disciplines including biological, mechanical, and materials sciences to determine the surface attributes of microscopic objects. However the SEM micrographs still remain 2D images. To effectively measure and visualize the surface properties, we need to truly restore the 3D shape model from 2D SEM images. Having 3D surfaces would provide anatomic shape of micro-samples which allows for quantitative measurements and informative visualization of the specimens being investigated. The 3DSEM is a dataset for 3D microscopy vision which is freely available at [1] for any academic, educational, and research purposes. The dataset includes both 2D images and 3D reconstructed surfaces of several real microscopic samples. PMID:26779561

  20. 3DSEM: A 3D microscopy dataset

    PubMed Central

    Tafti, Ahmad P.; Kirkpatrick, Andrew B.; Holz, Jessica D.; Owen, Heather A.; Yu, Zeyun

    2015-01-01

    The Scanning Electron Microscope (SEM) as a 2D imaging instrument has been widely used in many scientific disciplines including biological, mechanical, and materials sciences to determine the surface attributes of microscopic objects. However the SEM micrographs still remain 2D images. To effectively measure and visualize the surface properties, we need to truly restore the 3D shape model from 2D SEM images. Having 3D surfaces would provide anatomic shape of micro-samples which allows for quantitative measurements and informative visualization of the specimens being investigated. The 3DSEM is a dataset for 3D microscopy vision which is freely available at [1] for any academic, educational, and research purposes. The dataset includes both 2D images and 3D reconstructed surfaces of several real microscopic samples. PMID:26779561

  1. 3DSEM: A 3D microscopy dataset.

    PubMed

    Tafti, Ahmad P; Kirkpatrick, Andrew B; Holz, Jessica D; Owen, Heather A; Yu, Zeyun

    2016-03-01

    The Scanning Electron Microscope (SEM) as a 2D imaging instrument has been widely used in many scientific disciplines including biological, mechanical, and materials sciences to determine the surface attributes of microscopic objects. However the SEM micrographs still remain 2D images. To effectively measure and visualize the surface properties, we need to truly restore the 3D shape model from 2D SEM images. Having 3D surfaces would provide anatomic shape of micro-samples which allows for quantitative measurements and informative visualization of the specimens being investigated. The 3DSEM is a dataset for 3D microscopy vision which is freely available at [1] for any academic, educational, and research purposes. The dataset includes both 2D images and 3D reconstructed surfaces of several real microscopic samples.

  2. Perception of detail in 3D images

    NASA Astrophysics Data System (ADS)

    Heynderickx, Ingrid; Kaptein, Ronald

    2009-01-01

    A lot of current 3D displays suffer from the fact that their spatial resolution is lower compared to their 2D counterparts. One reason for this is that the multiple views needed to generate 3D are often spatially multiplexed. Besides this, imperfect separation of the left- and right-eye view leads to blurring or ghosting, and therefore to a decrease in perceived sharpness. However, people watching stereoscopic videos have reported that the 3D scene contained more details, compared to the 2D scene with identical spatial resolution. This is an interesting notion, that has never been tested in a systematic and quantitative way. To investigate this effect, we had people compare the amount of detail ("detailedness") in pairs of 2D and 3D images. A blur filter was applied to one of the two images, and the blur level was varied using an adaptive staircase procedure. In this way, the blur threshold for which the 2D and 3D image contained perceptually the same amount of detail could be found. Our results show that the 3D image needed to be blurred more than the 2D image. This confirms the earlier qualitative findings that 3D images contain perceptually more details than 2D images with the same spatial resolution.

  3. A comparison of 3D poly(ε-caprolactone) tissue engineering scaffolds produced with conventional and additive manufacturing techniques by means of quantitative analysis of SR μ-CT images

    NASA Astrophysics Data System (ADS)

    Brun, F.; Intranuovo, F.; Mohammadi, S.; Domingos, M.; Favia, P.; Tromba, G.

    2013-07-01

    The technique used to produce a 3D tissue engineering (TE) scaffold is of fundamental importance in order to guarantee its proper morphological characteristics. An accurate assessment of the resulting structural properties is therefore crucial in order to evaluate the effectiveness of the produced scaffold. Synchrotron radiation (SR) computed microtomography (μ-CT) combined with further image analysis seems to be one of the most effective techniques to this aim. However, a quantitative assessment of the morphological parameters directly from the reconstructed images is a non trivial task. This study considers two different poly(ε-caprolactone) (PCL) scaffolds fabricated with a conventional technique (Solvent Casting Particulate Leaching, SCPL) and an additive manufacturing (AM) technique (BioCell Printing), respectively. With the first technique it is possible to produce scaffolds with random, non-regular, rounded pore geometry. The AM technique instead is able to produce scaffolds with square-shaped interconnected pores of regular dimension. Therefore, the final morphology of the AM scaffolds can be predicted and the resulting model can be used for the validation of the applied imaging and image analysis protocols. It is here reported a SR μ-CT image analysis approach that is able to effectively and accurately reveal the differences in the pore- and throat-size distributions as well as connectivity of both AM and SCPL scaffolds.

  4. Quantitative structure-activity relationships for chronic toxicity of alkyl-chrysenes and alkyl-benz[a]anthracenes to Japanese medaka embryos (Oryzias latipes).

    PubMed

    Lin, Hongkang; Morandi, Garrett D; Brown, R Stephen; Snieckus, Victor; Rantanen, Toni; Jørgensen, Kåre B; Hodson, Peter V

    2015-02-01

    Alkylated polycyclic aromatic hydrocarbons (alkyl-PAHs) are a class of compounds found at significant concentrations in crude oils, and likely the main constituents responsible for the chronic toxicity of oil to fish. Alkyl substituents at different locations on the aromatic rings change the size and shape of PAH molecules, which results in different interactions with tissue receptors and different severities of toxicity. The present study is the first to report the toxicity of several alkylated derivatives of chrysene and benz[a]anthracene to the embryos of Japanese medaka (Oryzias latipes) using the partition controlled delivery (PCD) method of exposure. The PCD method maintained the desired exposure concentrations by equilibrium partitioning of hydrophobic test compounds from polydimethylsiloxane (PDMS) films. Test concentrations declined by only 13% over a period of 17 days. Based on the prevalence of signs of blue sac disease (BSD), as expressed by median effective concentrations (EC50s), benz[a]anthracene (B[a]A) was more toxic than chrysene. Alkylation generally increased toxicity, except at position 2 of B[a]A. Alkyl-PAHs substituted in the middle region had a lower EC50 than those substituted at the distal region. Except for B[a]A and 7-methylbenz[a]anthracene (7-MB), estimated EC50 values were higher than their solubility limits, which resulted in limited toxicity within the range of test concentrations. The regression between log EC50s and logKow values provided a rough estimation of structure-activity relationships for alkyl-PAHs, but Kow alone did not provide a complete explanation of the chronic toxicity of alkyl PAHs.

  5. Prominent rocks - 3D

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Many prominent rocks near the Sagan Memorial Station are featured in this image, taken in stereo by the Imager for Mars Pathfinder (IMP) on Sol 3. 3D glasses are necessary to identify surface detail. Wedge is at lower left; Shark, Half-Dome, and Pumpkin are at center. Flat Top, about four inches high, is at lower right. The horizon in the distance is one to two kilometers away.

    Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is an operating division of the California Institute of Technology (Caltech). The Imager for Mars Pathfinder (IMP) was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.

    Click below to see the left and right views individually. [figure removed for brevity, see original site] Left [figure removed for brevity, see original site] Right

  6. 'Diamond' in 3-D

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This 3-D, microscopic imager mosaic of a target area on a rock called 'Diamond Jenness' was taken after NASA's Mars Exploration Rover Opportunity ground into the surface with its rock abrasion tool for a second time.

    Opportunity has bored nearly a dozen holes into the inner walls of 'Endurance Crater.' On sols 177 and 178 (July 23 and July 24, 2004), the rover worked double-duty on Diamond Jenness. Surface debris and the bumpy shape of the rock resulted in a shallow and irregular hole, only about 2 millimeters (0.08 inch) deep. The final depth was not enough to remove all the bumps and leave a neat hole with a smooth floor. This extremely shallow depression was then examined by the rover's alpha particle X-ray spectrometer.

    On Sol 178, Opportunity's 'robotic rodent' dined on Diamond Jenness once again, grinding almost an additional 5 millimeters (about 0.2 inch). The rover then applied its Moessbauer spectrometer to the deepened hole. This double dose of Diamond Jenness enabled the science team to examine the rock at varying layers. Results from those grindings are currently being analyzed.

    The image mosaic is about 6 centimeters (2.4 inches) across.

  7. Martian terrain - 3D

    NASA Technical Reports Server (NTRS)

    1997-01-01

    This area of terrain near the Sagan Memorial Station was taken on Sol 3 by the Imager for Mars Pathfinder (IMP). 3D glasses are necessary to identify surface detail.

    The IMP is a stereo imaging system with color capability provided by 24 selectable filters -- twelve filters per 'eye.' It stands 1.8 meters above the Martian surface, and has a resolution of two millimeters at a range of two meters.

    Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is an operating division of the California Institute of Technology (Caltech). The Imager for Mars Pathfinder (IMP) was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.

    Click below to see the left and right views individually. [figure removed for brevity, see original site] Left [figure removed for brevity, see original site] Right

  8. The importance of 3D dosimetry

    NASA Astrophysics Data System (ADS)

    Low, Daniel

    2015-01-01

    Radiation therapy has been getting progressively more complex for the past 20 years. Early radiation therapy techniques needed only basic dosimetry equipment; motorized water phantoms, ionization chambers, and basic radiographic film techniques. As intensity modulated radiation therapy and image guided therapy came into widespread practice, medical physicists were challenged with developing effective and efficient dose measurement techniques. The complex 3-dimensional (3D) nature of the dose distributions that were being delivered demanded the development of more quantitative and more thorough methods for dose measurement. The quality assurance vendors developed a wide array of multidetector arrays that have been enormously useful for measuring and characterizing dose distributions, and these have been made especially useful with the advent of 3D dose calculation systems based on the array measurements, as well as measurements made using film and portal imagers. Other vendors have been providing 3D calculations based on data from the linear accelerator or the record and verify system, providing thorough evaluation of the dose but lacking quality assurance (QA) of the dose delivery process, including machine calibration. The current state of 3D dosimetry is one of a state of flux. The vendors and professional associations are trying to determine the optimal balance between thorough QA, labor efficiency, and quantitation. This balance will take some time to reach, but a necessary component will be the 3D measurement and independent calculation of delivered radiation therapy dose distributions.

  9. Determinants of activity at human Toll-like receptors 7 and 8: quantitative structure-activity relationship (QSAR) of diverse heterocyclic scaffolds.

    PubMed

    Yoo, Euna; Salunke, Deepak B; Sil, Diptesh; Guo, Xiaoqiang; Salyer, Alex C D; Hermanson, Alec R; Kumar, Manoj; Malladi, Subbalakshmi S; Balakrishna, Rajalakshmi; Thompson, Ward H; Tanji, Hiromi; Ohto, Umeharu; Shimizu, Toshiyuki; David, Sunil A

    2014-10-01

    Toll-like receptor (TLR) 7 and 8 agonists are potential vaccine adjuvants, since they directly activate APCs and enhance Th1-driven immune responses. Previous SAR investigations in several scaffolds of small molecule TLR7/8 activators pointed to the strict dependence of the selectivity for TLR7 vis-à-vis TLR8 on the electronic configurations of the heterocyclic systems, which we sought to examine quantitatively with the goal of developing "heuristics" to define structural requisites governing activity at TLR7 and/or TLR8. We undertook a scaffold-hopping approach, entailing the syntheses and biological evaluations of 13 different chemotypes. Crystal structures of TLR8 in complex with the two most active compounds confirmed important binding interactions playing a key role in ligand occupancy and biological activity. Density functional theory based quantum chemical calculations on these compounds followed by linear discriminant analyses permitted the classification of inactive, TLR8-active, and TLR7/8 dual-active compounds, confirming the critical role of partial charges in determining biological activity.

  10. 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.

  11. Quantitative structure-activity relationship investigation of the role of hydrophobicity in regulating mutagenicity in the Ames test: 2. Mutagenicity of aromatic and heteroaromatic nitro compounds in Salmonella typhimurium TA100

    SciTech Connect

    Debnath, A.K.; Hansch, C. ); Shusterman, A.J. ); Lopez de Compadre, R.L. )

    1992-01-01

    A quantitative structure-activity relationship (QSAR) has been derived for the mutagenic activity of 117 aromatic and heteroaromatic nitro compounds acting on Salmonella typhimurium TA100. Relative mutagenic activity is bilinearly dependent on hydrophobicity, with an optimal log P of 5.44, and is linearly dependent on the energy of the lowest unoccupied molecular orbital of the nitro compound. The dependence of mutagenic activity on hydrophobicity and electronic effects is very similar for TA98 and TA100. Mutagenic activity in TA100 does not depend on the size of the aromatic ring system, as it does in TA98. The effect of the choice of assay organism, TA98 versus TA100, on nitroarene QSAR is seen to be similar to the effect previously found for aminoarenes. Lateral verification of QSARs is presented as a tool for establishing the significance of a new QSAR.

  12. Inhibition of 2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) Formation by Alkoxy Radical Scavenging of Flavonoids and Their Quantitative Structure-Activity Relationship in a Model System.

    PubMed

    Yu, Chundi; Shao, Zeping; Liu, Bing; Zhang, Yan; Wang, Shuo

    2016-08-01

    The inhibitory effect of 10 flavonoids on the formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in a creatinine-phenylalanine model system was investigated through electronic spin resonance and a quantitative structure-activity relationship. Alkoxy radicals were observed during the heating process, providing evidence for a radical pathway in the formation of PhIP. The alkoxy radical scavenging capability of the flavonoids was proportional to their inhibition of PhIP formation (IC50 ). We deduced that flavonoid inhibition of PhIP generation occurs via scavenging of alkoxy radicals during the heating process. Multiple linear regression and partial least squares models were used to elucidate the relationship between PhIP inhibition activity and structure characteristics of the flavonoids. The lipo-hydro partition coefficient and molecular fractional polar surface area of the flavonoids were found to be predictive of the inhibition effect.

  13. Inhibition of 2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) Formation by Alkoxy Radical Scavenging of Flavonoids and Their Quantitative Structure-Activity Relationship in a Model System.

    PubMed

    Yu, Chundi; Shao, Zeping; Liu, Bing; Zhang, Yan; Wang, Shuo

    2016-08-01

    The inhibitory effect of 10 flavonoids on the formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in a creatinine-phenylalanine model system was investigated through electronic spin resonance and a quantitative structure-activity relationship. Alkoxy radicals were observed during the heating process, providing evidence for a radical pathway in the formation of PhIP. The alkoxy radical scavenging capability of the flavonoids was proportional to their inhibition of PhIP formation (IC50 ). We deduced that flavonoid inhibition of PhIP generation occurs via scavenging of alkoxy radicals during the heating process. Multiple linear regression and partial least squares models were used to elucidate the relationship between PhIP inhibition activity and structure characteristics of the flavonoids. The lipo-hydro partition coefficient and molecular fractional polar surface area of the flavonoids were found to be predictive of the inhibition effect. PMID:27384350

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

    NASA Astrophysics Data System (ADS)

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

    2013-11-01

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

  15. 3D Elevation Program—Virtual USA in 3D

    USGS Publications Warehouse

    Lukas, Vicki; Stoker, J.M.

    2016-01-01

    The U.S. Geological Survey (USGS) 3D Elevation Program (3DEP) uses a laser system called ‘lidar’ (light detection and ranging) to create a virtual reality map of the Nation that is very accurate. 3D maps have many uses with new uses being discovered all the time.  

  16. 3D Elevation Program—Virtual USA in 3D

    USGS Publications Warehouse

    Lukas, Vicki; Stoker, J.M.

    2016-04-14

    The U.S. Geological Survey (USGS) 3D Elevation Program (3DEP) uses a laser system called ‘lidar’ (light detection and ranging) to create a virtual reality map of the Nation that is very accurate. 3D maps have many uses with new uses being discovered all the time.  

  17. Market study: 3-D eyetracker

    NASA Technical Reports Server (NTRS)

    1977-01-01

    A market study of a proposed version of a 3-D eyetracker for initial use at NASA's Ames Research Center was made. The commercialization potential of a simplified, less expensive 3-D eyetracker was ascertained. Primary focus on present and potential users of eyetrackers, as well as present and potential manufacturers has provided an effective means of analyzing the prospects for commercialization.

  18. 3D World Building System

    ScienceCinema

    None

    2016-07-12

    This video provides an overview of the Sandia National Laboratories developed 3-D World Model Building capability that provides users with an immersive, texture rich 3-D model of their environment in minutes using a laptop and color and depth camera.

  19. 3D World Building System

    SciTech Connect

    2013-10-30

    This video provides an overview of the Sandia National Laboratories developed 3-D World Model Building capability that provides users with an immersive, texture rich 3-D model of their environment in minutes using a laptop and color and depth camera.

  20. LLNL-Earth3D

    SciTech Connect

    2013-10-01

    Earth3D is a computer code designed to allow fast calculation of seismic rays and travel times through a 3D model of the Earth. LLNL is using this for earthquake location and global tomography efforts and such codes are of great interest to the Earth Science community.

  1. [3-D ultrasound in gastroenterology].

    PubMed

    Zoller, W G; Liess, H

    1994-06-01

    Three-dimensional (3D) sonography represents a development of noninvasive diagnostic imaging by real-time two-dimensional (2D) sonography. The use of transparent rotating scans, comparable to a block of glass, generates a 3D effect. The objective of the present study was to optimate 3D presentation of abdominal findings. Additional investigations were made with a new volumetric program to determine the volume of selected findings of the liver. The results were compared with the estimated volumes of 2D sonography and 2D computer tomography (CT). For the processing of 3D images, typical parameter constellations were found for the different findings, which facilitated processing of 3D images. In more than 75% of the cases examined we found an optimal 3D presentation of sonographic findings with respect to the evaluation criteria developed by us for the 3D imaging of processed data. Great differences were found for the estimated volumes of the findings of the liver concerning the three different techniques applied. 3D ultrasound represents a valuable method to judge morphological appearance in abdominal findings. The possibility of volumetric measurements enlarges its potential diagnostic significance. Further clinical investigations are necessary to find out if definite differentiation between benign and malign findings is possible.

  2. MRI Volume Fusion Based on 3D Shearlet Decompositions

    PubMed Central

    Duan, Chang; Wang, Shuai; Wang, Xue Gang; Huang, Qi Hong

    2014-01-01

    Nowadays many MRI scans can give 3D volume data with different contrasts, but the observers may want to view various contrasts in the same 3D volume. The conventional 2D medical fusion methods can only fuse the 3D volume data layer by layer, which may lead to the loss of interframe correlative information. In this paper, a novel 3D medical volume fusion method based on 3D band limited shearlet transform (3D BLST) is proposed. And this method is evaluated upon MRI T2* and quantitative susceptibility mapping data of 4 human brains. Both the perspective impression and the quality indices indicate that the proposed method has a better performance than conventional 2D wavelet, DT CWT, and 3D wavelet, DT CWT based fusion methods. PMID:24817880

  3. Euro3D Science Conference

    NASA Astrophysics Data System (ADS)

    Walsh, J. R.

    2004-02-01

    The Euro3D RTN is an EU funded Research Training Network to foster the exploitation of 3D spectroscopy in Europe. 3D spectroscopy is a general term for spectroscopy of an area of the sky and derives its name from its two spatial + one spectral dimensions. There are an increasing number of instruments which use integral field devices to achieve spectroscopy of an area of the sky, either using lens arrays, optical fibres or image slicers, to pack spectra of multiple pixels on the sky (``spaxels'') onto a 2D detector. On account of the large volume of data and the special methods required to reduce and analyse 3D data, there are only a few centres of expertise and these are mostly involved with instrument developments. There is a perceived lack of expertise in 3D spectroscopy spread though the astronomical community and its use in the armoury of the observational astronomer is viewed as being highly specialised. For precisely this reason the Euro3D RTN was proposed to train young researchers in this area and develop user tools to widen the experience with this particular type of data in Europe. The Euro3D RTN is coordinated by Martin M. Roth (Astrophysikalisches Institut Potsdam) and has been running since July 2002. The first Euro3D science conference was held in Cambridge, UK from 22 to 23 May 2003. The main emphasis of the conference was, in keeping with the RTN, to expose the work of the young post-docs who are funded by the RTN. In addition the team members from the eleven European institutes involved in Euro3D also presented instrumental and observational developments. The conference was organized by Andy Bunker and held at the Institute of Astronomy. There were over thirty participants and 26 talks covered the whole range of application of 3D techniques. The science ranged from Galactic planetary nebulae and globular clusters to kinematics of nearby galaxies out to objects at high redshift. Several talks were devoted to reporting recent observations with newly

  4. 3D printing in dentistry.

    PubMed

    Dawood, A; Marti Marti, B; Sauret-Jackson, V; Darwood, A

    2015-12-01

    3D printing has been hailed as a disruptive technology which will change manufacturing. Used in aerospace, defence, art and design, 3D printing is becoming a subject of great interest in surgery. The technology has a particular resonance with dentistry, and with advances in 3D imaging and modelling technologies such as cone beam computed tomography and intraoral scanning, and with the relatively long history of the use of CAD CAM technologies in dentistry, it will become of increasing importance. Uses of 3D printing include the production of drill guides for dental implants, the production of physical models for prosthodontics, orthodontics and surgery, the manufacture of dental, craniomaxillofacial and orthopaedic implants, and the fabrication of copings and frameworks for implant and dental restorations. This paper reviews the types of 3D printing technologies available and their various applications in dentistry and in maxillofacial surgery. PMID:26657435

  5. PLOT3D user's manual

    NASA Technical Reports Server (NTRS)

    Walatka, Pamela P.; Buning, Pieter G.; Pierce, Larry; Elson, Patricia A.

    1990-01-01

    PLOT3D is a computer graphics program designed to visualize the grids and solutions of computational fluid dynamics. Seventy-four functions are available. Versions are available for many systems. PLOT3D can handle multiple grids with a million or more grid points, and can produce varieties of model renderings, such as wireframe or flat shaded. Output from PLOT3D can be used in animation programs. The first part of this manual is a tutorial that takes the reader, keystroke by keystroke, through a PLOT3D session. The second part of the manual contains reference chapters, including the helpfile, data file formats, advice on changing PLOT3D, and sample command files.

  6. 3D printing in dentistry.

    PubMed

    Dawood, A; Marti Marti, B; Sauret-Jackson, V; Darwood, A

    2015-12-01

    3D printing has been hailed as a disruptive technology which will change manufacturing. Used in aerospace, defence, art and design, 3D printing is becoming a subject of great interest in surgery. The technology has a particular resonance with dentistry, and with advances in 3D imaging and modelling technologies such as cone beam computed tomography and intraoral scanning, and with the relatively long history of the use of CAD CAM technologies in dentistry, it will become of increasing importance. Uses of 3D printing include the production of drill guides for dental implants, the production of physical models for prosthodontics, orthodontics and surgery, the manufacture of dental, craniomaxillofacial and orthopaedic implants, and the fabrication of copings and frameworks for implant and dental restorations. This paper reviews the types of 3D printing technologies available and their various applications in dentistry and in maxillofacial surgery.

  7. PLOT3D/AMES, APOLLO UNIX VERSION USING GMR3D (WITHOUT TURB3D)

    NASA Technical Reports Server (NTRS)

    Buning, P.

    1994-01-01

    PLOT3D is an interactive graphics program designed to help scientists visualize computational fluid dynamics (CFD) grids and solutions. Today, supercomputers and CFD algorithms can provide scientists with simulations of such highly complex phenomena that obtaining an understanding of the simulations has become a major problem. Tools which help the scientist visualize the simulations can be of tremendous aid. PLOT3D/AMES offers more functions and features, and has been adapted for more types of computers than any other CFD graphics program. Version 3.6b+ is supported for five computers and graphic libraries. Using PLOT3D, CFD physicists can view their computational models from any angle, observing the physics of problems and the quality of solutions. As an aid in designing aircraft, for example, PLOT3D's interactive computer graphics can show vortices, temperature, reverse flow, pressure, and dozens of other characteristics of air flow during flight. As critical areas become obvious, they can easily be studied more closely using a finer grid. PLOT3D is part of a computational fluid dynamics software cycle. First, a program such as 3DGRAPE (ARC-12620) helps the scientist generate computational grids to model an object and its surrounding space. Once the grids have been designed and parameters such as the angle of attack, Mach number, and Reynolds number have been specified, a "flow-solver" program such as INS3D (ARC-11794 or COS-10019) solves the system of equations governing fluid flow, usually on a supercomputer. Grids sometimes have as many as two million points, and the "flow-solver" produces a solution file which contains density, x- y- and z-momentum, and stagnation energy for each grid point. With such a solution file and a grid file containing up to 50 grids as input, PLOT3D can calculate and graphically display any one of 74 functions, including shock waves, surface pressure, velocity vectors, and particle traces. PLOT3D's 74 functions are organized into

  8. PLOT3D/AMES, APOLLO UNIX VERSION USING GMR3D (WITH TURB3D)

    NASA Technical Reports Server (NTRS)

    Buning, P.

    1994-01-01

    PLOT3D is an interactive graphics program designed to help scientists visualize computational fluid dynamics (CFD) grids and solutions. Today, supercomputers and CFD algorithms can provide scientists with simulations of such highly complex phenomena that obtaining an understanding of the simulations has become a major problem. Tools which help the scientist visualize the simulations can be of tremendous aid. PLOT3D/AMES offers more functions and features, and has been adapted for more types of computers than any other CFD graphics program. Version 3.6b+ is supported for five computers and graphic libraries. Using PLOT3D, CFD physicists can view their computational models from any angle, observing the physics of problems and the quality of solutions. As an aid in designing aircraft, for example, PLOT3D's interactive computer graphics can show vortices, temperature, reverse flow, pressure, and dozens of other characteristics of air flow during flight. As critical areas become obvious, they can easily be studied more closely using a finer grid. PLOT3D is part of a computational fluid dynamics software cycle. First, a program such as 3DGRAPE (ARC-12620) helps the scientist generate computational grids to model an object and its surrounding space. Once the grids have been designed and parameters such as the angle of attack, Mach number, and Reynolds number have been specified, a "flow-solver" program such as INS3D (ARC-11794 or COS-10019) solves the system of equations governing fluid flow, usually on a supercomputer. Grids sometimes have as many as two million points, and the "flow-solver" produces a solution file which contains density, x- y- and z-momentum, and stagnation energy for each grid point. With such a solution file and a grid file containing up to 50 grids as input, PLOT3D can calculate and graphically display any one of 74 functions, including shock waves, surface pressure, velocity vectors, and particle traces. PLOT3D's 74 functions are organized into

  9. Unassisted 3D camera calibration

    NASA Astrophysics Data System (ADS)

    Atanassov, Kalin; Ramachandra, Vikas; Nash, James; Goma, Sergio R.

    2012-03-01

    With the rapid growth of 3D technology, 3D image capture has become a critical part of the 3D feature set on mobile phones. 3D image quality is affected by the scene geometry as well as on-the-device processing. An automatic 3D system usually assumes known camera poses accomplished by factory calibration using a special chart. In real life settings, pose parameters estimated by factory calibration can be negatively impacted by movements of the lens barrel due to shaking, focusing, or camera drop. If any of these factors displaces the optical axes of either or both cameras, vertical disparity might exceed the maximum tolerable margin and the 3D user may experience eye strain or headaches. To make 3D capture more practical, one needs to consider unassisted (on arbitrary scenes) calibration. In this paper, we propose an algorithm that relies on detection and matching of keypoints between left and right images. Frames containing erroneous matches, along with frames with insufficiently rich keypoint constellations, are detected and discarded. Roll, pitch yaw , and scale differences between left and right frames are then estimated. The algorithm performance is evaluated in terms of the remaining vertical disparity as compared to the maximum tolerable vertical disparity.

  10. Mechanistic quantitative structure-activity relationship model for the photoinduced toxicity of polycyclic aromatic hydrocarbons. 2: An empirical model for the toxicity of 16 polycyclic aromatic hydrocarbons to the duckweed Lemna gibba L. G-3

    SciTech Connect

    Huang, X.D.; Krylov, S.N.; Ren, L.; McConkey, B.J.; Dixon, D.G.; Greenberg, B.M.

    1997-11-01

    Photoinduced toxicity of polycyclic aromatic hydrocarbons (PAHs) occurs via photosensitization reactions (e.g., generation of singlet-state oxygen) and by photomodification (photooxidation and/or photolysis) of the chemicals to more toxic species. The quantitative structure-activity relationship (QSAR) described in the companion paper predicted, in theory, that photosensitization and photomodification additively contribute to toxicity. To substantiate this QSAR modeling exercise it was necessary to show that toxicity can be described by empirically derived parameters. The toxicity of 16 PAHs to the duckweed Lemna gibba was measured as inhibition of leaf production in simulated solar radiation (a light source with a spectrum similar to that of sunlight). A predictive model for toxicity was generated based on the theoretical model developed in the companion paper. The photophysical descriptors required of each PAH for modeling were efficiency of photon absorbance, relative uptake, quantum yield for triplet-state formation, and the rate of photomodification. The photomodification rates of the PAHs showed a moderate correlation to toxicity, whereas a derived photosensitization factor (PSF; based on absorbance, triplet-state quantum yield, and uptake) for each PAH showed only a weak, complex correlation to toxicity. However, summing the rate of photomodification and the PSF resulted in a strong correlation to toxicity that had predictive value. When the PSF and a derived photomodification factor (PMF; based on the photomodification rate and toxicity of the photomodified PAHs) were summed, an excellent explanatory model of toxicity was produced, substantiating the additive contributions of the two factors.

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

    PubMed

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

    2015-03-01

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

  12. Spatially resolved 3D noise

    NASA Astrophysics Data System (ADS)

    Haefner, David P.; Preece, Bradley L.; Doe, Joshua M.; Burks, Stephen D.

    2016-05-01

    When evaluated with a spatially uniform irradiance, an imaging sensor exhibits both spatial and temporal variations, which can be described as a three-dimensional (3D) random process considered as noise. In the 1990s, NVESD engineers developed an approximation to the 3D power spectral density (PSD) for noise in imaging systems known as 3D noise. In this correspondence, we describe how the confidence intervals for the 3D noise measurement allows for determination of the sampling necessary to reach a desired precision. We then apply that knowledge to create a smaller cube that can be evaluated spatially across the 2D image giving the noise as a function of position. The method presented here allows for both defective pixel identification and implements the finite sampling correction matrix. In support of the reproducible research effort, the Matlab functions associated with this work can be found on the Mathworks file exchange [1].

  13. Autofocus for 3D imaging

    NASA Astrophysics Data System (ADS)

    Lee-Elkin, Forest

    2008-04-01

    Three dimensional (3D) autofocus remains a significant challenge for the development of practical 3D multipass radar imaging. The current 2D radar autofocus methods are not readily extendable across sensor passes. We propose a general framework that allows a class of data adaptive solutions for 3D auto-focus across passes with minimal constraints on the scene contents. The key enabling assumption is that portions of the scene are sparse in elevation which reduces the number of free variables and results in a system that is simultaneously solved for scatterer heights and autofocus parameters. The proposed method extends 2-pass interferometric synthetic aperture radar (IFSAR) methods to an arbitrary number of passes allowing the consideration of scattering from multiple height locations. A specific case from the proposed autofocus framework is solved and demonstrates autofocus and coherent multipass 3D estimation across the 8 passes of the "Gotcha Volumetric SAR Data Set" X-Band radar data.

  14. Accepting the T3D

    SciTech Connect

    Rich, D.O.; Pope, S.C.; DeLapp, J.G.

    1994-10-01

    In April, a 128 PE Cray T3D was installed at Los Alamos National Laboratory`s Advanced Computing Laboratory as part of the DOE`s High-Performance Parallel Processor Program (H4P). In conjunction with CRI, the authors implemented a 30 day acceptance test. The test was constructed in part to help them understand the strengths and weaknesses of the T3D. In this paper, they briefly describe the H4P and its goals. They discuss the design and implementation of the T3D acceptance test and detail issues that arose during the test. They conclude with a set of system requirements that must be addressed as the T3D system evolves.

  15. Combinatorial 3D Mechanical Metamaterials

    NASA Astrophysics Data System (ADS)

    Coulais, Corentin; Teomy, Eial; de Reus, Koen; Shokef, Yair; van Hecke, Martin

    2015-03-01

    We present a class of elastic structures which exhibit 3D-folding motion. Our structures consist of cubic lattices of anisotropic unit cells that can be tiled in a complex combinatorial fashion. We design and 3d-print this complex ordered mechanism, in which we combine elastic hinges and defects to tailor the mechanics of the material. Finally, we use this large design space to encode smart functionalities such as surface patterning and multistability.

  16. LASTRAC.3d: Transition Prediction in 3D Boundary Layers

    NASA Technical Reports Server (NTRS)

    Chang, Chau-Lyan

    2004-01-01

    Langley Stability and Transition Analysis Code (LASTRAC) is a general-purpose, physics-based transition prediction code released by NASA for laminar flow control studies and transition research. This paper describes the LASTRAC extension to general three-dimensional (3D) boundary layers such as finite swept wings, cones, or bodies at an angle of attack. The stability problem is formulated by using a body-fitted nonorthogonal curvilinear coordinate system constructed on the body surface. The nonorthogonal coordinate system offers a variety of marching paths and spanwise waveforms. In the extreme case of an infinite swept wing boundary layer, marching with a nonorthogonal coordinate produces identical solutions to those obtained with an orthogonal coordinate system using the earlier release of LASTRAC. Several methods to formulate the 3D parabolized stability equations (PSE) are discussed. A surface-marching procedure akin to that for 3D boundary layer equations may be used to solve the 3D parabolized disturbance equations. On the other hand, the local line-marching PSE method, formulated as an easy extension from its 2D counterpart and capable of handling the spanwise mean flow and disturbance variation, offers an alternative. A linear stability theory or parabolized stability equations based N-factor analysis carried out along the streamline direction with a fixed wavelength and downstream-varying spanwise direction constitutes an efficient engineering approach to study instability wave evolution in a 3D boundary layer. The surface-marching PSE method enables a consistent treatment of the disturbance evolution along both streamwise and spanwise directions but requires more stringent initial conditions. Both PSE methods and the traditional LST approach are implemented in the LASTRAC.3d code. Several test cases for tapered or finite swept wings and cones at an angle of attack are discussed.

  17. 3D microscopy for microfabrication quality control

    NASA Astrophysics Data System (ADS)

    Muller, Matthew S.; De Jean, Paul D.

    2015-03-01

    A novel stereo microscope adapter, the SweptVue, has been developed to rapidly perform quantitative 3D microscopy for cost-effective microfabrication quality control. The SweptVue adapter uses the left and right stereo channels of an Olympus SZX7 stereo microscope for sample illumination and detection, respectively. By adjusting the temporal synchronization between the illumination lines projected from a Texas Instruments DLP LightCrafter and the rolling shutter on a Point Grey Flea3 CMOS camera, micrometer-scale depth features can be easily and rapidly measured at up to 5 μm resolution on a variety of microfabricated samples. In this study, the build performance of an industrial-grade Stratasys Object 300 Connex 3D printer was examined. Ten identical parts were 3D printed with a lateral and depth resolution of 42 μm and 30 μm, respectively, using both a rigid and flexible Stratasys PolyJet material. Surface elevation precision and accuracy was examined over multiple regions of interest on plateau and hemispherical surfaces. In general, the dimensions of the examined features were reproducible across the parts built using both materials. However, significant systemic lateral and height build errors were discovered, such as: decreased heights when approaching the edges of plateaus, inaccurate height steps, and poor tolerances on channel width. For 3D printed parts to be used in functional applications requiring micro-scale tolerances, they need to conform to specification. Despite appearing identical, our 3D printed parts were found to have a variety of defects that the SweptVue adapter quickly revealed.

  18. From 3D view to 3D print

    NASA Astrophysics Data System (ADS)

    Dima, M.; Farisato, G.; Bergomi, M.; Viotto, V.; Magrin, D.; Greggio, D.; Farinato, J.; Marafatto, L.; Ragazzoni, R.; Piazza, D.

    2014-08-01

    In the last few years 3D printing is getting more and more popular and used in many fields going from manufacturing to industrial design, architecture, medical support and aerospace. 3D printing is an evolution of bi-dimensional printing, which allows to obtain a solid object from a 3D model, realized with a 3D modelling software. The final product is obtained using an additive process, in which successive layers of material are laid down one over the other. A 3D printer allows to realize, in a simple way, very complex shapes, which would be quite difficult to be produced with dedicated conventional facilities. Thanks to the fact that the 3D printing is obtained superposing one layer to the others, it doesn't need any particular work flow and it is sufficient to simply draw the model and send it to print. Many different kinds of 3D printers exist based on the technology and material used for layer deposition. A common material used by the toner is ABS plastics, which is a light and rigid thermoplastic polymer, whose peculiar mechanical properties make it diffusely used in several fields, like pipes production and cars interiors manufacturing. I used this technology to create a 1:1 scale model of the telescope which is the hardware core of the space small mission CHEOPS (CHaracterising ExOPlanets Satellite) by ESA, which aims to characterize EXOplanets via transits observations. The telescope has a Ritchey-Chrétien configuration with a 30cm aperture and the launch is foreseen in 2017. In this paper, I present the different phases for the realization of such a model, focusing onto pros and cons of this kind of technology. For example, because of the finite printable volume (10×10×12 inches in the x, y and z directions respectively), it has been necessary to split the largest parts of the instrument in smaller components to be then reassembled and post-processed. A further issue is the resolution of the printed material, which is expressed in terms of layers

  19. YouDash3D: exploring stereoscopic 3D gaming for 3D movie theaters

    NASA Astrophysics Data System (ADS)

    Schild, Jonas; Seele, Sven; Masuch, Maic

    2012-03-01

    Along with the success of the digitally revived stereoscopic cinema, events beyond 3D movies become attractive for movie theater operators, i.e. interactive 3D games. In this paper, we present a case that explores possible challenges and solutions for interactive 3D games to be played by a movie theater audience. We analyze the setting and showcase current issues related to lighting and interaction. Our second focus is to provide gameplay mechanics that make special use of stereoscopy, especially depth-based game design. Based on these results, we present YouDash3D, a game prototype that explores public stereoscopic gameplay in a reduced kiosk setup. It features live 3D HD video stream of a professional stereo camera rig rendered in a real-time game scene. We use the effect to place the stereoscopic effigies of players into the digital game. The game showcases how stereoscopic vision can provide for a novel depth-based game mechanic. Projected trigger zones and distributed clusters of the audience video allow for easy adaptation to larger audiences and 3D movie theater gaming.

  20. Remote 3D Medical Consultation

    NASA Astrophysics Data System (ADS)

    Welch, Greg; Sonnenwald, Diane H.; Fuchs, Henry; Cairns, Bruce; Mayer-Patel, Ketan; Yang, Ruigang; State, Andrei; Towles, Herman; Ilie, Adrian; Krishnan, Srinivas; Söderholm, Hanna M.

    Two-dimensional (2D) video-based telemedical consultation has been explored widely in the past 15-20 years. Two issues that seem to arise in most relevant case studies are the difficulty associated with obtaining the desired 2D camera views, and poor depth perception. To address these problems we are exploring the use of a small array of cameras to synthesize a spatially continuous range of dynamic three-dimensional (3D) views of a remote environment and events. The 3D views can be sent across wired or wireless networks to remote viewers with fixed displays or mobile devices such as a personal digital assistant (PDA). The viewpoints could be specified manually or automatically via user head or PDA tracking, giving the remote viewer virtual head- or hand-slaved (PDA-based) remote cameras for mono or stereo viewing. We call this idea remote 3D medical consultation (3DMC). In this article we motivate and explain the vision for 3D medical consultation; we describe the relevant computer vision/graphics, display, and networking research; we present a proof-of-concept prototype system; and we present some early experimental results supporting the general hypothesis that 3D remote medical consultation could offer benefits over conventional 2D televideo.

  1. Speaking Volumes About 3-D

    NASA Technical Reports Server (NTRS)

    2002-01-01

    In 1999, Genex submitted a proposal to Stennis Space Center for a volumetric 3-D display technique that would provide multiple users with a 360-degree perspective to simultaneously view and analyze 3-D data. The futuristic capabilities of the VolumeViewer(R) have offered tremendous benefits to commercial users in the fields of medicine and surgery, air traffic control, pilot training and education, computer-aided design/computer-aided manufacturing, and military/battlefield management. The technology has also helped NASA to better analyze and assess the various data collected by its satellite and spacecraft sensors. Genex capitalized on its success with Stennis by introducing two separate products to the commercial market that incorporate key elements of the 3-D display technology designed under an SBIR contract. The company Rainbow 3D(R) imaging camera is a novel, three-dimensional surface profile measurement system that can obtain a full-frame 3-D image in less than 1 second. The third product is the 360-degree OmniEye(R) video system. Ideal for intrusion detection, surveillance, and situation management, this unique camera system offers a continuous, panoramic view of a scene in real time.

  2. Registration of 3D spectral OCT volumes using 3D SIFT feature point matching

    NASA Astrophysics Data System (ADS)

    Niemeijer, Meindert; Garvin, Mona K.; Lee, Kyungmoo; van Ginneken, Bram; Abràmoff, Michael D.; Sonka, Milan

    2009-02-01

    The recent introduction of next generation spectral OCT scanners has enabled routine acquisition of high resolution, 3D cross-sectional volumetric images of the retina. 3D OCT is used in the detection and management of serious eye diseases such as glaucoma and age-related macular degeneration. For follow-up studies, image registration is a vital tool to enable more precise, quantitative comparison of disease states. This work presents a registration method based on a recently introduced extension of the 2D Scale-Invariant Feature Transform (SIFT) framework1 to 3D.2 The SIFT feature extractor locates minima and maxima in the difference of Gaussian scale space to find salient feature points. It then uses histograms of the local gradient directions around each found extremum in 3D to characterize them in a 4096 element feature vector. Matching points are found by comparing the distance between feature vectors. We apply this method to the rigid registration of optic nerve head- (ONH) and macula-centered 3D OCT scans of the same patient that have only limited overlap. Three OCT data set pairs with known deformation were used for quantitative assessment of the method's robustness and accuracy when deformations of rotation and scaling were considered. Three-dimensional registration accuracy of 2.0+/-3.3 voxels was observed. The accuracy was assessed as average voxel distance error in N=1572 matched locations. The registration method was applied to 12 3D OCT scans (200 x 200 x 1024 voxels) of 6 normal eyes imaged in vivo to demonstrate the clinical utility and robustness of the method in a real-world environment.

  3. 3D-Printed Microfluidics.

    PubMed

    Au, Anthony K; Huynh, Wilson; Horowitz, Lisa F; Folch, Albert

    2016-03-14

    The advent of soft lithography allowed for an unprecedented expansion in the field of microfluidics. However, the vast majority of PDMS microfluidic devices are still made with extensive manual labor, are tethered to bulky control systems, and have cumbersome user interfaces, which all render commercialization difficult. On the other hand, 3D printing has begun to embrace the range of sizes and materials that appeal to the developers of microfluidic devices. Prior to fabrication, a design is digitally built as a detailed 3D CAD file. The design can be assembled in modules by remotely collaborating teams, and its mechanical and fluidic behavior can be simulated using finite-element modeling. As structures are created by adding materials without the need for etching or dissolution, processing is environmentally friendly and economically efficient. We predict that in the next few years, 3D printing will replace most PDMS and plastic molding techniques in academia.

  4. 3D QSAR investigations on locomotor activity of 5-cyano-N1,6-disubstituted 2-thiouracil derivatives.

    PubMed

    Kuchekar, B S; Pore, Y V

    2010-06-01

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

  5. 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.

  6. 3D Computations and Experiments

    SciTech Connect

    Couch, R; Faux, D; Goto, D; Nikkel, D

    2004-04-05

    This project consists of two activities. Task A, Simulations and Measurements, combines all the material model development and associated numerical work with the materials-oriented experimental activities. The goal of this effort is to provide an improved understanding of dynamic material properties and to provide accurate numerical representations of those properties for use in analysis codes. Task B, ALE3D Development, involves general development activities in the ALE3D code with the focus of improving simulation capabilities for problems of mutual interest to DoD and DOE. Emphasis is on problems involving multi-phase flow, blast loading of structures and system safety/vulnerability studies.

  7. Segmentation and detection of fluorescent 3D spots.

    PubMed

    Ram, Sundaresh; Rodríguez, Jeffrey J; Bosco, Giovanni

    2012-03-01

    The 3D spatial organization of genes and other genetic elements within the nucleus is important for regulating gene expression. Understanding how this spatial organization is established and maintained throughout the life of a cell is key to elucidating the many layers of gene regulation. Quantitative methods for studying nuclear organization will lead to insights into the molecular mechanisms that maintain gene organization as well as serve as diagnostic tools for pathologies caused by loss of nuclear structure. However, biologists currently lack automated and high throughput methods for quantitative and qualitative global analysis of 3D gene organization. In this study, we use confocal microscopy and fluorescence in-situ hybridization (FISH) as a cytogenetic technique to detect and localize the presence of specific DNA sequences in 3D. FISH uses probes that bind to specific targeted locations on the chromosomes, appearing as fluorescent spots in 3D images obtained using fluorescence microscopy. In this article, we propose an automated algorithm for segmentation and detection of 3D FISH spots. The algorithm is divided into two stages: spot segmentation and spot detection. Spot segmentation consists of 3D anisotropic smoothing to reduce the effect of noise, top-hat filtering, and intensity thresholding, followed by 3D region-growing. Spot detection uses a Bayesian classifier with spot features such as volume, average intensity, texture, and contrast to detect and classify the segmented spots as either true or false spots. Quantitative assessment of the proposed algorithm demonstrates improved segmentation and detection accuracy compared to other techniques.

  8. [Real time 3D echocardiography in congenital heart disease].

    PubMed

    Acar, P; Dulac, Y; Taktak, A; Villacèque, M

    2004-05-01

    The introduction of the 3D mode in echocardiography has led to its use in everyday clinical practice. One hundred and fifty real time 3D echocardiographic examinations were performed in 20 foetus, 110 children and 20 adults with various congenital heart lesions (shunts, valvular lesions, aortic diseases). The 4x matricial probe enables the instantaneous acquisition of transthoracic volumes. Four modes of 3D imaging were used: real time, total volume, colour Doppler and biplane. Quantitative measurements were performed at an outlying station. The feasibility of the method in the foetus, the child and the adult was respectively 90%, 99% and 85%. Real time 3D echocardiography did not affect the diagnoses made by standard echocardiography. The 3D imaging gave a more accurate description of atrial septal defects and congenital valvular lesions. Biplane imaging was decisive in the quantitative approach to aortic dilatation of Marfan's syndrome and in segmental analysis of the foetal heart. 3D colour Doppler imaging has been disappointing but the possibilities of volumic quantification of blood flow are very promising. The present limitations of the method are the inadequate resolution in the small child and the absence of quantitative measurement on the echograph. The facility of utilisation of the matricial probe should lead to routine usage of 3D echocardiography as with 2D and the Doppler modes. Its value should be decisive in many congenital cardiac lesions requiring surgery or interventional catheterisation. PMID:15214550

  9. 3D stochastic inversion of magnetic data

    NASA Astrophysics Data System (ADS)

    Shamsipour, Pejman; Chouteau, Michel; Marcotte, Denis

    2011-04-01

    A stochastic inversion method based on a geostatistical approach is presented to recover 3D susceptibility models from magnetic data. The aim of applying geostatistics is to provide quantitative descriptions of natural variables distributed in space or in time and space. Cokriging, the method which is used in this paper, is a method of estimation that minimizes the theoretical estimation error variance by using auto- and cross-correlations of several variables. The covariances for total field, susceptibility and total field-susceptibility are estimated using the observed data. Then, the susceptibility is cokriged or simulated as the primary variable. In order to avoid the natural tendency of the estimated structure to lay near the surface, depth weighting is included in the cokriging system. The algorithm assumes there is no remanent magnetization and the observation data represent only induced magnetization effects. The method is applied on different synthetic models to demonstrate its suitability for 3D inversion of magnetic data. A case study using ground measurements of total field at the Perseverance mine (Quebec, Canada) is presented. The recovered 3D susceptibility model provides beneficial information that can be used to analyze the geology of massive sulfide for the domain under study.

  10. 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…

  11. SNL3dFace

    2007-07-20

    This software distribution contains MATLAB and C++ code to enable identity verification using 3D images that may or may not contain a texture component. The code is organized to support system performance testing and system capability demonstration through the proper configuration of the available user interface. Using specific algorithm parameters the face recognition system has been demonstrated to achieve a 96.6% verification rate (Pd) at 0.001 false alarm rate. The system computes robust facial featuresmore » of a 3D normalized face using Principal Component Analysis (PCA) and Fisher Linear Discriminant Analysis (FLDA). A 3D normalized face is obtained by alighning each face, represented by a set of XYZ coordinated, to a scaled reference face using the Iterative Closest Point (ICP) algorithm. The scaled reference face is then deformed to the input face using an iterative framework with parameters that control the deformed surface regulation an rate of deformation. A variety of options are available to control the information that is encoded by the PCA. Such options include the XYZ coordinates, the difference of each XYZ coordinates from the reference, the Z coordinate, the intensity/texture values, etc. In addition to PCA/FLDA feature projection this software supports feature matching to obtain similarity matrices for performance analysis. In addition, this software supports visualization of the STL, MRD, 2D normalized, and PCA synthetic representations in a 3D environment.« less

  12. SNL3dFace

    SciTech Connect

    Russ, Trina; Koch, Mark; Koudelka, Melissa; Peters, Ralph; Little, Charles; Boehnen, Chris; Peters, Tanya

    2007-07-20

    This software distribution contains MATLAB and C++ code to enable identity verification using 3D images that may or may not contain a texture component. The code is organized to support system performance testing and system capability demonstration through the proper configuration of the available user interface. Using specific algorithm parameters the face recognition system has been demonstrated to achieve a 96.6% verification rate (Pd) at 0.001 false alarm rate. The system computes robust facial features of a 3D normalized face using Principal Component Analysis (PCA) and Fisher Linear Discriminant Analysis (FLDA). A 3D normalized face is obtained by alighning each face, represented by a set of XYZ coordinated, to a scaled reference face using the Iterative Closest Point (ICP) algorithm. The scaled reference face is then deformed to the input face using an iterative framework with parameters that control the deformed surface regulation an rate of deformation. A variety of options are available to control the information that is encoded by the PCA. Such options include the XYZ coordinates, the difference of each XYZ coordinates from the reference, the Z coordinate, the intensity/texture values, etc. In addition to PCA/FLDA feature projection this software supports feature matching to obtain similarity matrices for performance analysis. In addition, this software supports visualization of the STL, MRD, 2D normalized, and PCA synthetic representations in a 3D environment.

  13. 3D Printing: Exploring Capabilities

    ERIC Educational Resources Information Center

    Samuels, Kyle; Flowers, Jim

    2015-01-01

    As 3D printers become more affordable, schools are using them in increasing numbers. They fit well with the emphasis on product design in technology and engineering education, allowing students to create high-fidelity physical models to see and test different iterations in their product designs. They may also help students to "think in three…

  14. TACO3D. 3-D Finite Element Heat Transfer Code

    SciTech Connect

    Mason, W.E.

    1992-03-04

    TACO3D is a three-dimensional, finite-element program for heat transfer analysis. An extension of the two-dimensional TACO program, it can perform linear and nonlinear analyses and can be used to solve either transient or steady-state problems. The program accepts time-dependent or temperature-dependent material properties, and materials may be isotropic or orthotropic. A variety of time-dependent and temperature-dependent boundary conditions and loadings are available including temperature, flux, convection, and radiation boundary conditions and internal heat generation. Additional specialized features treat enclosure radiation, bulk nodes, and master/slave internal surface conditions (e.g., contact resistance). Data input via a free-field format is provided. A user subprogram feature allows for any type of functional representation of any independent variable. A profile (bandwidth) minimization option is available. The code is limited to implicit time integration for transient solutions. TACO3D has no general mesh generation capability. Rows of evenly-spaced nodes and rows of sequential elements may be generated, but the program relies on separate mesh generators for complex zoning. TACO3D does not have the ability to calculate view factors internally. Graphical representation of data in the form of time history and spatial plots is provided through links to the POSTACO and GRAPE postprocessor codes.

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

    PubMed Central

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

    2014-01-01

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

  16. 3D RoboMET Characterization

    SciTech Connect

    Madison, Jonathan D.; Susan, Donald F.; Kilgo, Alice C.

    2015-10-01

    The goal of this project is to generate 3D microstructural data by destructive and non-destructive means and provide accompanying characterization and quantitative analysis of such data. This work is a continuing part of a larger effort to relate material performance variability to microstructural variability. That larger effort is called “Predicting Performance Margins” or PPM. In conjunction with that overarching initiative, the RoboMET.3D™ is a specific asset of Center 1800 and is an automated serialsectioning system for destructive analysis of microstructure, which is called upon to provide direct customer support to 1800 and non-1800 customers. To that end, data collection, 3d reconstruction and analysis of typical and atypical microstructures have been pursued for the purposes of qualitative and quantitative characterization with a goal toward linking microstructural defects and/or microstructural features with mechanical response. Material systems examined in FY15 include precipitation hardened 17-4 steel, laser-welds of 304L stainless steel, thermal spray coatings of 304L and geological samples of sandstone.

  17. Sodium 3D COncentration MApping (COMA 3D) using 23Na and proton MRI

    NASA Astrophysics Data System (ADS)

    Truong, Milton L.; Harrington, Michael G.; Schepkin, Victor D.; Chekmenev, Eduard Y.

    2014-10-01

    Functional changes of sodium 3D MRI signals were converted into millimolar concentration changes using an open-source fully automated MATLAB toolbox. These concentration changes are visualized via 3D sodium concentration maps, and they are overlaid over conventional 3D proton images to provide high-resolution co-registration for easy correlation of functional changes to anatomical regions. Nearly 5000/h concentration maps were generated on a personal computer (ca. 2012) using 21.1 T 3D sodium MRI brain images of live rats with spatial resolution of 0.8 × 0.8 × 0.8 mm3 and imaging matrices of 60 × 60 × 60. The produced concentration maps allowed for non-invasive quantitative measurement of in vivo sodium concentration in the normal rat brain as a functional response to migraine-like conditions. The presented work can also be applied to sodium-associated changes in migraine, cancer, and other metabolic abnormalities that can be sensed by molecular imaging. The MATLAB toolbox allows for automated image analysis of the 3D images acquired on the Bruker platform and can be extended to other imaging platforms. The resulting images are presented in a form of series of 2D slices in all three dimensions in native MATLAB and PDF formats. The following is provided: (a) MATLAB source code for image processing, (b) the detailed processing procedures, (c) description of the code and all sub-routines, (d) example data sets of initial and processed data. The toolbox can be downloaded at: http://www.vuiis.vanderbilt.edu/~truongm/COMA3D/.

  18. Sodium 3D COncentration MApping (COMA 3D) using (23)Na and proton MRI.

    PubMed

    Truong, Milton L; Harrington, Michael G; Schepkin, Victor D; Chekmenev, Eduard Y

    2014-10-01

    Functional changes of sodium 3D MRI signals were converted into millimolar concentration changes using an open-source fully automated MATLAB toolbox. These concentration changes are visualized via 3D sodium concentration maps, and they are overlaid over conventional 3D proton images to provide high-resolution co-registration for easy correlation of functional changes to anatomical regions. Nearly 5000/h concentration maps were generated on a personal computer (ca. 2012) using 21.1T 3D sodium MRI brain images of live rats with spatial resolution of 0.8×0.8×0.8 mm(3) and imaging matrices of 60×60×60. The produced concentration maps allowed for non-invasive quantitative measurement of in vivo sodium concentration in the normal rat brain as a functional response to migraine-like conditions. The presented work can also be applied to sodium-associated changes in migraine, cancer, and other metabolic abnormalities that can be sensed by molecular imaging. The MATLAB toolbox allows for automated image analysis of the 3D images acquired on the Bruker platform and can be extended to other imaging platforms. The resulting images are presented in a form of series of 2D slices in all three dimensions in native MATLAB and PDF formats. The following is provided: (a) MATLAB source code for image processing, (b) the detailed processing procedures, (c) description of the code and all sub-routines, (d) example data sets of initial and processed data. The toolbox can be downloaded at: http://www.vuiis.vanderbilt.edu/~truongm/COMA3D/.

  19. Sodium 3D COncentration MApping (COMA 3D) using (23)Na and proton MRI.

    PubMed

    Truong, Milton L; Harrington, Michael G; Schepkin, Victor D; Chekmenev, Eduard Y

    2014-10-01

    Functional changes of sodium 3D MRI signals were converted into millimolar concentration changes using an open-source fully automated MATLAB toolbox. These concentration changes are visualized via 3D sodium concentration maps, and they are overlaid over conventional 3D proton images to provide high-resolution co-registration for easy correlation of functional changes to anatomical regions. Nearly 5000/h concentration maps were generated on a personal computer (ca. 2012) using 21.1T 3D sodium MRI brain images of live rats with spatial resolution of 0.8×0.8×0.8 mm(3) and imaging matrices of 60×60×60. The produced concentration maps allowed for non-invasive quantitative measurement of in vivo sodium concentration in the normal rat brain as a functional response to migraine-like conditions. The presented work can also be applied to sodium-associated changes in migraine, cancer, and other metabolic abnormalities that can be sensed by molecular imaging. The MATLAB toolbox allows for automated image analysis of the 3D images acquired on the Bruker platform and can be extended to other imaging platforms. The resulting images are presented in a form of series of 2D slices in all three dimensions in native MATLAB and PDF formats. The following is provided: (a) MATLAB source code for image processing, (b) the detailed processing procedures, (c) description of the code and all sub-routines, (d) example data sets of initial and processed data. The toolbox can be downloaded at: http://www.vuiis.vanderbilt.edu/~truongm/COMA3D/. PMID:25261742

  20. 3D Printable Graphene Composite.

    PubMed

    Wei, Xiaojun; Li, Dong; Jiang, Wei; Gu, Zheming; Wang, Xiaojuan; Zhang, Zengxing; Sun, Zhengzong

    2015-07-08

    In human being's history, both the Iron Age and Silicon Age thrived after a matured massive processing technology was developed. Graphene is the most recent superior material which could potentially initialize another new material Age. However, while being exploited to its full extent, conventional processing methods fail to provide a link to today's personalization tide. New technology should be ushered in. Three-dimensional (3D) printing fills the missing linkage between graphene materials and the digital mainstream. Their alliance could generate additional stream to push the graphene revolution into a new phase. Here we demonstrate for the first time, a graphene composite, with a graphene loading up to 5.6 wt%, can be 3D printable into computer-designed models. The composite's linear thermal coefficient is below 75 ppm·°C(-1) from room temperature to its glass transition temperature (Tg), which is crucial to build minute thermal stress during the printing process.

  1. 3D Printed Robotic Hand

    NASA Technical Reports Server (NTRS)

    Pizarro, Yaritzmar Rosario; Schuler, Jason M.; Lippitt, Thomas C.

    2013-01-01

    Dexterous robotic hands are changing the way robots and humans interact and use common tools. Unfortunately, the complexity of the joints and actuations drive up the manufacturing cost. Some cutting edge and commercially available rapid prototyping machines now have the ability to print multiple materials and even combine these materials in the same job. A 3D model of a robotic hand was designed using Creo Parametric 2.0. Combining "hard" and "soft" materials, the model was printed on the Object Connex350 3D printer with the purpose of resembling as much as possible the human appearance and mobility of a real hand while needing no assembly. After printing the prototype, strings where installed as actuators to test mobility. Based on printing materials, the manufacturing cost of the hand was $167, significantly lower than other robotic hands without the actuators since they have more complex assembly processes.

  2. Pharmacophore modeling of nilotinib as an inhibitor of ATP-binding cassette drug transporters and BCR-ABL kinase using a three-dimensional quantitative structure-activity relationship approach.

    PubMed

    Shukla, Suneet; Kouanda, Abdul; Silverton, Latoya; Talele, Tanaji T; Ambudkar, Suresh V

    2014-07-01

    Nilotinib (Tasigna) is a tyrosine kinase inhibitor approved by the FDA to treat chronic phase chronic myeloid leukemia patients. It is also a transport substrate of the ATP-binding cassette (ABC) drug efflux transporters ABCB1 (P-glycoprotein, P-gp) and ABCG2 (BCRP), which may have an effect on the pharmacokinetics and toxicity of this drug. The goal of this study was to identify pharmacophoric features of nilotinib in order to potentially develop specific inhibitors of BCR-ABL kinase with minimal interactions with ABC drug transporters. Three-dimensional pharmacophore modeling and quantitative structure-activity relationship (QSAR) studies were carried out on a series of nilotinib analogues to identify chemical features that contribute to inhibitory activity of nilotinib against BCR-ABL kinase activity, P-gp, and ABCG2. Twenty-five derivatives of nilotinib were synthesized and were then tested to measure their activity to inhibit BCR-ABL kinase and to inhibit the function of ABC drug transporters. A set of in vitro experiments including kinase activity and cell-based transport assays and photolabeling of P-gp and ABCG2 with a transport substrate, [(125)I]-iodoarylazido-prazosin (IAAP), were carried out in isolated membranes to evaluate the potency of the derivatives to inhibit the function of ABC drug transporters and BCR-ABL kinase. Sixteen, fourteen, and ten compounds were selected as QSAR data sets, respectively, to generate PHASE v3.1 pharmacophore models for BCR-ABL kinase, ABCG2, and P-gp inhibitors. The IC50 values of these derivatives against P-gp, ABCG2, or BCR-ABL kinase were used to generate pharmacophore features required for optimal interactions with these targets. A seven-point pharmacophore (AADDRRR) for BCR-ABL kinase inhibitory activity, a six-point pharmacophore (ADHRRR) for ABCG2 inhibitory activity, and a seven-point pharmacophore (AADDRRR) for P-gp inhibitory activity were generated. The derived models clearly demonstrate high predictive power

  3. DYNA3D. Explicit 3-d Hydrodynamic FEM Program

    SciTech Connect

    Whirley, R.G.; Englemann, B.E. )

    1993-11-30

    DYNA3D is an explicit, three-dimensional, finite element program for analyzing the large deformation dynamic response of inelastic solids and structures. DYNA3D contains 30 material models and 10 equations of state (EOS) to cover a wide range of material behavior. The material models implemented are: elastic, orthotropic elastic, kinematic/isotropic plasticity, thermoelastoplastic, soil and crushable foam, linear viscoelastic, Blatz-Ko rubber, high explosive burn, hydrodynamic without deviatoric stresses, elastoplastic hydrodynamic, temperature-dependent elastoplastic, isotropic elastoplastic, isotropic elastoplastic with failure, soil and crushable foam with failure, Johnson/Cook plasticity model, pseudo TENSOR geological model, elastoplastic with fracture, power law isotropic plasticity, strain rate dependent plasticity, rigid, thermal orthotropic, composite damage model, thermal orthotropic with 12 curves, piecewise linear isotropic plasticity, inviscid two invariant geologic cap, orthotropic crushable model, Moonsy-Rivlin rubber, resultant plasticity, closed form update shell plasticity, and Frazer-Nash rubber model. The hydrodynamic material models determine only the deviatoric stresses. Pressure is determined by one of 10 equations of state including linear polynomial, JWL high explosive, Sack Tuesday high explosive, Gruneisen, ratio of polynomials, linear polynomial with energy deposition, ignition and growth of reaction in HE, tabulated compaction, tabulated, and TENSOR pore collapse. DYNA3D generates three binary output databases. One contains information for complete states at infrequent intervals; 50 to 100 states is typical. The second contains information for a subset of nodes and elements at frequent intervals; 1,000 to 10,000 states is typical. The last contains interface data for contact surfaces.

  4. GPU-Accelerated Denoising in 3D (GD3D)

    2013-10-01

    The raw computational power GPU Accelerators enables fast denoising of 3D MR images using bilateral filtering, anisotropic diffusion, and non-local means. This software addresses two facets of this promising application: what tuning is necessary to achieve optimal performance on a modern GPU? And what parameters yield the best denoising results in practice? To answer the first question, the software performs an autotuning step to empirically determine optimal memory blocking on the GPU. To answer themore » second, it performs a sweep of algorithm parameters to determine the combination that best reduces the mean squared error relative to a noiseless reference image.« less

  5. Magmatic Systems in 3-D

    NASA Astrophysics Data System (ADS)

    Kent, G. M.; Harding, A. J.; Babcock, J. M.; Orcutt, J. A.; Bazin, S.; Singh, S.; Detrick, R. S.; Canales, J. P.; Carbotte, S. M.; Diebold, J.

    2002-12-01

    Multichannel seismic (MCS) images of crustal magma chambers are ideal targets for advanced visualization techniques. In the mid-ocean ridge environment, reflections originating at the melt-lens are well separated from other reflection boundaries, such as the seafloor, layer 2A and Moho, which enables the effective use of transparency filters. 3-D visualization of seismic reflectivity falls into two broad categories: volume and surface rendering. Volumetric-based visualization is an extremely powerful approach for the rapid exploration of very dense 3-D datasets. These 3-D datasets are divided into volume elements or voxels, which are individually color coded depending on the assigned datum value; the user can define an opacity filter to reject plotting certain voxels. This transparency allows the user to peer into the data volume, enabling an easy identification of patterns or relationships that might have geologic merit. Multiple image volumes can be co-registered to look at correlations between two different data types (e.g., amplitude variation with offsets studies), in a manner analogous to draping attributes onto a surface. In contrast, surface visualization of seismic reflectivity usually involves producing "fence" diagrams of 2-D seismic profiles that are complemented with seafloor topography, along with point class data, draped lines and vectors (e.g. fault scarps, earthquake locations and plate-motions). The overlying seafloor can be made partially transparent or see-through, enabling 3-D correlations between seafloor structure and seismic reflectivity. Exploration of 3-D datasets requires additional thought when constructing and manipulating these complex objects. As numbers of visual objects grow in a particular scene, there is a tendency to mask overlapping objects; this clutter can be managed through the effective use of total or partial transparency (i.e., alpha-channel). In this way, the co-variation between different datasets can be investigated

  6. SOAX: A software for quantification of 3D biopolymer networks

    PubMed Central

    Xu, Ting; Vavylonis, Dimitrios; Tsai, Feng-Ching; Koenderink, Gijsje H.; Nie, Wei; Yusuf, Eddy; I-Ju Lee; Wu, Jian-Qiu; Huang, Xiaolei

    2015-01-01

    Filamentous biopolymer networks in cells and tissues are routinely imaged by confocal microscopy. Image analysis methods enable quantitative study of the properties of these curvilinear networks. However, software tools to quantify the geometry and topology of these often dense 3D networks and to localize network junctions are scarce. To fill this gap, we developed a new software tool called “SOAX”, which can accurately extract the centerlines of 3D biopolymer networks and identify network junctions using Stretching Open Active Contours (SOACs). It provides an open-source, user-friendly platform for network centerline extraction, 2D/3D visualization, manual editing and quantitative analysis. We propose a method to quantify the performance of SOAX, which helps determine the optimal extraction parameter values. We quantify several different types of biopolymer networks to demonstrate SOAX's potential to help answer key questions in cell biology and biophysics from a quantitative viewpoint. PMID:25765313

  7. Systems biology in 3D space--enter the morphome.

    PubMed

    Lucocq, John M; Mayhew, Terry M; Schwab, Yannick; Steyer, Anna M; Hacker, Christian

    2015-02-01

    Systems-based understanding of living organisms depends on acquiring huge datasets from arrays of genes, transcripts, proteins, and lipids. These data, referred to as 'omes', are assembled using 'omics' methodologies. Currently a comprehensive, quantitative view of cellular and organellar systems in 3D space at nanoscale/molecular resolution is missing. We introduce here the term 'morphome' for the distribution of living matter within a 3D biological system, and 'morphomics' for methods of collecting 3D data systematically and quantitatively. A sampling-based approach termed stereology currently provides rapid, precise, and minimally biased morphomics. We propose that stereology solves the 'big data' problem posed by emerging wide-scale electron microscopy (EM) and can establish quantitative links between the newer nanoimaging platforms such as electron tomography, cryo-EM, and correlative microscopy.

  8. SOAX: a software for quantification of 3D biopolymer networks.

    PubMed

    Xu, Ting; Vavylonis, Dimitrios; Tsai, Feng-Ching; Koenderink, Gijsje H; Nie, Wei; Yusuf, Eddy; I-Ju Lee; Wu, Jian-Qiu; Huang, Xiaolei

    2015-03-13

    Filamentous biopolymer networks in cells and tissues are routinely imaged by confocal microscopy. Image analysis methods enable quantitative study of the properties of these curvilinear networks. However, software tools to quantify the geometry and topology of these often dense 3D networks and to localize network junctions are scarce. To fill this gap, we developed a new software tool called "SOAX", which can accurately extract the centerlines of 3D biopolymer networks and identify network junctions using Stretching Open Active Contours (SOACs). It provides an open-source, user-friendly platform for network centerline extraction, 2D/3D visualization, manual editing and quantitative analysis. We propose a method to quantify the performance of SOAX, which helps determine the optimal extraction parameter values. We quantify several different types of biopolymer networks to demonstrate SOAX's potential to help answer key questions in cell biology and biophysics from a quantitative viewpoint.

  9. Interactive 3D Mars Visualization

    NASA Technical Reports Server (NTRS)

    Powell, Mark W.

    2012-01-01

    The Interactive 3D Mars Visualization system provides high-performance, immersive visualization of satellite and surface vehicle imagery of Mars. The software can be used in mission operations to provide the most accurate position information for the Mars rovers to date. When integrated into the mission data pipeline, this system allows mission planners to view the location of the rover on Mars to 0.01-meter accuracy with respect to satellite imagery, with dynamic updates to incorporate the latest position information. Given this information so early in the planning process, rover drivers are able to plan more accurate drive activities for the rover than ever before, increasing the execution of science activities significantly. Scientifically, this 3D mapping information puts all of the science analyses to date into geologic context on a daily basis instead of weeks or months, as was the norm prior to this contribution. This allows the science planners to judge the efficacy of their previously executed science observations much more efficiently, and achieve greater science return as a result. The Interactive 3D Mars surface view is a Mars terrain browsing software interface that encompasses the entire region of exploration for a Mars surface exploration mission. The view is interactive, allowing the user to pan in any direction by clicking and dragging, or to zoom in or out by scrolling the mouse or touchpad. This set currently includes tools for selecting a point of interest, and a ruler tool for displaying the distance between and positions of two points of interest. The mapping information can be harvested and shared through ubiquitous online mapping tools like Google Mars, NASA WorldWind, and Worldwide Telescope.

  10. What Lies Ahead (3-D)

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This 3-D cylindrical-perspective mosaic taken by the navigation camera on the Mars Exploration Rover Spirit on sol 82 shows the view south of the large crater dubbed 'Bonneville.' The rover will travel toward the Columbia Hills, seen here at the upper left. The rock dubbed 'Mazatzal' and the hole the rover drilled in to it can be seen at the lower left. The rover's position is referred to as 'Site 22, Position 32.' This image was geometrically corrected to make the horizon appear flat.

  11. 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.

  12. 3D Printed Shelby Cobra

    SciTech Connect

    Love, Lonnie

    2015-01-09

    ORNL's newly printed 3D Shelby Cobra was showcased at the 2015 NAIAS in Detroit. This "laboratory on wheels" uses the Shelby Cobra design, celebrating the 50th anniversary of this model and honoring the first vehicle to be voted a national monument. The Shelby was printed at the Department of Energy’s Manufacturing Demonstration Facility at ORNL using the BAAM (Big Area Additive Manufacturing) machine and is intended as a “plug-n-play” laboratory on wheels. The Shelby will allow research and development of integrated components to be tested and enhanced in real time, improving the use of sustainable, digital manufacturing solutions in the automotive industry.

  13. Computer-aided 3D display system and its application in 3D vision test

    NASA Astrophysics Data System (ADS)

    Shen, XiaoYun; Ma, Lan; Hou, Chunping; Wang, Jiening; Tang, Da; Li, Chang

    1998-08-01

    The computer aided 3D display system, flicker-free field sequential stereoscopic image display system, is newly developed. This system is composed of personal computer, liquid crystal glasses driving card, stereoscopic display software and liquid crystal glasses. It can display field sequential stereoscopic images at refresh rate of 70 Hz to 120 Hz. A typical application of this system, 3D vision test system, is mainly discussed in this paper. This stereoscopic vision test system can test stereoscopic acuity, cross disparity, uncross disparity and dynamic stereoscopic vision quantitatively. We have taken the use of random-dot- stereograms as stereoscopic vision test charts. Through practical test experiment between Anaglyph Stereoscopic Vision Test Charts and this stereoscopic vision test system, the statistical figures and test result is given out.

  14. THE PRACTICE OF STRUCTURE ACTIVITY RELATIONSHIPS (SAR) IN TOXICOLOGY

    EPA Science Inventory

    Both qualitative and quantitative modeling methods relating chemical structure to biological activity, called structure-activity relationship analyses or SAR, are applied to the prediction and characterization of chemical toxicity. This minireview will discuss some generic issue...

  15. Positional Awareness Map 3D (PAM3D)

    NASA Technical Reports Server (NTRS)

    Hoffman, Monica; Allen, Earl L.; Yount, John W.; Norcross, April Louise

    2012-01-01

    The Western Aeronautical Test Range of the National Aeronautics and Space Administration s Dryden Flight Research Center needed to address the aging software and hardware of its current situational awareness display application, the Global Real-Time Interactive Map (GRIM). GRIM was initially developed in the late 1980s and executes on older PC architectures using a Linux operating system that is no longer supported. Additionally, the software is difficult to maintain due to its complexity and loss of developer knowledge. It was decided that a replacement application must be developed or acquired in the near future. The replacement must provide the functionality of the original system, the ability to monitor test flight vehicles in real-time, and add improvements such as high resolution imagery and true 3-dimensional capability. This paper will discuss the process of determining the best approach to replace GRIM, and the functionality and capabilities of the first release of the Positional Awareness Map 3D.

  16. Computational vaccinology: quantitative approaches.

    PubMed

    Flower, Darren R; McSparron, Helen; Blythe, Martin J; Zygouri, Christianna; Taylor, Debra; Guan, Pingping; Wan, Shouzhan; Coveney, Peter V; Walshe, Valerie; Borrow, Persephone; Doytchinova, Irini A

    2003-01-01

    The immune system is hierarchical and has many levels, exhibiting much emergent behaviour. However, at its heart are molecular recognition events that are indistinguishable from other types of biomacromolecular interaction. These can be addressed well by quantitative experimental and theoretical biophysical techniques, and particularly by methods from drug design. We review here our approach to computational immunovaccinology. In particular, we describe the JenPep database and two new techniques for T cell epitope prediction. One is based on quantitative structure-activity relationships (a 3D-QSAR method based on CoMSIA and another 2D method based on the Free-Wilson approach) and the other on atomistic molecular dynamic simulations using high performance computing. JenPep (http://www.jenner.ar.uk/ JenPep) is a relational database system supporting quantitative data on peptide binding to major histocompatibility complexes, TAP transporters, TCR-pMHC complexes, and an annotated list of B cell and T cell epitopes. Our 2D-QSAR method factors the contribution to peptide binding from individual amino acids as well as 1-2 and 1-3 residue interactions. In the 3D-QSAR approach, the influence of five physicochemical properties (volume, electrostatic potential, hydrophobicity, hydrogen-bond donor and acceptor abilities) on peptide affinity were considered. Both methods are exemplified through their application to the well-studied problem of peptide binding to the human class I MHC molecule HLA-A*0201. PMID:14712934

  17. 3D acoustic atmospheric tomography

    NASA Astrophysics Data System (ADS)

    Rogers, Kevin; Finn, Anthony

    2014-10-01

    This paper presents a method for tomographically reconstructing spatially varying 3D atmospheric temperature profiles and wind velocity fields based. Measurements of the acoustic signature measured onboard a small Unmanned Aerial Vehicle (UAV) are compared to ground-based observations of the same signals. The frequency-shifted signal variations are then used to estimate the acoustic propagation delay between the UAV and the ground microphones, which are also affected by atmospheric temperature and wind speed vectors along each sound ray path. The wind and temperature profiles are modelled as the weighted sum of Radial Basis Functions (RBFs), which also allow local meteorological measurements made at the UAV and ground receivers to supplement any acoustic observations. Tomography is used to provide a full 3D reconstruction/visualisation of the observed atmosphere. The technique offers observational mobility under direct user control and the capacity to monitor hazardous atmospheric environments, otherwise not justifiable on the basis of cost or risk. This paper summarises the tomographic technique and reports on the results of simulations and initial field trials. The technique has practical applications for atmospheric research, sound propagation studies, boundary layer meteorology, air pollution measurements, analysis of wind shear, and wind farm surveys.

  18. Gravitation in 3D Spacetime

    NASA Astrophysics Data System (ADS)

    Laubenstein, John; Cockream, Kandi

    2009-05-01

    3D spacetime was developed by the IWPD Scale Metrics (SM) team using a coordinate system that translates n dimensions to n-1. 4-vectors are expressed in 3D along with a scaling factor representing time. Time is not orthogonal to the three spatial dimensions, but rather in alignment with an object's axis-of-motion. We have defined this effect as the object's ``orientation'' (X). The SM orientation (X) is equivalent to the orientation of the 4-velocity vector positioned tangent to its worldline, where X-1=θ+1 and θ is the angle of the 4-vector relative to the axis-of -motion. Both 4-vectors and SM appear to represent valid conceptualizations of the relationship between space and time. Why entertain SM? Scale Metrics gravity is quantized and may suggest a path for the full unification of gravitation with quantum theory. SM has been tested against current observation and is in agreement with the age of the universe, suggests a physical relationship between dark energy and dark matter, is in agreement with the accelerating expansion rate of the universe, contributes to the understanding of the fine-structure constant and provides a physical explanation of relativistic effects.

  19. 3D printed bionic ears.

    PubMed

    Mannoor, Manu S; Jiang, Ziwen; James, Teena; Kong, Yong Lin; Malatesta, Karen A; Soboyejo, Winston O; Verma, Naveen; Gracias, David H; McAlpine, Michael C

    2013-06-12

    The ability to three-dimensionally interweave biological tissue with functional electronics could enable the creation of bionic organs possessing enhanced functionalities over their human counterparts. Conventional electronic devices are inherently two-dimensional, preventing seamless multidimensional integration with synthetic biology, as the processes and materials are very different. Here, we present a novel strategy for overcoming these difficulties via additive manufacturing of biological cells with structural and nanoparticle derived electronic elements. As a proof of concept, we generated a bionic ear via 3D printing of a cell-seeded hydrogel matrix in the anatomic geometry of a human ear, along with an intertwined conducting polymer consisting of infused silver nanoparticles. This allowed for in vitro culturing of cartilage tissue around an inductive coil antenna in the ear, which subsequently enables readout of inductively-coupled signals from cochlea-shaped electrodes. The printed ear exhibits enhanced auditory sensing for radio frequency reception, and complementary left and right ears can listen to stereo audio music. Overall, our approach suggests a means to intricately merge biologic and nanoelectronic functionalities via 3D printing.

  20. 3D medical thermography device

    NASA Astrophysics Data System (ADS)

    Moghadam, Peyman

    2015-05-01

    In this paper, a novel handheld 3D medical thermography system is introduced. The proposed system consists of a thermal-infrared camera, a color camera and a depth camera rigidly attached in close proximity and mounted on an ergonomic handle. As a practitioner holding the device smoothly moves it around the human body parts, the proposed system generates and builds up a precise 3D thermogram model by incorporating information from each new measurement in real-time. The data is acquired in motion, thus it provides multiple points of view. When processed, these multiple points of view are adaptively combined by taking into account the reliability of each individual measurement which can vary due to a variety of factors such as angle of incidence, distance between the device and the subject and environmental sensor data or other factors influencing a confidence of the thermal-infrared data when captured. Finally, several case studies are presented to support the usability and performance of the proposed system.

  1. 3D printed bionic ears.

    PubMed

    Mannoor, Manu S; Jiang, Ziwen; James, Teena; Kong, Yong Lin; Malatesta, Karen A; Soboyejo, Winston O; Verma, Naveen; Gracias, David H; McAlpine, Michael C

    2013-06-12

    The ability to three-dimensionally interweave biological tissue with functional electronics could enable the creation of bionic organs possessing enhanced functionalities over their human counterparts. Conventional electronic devices are inherently two-dimensional, preventing seamless multidimensional integration with synthetic biology, as the processes and materials are very different. Here, we present a novel strategy for overcoming these difficulties via additive manufacturing of biological cells with structural and nanoparticle derived electronic elements. As a proof of concept, we generated a bionic ear via 3D printing of a cell-seeded hydrogel matrix in the anatomic geometry of a human ear, along with an intertwined conducting polymer consisting of infused silver nanoparticles. This allowed for in vitro culturing of cartilage tissue around an inductive coil antenna in the ear, which subsequently enables readout of inductively-coupled signals from cochlea-shaped electrodes. The printed ear exhibits enhanced auditory sensing for radio frequency reception, and complementary left and right ears can listen to stereo audio music. Overall, our approach suggests a means to intricately merge biologic and nanoelectronic functionalities via 3D printing. PMID:23635097

  2. 3D Printable Graphene Composite

    PubMed Central

    Wei, Xiaojun; Li, Dong; Jiang, Wei; Gu, Zheming; Wang, Xiaojuan; Zhang, Zengxing; Sun, Zhengzong

    2015-01-01

    In human being’s history, both the Iron Age and Silicon Age thrived after a matured massive processing technology was developed. Graphene is the most recent superior material which could potentially initialize another new material Age. However, while being exploited to its full extent, conventional processing methods fail to provide a link to today’s personalization tide. New technology should be ushered in. Three-dimensional (3D) printing fills the missing linkage between graphene materials and the digital mainstream. Their alliance could generate additional stream to push the graphene revolution into a new phase. Here we demonstrate for the first time, a graphene composite, with a graphene loading up to 5.6 wt%, can be 3D printable into computer-designed models. The composite’s linear thermal coefficient is below 75 ppm·°C−1 from room temperature to its glass transition temperature (Tg), which is crucial to build minute thermal stress during the printing process. PMID:26153673

  3. 3D Printable Graphene Composite

    NASA Astrophysics Data System (ADS)

    Wei, Xiaojun; Li, Dong; Jiang, Wei; Gu, Zheming; Wang, Xiaojuan; Zhang, Zengxing; Sun, Zhengzong

    2015-07-01

    In human being’s history, both the Iron Age and Silicon Age thrived after a matured massive processing technology was developed. Graphene is the most recent superior material which could potentially initialize another new material Age. However, while being exploited to its full extent, conventional processing methods fail to provide a link to today’s personalization tide. New technology should be ushered in. Three-dimensional (3D) printing fills the missing linkage between graphene materials and the digital mainstream. Their alliance could generate additional stream to push the graphene revolution into a new phase. Here we demonstrate for the first time, a graphene composite, with a graphene loading up to 5.6 wt%, can be 3D printable into computer-designed models. The composite’s linear thermal coefficient is below 75 ppm·°C-1 from room temperature to its glass transition temperature (Tg), which is crucial to build minute thermal stress during the printing process.

  4. Quantitative 3D analysis of huge nanoparticle assemblies† †Electronic supplementary information (ESI) available.CCDC 1417516–1417520 contain the supplementary crystallographic data for this paper. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5nr06962a Click here for additional data file.

    PubMed Central

    Zanaga, Daniele; Bleichrodt, Folkert; Altantzis, Thomas; Winckelmans, Naomi; Palenstijn, Willem Jan; Sijbers, Jan; de Nijs, Bart; van Huis, Marijn A.; Sánchez-Iglesias, Ana; Liz-Marzán, Luis M.; van Blaaderen, Alfons; Joost Batenburg, K.; Van Tendeloo, Gustaaf

    2016-01-01

    Nanoparticle assemblies can be investigated in 3 dimensions using electron tomography. However, it is not straightforward to obtain quantitative information such as the number of particles or their relative position. This becomes particularly difficult when the number of particles increases. We propose a novel approach in which prior information on the shape of the individual particles is exploited. It improves the quality of the reconstruction of these complex assemblies significantly. Moreover, this quantitative Sparse Sphere Reconstruction approach yields directly the number of particles and their position as an output of the reconstruction technique, enabling a detailed 3D analysis of assemblies with as many as 10 000 particles. The approach can also be used to reconstruct objects based on a very limited number of projections, which opens up possibilities to investigate beam sensitive assemblies where previous reconstructions with the available electron tomography techniques failed. PMID:26607629

  5. LOTT RANCH 3D PROJECT

    SciTech Connect

    Larry Lawrence; Bruce Miller

    2004-09-01

    The Lott Ranch 3D seismic prospect located in Garza County, Texas is a project initiated in September of 1991 by the J.M. Huber Corp., a petroleum exploration and production company. By today's standards the 126 square mile project does not seem monumental, however at the time it was conceived it was the most intensive land 3D project ever attempted. Acquisition began in September of 1991 utilizing GEO-SEISMIC, INC., a seismic data contractor. The field parameters were selected by J.M. Huber, and were of a radical design. The recording instruments used were GeoCor IV amplifiers designed by Geosystems Inc., which record the data in signed bit format. It would not have been practical, if not impossible, to have processed the entire raw volume with the tools available at that time. The end result was a dataset that was thought to have little utility due to difficulties in processing the field data. In 1997, Yates Energy Corp. located in Roswell, New Mexico, formed a partnership to further develop the project. Through discussions and meetings with Pinnacle Seismic, it was determined that the original Lott Ranch 3D volume could be vastly improved upon reprocessing. Pinnacle Seismic had shown the viability of improving field-summed signed bit data on smaller 2D and 3D projects. Yates contracted Pinnacle Seismic Ltd. to perform the reprocessing. This project was initiated with high resolution being a priority. Much of the potential resolution was lost through the initial summing of the field data. Modern computers that are now being utilized have tremendous speed and storage capacities that were cost prohibitive when this data was initially processed. Software updates and capabilities offer a variety of quality control and statics resolution, which are pertinent to the Lott Ranch project. The reprocessing effort was very successful. The resulting processed data-set was then interpreted using modern PC-based interpretation and mapping software. Production data, log data

  6. Surface reconstruction for 3D remote sensing

    NASA Astrophysics Data System (ADS)

    Baran, Matthew S.; Tutwiler, Richard L.; Natale, Donald J.

    2012-05-01

    This paper examines the performance of the local level set method on the surface reconstruction problem for unorganized point clouds in three dimensions. Many laser-ranging, stereo, and structured light devices produce three dimensional information in the form of unorganized point clouds. The point clouds are sampled from surfaces embedded in R3 from the viewpoint of a camera focal plane or laser receiver. The reconstruction of these objects in the form of a triangulated geometric surface is an important step in computer vision and image processing. The local level set method uses a Hamilton-Jacobi partial differential equation to describe the motion of an implicit surface in threespace. An initial surface which encloses the data is allowed to move until it becomes a smooth fit of the unorganized point data. A 3D point cloud test suite was assembled from publicly available laser-scanned object databases. The test suite exhibits nonuniform sampling rates and various noise characteristics to challenge the surface reconstruction algorithm. Quantitative metrics are introduced to capture the accuracy and efficiency of surface reconstruction on the degraded data. The results characterize the robustness of the level set method for surface reconstruction as applied to 3D remote sensing.

  7. High resolution 3D nonlinear integrated inversion

    NASA Astrophysics Data System (ADS)

    Li, Yong; Wang, Xuben; Li, Zhirong; Li, Qiong; Li, Zhengwen

    2009-06-01

    The high resolution 3D nonlinear integrated inversion method is based on nonlinear theory. Under layer control, the log data from several wells (or all wells) in the study area and seismic trace data adjacent to the wells are input to a network with multiple inputs and outputs and are integratedly trained to obtain an adaptive weight function of the entire study area. Integrated nonlinear mapping relationships are built and updated by the lateral and vertical geologic variations of the reservoirs. Therefore, the inversion process and its inversion results can be constrained and controlled and a stable seismic inversion section with high resolution with velocity inversion, impedance inversion, and density inversion sections, can be gained. Good geologic effects have been obtained in model computation tests and real data processing, which verified that this method has high precision, good practicality, and can be used for quantitative reservoir analysis.

  8. 3D Printing of Graphene Aerogels.

    PubMed

    Zhang, Qiangqiang; Zhang, Feng; Medarametla, Sai Pradeep; Li, Hui; Zhou, Chi; Lin, Dong

    2016-04-01

    3D printing of a graphene aerogel with true 3D overhang structures is highlighted. The aerogel is fabricated by combining drop-on-demand 3D printing and freeze casting. The water-based GO ink is ejected and freeze-cast into designed 3D structures. The lightweight (<10 mg cm(-3) ) 3D printed graphene aerogel presents superelastic and high electrical conduction.

  9. 3D Printing of Graphene Aerogels.

    PubMed

    Zhang, Qiangqiang; Zhang, Feng; Medarametla, Sai Pradeep; Li, Hui; Zhou, Chi; Lin, Dong

    2016-04-01

    3D printing of a graphene aerogel with true 3D overhang structures is highlighted. The aerogel is fabricated by combining drop-on-demand 3D printing and freeze casting. The water-based GO ink is ejected and freeze-cast into designed 3D structures. The lightweight (<10 mg cm(-3) ) 3D printed graphene aerogel presents superelastic and high electrical conduction. PMID:26861680

  10. Representation of chemical information in OASIS centralized 3D database for existing chemicals.

    PubMed

    Nikolov, Nikolai; Grancharov, Vanio; Stoyanova, Galya; Pavlov, Todor; Mekenyan, Ovanes

    2006-01-01

    data items. Database statistics are maintained on the number and quality of structures, conformers, and descriptors. Reports can be generated presenting any chosen subset of structures and descriptors into different formats suitable for inclusion into documents. In addition to fixed report formats, there is a powerful report template designer module with a visual report template editor to produce a customized page layout. The database is compatible at the import/export level with SDF, MOL, SMILES, and other known formats. The precalculated centralized 3D database could be useful for quantitative structure-activity relationship developers avoiding the time-consuming and cumbersome 3D calculation phase of model development.

  11. Representation of chemical information in OASIS centralized 3D database for existing chemicals.

    PubMed

    Nikolov, Nikolai; Grancharov, Vanio; Stoyanova, Galya; Pavlov, Todor; Mekenyan, Ovanes

    2006-01-01

    data items. Database statistics are maintained on the number and quality of structures, conformers, and descriptors. Reports can be generated presenting any chosen subset of structures and descriptors into different formats suitable for inclusion into documents. In addition to fixed report formats, there is a powerful report template designer module with a visual report template editor to produce a customized page layout. The database is compatible at the import/export level with SDF, MOL, SMILES, and other known formats. The precalculated centralized 3D database could be useful for quantitative structure-activity relationship developers avoiding the time-consuming and cumbersome 3D calculation phase of model development. PMID:17125194

  12. ShowMe3D

    SciTech Connect

    Sinclair, Michael B

    2012-01-05

    ShowMe3D is a data visualization graphical user interface specifically designed for use with hyperspectral image obtained from the Hyperspectral Confocal Microscope. The program allows the user to select and display any single image from a three dimensional hyperspectral image stack. By moving a slider control, the user can easily move between images of the stack. The user can zoom into any region of the image. The user can select any pixel or region from the displayed image and display the fluorescence spectrum associated with that pixel or region. The user can define up to 3 spectral filters to apply to the hyperspectral image and view the image as it would appear from a filter-based confocal microscope. The user can also obtain statistics such as intensity average and variance from selected regions.

  13. 3D Elastic Wavefield Tomography

    NASA Astrophysics Data System (ADS)

    Guasch, L.; Warner, M.; Stekl, I.; Umpleby, A.; Shah, N.

    2010-12-01

    Wavefield tomography, or waveform inversion, aims to extract the maximum information from seismic data by matching trace by trace the response of the solid earth to seismic waves using numerical modelling tools. Its first formulation dates from the early 80's, when Albert Tarantola developed a solid theoretical basis that is still used today with little change. Due to computational limitations, the application of the method to 3D problems has been unaffordable until a few years ago, and then only under the acoustic approximation. Although acoustic wavefield tomography is widely used, a complete solution of the seismic inversion problem requires that we account properly for the physics of wave propagation, and so must include elastic effects. We have developed a 3D tomographic wavefield inversion code that incorporates the full elastic wave equation. The bottle neck of the different implementations is the forward modelling algorithm that generates the synthetic data to be compared with the field seismograms as well as the backpropagation of the residuals needed to form the direction update of the model parameters. Furthermore, one or two extra modelling runs are needed in order to calculate the step-length. Our approach uses a FD scheme explicit time-stepping by finite differences that are 4th order in space and 2nd order in time, which is a 3D version of the one developed by Jean Virieux in 1986. We chose the time domain because an explicit time scheme is much less demanding in terms of memory than its frequency domain analogue, although the discussion of wich domain is more efficient still remains open. We calculate the parameter gradients for Vp and Vs by correlating the normal and shear stress wavefields respectively. A straightforward application would lead to the storage of the wavefield at all grid points at each time-step. We tackled this problem using two different approaches. The first one makes better use of resources for small models of dimension equal

  14. Conducting Polymer 3D Microelectrodes

    PubMed Central

    Sasso, Luigi; Vazquez, Patricia; Vedarethinam, Indumathi; Castillo-León, Jaime; Emnéus, Jenny; Svendsen, Winnie E.

    2010-01-01

    Conducting polymer 3D microelectrodes have been fabricated for possible future neurological applications. A combination of micro-fabrication techniques and chemical polymerization methods has been used to create pillar electrodes in polyaniline and polypyrrole. The thin polymer films obtained showed uniformity and good adhesion to both horizontal and vertical surfaces. Electrodes in combination with metal/conducting polymer materials have been characterized by cyclic voltammetry and the presence of the conducting polymer film has shown to increase the electrochemical activity when compared with electrodes coated with only metal. An electrochemical characterization of gold/polypyrrole electrodes showed exceptional electrochemical behavior and activity. PC12 cells were finally cultured on the investigated materials as a preliminary biocompatibility assessment. These results show that the described electrodes are possibly suitable for future in-vitro neurological measurements. PMID:22163508

  15. ShowMe3D

    2012-01-05

    ShowMe3D is a data visualization graphical user interface specifically designed for use with hyperspectral image obtained from the Hyperspectral Confocal Microscope. The program allows the user to select and display any single image from a three dimensional hyperspectral image stack. By moving a slider control, the user can easily move between images of the stack. The user can zoom into any region of the image. The user can select any pixel or region from themore » displayed image and display the fluorescence spectrum associated with that pixel or region. The user can define up to 3 spectral filters to apply to the hyperspectral image and view the image as it would appear from a filter-based confocal microscope. The user can also obtain statistics such as intensity average and variance from selected regions.« less

  16. Physical sensor difference-based method and virtual sensor difference-based method for visual and quantitative estimation of lower limb 3D gait posture using accelerometers and magnetometers.

    PubMed

    Liu, Kun; Inoue, Yoshio; Shibata, Kyoko

    2012-01-01

    An approach using a physical sensor difference-based algorithm and a virtual sensor difference-based algorithm to visually and quantitatively confirm lower limb posture was proposed. Three accelerometers and two MAG(3)s (inertial sensor module) were used to measure the accelerations and magnetic field data for the calculation of flexion/extension (FE) and abduction/adduction (AA) angles of hip joint and FE, AA and internal/external rotation (IE) angles of knee joint; then, the trajectories of knee and ankle joints were obtained with the joint angles and segment lengths. There was no integration of acceleration or angular velocity for the joint rotations and positions, which is an improvement on the previous method in recent literature. Compared with the camera motion capture system, the correlation coefficients in five trials were above 0.91 and 0.92 for the hip FE and AA, respectively, and higher than 0.94, 0.93 and 0.93 for the knee joint FE, AA and IE, respectively.

  17. Supernova Remnant in 3-D

    NASA Technical Reports Server (NTRS)

    2009-01-01

    wavelengths. Since the amount of the wavelength shift is related to the speed of motion, one can determine how fast the debris are moving in either direction. Because Cas A is the result of an explosion, the stellar debris is expanding radially outwards from the explosion center. Using simple geometry, the scientists were able to construct a 3-D model using all of this information. A program called 3-D Slicer modified for astronomical use by the Astronomical Medicine Project at Harvard University in Cambridge, Mass. was used to display and manipulate the 3-D model. Commercial software was then used to create the 3-D fly-through.

    The blue filaments defining the blast wave were not mapped using the Doppler effect because they emit a different kind of light synchrotron radiation that does not emit light at discrete wavelengths, but rather in a broad continuum. The blue filaments are only a representation of the actual filaments observed at the blast wave.

    This visualization shows that there are two main components to this supernova remnant: a spherical component in the outer parts of the remnant and a flattened (disk-like) component in the inner region. The spherical component consists of the outer layer of the star that exploded, probably made of helium and carbon. These layers drove a spherical blast wave into the diffuse gas surrounding the star. The flattened component that astronomers were unable to map into 3-D prior to these Spitzer observations consists of the inner layers of the star. It is made from various heavier elements, not all shown in the visualization, such as oxygen, neon, silicon, sulphur, argon and iron.

    High-velocity plumes, or jets, of this material are shooting out from the explosion in the plane of the disk-like component mentioned above. Plumes of silicon appear in the northeast and southwest, while those of iron are seen in the southeast and north. These jets were already known and Doppler velocity measurements have been made for these

  18. Optimized Bayes variational regularization prior for 3D PET images.

    PubMed

    Rapisarda, Eugenio; Presotto, Luca; De Bernardi, Elisabetta; Gilardi, Maria Carla; Bettinardi, Valentino

    2014-09-01

    A new prior for variational Maximum a Posteriori regularization is proposed to be used in a 3D One-Step-Late (OSL) reconstruction algorithm accounting also for the Point Spread Function (PSF) of the PET system. The new regularization prior strongly smoothes background regions, while preserving transitions. A detectability index is proposed to optimize the prior. The new algorithm has been compared with different reconstruction algorithms such as 3D-OSEM+PSF, 3D-OSEM+PSF+post-filtering and 3D-OSL with a Gauss-Total Variation (GTV) prior. The proposed regularization allows controlling noise, while maintaining good signal recovery; compared to the other algorithms it demonstrates a very good compromise between an improved quantitation and good image quality. PMID:24958594

  19. 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.

  20. 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

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

    PubMed

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

    2012-02-01

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

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

    PubMed

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

    2015-06-11

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

  3. 3D Printing and Digital Rock Physics for Geomaterials

    NASA Astrophysics Data System (ADS)

    Martinez, M. J.; Yoon, H.; Dewers, T. A.

    2015-12-01

    Imaging techniques for the analysis of porous structures have revolutionized our ability to quantitatively characterize geomaterials. Digital representations of rock from CT images and physics modeling based on these pore structures provide the opportunity to further advance our quantitative understanding of fluid flow, geomechanics, and geochemistry, and the emergence of coupled behaviors. Additive manufacturing, commonly known as 3D printing, has revolutionized production of custom parts with complex internal geometries. For the geosciences, recent advances in 3D printing technology may be co-opted to print reproducible porous structures derived from CT-imaging of actual rocks for experimental testing. The use of 3D printed microstructure allows us to surmount typical problems associated with sample-to-sample heterogeneity that plague rock physics testing and to test material response independent from pore-structure variability. Together, imaging, digital rocks and 3D printing potentially enables a new workflow for understanding coupled geophysical processes in a real, but well-defined setting circumventing typical issues associated with reproducibility, enabling full characterization and thus connection of physical phenomena to structure. In this talk we will discuss the possibilities that these technologies can bring to geosciences and present early experiences with coupled multiscale experimental and numerical analysis using 3D printed fractured rock specimens. In particular, we discuss the processes of selection and printing of transparent fractured specimens based on 3D reconstruction of micro-fractured rock to study fluid flow characterization and manipulation. Micro-particle image velocimetry is used to directly visualize 3D single and multiphase flow velocity in 3D fracture networks. 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

  4. Supernova Remnant in 3-D

    NASA Technical Reports Server (NTRS)

    2009-01-01

    wavelengths. Since the amount of the wavelength shift is related to the speed of motion, one can determine how fast the debris are moving in either direction. Because Cas A is the result of an explosion, the stellar debris is expanding radially outwards from the explosion center. Using simple geometry, the scientists were able to construct a 3-D model using all of this information. A program called 3-D Slicer modified for astronomical use by the Astronomical Medicine Project at Harvard University in Cambridge, Mass. was used to display and manipulate the 3-D model. Commercial software was then used to create the 3-D fly-through.

    The blue filaments defining the blast wave were not mapped using the Doppler effect because they emit a different kind of light synchrotron radiation that does not emit light at discrete wavelengths, but rather in a broad continuum. The blue filaments are only a representation of the actual filaments observed at the blast wave.

    This visualization shows that there are two main components to this supernova remnant: a spherical component in the outer parts of the remnant and a flattened (disk-like) component in the inner region. The spherical component consists of the outer layer of the star that exploded, probably made of helium and carbon. These layers drove a spherical blast wave into the diffuse gas surrounding the star. The flattened component that astronomers were unable to map into 3-D prior to these Spitzer observations consists of the inner layers of the star. It is made from various heavier elements, not all shown in the visualization, such as oxygen, neon, silicon, sulphur, argon and iron.

    High-velocity plumes, or jets, of this material are shooting out from the explosion in the plane of the disk-like component mentioned above. Plumes of silicon appear in the northeast and southwest, while those of iron are seen in the southeast and north. These jets were already known and Doppler velocity measurements have been made for these

  5. 3D multiplexed immunoplasmonics microscopy

    NASA Astrophysics Data System (ADS)

    Bergeron, Éric; Patskovsky, Sergiy; Rioux, David; Meunier, Michel

    2016-07-01

    Selective labelling, identification and spatial distribution of cell surface biomarkers can provide important clinical information, such as distinction between healthy and diseased cells, evolution of a disease and selection of the optimal patient-specific treatment. Immunofluorescence is the gold standard for efficient detection of biomarkers expressed by cells. However, antibodies (Abs) conjugated to fluorescent dyes remain limited by their photobleaching, high sensitivity to the environment, low light intensity, and wide absorption and emission spectra. Immunoplasmonics is a novel microscopy method based on the visualization of Abs-functionalized plasmonic nanoparticles (fNPs) targeting cell surface biomarkers. Tunable fNPs should provide higher multiplexing capacity than immunofluorescence since NPs are photostable over time, strongly scatter light at their plasmon peak wavelengths and can be easily functionalized. In this article, we experimentally demonstrate accurate multiplexed detection based on the immunoplasmonics approach. First, we achieve the selective labelling of three targeted cell surface biomarkers (cluster of differentiation 44 (CD44), epidermal growth factor receptor (EGFR) and voltage-gated K+ channel subunit KV1.1) on human cancer CD44+ EGFR+ KV1.1+ MDA-MB-231 cells and reference CD44- EGFR- KV1.1+ 661W cells. The labelling efficiency with three stable specific immunoplasmonics labels (functionalized silver nanospheres (CD44-AgNSs), gold (Au) NSs (EGFR-AuNSs) and Au nanorods (KV1.1-AuNRs)) detected by reflected light microscopy (RLM) is similar to the one with immunofluorescence. Second, we introduce an improved method for 3D localization and spectral identification of fNPs based on fast z-scanning by RLM with three spectral filters corresponding to the plasmon peak wavelengths of the immunoplasmonics labels in the cellular environment (500 nm for 80 nm AgNSs, 580 nm for 100 nm AuNSs and 700 nm for 40 nm × 92 nm AuNRs). Third, the developed

  6. Objective and subjective quality assessment of geometry compression of reconstructed 3D humans in a 3D virtual room

    NASA Astrophysics Data System (ADS)

    Mekuria, Rufael; Cesar, Pablo; Doumanis, Ioannis; Frisiello, Antonella

    2015-09-01

    Compression of 3D object based video is relevant for 3D Immersive applications. Nevertheless, the perceptual aspects of the degradation introduced by codecs for meshes and point clouds are not well understood. In this paper we evaluate the subjective and objective degradations introduced by such codecs in a state of art 3D immersive virtual room. In the 3D immersive virtual room, users are captured with multiple cameras, and their surfaces are reconstructed as photorealistic colored/textured 3D meshes or point clouds. To test the perceptual effect of compression and transmission, we render degraded versions with different frame rates in different contexts (near/far) in the scene. A quantitative subjective study with 16 users shows that negligible distortion of decoded surfaces compared to the original reconstructions can be achieved in the 3D virtual room. In addition, a qualitative task based analysis in a full prototype field trial shows increased presence, emotion, user and state recognition of the reconstructed 3D Human representation compared to animated computer avatars.

  7. 3D multiplexed immunoplasmonics microscopy.

    PubMed

    Bergeron, Éric; Patskovsky, Sergiy; Rioux, David; Meunier, Michel

    2016-07-21

    Selective labelling, identification and spatial distribution of cell surface biomarkers can provide important clinical information, such as distinction between healthy and diseased cells, evolution of a disease and selection of the optimal patient-specific treatment. Immunofluorescence is the gold standard for efficient detection of biomarkers expressed by cells. However, antibodies (Abs) conjugated to fluorescent dyes remain limited by their photobleaching, high sensitivity to the environment, low light intensity, and wide absorption and emission spectra. Immunoplasmonics is a novel microscopy method based on the visualization of Abs-functionalized plasmonic nanoparticles (fNPs) targeting cell surface biomarkers. Tunable fNPs should provide higher multiplexing capacity than immunofluorescence since NPs are photostable over time, strongly scatter light at their plasmon peak wavelengths and can be easily functionalized. In this article, we experimentally demonstrate accurate multiplexed detection based on the immunoplasmonics approach. First, we achieve the selective labelling of three targeted cell surface biomarkers (cluster of differentiation 44 (CD44), epidermal growth factor receptor (EGFR) and voltage-gated K(+) channel subunit KV1.1) on human cancer CD44(+) EGFR(+) KV1.1(+) MDA-MB-231 cells and reference CD44(-) EGFR(-) KV1.1(+) 661W cells. The labelling efficiency with three stable specific immunoplasmonics labels (functionalized silver nanospheres (CD44-AgNSs), gold (Au) NSs (EGFR-AuNSs) and Au nanorods (KV1.1-AuNRs)) detected by reflected light microscopy (RLM) is similar to the one with immunofluorescence. Second, we introduce an improved method for 3D localization and spectral identification of fNPs based on fast z-scanning by RLM with three spectral filters corresponding to the plasmon peak wavelengths of the immunoplasmonics labels in the cellular environment (500 nm for 80 nm AgNSs, 580 nm for 100 nm AuNSs and 700 nm for 40 nm × 92 nm AuNRs). Third

  8. NIF Ignition Target 3D Point Design

    SciTech Connect

    Jones, O; Marinak, M; Milovich, J; Callahan, D

    2008-11-05

    We have developed an input file for running 3D NIF hohlraums that is optimized such that it can be run in 1-2 days on parallel computers. We have incorporated increasing levels of automation into the 3D input file: (1) Configuration controlled input files; (2) Common file for 2D and 3D, different types of capsules (symcap, etc.); and (3) Can obtain target dimensions, laser pulse, and diagnostics settings automatically from NIF Campaign Management Tool. Using 3D Hydra calculations to investigate different problems: (1) Intrinsic 3D asymmetry; (2) Tolerance to nonideal 3D effects (e.g. laser power balance, pointing errors); and (3) Synthetic diagnostics.

  9. 3D Kitaev spin liquids

    NASA Astrophysics Data System (ADS)

    Hermanns, Maria

    The Kitaev honeycomb model has become one of the archetypal spin models exhibiting topological phases of matter, where the magnetic moments fractionalize into Majorana fermions interacting with a Z2 gauge field. In this talk, we discuss generalizations of this model to three-dimensional lattice structures. Our main focus is the metallic state that the emergent Majorana fermions form. In particular, we discuss the relation of the nature of this Majorana metal to the details of the underlying lattice structure. Besides (almost) conventional metals with a Majorana Fermi surface, one also finds various realizations of Dirac semi-metals, where the gapless modes form Fermi lines or even Weyl nodes. We introduce a general classification of these gapless quantum spin liquids using projective symmetry analysis. Furthermore, we briefly outline why these Majorana metals in 3D Kitaev systems provide an even richer variety of Dirac and Weyl phases than possible for electronic matter and comment on possible experimental signatures. Work done in collaboration with Kevin O'Brien and Simon Trebst.

  10. Locomotive wheel 3D reconstruction

    NASA Astrophysics Data System (ADS)

    Guan, Xin; Luo, Zhisheng; Gao, Xiaorong; Wu, Jianle

    2010-08-01

    In the article, a system, which is used to reconstruct locomotive wheels, is described, helping workers detect the condition of a wheel through a direct view. The system consists of a line laser, a 2D camera, and a computer. We use 2D camera to capture the line-laser light reflected by the object, a wheel, and then compute the final coordinates of the structured light. Finally, using Matlab programming language, we transform the coordinate of points to a smooth surface and illustrate the 3D view of the wheel. The article also proposes the system structure, processing steps and methods, and sets up an experimental platform to verify the design proposal. We verify the feasibility of the whole process, and analyze the results comparing to standard date. The test results show that this system can work well, and has a high accuracy on the reconstruction. And because there is still no such application working in railway industries, so that it has practical value in railway inspection system.

  11. 3D ultrafast laser scanner

    NASA Astrophysics Data System (ADS)

    Mahjoubfar, A.; Goda, K.; Wang, C.; Fard, A.; Adam, J.; Gossett, D. R.; Ayazi, A.; Sollier, E.; Malik, O.; Chen, E.; Liu, Y.; Brown, R.; Sarkhosh, N.; Di Carlo, D.; Jalali, B.

    2013-03-01

    Laser scanners are essential for scientific research, manufacturing, defense, and medical practice. Unfortunately, often times the speed of conventional laser scanners (e.g., galvanometric mirrors and acousto-optic deflectors) falls short for many applications, resulting in motion blur and failure to capture fast transient information. Here, we present a novel type of laser scanner that offers roughly three orders of magnitude higher scan rates than conventional methods. Our laser scanner, which we refer to as the hybrid dispersion laser scanner, performs inertia-free laser scanning by dispersing a train of broadband pulses both temporally and spatially. More specifically, each broadband pulse is temporally processed by time stretch dispersive Fourier transform and further dispersed into space by one or more diffractive elements such as prisms and gratings. As a proof-of-principle demonstration, we perform 1D line scans at a record high scan rate of 91 MHz and 2D raster scans and 3D volumetric scans at an unprecedented scan rate of 105 kHz. The method holds promise for a broad range of scientific, industrial, and biomedical applications. To show the utility of our metho