WorldWideScience

Sample records for qsar lumping analysis

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

    Science.gov (United States)

    Van Damme, Sofie; Bultinck, Patrick

    2007-08-01

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

  2. A Lumped Computational Model for Sodium Sulfur Battery Analysis

    Science.gov (United States)

    Wu, Fan

    Due to the cost of materials and time consuming testing procedures, development of new batteries is a slow and expensive practice. The purpose of this study is to develop a computational model and assess the capabilities of such a model designed to aid in the design process and control of sodium sulfur batteries. To this end, a transient lumped computational model derived from an integral analysis of the transport of species, energy and charge throughout the battery has been developed. The computation processes are coupled with the use of Faraday's law, and solutions for the species concentrations, electrical potential and current are produced in a time marching fashion. Properties required for solving the governing equations are calculated and updated as a function of time based on the composition of each control volume. The proposed model is validated against multi- dimensional simulations and experimental results from literatures, and simulation results using the proposed model is presented and analyzed. The computational model and electrochemical model used to solve the equations for the lumped model are compared with similar ones found in the literature. The results obtained from the current model compare favorably with those from experiments and other models.

  3. Devolatilization Characteristics and Kinetic Analysis of Lump Coal from China COREX3000 Under High Temperature

    Science.gov (United States)

    Xu, Runsheng; Zhang, Jianliang; Wang, Guangwei; Zuo, Haibin; Liu, Zhengjian; Jiao, Kexin; Liu, Yanxiang; Li, Kejiang

    2016-08-01

    A devolatilization study of two lump coals used in China COREX3000 was carried out in a self-developed thermo-gravimetry at four temperature conditions [1173 K, 1273 K, 1373 K, and 1473 K (900 °C, 1000 °C, 1100 °C, and 1200 °C)] under N2. This study reveals that the working temperature has a strong impact on the devolatilization rate of the lump coal: the reaction rate increases with the increasing temperature. However, the temperature has little influence on the maximum mass loss. The conversion rate curve shows that the reaction rate of HY lump coal is higher than KG lump coal. The lump coals were analyzed by XRD, FTIR, and optical microscopy to explore the correlation between devolatilization rate and properties of lump coal. The results show that the higher reaction rate of HY lump coal attributes to its more active maceral components, less aromaticity and orientation degree of the crystallite, and more oxygenated functional groups. The random nucleation and nuclei growth model (RNGM), volume model (VM), and unreacted shrinking core model (URCM) were employed to describe the reaction behavior of lump coal. It was concluded from kinetics analysis that RNGM model was the best model for describing the devolatilization of lump coals. The apparent activation energies of isothermal devolatilization of HY lump coal and KG lump coal are 42.35 and 45.83 kJ/mol, respectively. This study has implications for the characteristics and mechanism modeling of devolatilization of lump coal in COREX gasifier.

  4. Lumped impulses, discrete displacements and a moving load analysis

    NARCIS (Netherlands)

    Kok, A.W.M.

    1997-01-01

    Finite element models are usually presented as relations between lumped forces and discrete displacements. Mostly finite element models are found by the elaboration of the method of the virtual work - which is a special case of the Galerkin's variational principle -. By application of Galerkin's var

  5. Analysis and synthesis of distributed-lumped-active networks by digital computer

    Science.gov (United States)

    1973-01-01

    The use of digital computational techniques in the analysis and synthesis of DLA (distributed lumped active) networks is considered. This class of networks consists of three distinct types of elements, namely, distributed elements (modeled by partial differential equations), lumped elements (modeled by algebraic relations and ordinary differential equations), and active elements (modeled by algebraic relations). Such a characterization is applicable to a broad class of circuits, especially including those usually referred to as linear integrated circuits, since the fabrication techniques for such circuits readily produce elements which may be modeled as distributed, as well as the more conventional lumped and active ones.

  6. Recent Advances in Fragment-Based QSAR and Multi-Dimensional QSAR Methods

    Directory of Open Access Journals (Sweden)

    Kyaw Zeyar Myint

    2010-10-01

    Full Text Available This paper provides an overview of recently developed two dimensional (2D fragment-based QSAR methods as well as other multi-dimensional approaches. In particular, we present recent fragment-based QSAR methods such as fragment-similarity-based QSAR (FS-QSAR, fragment-based QSAR (FB-QSAR, Hologram QSAR (HQSAR, and top priority fragment QSAR in addition to 3D- and nD-QSAR methods such as comparative molecular field analysis (CoMFA, comparative molecular similarity analysis (CoMSIA, Topomer CoMFA, self-organizing molecular field analysis (SOMFA, comparative molecular moment analysis (COMMA, autocorrelation of molecular surfaces properties (AMSP, weighted holistic invariant molecular (WHIM descriptor-based QSAR (WHIM, grid-independent descriptors (GRIND-based QSAR, 4D-QSAR, 5D-QSAR and 6D-QSAR methods.

  7. FEM analysis of springback control with lump-punch penetration after V-bending

    Science.gov (United States)

    Aso, Takayuki; Iizuka, Takashi

    2016-08-01

    In actual manufacturing, some empirical methods such as the bottoming technique are generally used in order to adjust the bend angles of products. However, the problem with this is that it relies on the technique of the engineer. In this study, quantitative springback control by lump-punch penetration after V-bending is investigated with FEM analysis and experimentation. The lump at the punch tip is pushed into a bent section at the final stage of V-bending and stretches the inside surface at the bent section. The method of springback control is suggested based on the deformation state. Then, the suitability of springback control using this mechanism is investigated. It is confirmed that the springback amount is reduced by lump-punch penetration. Accordingly, it is recommended to control springback by sheet forging with a lump punch.

  8. Stability analysis of the extended ADI-FDTD technique including lumped models

    Institute of Scientific and Technical Information of China (English)

    CHEN ZhiHui; CHU QingXin

    2008-01-01

    The numerical stability of the extended alternating-direction-implicit-finite-difference-time-domain (ADI-FDTD) method including lumped models is analyzed.Three common lumped models are investigated:resistor,capacitor,and inductor,and three different formulations for each model are analyzed:the explicit,semi-implicit and implicit schemes.Analysis results show that the extended ADI-FDTD algorithm is not unconditionally stable in the explicit scheme case,and the stability criterion depends on the value of lumped models,but in the semi-implicit and implicit cases,the algorithm is stable.Finally,two simple microstrip circuits including lumped elements are simulated to demonstrate validity of the theoretical results.

  9. Analysis of transients in advanced heavy water reactor using lumped parameter models

    Energy Technology Data Exchange (ETDEWEB)

    Manmohan Pandey; Venkata Ramana Eaga; Sankar Sastry, P. [Department of Mechanical Engineering, Indian Institute of Technology Guwahati, Guwahati (India); Gupta, S.K.; Lele, H.G.; Chatterjee, B. [Reactor Safety Division, Bhabha Atomic Research Centre, Mumbai (India)

    2005-07-01

    Full text of publication follows: Analysis of transients occurring in nuclear power plants, arising from the complex interplay between core neutronics and thermal-hydraulics, is important for their operation and safety. Numerical simulations of such transients can be carried out extensively at very low computational cost by using lumped parameter mathematical models. The Advanced Heavy Water Reactor (AHWR), being developed in India, is a vertical pressure tube type reactor cooled by boiling light water under natural circulation, using thorium as fuel and heavy water as moderator. In the present work, nonlinear and linear lumped parameter dynamic models for AHWR have been developed and validated with a distributed parameter model. The nonlinear lumped model is based on point reactor kinetics equations and one-dimensional homogeneous equilibrium model of two-phase flow. The distributed model is built with RELAP5/MOD3.2 code. Various types of transients have been simulated numerically, using the lumped model as well as RELAP5. The results have been compared and parameters tuned to make the lumped model match the distributed model (RELAP5) in terms of steady state as well as dynamic behaviour. The linear model has been derived by linearizing the nonlinear model for small perturbations about the steady state. Numerical simulations of transients using the linear model have been compared with results obtained from the nonlinear model. Thus, the range of validity of the linear model has been determined. Stability characteristics of AHWR have been investigated using the lumped parameter models. (authors)

  10. Comparison of NASCAP modelling results with lumped circuit analysis

    Science.gov (United States)

    Stang, D. B.; Purvis, C. K.

    1980-01-01

    Engineering design tools that can be used to predict the development of absolute and differential potentials by realistic spacecraft under geomagnetic substorm conditions are described. Two types of analyses are in use: (1) the NASCAP code, which computes quasistatic charging of geometrically complex objects with multiple surface materials in three dimensions; (2) lumped element equivalent circuit models that are used for analyses of particular spacecraft. The equivalent circuit models require very little computation time, however, they cannot account for effects, such as the formation of potential barriers, that are inherently multidimensional. Steady state potentials of structure and insulation are compared with those resulting from the equivalent circuit model.

  11. A lumped mass finite element method for vibration analysis of elastic plate-plate structures

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The fully discrete lumped mass finite element method is proposed for vibration analysis of elastic plate-plate structures.In the space directions,the longitudinal displacements on plates are discretized by conforming linear elements,and the transverse displacements are discretized by the Morley element.By means of the second order central difference for discretizing the time derivative and the technique of lumped masses,a fully discrete lumped mass finite element method is obtained,and two approaches to choosing the initial functions are also introduced.The error analysis for the method in the energy norm is established,and some numerical examples are included to validate the theoretical analysis.

  12. Prediction of eye irritation from organic chemicals using membrane-interaction QSAR analysis.

    Science.gov (United States)

    Kulkarni, A; Hopfinger, A J; Osborne, R; Bruner, L H; Thompson, E D

    2001-02-01

    Eye irritation potency of a compound or mixture has traditionally been evaluated using the Draize rabbit-eye test (Draize et al., 1944). In order to aid predictions of eye irritation and to explore possible corresponding mechanisms of eye irritation, a methodology termed "membrane-interaction QSAR analysis" (MI-QSAR) has been developed (Kulkarni and Hopfinger 1999). A set of Draize eye-irritation data established by the European Center for Ecotoxicology and Toxicology of Chemicals (ECETOC) (Bagley et al., 1992) was used as a structurally diverse training set in an MI-QSAR analysis. Significant QSAR models were constructed based primarily upon aqueous solvation-free energy of the solute and the strength of solute binding to a model phospholipid (DMPC) monolayer. The results demonstrate that inclusion of parameters to model membrane interactions of potentially irritating chemicals provides significantly better predictions of eye irritation for structurally diverse compounds than does modeling based solely on physiochemical properties of chemicals. The specific MI-QSAR models reported here are, in fact, close to the upper limit in both significance and robustness that can be expected for the variability inherent to the eye-irritation scores of the ECETOC training set. The MI-QSAR models can be used with high reliability to classify compounds of low- and high-predicted eye irritation scores. Thus, the models offer the opportunity to reduce animal testing for compounds predicted to fall into these two extreme eye-irritation score sets. The MI-QSAR paradigm may also be applicable to other toxicological endpoints, such as skin irritation, where interactions with cellular membranes are likely.

  13. Armpit lump

    Science.gov (United States)

    An armpit lump in a woman may be a sign of breast cancer, and it should be checked by a health care provider right away. Call your provider if you have an unexplained armpit lump. Do not try to diagnose lumps by yourself.

  14. Predicting MDCK cell permeation coefficients of organic molecules using membrane-interaction QSAR analysis

    Institute of Scientific and Technical Information of China (English)

    Li-li CHEN; Jia YAO; Jian-bo YANG; Jie YANG

    2005-01-01

    Aim: To use membrane-interaction quantitative structure-activity relationship analysis (MI-QSAR) to develop predictive models of partitioning of organic compounds in gastrointestinal cells. Methods: A training set of 22 structurally diverse compounds, whose apparent permeability accross cellular membranes of MadinDarby canine kidney (MDCK) cells were measured, were used to construct MIQSAR models. Molecular dynamic simulations were used to determine the explicit interaction of each test compound (solute) with a dimyristoyl-phosphatidyl-choline monolayer membrane model. An additional set of intramolecular solute descriptors were computed and considered in the trial pool of descriptors for building MI-QSAR models. The QSAR models were optimized using multidimensional linear regression fitting and the stepwise method. A test set of 8 compounds were evaluated using the MI-QSAR models as part of a validation process. Results:MI-QSAR models of the gastrointestinal absorption process were constructed.The descriptors found in the best MI-QSAR models are as follows: 1) ClogP (the logarithm of the 1-octanol/water partition coefficient); 2) EHOMO (the highest occupied molecular orbital energy); 3) Es (stretch energy); 4) PMY (the principal moment of inertia Y, the inertia along the y axis in the rectangular coordinates; 5) Ct(total connectivity); and 6) Enb (the energy of interactions between all of the nonbonded atoms). The most important descriptor in the models is ClogP. Conclusion:Permeability is not only determined by the properties of drug molecules, but is also very much influenced by the molecule-membrane interaction process.

  15. QSAR analysis on Spodoptera litura antifeedant activities for flavone derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Duchowicz, Pablo R., E-mail: pabloducho@gmail.com [Instituto de Investigaciones Fisicoquimicas Teoricas y Aplicadas INIFTA (UNLP, CCT La Plata-CONICET), Diag. 113 y 64, Sucursal 4, C.C. 16, 1900 La Plata (Argentina); Goodarzi, Mohammad [Instituto de Investigaciones Fisicoquimicas Teoricas y Aplicadas INIFTA (UNLP, CCT La Plata-CONICET), Diag. 113 y 64, Sucursal 4, C.C. 16, 1900 La Plata (Argentina); Ocsachoque, Marco A. [Centro de Investigacion y Desarrollo en Ciencias Aplicadas ' Dr. J. J. Ronco' (CINDECA), Departamento de Quimica, Facultad de Ciencias Exactas, UNLP-CONICET. Calle 47 No 257, B1900AJK La Plata (Argentina); Romanelli, Gustavo P. [Centro de Investigacion y Desarrollo en Ciencias Aplicadas ' Dr. J. J. Ronco' (CINDECA), Departamento de Quimica, Facultad de Ciencias Exactas, UNLP-CONICET. Calle 47 No 257, B1900AJK La Plata (Argentina); Catedra de Quimica Organica, Facultad de Ciencias Agrarias y Forestales, UNLP. Calles 60 y 119, B1904AAN La Plata (Argentina); Ortiz, Erlinda del V. [Facultad de Tecnologia y Ciencias Aplicadas, Universidad Nacional de Catamarca, Av. Maximio Victoria 55, (4700), Catamarca (Argentina); Autino, Juan C.; Bennardi, Daniel O.; Ruiz, Diego M. [Catedra de Quimica Organica, Facultad de Ciencias Agrarias y Forestales, UNLP. Calles 60 y 119, B1904AAN La Plata (Argentina); Castro, Eduardo A. [Instituto de Investigaciones Fisicoquimicas Teoricas y Aplicadas INIFTA (UNLP, CCT La Plata-CONICET), Diag. 113 y 64, Sucursal 4, C.C. 16, 1900 La Plata (Argentina)

    2009-12-20

    We establish useful models that relate experimentally measured biological activities of compounds to their molecular structure. The pED{sub 50} feeding inhibition on Spodoptera litura species exhibited by aurones, chromones, 3-coumarones and flavones is analyzed in this work through the hypothesis encompassed in the Quantitative Structure-Activity Relationships (QSAR) Theory. This constitutes a first necessary computationally based step during the design of more bio-friendly repellents that could lead to insights for improving the insecticidal activities of the investigated compounds. After optimizing the molecular structure of each furane and pyrane benzoderivative with the semiempirical molecular orbitals method PM3, more than a thousand of constitutional, topological, geometrical and electronic descriptors are calculated and multiparametric linear regression models are established on the antifeedant potencies. The feature selection method employed in this study is the Replacement Method, which has proven to be successful in previous analyzes. We establish the QSAR both for the complete molecular set of compounds and also for each chemical class, so that acceptably describing the variation of the inhibitory activities from the knowledge of their structure and thus achieving useful predictive results. The main interest of developing trustful QSAR models is that these enable the prediction of compounds having no experimentally measured activities for any reason. Therefore, the structure-activity relationships are further employed for investigating the antifeedant activity on previously synthesized 2-,7-substituted benzopyranes, which do not pose any measured values on the biological expression. One of them, 2-({alpha}-naphtyl)-4H-1-benzopyran-4-one, results in a promising structure to be experimentally analyzed as it has predicted pED{sub 50} = 1.162.

  16. QSAR analysis for some β-carboline derivatives as anti-tumor

    Directory of Open Access Journals (Sweden)

    Ravindra Kumar Chourasiya

    2016-09-01

    Full Text Available β-Carboline moieties are important structural subunits which occur as components of many biologically interesting molecules for antitumor activity. Quantitative structure–activity relationship (QSAR studies have been performed on β-carboline derivatives to explore the structural necessities for antitumor activity. 3D QSAR studies were done using V-Life Sciences MDS 3.0 drug designing module to explain the structural requirements for the anti-tumor activity. The 3D-QSAR was performed using the Step Wise K Nearest Neighbour Molecular Field Analysis [(SW kNN MFA] technique with the partial least-square (PLS method on a database. Obtained best 3D-QSAR model having high predictive ability with q2 = 0.743, r2 = 0.721, pred_r2 = 0.708 and standard error = 0.346, explaining the majority of the variance in the data with partial least square (PLS components. The results of the present study may be useful on the designing of more potent compounds as antitumor drugs.

  17. Comparative study of contrast-enhanced ultrasound qualitative and quantitative analysis for identifying benign and malignant breast tumor lumps.

    Science.gov (United States)

    Liu, Jian; Gao, Yun-Hua; Li, Ding-Dong; Gao, Yan-Chun; Hou, Ling-Mi; Xie, Ting

    2014-01-01

    To compare the value of contrast-enhanced ultrasound (CEUS) qualitative and quantitative analysis in the identification of breast tumor lumps. Qualitative and quantitative indicators of CEUS for 73 cases of breast tumor lumps were retrospectively analyzed by univariate and multivariate approaches. Logistic regression was applied and ROC curves were drawn for evaluation and comparison. The CEUS qualitative indicator-generated regression equation contained three indicators, namely enhanced homogeneity, diameter line expansion and peak intensity grading, which demonstrated prediction accuracy for benign and malignant breast tumor lumps of 91.8%; the quantitative indicator-generated regression equation only contained one indicator, namely the relative peak intensity, and its prediction accuracy was 61.5%. The corresponding areas under the ROC curve for qualitative and quantitative analyses were 91.3% and 75.7%, respectively, which exhibited a statistically significant difference by the Z test (Pqualitative analysis to identify breast tumor lumps is better than with quantitative analysis.

  18. Breast lump

    Science.gov (United States)

    ... a woman are often caused by fibrocystic changes, fibroadenomas, and cysts. Fibrocystic changes are painful, lumpy breasts. ... period, and then improve after your period starts. Fibroadenomas are noncancerous lumps that feel rubbery. They move ...

  19. Breast Lumps

    Science.gov (United States)

    ... You might notice: A distinct lump with definite borders A firm, hard area within your breast A ... MayoClinic.org," "Mayo Clinic Healthy Living," and the triple-shield Mayo Clinic logo are trademarks of Mayo ...

  20. QSAR analysis for ADA upon interaction with a series of adenine derivatives as inhibitors.

    Science.gov (United States)

    Moosavi-Movahedi, A A; Safarian, S; Hakimelahi, G H; Ataei, G; Ajloo, D; Panjehpour, S; Riahi, S; Mousavi, M F; Mardanyan, S; Soltani, N; Khalafi-Nezhad, A; Sharghi, H; Moghadamnia, H; Saboury, A A

    2004-01-01

    The kinetic parameters of adenosine deaminase such as Km and Ki were determined in the absence and presence of adenine derivatives (R1-R24) in sodium phosphate buffer (50 mM; pH 7.5) solution at 27 degrees C. These kinetic parameters were used for QSAR analysis. As such, we found some theoretical descriptors to which the binding affinity of adenosine deaminase (ADA) towards several adenine nucleosides as inhibitors is correlated. QSAR analysis has revealed that binding affinity of the adenine nucleosides upon interaction with ADA depends on the molecular volume, dipole moment of the molecule, electric charge around the N1 atom, and the highest of positive charge for the related molecules.

  1. 3D-QSAR studies on glycogen phosphorylase inhibitors by flexible comparative molecular field analysis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Canceling grids accommodating probes in comparative molecular field analysis (CoMFA), the idea of flexibleness is introduced into the CoMFA, and in combination with swarm intelligent algorithm which attempts to optimize distributions of diverse probes around drug molecules, a new 3D-QSAR method is proposed in this context as flexible comparative molecular field analysis (FCoMFA). In preliminary at-tempts to performing QSAR studies on 47 glycogen phosphorylase inhibitors, FCoMFA is employed and confirmed to be potent to exploring ligand-receptor interaction manners at active positions and thus to generating stable and predictable models. Simultaneously by an intuitive graphics regarding probe distribution patterns, impacts of different substituted groups on activities is also given an insight into.

  2. 3D-QSAR studies on glycogen phosphorylase inhibitors by flexible comparative molecular field analysis

    Institute of Scientific and Technical Information of China (English)

    ZHOU Peng; LI ZhiLiang

    2007-01-01

    Canceling grids accommodating probes in comparative molecular field analysis (CoMFA), the idea of flexibleness is introduced into the CoMFA, and in combination with swarm intelligent algorithm which attempts to optimize distributions of diverse probes around drug molecules, a new 3D-QSAR method is proposed in this context as flexible comparative molecular field analysis (FCoMFA). In preliminary attempts to performing QSAR studies on 47 glycogen phosphorylase inhibitors, FCoMFA is employed and confirmed to be potent to exploring ligand-receptor interaction manners at active positions and thus to generating stable and predictable models. Simultaneously by an intuitive graphics regarding probe distribution patterns, impacts of different substituted groups on activities is also given an insight into.

  3. QSAR analysis of furanone derivatives as potential COX-2 inhibitors: kNN MFA approach

    Directory of Open Access Journals (Sweden)

    Ruchi Bhatiya

    2014-12-01

    Full Text Available A series of thirty-two furanone derivatives with their cyclooxygenase-2 inhibitory activity were subjected to quantitative structural–activity relationship analysis to derive a correlation between biological activity as a dependent variable and various descriptors as independent variables by using V-LIFE MDS3.5 software. The significant 2D QSAR model showed correlation coefficient (r2 = 0.840, standard error of estimation (SEE = 0.195, and a cross-validated squared correlation coefficient (q2 = 0.773. The descriptors involved in the building of 2D QSAR model are retention index for six membered rings, total number of oxygen connected with two single bonds, polar surface area excluding P and S plays a significant role in COX-2 inhibition. 3D-QSAR performed via Step Wise K Nearest Neighbor Molecular Field Analysis [(SW kNN MFA] with partial least-square (PLS technique showed high predictive ability (r2 = 0.7622, q2 = 0.7031 and standard error = 0.3660 explaining the majority of the variance in the data with two principle components. The results of the present study may be useful in the design of more potent furanone derivatives as COX-2 inhibitors.

  4. Evaluation on joint toxicity of chlorinated anilines and cadmium to Photobacterium phosphoreum and QSAR analysis

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Hao, E-mail: realking163@163.com [School of Life and Chemistry, Jiangsu Second Normal University, Nanjing, Jiangsu 210013 (China); Wang, Chao; Shi, Jiaqi [State Key Laboratory of Pollution Control and Resources Reuse, School of Environment, Nanjing University, Nanjing, Jiangsu 210023 (China); Chen, Lei [School of Life and Chemistry, Jiangsu Second Normal University, Nanjing, Jiangsu 210013 (China)

    2014-08-30

    Highlights: • Cd has different effects on joint toxicity when in different concentrations. • The toxicity of most binary mixtures decreases when Cd concentration rises. • Different QSAR models are developed to predict the joint toxicity. • Descriptors in QSARs can help to elucidate the joint toxicity mechanism. • Van der Waals’ force or complexation may reduce the toxicity of mixtures. - Abstract: The individual IC{sub 50} (the concentrations causing a 50% inhibition of bioluminescence after 15 min exposure) of cadmium ion (Cd) and nine chlorinated anilines to Photobacterium phosphoreum (P. phosphoreum) were determined. In order to evaluate the combined effects of the nine chlorinated anilines and Cd, the toxicities of chlorinated anilines combined with different concentrations of Cd were determined, respectively. The results showed that the number of chlorinated anilines manifesting synergy with Cd decreased with the increasing Cd concentration, and the number manifesting antagonism decreased firstly and then increased. The joint toxicity of mixtures at low Cd concentration was weaker than that of most binary mixtures when combined with Cd at medium and high concentrations as indicated by TU{sub Total}. QSAR analysis showed that the single toxicity of chlorinated anilines was related to the energy of the lowest unoccupied molecular orbital (E{sub LUMO}). When combined with different concentrations of Cd, the toxicity was related to the energy difference (E{sub HOMO} − E{sub LUMO}) with different coefficients. Van der Waals’ force or the complexation between chlorinated anilines and Cd had an impact on the toxicity of combined systems, which could account for QSAR models with different physico-chemical descriptors.

  5. Molecular field analysis (MFA) and other QSAR techniques in development of phosphatase inhibitors.

    Science.gov (United States)

    Nair, Pramod C

    2011-01-01

    Phosphatases are well known drug targets for diseases such as diabetes, obesity and other autoimmune diseases. Their role in cancer is due to unusual expression patterns in different types of cancer. However, there is strong evidence for selective targeting of phosphatases in cancer therapy. Several experimental and in silico techniques have been attempted for design of phosphatase inhibitors, with focus on diseases such as diabetes, inflammation and obesity. Their utility for cancer therapy is limited and needs to be explored vastly. Quantitative Structure Activity relationship (QSAR) is well established in silico ligand based drug design technique, used by medicinal chemists for prediction of ligand binding affinity and lead design. These techniques have shown promise for subsequent optimization of already existing lead compounds, with an aim of increased potency and pharmacological properties for a particular drug target. Furthermore, their utility in virtual screening and scaffold hopping is highlighted in recent years. This review focuses on the recent molecular field analysis (MFA) and QSAR techniques, directed for design and development of phosphatase inhibitors and their potential use in cancer therapy. In addition, this review also addresses issues concerning the binding orientation and binding conformation of ligands for alignment sensitive QSAR approaches.

  6. Gravitating lumps

    CERN Document Server

    Galtsov, D V

    2001-01-01

    Recent progress in the study of solitons and black holes in non-Abelian field theories coupled to gravity is reviewed. New topics include gravitational binding of monopoles, black holes with non-trivial topology, Lue-Weinberg bifurcation, asymptotically AdS lumps, solutions to the Freedman-Schwarz model with applications to holography, non-Abelian Born-Infeld solutions

  7. Neck lump

    Science.gov (United States)

    ... the neck lump treated. When to Contact a Medical Professional Call your health care provider if you have an abnormal neck swelling or ... to Expect at Your Office Visit The health care provider will take your medical history and do a physical exam. You may ...

  8. Analysis, simulation and modeling of atmospheric stratification erosion with lumped parameter codes; Analyse, Simulation und Modellierung der Erosion atmosphaerischer Schichtungen mit Lumped Parameter-Codes

    Energy Technology Data Exchange (ETDEWEB)

    Burkhardt, Joerg

    2013-07-01

    The courses and consequences of severe accidents in nuclear power plants are usually simulated with the help of so called Lumped Parameter-Codes which are especially designed for this purpose. These codes are able to simulate complex physical phenomena within short computing times since they are based on a simplified zone principle. Furthermore they are provided with a simplified flow model basis. This dissertation aims at the ability of the German Containment Code System (COCOSYS) to simulate local accumulations of hydrogen. During severe accidents with a melting reactor core (as in Harrisburg or Fukushima) hydrogen can be generated and then be released to the containment. In case of a local accumulation a detonation can occur that endangers the buildings integrity. The results show that the development and the erosion of these hydrogen accumulations based on bouant flows are qualitatively well simulated. From a systematic grid study general rules concerning the simulation of the stratification erosion have been derivated. Those have been applied and confirmed by several blind code-benchmarks. A detailed analysis has shown that the simulated erosion rate and the resistance of simulated hydrogen accumulations are directly related to the grid discretisation chosen by the user. Based upon this analysis a model concept has been developed, which is able to detect hydrogen accumulations and to determine their intensity of interaction with impinging flows by non-dimensional numbers. The erosion flow is controlled by adjusting local grid effects. The model is in the development phase.

  9. Frequency domain analysis and synthesis of lumped parameter systems using nonlinear least squares techniques

    Science.gov (United States)

    Hays, J. R.

    1969-01-01

    Lumped parametric system models are simplified and computationally advantageous in the frequency domain of linear systems. Nonlinear least squares computer program finds the least square best estimate for any number of parameters in an arbitrarily complicated model.

  10. Breast lumps: A 21-year single-center clinical and histological analysis

    OpenAIRE

    Njeze, Gabriel E

    2014-01-01

    Objective: To review the presentation and histological diagnosis of breast lumps of patients seen in Trans Ekulu Hospital Enugu Southeastern Nigeria from 1993 to 2013 in a period of 21 years. Materials and Methods: This is a retrospective study covering a period of 21 years. Case notes of patients containing clinical information and their histology reports were studied. Results: Only 38% of the patients came within 3 months of finding lumps in their breast. One hundred and thirty-seven patien...

  11. Linear stability analysis of a nuclear reactor using the lumped model

    Directory of Open Access Journals (Sweden)

    Kale Vivek A.

    2016-01-01

    Full Text Available The stability analysis of a nuclear reactor is an important aspect in the design and operation of the reactor. A stable neutronic response to perturbations is essential from the safety point of view. In this paper, a general methodology has been developed for the linear stability analysis of nuclear reactors using the lumped reactor model. The reactor kinetics has been modelled using the point kinetics equations and the reactivity feedbacks from fuel, coolant and xenon have been modelled through the appropriate time dependent equations. These governing equations are linearized considering small perturbations in the reactor state around a steady operating point. The characteristic equation of the system is used to establish the stability zone of the reactor considering the reactivity coefficients as parameters. This methodology has been used to identify the stability region of a typical pressurized heavy water reactor. It is shown that the positive reactivity feedback from xenon narrows down the stability region. Further, it is observed that the neutron kinetics parameters (such as the number of delayed neutron precursor groups considered, the neutron generation time, the delayed neutron fractions, etc. do not have a significant influence on the location of the stability boundary. The stability boundary is largely influenced by the parameters governing the evolution of the fuel and coolant temperature and xenon concentration.

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

    Science.gov (United States)

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

    2015-03-01

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

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

    Science.gov (United States)

    Doosti, Elham; Shahlaei, Mohsen

    2015-01-01

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

  14. 3D-QSAR Investigation of Synthetic Antioxidant Chromone Derivatives by Molecular Field Analysis

    Science.gov (United States)

    Samee, Weerasak; Nunthanavanit, Patcharawee; Ungwitayatorn, Jiraporn

    2008-01-01

    A series of 7-hydroxy, 8-hydroxy and 7,8-dihydroxy synthetic chromone derivatives was evaluated for their DPPH free radical scavenging activities. A training set of 30 synthetic chromone derivatives was subject to three-dimensional quantitative structure-activity relationship (3D-QSAR) studies using molecular field analysis (MFA). The substitutional requirements for favorable antioxidant activity were investigated and a predictive model that could be used for the design of novel antioxidants was derived. Regression analysis was carried out using genetic partial least squares (G/PLS) method. A highly predictive and statistically significant model was generated. The predictive ability of the developed model was assessed using a test set of 5 compounds (r2pred = 0.924). The analyzed MFA model demonstrated a good fit, having r2 value of 0.868 and cross-validated coefficient r2cv value of 0.771. PMID:19325746

  15. 3D-QSAR Investigation of Synthetic Antioxidant Chromone Derivatives by Molecular Field Analysis

    Directory of Open Access Journals (Sweden)

    Jiraporn Ungwitayatorn

    2008-02-01

    Full Text Available A series of 7-hydroxy, 8-hydroxy and 7,8-dihydroxy synthetic chromone derivatives was evaluated for their DPPH free radical scavenging activities. A training set of 30 synthetic chromone derivatives was subject to three-dimensional quantitative structure-activity relationship (3D-QSAR studies using molecular field analysis (MFA. The substitutional requirements for favorable antioxidant activity were investigated and a predictive model that could be used for the design of novel antioxidants was derived. Regression analysis was carried out using genetic partial least squares (G/PLS method. A highly predictive and statistically significant model was generated. The predictive ability of the developed model was assessed using a test set of 5 compounds (r2pred = 0.924. The analyzed MFA model demonstrated a good fit, having r2 value of 0.868 and crossvalidated coefficient r2cv value of 0.771.

  16. CoMFA 3D-QSAR Analysis of Epothilones Based on Docking Conformation and Alignment

    Institute of Scientific and Technical Information of China (English)

    YUAN,Wei; LUAN,Lin-Bo; LI,Yan-Ni

    2007-01-01

    Epothilones belong to a class of novel microtubule stabilizing and anti-mitotic agents.which have a paclitaxel-like mechanism of action.A three-dimensional quantitative structure-activity relationship(3D-QSAR)model was built for epothilones by the method of comparative molecular field analysis (CoMFA)combined with the flexible docking technology.The docking CoMFA model gave a good cross-validated value of q2=0.784 with an optimized component of 6 and the conventional correlation coefficient of r2=0.985.The statistical results show that the model has good ability to predict the activity of the studied compounds.At last.the docking CoMFA model was analyzed through contour maps complemented with MOLCAD-generated active site potential surface in the α,β-tubulin receptor,which can provide important information for the structure-based drug design.

  17. 3D-QSAR analysis of a new type of acetylcholinesterase inhibitors

    Institute of Scientific and Technical Information of China (English)

    LIU; AiLin; GUANG; HongMei; ZHU; LiYa; DU; GuanHua; LEE; Simon; M.; Y.; WANG; YiTao

    2007-01-01

    Acetylcholinesterase (AChE) inhibitors are an important class of medicinal agents used for the treatment of Alzheimer's disease. A screening model of AChE inhibitor was used to evaluate the inhibition of a series of phenyl pentenone derivatives. The assay result showed that some compounds displayed higher inhibitory effects. In order to study the relationship between the bioactivities and the structures, 26 compounds with phenyl pentenone scaffold were analyzed. A 3D-QSAR model was constructed using the method of comparative molecular field analysis (CoMFA). The results of cross-validated R2cv=0.629, non-cross-validated R2=0.972, SE=0.331, and F=72.41 indicate that the 3D-model possesses an ability to predict the activities of new inhibitors, and the CoMFA model would be useful for the future design of new AChE inhibitors.

  18. Molecular determinants of juvenile hormone action as revealed by 3D QSAR analysis in Drosophila.

    Directory of Open Access Journals (Sweden)

    Denisa Liszeková

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

  19. Lumped-parameter models

    Energy Technology Data Exchange (ETDEWEB)

    Ibsen, Lars Bo; Liingaard, M.

    2006-12-15

    A lumped-parameter model represents the frequency dependent soil-structure interaction of a massless foundation placed on or embedded into an unbounded soil domain. In this technical report the steps of establishing a lumped-parameter model are presented. Following sections are included in this report: Static and dynamic formulation, Simple lumped-parameter models and Advanced lumped-parameter models. (au)

  20. Multi-Layer Identification of Highly-Potent ABCA1 Up-Regulators Targeting LXRβ Using Multiple QSAR Modeling, Structural Similarity Analysis, and Molecular Docking

    Directory of Open Access Journals (Sweden)

    Meimei Chen

    2016-11-01

    Full Text Available In this study, in silico approaches, including multiple QSAR modeling, structural similarity analysis, and molecular docking, were applied to develop QSAR classification models as a fast screening tool for identifying highly-potent ABCA1 up-regulators targeting LXRβ based on a series of new flavonoids. Initially, four modeling approaches, including linear discriminant analysis, support vector machine, radial basis function neural network, and classification and regression trees, were applied to construct different QSAR classification models. The statistics results indicated that these four kinds of QSAR models were powerful tools for screening highly potent ABCA1 up-regulators. Then, a consensus QSAR model was developed by combining the predictions from these four models. To discover new ABCA1 up-regulators at maximum accuracy, the compounds in the ZINC database that fulfilled the requirement of structural similarity of 0.7 compared to known potent ABCA1 up-regulator were subjected to the consensus QSAR model, which led to the discovery of 50 compounds. Finally, they were docked into the LXRβ binding site to understand their role in up-regulating ABCA1 expression. The excellent binding modes and docking scores of 10 hit compounds suggested they were highly-potent ABCA1 up-regulators targeting LXRβ. Overall, this study provided an effective strategy to discover highly potent ABCA1 up-regulators.

  1. Breast lumps: A 21-year single-center clinical and histological analysis

    Directory of Open Access Journals (Sweden)

    Gabriel E Njeze

    2014-01-01

    Full Text Available Objective: To review the presentation and histological diagnosis of breast lumps of patients seen in Trans Ekulu Hospital Enugu Southeastern Nigeria from 1993 to 2013 in a period of 21 years. Materials and Methods: This is a retrospective study covering a period of 21 years. Case notes of patients containing clinical information and their histology reports were studied. Results: Only 38% of the patients came within 3 months of finding lumps in their breast. One hundred and thirty-seven patients (83% had benign disease, i.e., fibroadenoma, mammary dysplasia, cysts, adenomas, tuberculosis, phyllodes tumor, mastitis, and lipoma. Only 16.9% i.e., 28 patients had breast cancer, out of which two females were in their 20s, and three were males. Conclusions: Benign breast diseases, i.e., fibroadenoma, fibroadenosis, cysts, adenomas, tuberculosis, phyllodes, mastitis, and lipoma are the commoner breast diseases in our locality.

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

    Science.gov (United States)

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

    2005-05-01

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

  3. Lump in the abdomen

    Science.gov (United States)

    Abdominal hernia; Hernia - abdominal; Abdominal wall defects; Lump in the abdominal wall; Abdominal wall mass ... Most often, a lump in the abdomen is caused by a hernia. An abdominal hernia occurs when there is a weak spot in the abdominal ...

  4. FORMING AND PRECISION MACHINING TO NANOMATERIALS LUMP

    Institute of Scientific and Technical Information of China (English)

    Zhan Jie; Zhang Jin; Chen Bingkui; Chen Xiaoan

    2004-01-01

    The technology of forming and machining lump nano-materials has been investigated. Grinding, abrasive machining test has been conducted to Fe, Co, Ni and Al lump nano-materials. Experiments have been done to measure grinding force, grinding thermal, machining roughness and micro-hardness. Image analysis is carried out by metallographic and scanning tunnel microscopic microscope. Researches provide the basis data for forming and machining lump nano-materials.

  5. Grid-based continual analysis of molecular interior for drug discovery, QSAR and QSPR.

    Science.gov (United States)

    Potemkin, A V; Grishina, M A; Potemkin, V A

    2017-02-07

    In 1979, R.D.Cramer and M.Milne made a first realization of the above mentioned principles attempting to compare molecules by aligning them in space and by mapping their molecular fields to a 3D grid. Further, this approach was developed as the DYLOMMS (DYnamic Lattice-Oriented Molecular Modelling System) approach. In 1984, H.Wold and S.Wold proposed the use of partial least squares (PLS) analysis, instead of principal component analysis, to correlate the field values with biological activities. Then, in 1988 the method which was called CoMFA (Comparative Molecular Field Analysis) was introduced and the appropriate software became commercially available. Since 1988, a lot of 3D QSAR methods, algorithms and their modifications are introduced for solving of virtual drug discovery problems (e.g., CoMSIA, CoMMA, HINT, HASL, GOLPE, GRID, PARM, Raptor, BiS, CiS, ConGO,). All the methods can be divided into two groups (classes):1. Methods studying the exterior of molecules; 2) Methods studying the interior of molecules. A series of grid-based computational technologies for Continual Molecular Interior analysis (CoMIn) is invented in the current paper. The grid-based analysis is fulfilled by means of a lattice construction analogously to many other grid-based methods. The further continual elucidation of molecular structure is performed in various ways. (i) In the terms of intermolecular interactions potentials. This can be represented as a superposition of Coulomb, Van der Waals interactions and hydrogen bonds. All the potentials are well known continual functions and their values can be determined in all lattice points for a molecule. (ii) In the terms of quantum functions such as electron density distribution, Laplacian and Hamiltonian of electron density distribution, potential energy distribution, the highest occupied and the lowest unoccupied molecular orbitals distribution and their superposition. To reduce time of calculations using quantum methods based on the

  6. Proposição, validação e análise dos modelos que correlacionam estrutura química e atividade biológica Proposition, validation and analysis of QSAR models

    Directory of Open Access Journals (Sweden)

    Anderson Coser Gaudio

    2001-10-01

    Full Text Available The present paper aims to bring under discussion some theoretical and practical aspects about the proposition, validation and analysis of QSAR models based on multiple linear regression. A comprehensive approach for the derivation of extrathermodynamic equations is reviewed. Some examples of QSAR models published in the literature are analyzed and criticized.

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

    Science.gov (United States)

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

    2014-02-01

    Bioaccumulation in fish is a function of competing rates of chemical uptake and elimination. For hydrophobic organic chemicals bioconcentration, bioaccumulation and biomagnification potential are high and the biotransformation rate constant is a key parameter. Few measured biotransformation rate constant data are available compared to the number of chemicals that are being evaluated for bioaccumulation hazard and for exposure and risk assessment. Three new Quantitative Structure-Activity Relationships (QSARs) for predicting whole body biotransformation half-lives (HLN) in fish were developed and validated using theoretical molecular descriptors that seek to capture structural characteristics of the whole molecule and three data set splitting schemes. The new QSARs were developed using a minimal number of theoretical descriptors (n=9) and compared to existing QSARs developed using fragment contribution methods that include up to 59 descriptors. The predictive statistics of the models are similar thus further corroborating the predictive performance of the different QSARs; Q(2)ext ranges from 0.75 to 0.77, CCCext ranges from 0.86 to 0.87, RMSE in prediction ranges from 0.56 to 0.58. The new QSARs provide additional mechanistic insights into the biotransformation capacity of organic chemicals in fish by including whole molecule descriptors and they also include information on the domain of applicability for the chemical of interest. Advantages of consensus modeling for improving overall prediction and minimizing false negative errors in chemical screening assessments, for identifying potential sources of residual error in the empirical HLN database, and for identifying structural features that are not well represented in the HLN dataset to prioritize future testing needs are illustrated. © 2013.

  8. QSAR analysis on benzodithiazine derivatives as HIV-1 in-tegrase inhibitors

    Institute of Scientific and Technical Information of China (English)

    Ravichandran V; Jain A; Mourya VK; Agrawal RK

    2009-01-01

    Objective:Inhibition of HIV-1 integrase is an important strategy for the treatment of HIV and AIDS.There-fore,HIV-1 integrase inhibitory activity of 3-aroyl-1,1-dioxo-1,4,2-benzodithiazines has been analyzed with different physicochemical parameters.Methods:In the present work,quantitative structure activity relation-ship studies were performed on a series of benzodithiazines as HIV-1 integrase inhibitors using the modeling software Win CAChe version 6.1.Multiple linear regression analysis was performed to derive quantitative structure activity relationship models which were further evaluated for statistical significance and predictive power by internal and external validation.Results:The best QSAR models were having good correlation coeffi-cient (r)with low standard error of estimation (SEE)and cross validated square of correlation coefficient (q2 ).The robustness of the models was checked by Y-randomization test and they were identified as good pre-dictive models.The model for HIV integrase (wt)inhibitory activity of benzodithiazines suggest that the in-crease of dipole moment (Z)of molecules leads to reduce 3'processing and strand transfer inhibitory activity, substitution with high electro positive groups is conducive for the 3'processing inhibitory activity,and the in-crease in heat of formation is favorable for 3'-processing and strand transfer inhibitory activity.Conclusion:The model for HIV integrase (C65s)inhibitory activity of benzodithiazines suggest that the increase of dipole moment (X)of molecules leads to reduce 3'processing and strand transfer inhibitory activity,and the substitu-tion with high hydrophobic groups is conducive for the 3'processing and strand transfer inhibitory.

  9. Employing conformational analysis in the molecular modeling of agrochemicals: insights on QSAR parameters of 2,4-D

    Directory of Open Access Journals (Sweden)

    Matheus Puggina de Freitas

    2013-12-01

    Full Text Available A common practice to compute ligand conformations of compounds with various degrees of freedom to be used in molecular modeling (QSAR and docking studies is to perform a conformational distribution based on repeated random sampling, such as Monte-Carlo methods. Further calculations are often required. This short review describes some methods used for conformational analysis and the implications of using selected conformations in QSAR. A case study is developed for 2,4-dichlorophenoxyacetic acid (2,4-D, a widely used herbicide which binds to TIR1 ubiquitin ligase enzyme. The use of such an approach and semi-empirical calculations did not achieve all possible minima for 2,4-D. In addition, the conformations and respective energies obtained by the semi-empirical AM1 method do not match the calculated trends obtained by a high level DFT method. Similar findings were obtained for the carboxylate anion, which is the bioactive form. Finally, the crystal bioactive structure of 2,4-D was not found as a minimum when using Monte-Carlo/AM1 and is similarly populated with another conformer in implicit water solution according to optimization at the B3LYP/aug-cc-pVDZ level. Therefore, quantitative structure-activity relationship (QSAR methods based on three dimensional chemical structures are not fundamental to provide predictive models for 2,4-D congeners as TIR1 ubiquitin ligase ligands, since they do not necessarily reflect the bioactive conformation of this molecule. This probably extends to other systems.

  10. Stability analysis of non-axisymmetric three-dimensional finite element rotor models with partial and full mass lumping

    Indian Academy of Sciences (India)

    Smitadhi Ganguly; A Nandi; S Neogy

    2014-06-01

    Unlike structural dynamics, the three-dimensional finite-element model of non-axisymmetric rotors on orthotropic bearings generates a large gyroscopic system with parametric stiffness. The present work explores the use of mass-lumping in stability analysis of such systems. Using a variant of Hill’s method, the problem reduces to a generalized Eigen value problem of order $nm \\times nm$, with as the order of the system in state vector representation and as the number of terms in the assumed solution. The matrices in both the sides of the Eigen value problem are expressed in terms of Kronecker products where the mass-matrix appears twice as a sub-matrix in both the sides of the equation. A particular one or both of them can be made diagonal. Both options produce sufficiently accurate results with considerable savings, even with a coarse mesh.

  11. Analysis of direct contact membrane distillation based on a lumped-parameter dynamic predictive model

    KAUST Repository

    Karam, Ayman M.

    2016-10-03

    Membrane distillation (MD) is an emerging technology that has a great potential for sustainable water desalination. In order to pave the way for successful commercialization of MD-based water desalination techniques, adequate and accurate dynamical models of the process are essential. This paper presents the predictive capabilities of a lumped-parameter dynamic model for direct contact membrane distillation (DCMD) and discusses the results under wide range of steady-state and dynamic conditions. Unlike previous studies, the proposed model captures the time response of the spacial temperature distribution along the flow direction. It also directly solves for the local temperatures at the membrane interfaces, which allows to accurately model and calculate local flux values along with other intrinsic variables of great influence on the process, like the temperature polarization coefficient (TPC). The proposed model is based on energy and mass conservation principles and analogy between thermal and electrical systems. Experimental data was collected to validated the steady-state and dynamic responses of the model. The obtained results shows great agreement with the experimental data. The paper discusses the results of several simulations under various conditions to optimize the DCMD process efficiency and analyze its response. This demonstrates some potential applications of the proposed model to carry out scale up and design studies. © 2016

  12. Lumped-parameter models

    DEFF Research Database (Denmark)

    Ibsen, Lars Bo; Liingaard, Morten

    A lumped-parameter model represents the frequency dependent soil-structure interaction of a massless foundation placed on or embedded into an unbounded soil domain. The lumped-parameter model development have been reported by (Wolf 1991b; Wolf 1991a; Wolf and Paronesso 1991; Wolf and Paronesso 19...

  13. Analysis of groundwater discharge with a lumped-parameter model, using a case study from Tajikistan

    Science.gov (United States)

    Pozdniakov, S. P.; Shestakov, V. M.

    A lumped-parameter model of groundwater balance is proposed that permits an estimate of discharge variability in comparison with the variability of recharge, by taking into account the influence of aquifer parameters. Recharge-discharge relationships are analysed with the model for cases of deterministic and stochastic recharge time-series variations. The model is applied to study the temporal variability of groundwater discharge in a river valley in the territory of Tajikistan, an independent republic in Central Asia. Résumé Un modèle global de bilan d'eau souterraine a été développé pour estimer la variabilité de l'écoulement par rapport à celle de la recharge, en prenant en compte l'influence des paramètres de l'aquifère. Les relations entre recharge et écoulement sont analysées à l'aide du modèle pour des variations des chroniques de recharge soit déterministes, soit stochastiques. Le modèle est appliquéà l'étude de la variabilité temporelle de l'écoulement souterrain vers une rivière, dans le Tadjikistan, une république indépendante d'Asie centrale. Resumen Se propone un modelo de parámetros concentrados para realizar el balance de aguas subterráneas, el cual permite estimar la variabilidad en la descarga con respecto a la variabilidad en la recarga, en función de los parámetros que caracterizan el acuífero. Las relaciones entre recarga y descarga se analizan con el modelo para distintos casos de series temporales de recarga, tanto deterministas como estocásticas. El modelo se aplica al estudio de la variabilidad temporal de la descarga en un valle aluvial de Tadyikistán, una república independiente del Asia Central.

  14. Causes of breast lumps (image)

    Science.gov (United States)

    ... breast lumps are benign (non-cancerous), as in fibroadenoma, a condition that mostly affects women under age ... with the menstrual cycle, whereas a lump from fibroadenoma does not. While most breast lumps are benign, ...

  15. Breast lump removal - series (image)

    Science.gov (United States)

    ... a breast lump is very important to a patient's prognosis (probable outcome). Most breast lumps are not diagnosed at the ... is required. If the lump is malignant, the outcome depends on the ... lumpectomy does not require a breast replacement (prosthesis).

  16. Lump and lump-soliton solutions to the (2+1) -dimensional Ito equation

    Science.gov (United States)

    Yang, Jin-Yun; Ma, Wen-Xiu; Qin, Zhenyun

    2017-06-01

    Based on the Hirota bilinear form of the (2+1) -dimensional Ito equation, one class of lump solutions and two classes of interaction solutions between lumps and line solitons are generated through analysis and symbolic computations with Maple. Analyticity is naturally guaranteed for the presented lump and interaction solutions, and the interaction solutions reduce to lumps (or line solitons) while the hyperbolic-cosine (or the quadratic function) disappears. Three-dimensional plots and contour plots are made for two specific examples of the resulting interaction solutions.

  17. Development of QSAR Model of substituted Benzene Sulphonamide using Multiple Regression Analysis

    Directory of Open Access Journals (Sweden)

    R.G.Varma

    2014-01-01

    Full Text Available In continuation of our earlier work in this paper we studied 50 substituted Benzenesulphonamide using substituent nanofluorobutyl sulphonyl chloride (C4F9SO2Cl and pentafluoro benzene sulphonyl chloride (C6F5SO2Cl Accordingly we have development QSAR model of studied compounds. These models were derived using the parameters Balaban Index, Balaban-type index,(Jhetz, Jhetm, Jhetv, Jhete, Jhetp Balaban related index (F,G. and Randic connectivity index (χ1. The best suitable model is predicted on the basis of Maximum-R2 (R-squared.

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

    Science.gov (United States)

    Li, Jiazhong; Gramatica, Paola

    2010-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Nannan Zhou

    2015-06-01

    Full Text Available 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.

  20. Xanthone as Antimalarial: QSAR Analysis, Synthesis, Molecular Docking and In-vitro Antimalarial Evaluation

    Directory of Open Access Journals (Sweden)

    Jufrizal Syahri

    2017-02-01

    Full Text Available The rational design of eighteen new antimalarial compounds from xanthone derivatives has been conducted based on Quantitative Structure-Activity Relationship(QSAR calculation using semi-empirical AM1 methods. The best equation model obtained from QSAR calculation was Log pIC50 = 2.997 - 29.256 (qO8 - 138.234 (qC9 - 6.882 (qC12 - 107.836 (qC14 + 48.764 (qO15. Among the designed compounds, 3,6-dihydroxy-9H-xanthen-9-one (26 and 3,4,6-trihydroxy-9H-xanthen-9-one (27 have been synthesized and investigated their in-vitro antimalarial activities against the chloroquine-sensitive 3D7 strain. An in-vitro antimalarial activity of compound 26 and 27 showed to be highly potential as antimalarial compounds with IC50 of 0.71 and 0.11 µM respectively. Molecular docking studies of compound 26 and 27 showed the formation of a binding interaction between the compounds with the amino acids Ala16, Ser108, Phe58, Asp54 and Leu46, which is the crucial amino acids for antimalarial activity based on the protein-ligand co-crystal structure of WR99210(1,3,5-triazine, a pre-clinical molecule as P. falciparum DHFR-TS inhibitor.

  1. QSAR analysis of nicotinamidic compounds and design of potential Bruton's tyrosine kinase (Btk) inhibitors.

    Science.gov (United States)

    Santos-Garcia, Letícia; Assis, Letícia C; Silva, Daniela R; Ramalho, Teodorico C; da Cunha, Elaine F F

    2016-07-01

    Bruton's tyrosine kinase (Btk) is an important enzyme in B-lymphocyte development and differentiation. Furthermore, Btk expression is considered essential for the proliferation and survival of these cells. Btk inhibition has become an attractive strategy for treating autoimmune diseases, B-cell leukemia, and lymphomas. With the objective of proposing new candidates for Btk inhibitors, we applied receptor-dependent four-dimensional quantitative structure-activity relationship (QSAR) methodology to a series of 96 nicotinamide analogs useful as Btk modulators. The QSAR models were developed using 71 compounds, the training set, and externally validated using 25 compounds, the test set. The conformations obtained by molecular dynamics simulation were overlapped in a virtual three-dimensional cubic box comprised of 2 and 5 Å cells, according to the six trial alignments. The models were generated by combining genetic function approximation and partial least squares regression technique. The analyses suggest that Model 1a yields the best results. The best equation shows [Formula: see text], r(2) = .743, RMSEC = .831, RMSECV = .879. Given the importance of the Tyr551, this residue could become a strategic target for the design of novel Btk inhibitors with improved potency. In addition, the good potency predicted for the proposed M2 compound indicates this compound as a potential Btk inhibitor candidate.

  2. 3D-QSAR Study on Diindolylmethane and Its Analogues with Comparative Molecular Field Analysis (CoMFA)

    Institute of Scientific and Technical Information of China (English)

    BENABADJI,Sakina Hayat; CHEN,Hai-Feng; YUAN,Shen-Gang; WEN,Ren

    2003-01-01

    Comparative molecular field analysis (CoMFA), a three dimensional quantitative structure-activity relationship (3D-QSAR)method was applied to a series of diindolylmethane(DIM) analogs to study the relationship between their structure and theirinnduction of CYP 1A1-associated ethoxyresorufin-O-deethylase (EROD) activity. A DISCO model of pharmacophore was derived to guide the superposition of the compounds. The coefficient of cross-validation (p2) and non cross-validation (r2) for the model established by the study are 0.827 and 0.988 respectively, the value of variance ratio(F) is 103.53 and standard error estimate (SEE) is 0.044. These values indicate that the CoMFA model derived is significant and might have a good prediction for the catalytic activity of DIM compound. As a consequence, the predicted activity values of new designed compounds were all higher than that of the reported value.

  3. Breast lump removal

    Science.gov (United States)

    ... cannot feel it when examining you, a wire localization will be done before the surgery. A radiologist ... send the lump to a laboratory for more testing. Why the Procedure is Performed Surgery to remove ...

  4. Lumped Thermal Household Model

    DEFF Research Database (Denmark)

    Biegel, Benjamin; Andersen, Palle; Stoustrup, Jakob

    2013-01-01

    a lumped model approach as an alternative to the individual models. In the lumped model, the portfolio is seen as baseline consumption superimposed with an ideal storage of limited power and energy capacity. The benefit of such a lumped model is that the computational effort of flexibility optimization......In this paper we discuss two different approaches to model the flexible power consumption of heat pump heated households: individual household modeling and lumped modeling. We illustrate that a benefit of individual modeling is that we can overview and optimize the complete flexibility of a heat...... pump portfolio. Following, we illustrate two disadvantages of individual models, namely that it requires much computational effort to optimize over a large portfolio, and second that it is difficult to accurately model the houses in certain time periods due to local disturbances. Finally, we propose...

  5. Lumping in pharmacokinetics.

    Science.gov (United States)

    Brochot, Céline; Tóth, János; Bois, Frédéric Y

    2005-12-01

    Pharmacokinetic (PK) models simplify biological complexity by dividing the body into interconnected compartments. The time course of the chemical's amount (or concentration) in each compartment is then expressed as a system of ordinary differential equations. The complexity of the resulting system of equations can rapidly increase if a precise description of the organism is needed. However, difficulties arise when the PK model contains more variables and parameters than comfortable for mathematical and computational treatment. To overcome such difficulties, mathematical lumping methods are new and powerful tools. Such methods aim at reducing a differential system by aggregating several variables into one. Typically, the lumped model is still a differential equation system, whose variables are interpretable in terms of variables of the original system. In practice, the reduced model is usually required to satisfy some constraints. For example, it may be necessary to keep state variables of interest for prediction unlumped. To accommodate such constraints, constrained lumping methods have are also available. After presenting the theory, we study, here, through practical examples, the potential of such methods in toxico/pharmacokinetics. As a tutorial, we first simplify a 2-compartment pharmacokinetic model by symbolic lumping. We then explore the reduction of a 6-compartment physiologically based pharmacokinetic model for 1,3-butadiene with numerical constrained lumping. The lumping methods presented here can be easily automated, and are applicable to first-order ordinary differential equation systems.

  6. Transient Heat Transfer in Radiant Floors: A Comparative Analysis between the Lumped Capacitance Method and Infrared Thermography Measurements

    Directory of Open Access Journals (Sweden)

    Giorgio Baldinelli

    2016-07-01

    Full Text Available The paper presents a simplified mathematical model to describe the transient heat transfer of a radiant floor heating system. A purpose-built test room has been realized to investigate the actual thermal response of a concrete radiant floor in unsteady-state conditions. Beyond the temperature sensors needed for the standard thermal analysis of the heat transfer inside the chamber, the floor temperature was retrieved by means of an infrared thermography camera, in order to validate more precisely the proposed analytical model. The infrared thermography analysis gives interesting information on the floor temperature distribution during the transient, highlighting the pipes’ layout and, if present, inhomogeneous floor zones. The thermal images have been elaborated in order to set and tune the colour map. A portion of the image has been defined for measuring the surface floor temperatures with a previous evaluation of the parameters dealing with the thermographic technique, in order to perform the quantitative survey. The comparison results show that the calculated air and floor temperatures substantially agree with the temperatures measured by infrared thermography and thermocouples, provided that the boundary conditions obtained by the field measurements are strictly reproduced in the lumped capacitance mathematical model. The difference between the two approaches results in values lower than 4 °C during the entire monitoring period: a satisfactory outcome, considering the approximations of the analytical method. The proposed model and its infrared thermography measurements validation represent a useful tool to understand at first sight the floor radiant panels behaviour in the start-up and switch off period, at the aim of gather useful information for the difficult task of their regulation.

  7. A 3D Lumped Thermal Network Model for Long-term Load Profiles Analysis in High Power IGBT Modules

    DEFF Research Database (Denmark)

    Bahman, Amir Sajjad; Ma, Ke; Ghimire, Pramod;

    2016-01-01

    three-dimensional RC lumped thermal network for the high power IGBT modules. The thermal-coupling effects among the chips and among the critical layers are modelled, and boundary conditions including the cooling conditions are also taken into account. It is concluded that, the proposed thermal model...

  8. Unified QSAR & network-based computational chemistry approach to antimicrobials. II. Multiple distance and triadic census analysis of antiparasitic drugs complex networks.

    Science.gov (United States)

    Prado-Prado, Francisco J; Ubeira, Florencio M; Borges, Fernanda; González-Díaz, Humberto

    2010-01-15

    In the previous work, we reported a multitarget Quantitative Structure-Activity Relationship (mt-QSAR) model to predict drug activity against different fungal species. This mt-QSAR allowed us to construct a drug-drug multispecies Complex Network (msCN) to investigate drug-drug similarity (González-Díaz and Prado-Prado, J Comput Chem 2008, 29, 656). However, important methodological points remained unclear, such as follows: (1) the accuracy of the methods when applied to other problems; (2) the effect of the distance type used to construct the msCN; (3) how to perform the inverse procedure to study species-species similarity with multidrug resistance CNs (mdrCN); and (4) the implications and necessary steps to perform a substructural Triadic Census Analysis (TCA) of the msCN. To continue the present series with other important problem, we developed here a mt-QSAR model for more than 700 drugs tested in the literature against different parasites (predicting antiparasitic drugs). The data were processed by Linear Discriminate Analysis (LDA) and the model classifies correctly 93.62% (1160 out of 1239 cases) in training. The model validation was carried out by means of external predicting series; the model classified 573 out of 607, that is, 94.4% of cases. Next, we carried out the first comparative study of the topology of six different drug-drug msCNs based on six different distances such as Euclidean, Chebychev, Manhattan, etc. Furthermore, we compared the selected drug-drug msCN and species-species mdsCN with random networks. We also introduced here the inverse methodology to construct species-species msCN based on a mt-QSAR model. Last, we reported the first substructural analysis of drug-drug msCN using Triadic Census Analysis (TCA) algorithm. Copyright 2009 Wiley Periodicals, Inc.

  9. Design and analysis of lumped resistor loaded metamaterial absorber with transmission band.

    Science.gov (United States)

    Chen, Xi; Li, Youquan; Fu, Yunqi; Yuan, Naichang

    2012-12-17

    A new type of multi-layer metamaterial (MM) absorber is represented in this paper, which behave as a dielectric slab in transmission band and act as an absorber in another lower band. The equivalent circuit model of each layer in this MM absorber has been established. The transmission line (TL) model is introduced to analysis the mechanism of electromagnetic wave traveling through this MM absorber. Both theoretical and experimental results indicate this MM absorber has a transmission band at 21GHz and an absorptive band from 5GHz to 13GHz. A good match of TL model results and measurement results verified the validity of TL model in analyzing and optimizing the performances of this kind of absorber.

  10. Transient Analysis of Lumped Circuit Networks Loaded Thin Wires By DGTD Method

    KAUST Repository

    Li, Ping

    2016-03-31

    With the purpose of avoiding very fine mesh cells in the proximity of a thin wire, the modified telegrapher’s equations (MTEs) are employed to describe the thin wire voltage and current distributions, which consequently results in reduced number of unknowns and augmented Courant-Friedrichs-Lewy (CFL) number. As hyperbolic systems, both the MTEs and the Maxwell’s equations are solved by the discontinuous Galerkin time-domain (DGTD) method. In realistic situations, the thin wires could be either driven or loaded by circuit networks. The thin wire-circuit interface performs as a boundary condition for the thin wire solver, where the thin wire voltage and current used for the incoming flux evaluation involved in the DGTD analyzed MTEs are not available. To obtain this voltage and current, an auxiliary current flowing through the thin wire-circuit interface is introduced at each interface. Corresponding auxiliary equations derived from the invariable property of characteristic variable for hyperbolic systems are developed and solved together with the circuit equations established by the modified nodal analysis (MNA) modality. Furthermore, in order to characterize the field and thin wire interactions, a weighted electric field and a volume current density are added into the MTEs and Maxwell-Ampere’s law equation, respectively. To validate the proposed algorithm, three representative examples are presented.

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

    Science.gov (United States)

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

    2012-06-14

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

  12. 3D-QSAR analysis of a series of S-DABO derivatives as anti-HIV agents by CoMFA and CoMSIA.

    Science.gov (United States)

    Xu, H R; Fu, L; Zhan, P; Liu, X Y

    2016-12-01

    In this study, we retrieved a series of 59 dihydroalkylthio-benzyloxopyrimidine (S-DABO) derivatives, which is a class of highly potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) reported from published articles, and analysed them with comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Statistically significant three-dimensional quantitative structure-activity relationship (3D-QSAR) models by CoMFA and CoMSIA were derived from a training set of 46 compounds on the basis of the rigid body alignment. Further, the predictive ability of the QSAR models was validated by a test set of 13 compounds. Based on the information derived from CoMFA and CoMSIA contour maps, we have identified some steric and electrostatic features for improving the activities of these inhibitors, and we validated the 3D-QSAR results by a molecular docking method. On the basis of the obtained results, we designed a new series of S-DABO derivatives with high activities. Therefore, this study could be utilized to design more potent S-DABO analogues as anti-HIV agents.

  13. 3D-QSAR and molecular docking analysis of (4-piperidinyl-piperazines as acetyl-CoA carboxylases inhibitors

    Directory of Open Access Journals (Sweden)

    Udghosh Singh

    2017-02-01

    Full Text Available Acetyl-CoA carboxylase (ACC is a crucial metabolic enzyme, which plays a vital role in fatty acid metabolism and obesity induced type 2 diabetes. Herein, we have performed 3D-QSAR and molecular docking analysis on a novel series of (4-piperidinyl-piperazines to design potent ACC inhibitors. This study correlates the ACC inhibitory activities of 68 (4-piperidinyl-piperazine derivatives with several stereo-chemical parameters representing steric, electrostatic, hydrophobic, hydrogen bond donor and acceptor fields. The CoMFA and CoMSIA models exhibited excellent rncv2 values of 0.974 and 0.985, and rcv2 values of 0.671 and 0.693, respectively. CoMFA predicted rpred2 of 0.910 and CoMSIA predicted rpred2 of 0.963 showed that the predicted values were in good agreement with experimental values. Glide5.5 program was used to explore the binding mode of inhibitors inside the active site of ACC. We have accordingly designed novel ACC inhibitors by utilising the LeapFrog and predicted with excellent inhibitory activity in the developed models.

  14. Lump Kinetic Analysis of Syngas Composition Effect on Fischer-Tropsch Synthesis over Cobalt and Cobalt-Rhenium Alumina Supported Catalyst

    Directory of Open Access Journals (Sweden)

    Dewi Tristantini

    2016-03-01

    Received: 10th November 2015; Revised: 10th February 2016; Accepted: 16th February 2016 How to Cite: Tristantini, D., Suwignjo, R.K. (2016. Lump Kinetic Analysis of Syngas Composition Effect on Fischer-Tropsch Synthesis over Cobalt and Cobalt-Rhenium Alumina Supported Catalyst. Bulletin of Chemical Reaction Engineering & Catalysis, 11 (1: 84-92. (doi:10.9767/bcrec.11.1.424.84-92 Permalink/DOI: http://dx.doi.org/10.9767/bcrec.11.1.424.84-92

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

    NARCIS (Netherlands)

    Hendriks, A.J.; Traas, T.P.; Huijbregts, M.A.J.

    2005-01-01

    To protect thousands of species from thousands of chemicals released in the environment, various risk assessment tools have been developed. Here, we link quantitative structure-activity relationships (QSARs) for response concentrations in water (LC50) to critical concentrations in organisms (C-50) b

  16. Comments on lump solutions in SFT

    Energy Technology Data Exchange (ETDEWEB)

    Bonora, Loriano; Tolla, Driba D. [International School for Advanced Studies (SISSA), Trieste (Italy); INFN, Sezione di Trieste, Trieste (Italy)

    2016-04-15

    We analyze a recently proposed scheme to construct analytic lump solutions in open SFT. We argue that in order for the scheme to be operative and to guarantee background independence it must be implemented in the same 2D conformal field theory in which SFT is formulated. We outline and discuss two different possible approaches. Next we reconsider an older proposal for analytic lump solutions and implement a few improvements. In the course of the analysis we formulate a distinction between regular and singular gauge transformations and advocate the necessity of defining a topology in the space of string fields. (orig.)

  17. QSAR and pharmacophore analysis of a series of piperidinyl urea derivatives as HERG blockers and H3 antagonists.

    Science.gov (United States)

    Moorthy, N S Hari Narayana; Ramos, Maria J; Fernandes, Pedro A

    2013-03-01

    In the present study, a computational based pharmacophore and structural analysis were performed on a series of piperidinyl urea derivatives, a limited number of compounds which have variation in structures and activities that exhibit hERG blocking and H3 antagonistic activities. The conducted QSAR studies demonstrated that the developed models are statistically significant, which have been confirmed through validation. The Q2 values for the models developed with hERG blocking activity are > 0.8 and with the H3 antagonistic activity are > 0.6. The descriptors contributed in the models show that the distributed polar properties on the vdW surface of the molecules are important for the hERG blocking activity. The vsurf_ descriptors (surface area, volume and shape) such as vsurf_DD13 and vsurf_Wp4 correlate with the H3 antagonistic activity of these compounds. The distances between the pharmacophore sites were measured in order to confirm their significance to the activities. The results reveal that the acceptor (acc), donor (don), hydrophobic (hyd) and aromatic/hydrophobic (aro/hyd) pharmacophore properties are favorable contours sites for both the activities. Also, our study reveals that the distance between the polar contours (acc, don, etc) has to be small for better hERG blocking activity. The distances between the aro/hyd to the polar groups should be higher for better hERG blocking activity. However, the H3 antagonistic activity for these series depends upon hydrophobic property of the molecules, particularly the hyd and the hyd/aro contours of the molecules. Hence, these results reveal the requirements on the structural properties and the distances between the pharmacophore contour sites of the molecules responsible for their hERG and H3 antagonistic activities.

  18. Benchmarking a new closed-form thermal analysis technique against a traditional lumped parameter, finite-difference method

    Energy Technology Data Exchange (ETDEWEB)

    Huff, K. D.; Bauer, T. H. (Nuclear Engineering Division)

    2012-08-20

    A benchmarking effort was conducted to determine the accuracy of a new analytic generic geology thermal repository model developed at LLNL relative to a more traditional, numerical, lumped parameter technique. The fast-running analytical thermal transport model assumes uniform thermal properties throughout a homogenous storage medium. Arrays of time-dependent heat sources are included geometrically as arrays of line segments and points. The solver uses a source-based linear superposition of closed form analytical functions from each contributing point or line to arrive at an estimate of the thermal evolution of a generic geologic repository. Temperature rise throughout the storage medium is computed as a linear superposition of temperature rises. It is modeled using the MathCAD mathematical engine and is parameterized to allow myriad gridded repository geometries and geologic characteristics [4]. It was anticipated that the accuracy and utility of the temperature field calculated with the LLNL analytical model would provide an accurate 'birds-eye' view in regions that are many tunnel radii away from actual storage units; i.e., at distances where tunnels and individual storage units could realistically be approximated as physical lines or points. However, geometrically explicit storage units, waste packages, tunnel walls and close-in rock are not included in the MathCAD model. The present benchmarking effort therefore focuses on the ability of the analytical model to accurately represent the close-in temperature field. Specifically, close-in temperatures computed with the LLNL MathCAD model were benchmarked against temperatures computed using geometrically-explicit lumped-parameter, repository thermal modeling technique developed over several years at ANL using the SINDAG thermal modeling code [5]. Application of this numerical modeling technique to underground storage of heat generating nuclear waste streams within the proposed YMR Site has been widely

  19. Development of QSAR models using artificial neural network analysis for risk assessment of repeated-dose, reproductive, and developmental toxicities of cosmetic ingredients.

    Science.gov (United States)

    Hisaki, Tomoka; Aiba Née Kaneko, Maki; Yamaguchi, Masahiko; Sasa, Hitoshi; Kouzuki, Hirokazu

    2015-04-01

    Use of laboratory animals for systemic toxicity testing is subject to strong ethical and regulatory constraints, but few alternatives are yet available. One possible approach to predict systemic toxicity of chemicals in the absence of experimental data is quantitative structure-activity relationship (QSAR) analysis. Here, we present QSAR models for prediction of maximum "no observed effect level" (NOEL) for repeated-dose, developmental and reproductive toxicities. NOEL values of 421 chemicals for repeated-dose toxicity, 315 for reproductive toxicity, and 156 for developmental toxicity were collected from Japan Existing Chemical Data Base (JECDB). Descriptors to predict toxicity were selected based on molecular orbital (MO) calculations, and QSAR models employing multiple independent descriptors as the input layer of an artificial neural network (ANN) were constructed to predict NOEL values. Robustness of the models was indicated by the root-mean-square (RMS) errors after 10-fold cross-validation (0.529 for repeated-dose, 0.508 for reproductive, and 0.558 for developmental toxicity). Evaluation of the models in terms of the percentages of predicted NOELs falling within factors of 2, 5 and 10 of the in-vivo-determined NOELs suggested that the model is applicable to both general chemicals and the subset of chemicals listed in International Nomenclature of Cosmetic Ingredients (INCI). Our results indicate that ANN models using in silico parameters have useful predictive performance, and should contribute to integrated risk assessment of systemic toxicity using a weight-of-evidence approach. Availability of predicted NOELs will allow calculation of the margin of safety, as recommended by the Scientific Committee on Consumer Safety (SCCS).

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

    Science.gov (United States)

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

    2015-11-01

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

  1. Development of QSAR for antimicrobial activity of substituted benzimidazoles.

    Science.gov (United States)

    Vashist, N; Sambi, S S; Kumar, P; Narasimhan, B

    2015-05-01

    QSAR analysis has been done to correlate antimicrobial activity of substituted benzimidazole derivatives with their physicochemical parameters. Developed QSAR models have been cross validated using leave one out (LOO) method. Statistical parameters like probable error of the coefficient of correlation (PE), least square error (LSE), Friedman's lack of fit measure (LOF), standard error of prediction (SEP) and quality value (Q) were also used to cross validate the models. QSAR studies established the importance of WAP, Mlog P and UI in describing the antimicrobial activities of substituted benzimidazole derivatives.

  2. Understanding mean transit times in Andean tropical montane cloud forest catchments: combining tracer data, lumped parameter models and uncertainty analysis

    Science.gov (United States)

    Timbe, E.; Windhorst, D.; Crespo, P.; Frede, H.-G.; Feyen, J.; Breuer, L.

    2013-12-01

    Weekly samples from surface waters, springs, soil water and rainfall were collected in a 76.9 km2 mountain rain forest catchment and its tributaries in southern Ecuador. Time series of the stable water isotopes δ18O and δ2H were used to calculate mean transit times (MTTs) and the transit time distribution functions (TTDs) solving the convolution method for seven lumped parameter models. For each model setup, the Generalized Likelihood Uncertainty Estimation (GLUE) methodology was applied to find the best predictions, behavioral solutions and parameter identifiability. For the study basin, TTDs based on model types such as the Linear-Piston Flow for soil waters and the Exponential-Piston Flow for surface waters and springs performed better than more versatile equations such as the Gamma and the Two Parallel Linear Reservoirs. Notwithstanding both approaches yielded a better goodness of fit for most sites, but with considerable larger uncertainty shown by GLUE. Among the tested models, corresponding results were obtained for soil waters with short MTTs (ranging from 3 to 12 weeks). For waters with longer MTTs differences were found, suggesting that for those cases the MTT should be based at least on an intercomparison of several models. Under dominant baseflow conditions long MTTs for stream water ≥2 yr were detected, a phenomenon also observed for shallow springs. Short MTTs for water in the top soil layer indicate a rapid exchange of surface waters with deeper soil horizons. Differences in travel times between soils suggest that there is evidence of a land use effect on flow generation.

  3. QSAR analysis of N-Alkyl imidazole analogues as antibacterial agents

    Directory of Open Access Journals (Sweden)

    Khan Nazneen

    2006-01-01

    Full Text Available A quantitative structure activity relationship study on a series of N-alkyl imidazole analogues was made using combination of various thermodynamic electronic and spatial descriptors. Several statistical expressions were developed using stepwise multiple liner regression analysis. The best quantitative structure activity relationship models were further validated by leave-one-out method of cross-validation. The study revealed that the electronic property, i.e., dipole moment contributed positively, and spatial descriptor (principal moment of inertia at Y axis contributed negatively. The study suggested that substitution of group at R1 position on imidazole ring with hydrophobic nature and low bulkiness are favourable for the antibacterial activity in the concerned microbes. The quantitative structure activity relationship study provides important structural insights in designing of potent antibacterial agents.

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

    Science.gov (United States)

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

    2005-01-01

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

  5. Novel N-(3-carboxyl-9-benzyl-beta-carboline-1-yl)ethylamino acids: synthesis, anti-tumor evaluation, intercalating determination, 3D QSAR analysis and docking investigation.

    Science.gov (United States)

    Wu, Jianhui; Zhao, Ming; Qian, Keduo; Lee, Kuo-Hsiung; Morris-Natschke, Susan; Peng, Shiqi

    2009-10-01

    Sixteen novel N-(3-carboxyl-9-benzyl-beta-carboline-1-yl)ethylamino acids (6a-p) were synthesized as intercalating lead compounds. In the in vitro cytotoxic assay their IC(50) values against five human carcinoma cell lines ranged from 10.95 microM to about 400 microM. On S180 mouse model eight of them exhibited anti-tumor action, four of them showed the same anti-tumor potency as that of cytarabine. The preliminary toxicity evaluation revealed that the LD(50) values of 6a-p should be more than 500 mg/kg. With CT DNA as model system an intercalating mechanism was explored. Using 3D QSAR analysis the relationship of the in vivo anti-tumor activity and the structure was quantitatively described. By docking 6a-p onto d(CGATCG)(2) oligonucleotides the intercalation was demonstrated.

  6. Implementation of QSAR's in ecotoxicological risk assessments

    NARCIS (Netherlands)

    Posthumus R; Slooff W; CSR

    2001-01-01

    Quantitative Structure Activity Relationship (QSAR) modelling techniques are overviewed here, along with descriptors which can be used in QSAR equations and the different statistical methods suitable for deriving QSARs. Discussed is the current state of the art on the use of QSAR estimates within th

  7. Optimization of antisense drug design againstconservative local motif in simulant secondary structures of HER-2 mRNA and QSAR analysis

    Institute of Scientific and Technical Information of China (English)

    YANGShuan-Ping; SONGSan-Tai; TANGZhong-Ming; SONGHai-Feng

    2003-01-01

    AIM: To study the role of mRNA secondary structure stability in antisense drug design and obtain better antisensecandidates against neu/HER-2/erbB-2 mRNA than previous report. METHODS: Program RNAstructure wasutilized to simulate the secondary structures of HER-2 mRNA. Then 21 antisense phosphorothioateoligodeoxynucleotides (S-ODN) targeting different parts of secondary structural motif were designed. HA4 wasset as positive control. Mean 50 % inhibitory effects (IC50) of S-ODN on proliferations of SK-BR-3 breast cancercells were evaluated. The expression of target mRNA was detected by RT-PCR. The multiple regression andquantitative structure-activity relationship (QSAR) analysis was preformed by SPSS software. RESULTS: Oneoptimal and two suboptimal secondary structures of target mRNA were obtained. Nine out of 11 S-ODN againstcompletely conservative local motif (LM) (conservative among all simulant secondary structures) got lower orsimilar IC50 values compared with HA4. On the other hand, 2 out of 3 S-ODN against relatively conservative LM(conservative between any two simulant secondary structures) got lower or similar IC50 values compared withHA4. Only 2 out of 5 S-ODN targeting variable LM (variable among different predicted secondary structures) hadacceptable activities. Average IC50 of S-ODN against completely conservative LM was significantly lower than thatof S-ODN against diverse LM. QSAR analysis suggested that stability, base number of bulge loops, and target freeenergies △G°T were statistically significant. In the multiple regression, R was 0.967, P=0.005. CONCLUSION:Antisense drug design against conservative LM was helpful for improving the positive rate. Several S-ODN candidates better than positive control were screened.

  8. Identification of cytochrome P450 2D6 and 2C9 substrates and inhibitors by QSAR analysis

    DEFF Research Database (Denmark)

    Jónsdóttir, Svava Ósk; Ringsted, Tine; Nikolov, Nikolai G.;

    2012-01-01

    these compounds. A large fraction of these chemicals were found to be CYP active, and thus potentially capable of affecting human physiology. 20% of the compounds within applicability domain of the models were predicted to be CYP2C9 substrates, and 17% to be inhibitors. The corresponding numbers for CYP2D6 were 9...... of specific CYP activity. An overrepresentation was seen for poly-aromatic hydrocarbons (group of procarcinogens) among CYP2C9 active and mutagenic compounds compared to CYP2C9 inactive and mutagenic compounds. The mutagenicity was predicted with a QSAR model based on Ames in vitro test data.......% and 21%. Where the majority of CYP2C9 active compounds were predicted to be both a substrate and an inhibitor at the same time, the CYP2D6 active compounds were primarily predicted to be only inhibitors. It was demonstrated that the models could identify compound classes with a high occurrence...

  9. A QSAR Study of Some Cyclobutenediones as CCR1 Antagonists by Artificial Neural Networks Based on Principal Component Analysis

    Directory of Open Access Journals (Sweden)

    E Arkan

    2011-12-01

    Full Text Available Background and the purpose of the study: A quantitative structure activity relationship (QSAR model based on artificial neural networks (ANN was developed to study the activities of 29 derivatives of 3-amino-4-(2-(2-(4-benzylpiperazin-1-yl-2-oxoethoxy phenylamino cyclobutenedione as C-C chemokine receptor type 1(CCR1 inhibitors. Methods: A feed-forward ANN with error back-propagation learning algorithm was used for model building which was achieved by optimizing initial learning rate, learning momentum, epoch and the number of hidden neurons. Results: Good results were obtained with a Root Mean Square Error (RMSE and correlation coefficients (R2 of 0.189 and 0.906 for the training and 0.103 and 0.932 prediction sets, respectively. Conclusion: The results reflect a nonlinear relationship between the Principal components obtained from calculated molecular descriptors and the inhibitory activities of the investigated molecules.

  10. Construction and analysis of a human hepatotoxicity database suitable for QSAR modeling using post-market safety data.

    Science.gov (United States)

    Zhu, Xiao; Kruhlak, Naomi L

    2014-07-01

    Drug-induced liver injury (DILI) is one of the most common drug-induced adverse events (AEs) leading to life-threatening conditions such as acute liver failure. It has also been recognized as the single most common cause of safety-related post-market withdrawals or warnings. Efforts to develop new predictive methods to assess the likelihood of a drug being a hepatotoxicant have been challenging due to the complexity and idiosyncrasy of clinical manifestations of DILI. The FDA adverse event reporting system (AERS) contains post-market data that depict the morbidity of AEs. Here, we developed a scalable approach to construct a hepatotoxicity database using post-market data for the purpose of quantitative structure-activity relationship (QSAR) modeling. A set of 2029 unique and modelable drug entities with 13,555 drug-AE combinations was extracted from the AERS database using 37 hepatotoxicity-related query preferred terms (PTs). In order to determine the optimal classification scheme to partition positive from negative drugs, a manually-curated DILI calibration set composed of 105 negatives and 177 positives was developed based on the published literature. The final classification scheme combines hepatotoxicity-related PT data with supporting information that optimize the predictive performance across the calibration set. Data for other toxicological endpoints related to liver injury such as liver enzyme abnormalities, cholestasis, and bile duct disorders, were also extracted and classified. Collectively, these datasets can be used to generate a battery of QSAR models that assess a drug's potential to cause DILI.

  11. Transient Heat Transfer in Radiant Floors: A Comparative Analysis between the Lumped Capacitance Method and Infrared Thermography Measurements

    National Research Council Canada - National Science Library

    Baldinelli, Giorgio; Bianchi, Francesco; Rotili, Antonella; Presciutti, Andrea

    2016-01-01

    .... Beyond the temperature sensors needed for the standard thermal analysis of the heat transfer inside the chamber, the floor temperature was retrieved by means of an infrared thermography camera...

  12. QSAR-analysis and mixture toxicity as diagnostic tools: Influence of degradation on the toxicity and mode of action of diuron in algae and daphnids.

    Science.gov (United States)

    Neuwoehner, Judith; Zilberman, Tobias; Fenner, Kathrin; Escher, Beate I

    2010-04-01

    Even though the environmental occurrence of pesticide transformation products is well established, ecotoxicological data for transformation products are often lacking. Therefore, it remains an open question for regulators how to handle transformation products in the process of authorization and risk assessment. Transformation products may (1) possess a similar mode of toxic action as the parent compound, (2) exhibit unexpected effects towards non-target organisms or (3) contribute to overall mixture toxicity through baseline toxicity even if the specific activity of the parent compound is lost. In the present study, a systematic and integrated approach is presented to differentiate between these three options with the goal of identifying transformation products that significantly add to the risk posed by the parent compound. Quantitative structure-activity relationships (QSAR) and a toxic ratio (TR) analysis were used to evaluate the toxicity and mode of toxic action of the transformation products relative to the parent compound. In addition, mixture toxicity experiments were used as diagnostic tools to underpin the mode of action analysis and to elucidate whether the transformation products possess a similar risk potential as the parent compound. As an illustrative example, the phenylurea herbicide diuron was chosen since a sound basis of ecotoxicological data was available not only for diuron itself but also for most of its transformation products. Effects were investigated using the most sensitive species, algae, and the non-target organism Daphnia magna, for which a previous QSAR-analysis of literature data suggested a specific hazard. In the present study the primary transformation products 1-(3,4-dichlorophenyl)-3-methlyurea (DCPMU), 3-(3-chlorophenyl)-1,1-dimethylurea (MCPDMU), and 1-(3,4-dichlorophenyl)urea (DCPU) were identified as specific toxicants in algae, but as baseline toxicants in daphnids. The subsequent loss of the methylurea group during

  13. Lump solutions in SFT. Complements

    CERN Document Server

    Bonora, L; Tolla, D D

    2011-01-01

    Recently a possible violation of the equation of motion for the recently proposed lump solutions in open SFT has been pointed out in the literature. In this paper we argue that, when the issue is considered in the appropriate mathematical setting of distribution theory, no violations to the equation of motion occur.

  14. Lumped transmission line avalanche pulser

    Science.gov (United States)

    Booth, Rex

    1995-01-01

    A lumped linear avalanche transistor pulse generator utilizes stacked transistors in parallel within a stage and couples a plurality of said stages, in series with increasing zener diode limited voltages per stage and decreasing balanced capacitance load per stage to yield a high voltage, high and constant current, very short pulse.

  15. Analysis of Material Transfer From a Soft Workpiece to a Hard Tool: Part II-Experimental Verification of the Proposed Lump Growth Model

    NARCIS (Netherlands)

    Rooij, de M.B.; Schipper, D.J.

    2001-01-01

    In this study, the lump growth model, described in an accompanying paper (de Rooij and Schipper, 2000) is validated by means of experiments performed on a deepdrawing simulator. In the experiments, the influence of material and roughness properties of both sheet and tool on the galling behavior is d

  16. N-tuple topological/geometric cutoffs for 3D N-linear algebraic molecular codifications: variability, linear independence and QSAR analysis.

    Science.gov (United States)

    García-Jacas, C R; Marrero-Ponce, Y; Barigye, S J; Hernández-Ortega, T; Cabrera-Leyva, L; Fernández-Castillo, A

    2016-12-01

    Novel N-tuple topological/geometric cutoffs to consider specific inter-atomic relations in the QuBiLS-MIDAS framework are introduced in this manuscript. These molecular cutoffs permit the taking into account of relations between more than two atoms by using (dis-)similarity multi-metrics and the concepts related with topological and Euclidean-geometric distances. To this end, the kth two-, three- and four-tuple topological and geometric neighbourhood quotient (NQ) total (or local-fragment) spatial-(dis)similarity matrices are defined, to represent 3D information corresponding to the relations between two, three and four atoms of the molecular structures that satisfy certain cutoff criteria. First, an analysis of a diverse chemical space for the most common values of topological/Euclidean-geometric distances, bond/dihedral angles, triangle/quadrilateral perimeters, triangle area and volume was performed in order to determine the intervals to take into account in the cutoff procedures. A variability analysis based on Shannon's entropy reveals that better distribution patterns are attained with the descriptors based on the cutoffs proposed (QuBiLS-MIDAS NQ-MDs) with regard to the results obtained when all inter-atomic relations are considered (QuBiLS-MIDAS KA-MDs - 'Keep All'). A principal component analysis shows that the novel molecular cutoffs codify chemical information captured by the respective QuBiLS-MIDAS KA-MDs, as well as information not captured by the latter. Lastly, a QSAR study to obtain deeper knowledge of the contribution of the proposed methods was carried out, using four molecular datasets (steroids (STER), angiotensin converting enzyme (ACE), thermolysin inhibitors (THER) and thrombin inhibitors (THR)) widely used as benchmarks in the evaluation of several methodologies. One to four variable QSAR models based on multiple linear regression were developed for each compound dataset following the original division into training and test sets. The

  17. Using SAR and QSAR analysis to model the activity and structure of the quinolone-DNA complex.

    Science.gov (United States)

    Llorente, B; Leclerc, F; Cedergren, R

    1996-01-01

    A set of 78 quinolone derivatives were used in a structure-activity study to identify structural features correlating with antibacterial activity. Distinct combinations of functional properties were identified for Gram-negative and Gram-positive bacteria. 3-D Quantitative structure-activity relationship (QSAR) studies identified specific hydrophobic, topologic and electronic properties of the molecules for both in vitro and in vivo activities. From these results, a three-dimensional model of a DNA-quinolone complex was built using molecular modeling techniques. It was based on the intercalation of quinolone into the double helix of DNA. We conclude that the intercalation model is consistent with most available data on the structure of the quinolone complex. This predicted structure is stabilized by the binding of magnesium ion with the sp2 oxygens present in quinolone, a phosphate and a purine base of the DNA. Substituents R1 and R7 are predicted to make hydrophobic interactions in the major and minor groove of DNA, respectively. R7 could also form hydrogen bonds with amino groups of guanines and the aspartic acid residue at position 87 in DNA gyrase subunit A.

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

    Science.gov (United States)

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

    2013-07-01

    Malaria is a fatal tropical and subtropical disease caused by the protozoal species Plasmodium. Many commonly available antimalarial drugs and therapies are becoming ineffective because of the emergence of multidrug resistant Plasmodium falciparum, which drives the need for the development of new antimalarial drugs. Recently, a series of 3-carboxyl-4(1H)-quinolone analogs, derived from the famous compound endochin, were reported as promising candidates for orally efficacious antimalarials. In this study, to analyze the structure-activity relationships (SAR) of these quinolones and investigate the structural requirements for antimalarial activity, the 2D multiple linear regressions (MLR) method and 3D comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods are employed to evolve different QSAR models. All these models give satisfactory results with highly accurate fitting and strong external predictive abilities for chemicals not used in model development. Furthermore, the contour maps from 3D models can provide an intuitive understanding of the key structure features responsible for the antimalarial activities. In conclusion, we summarize the detailed position-specific structural requirements of these derivatives accordingly. All these results are helpful for the rational design of new compounds with higher antimalarial bioactivities. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. QSAR modeling for anti-human African trypanosomiasis activity of substituted 2-Phenylimidazopyridines

    Science.gov (United States)

    Masand, Vijay H.; El-Sayed, Nahed N. E.; Mahajan, Devidas T.; Mercader, Andrew G.; Alafeefy, Ahmed M.; Shibi, I. G.

    2017-02-01

    In the present work, sixty substituted 2-Phenylimidazopyridines previously reported with potent anti-human African trypanosomiasis (HAT) activity were selected to build genetic algorithm (GA) based QSAR models to determine the structural features that have significant correlation with the activity. Multiple QSAR models were built using easily interpretable descriptors that are directly associated with the presence or the absence of a structural scaffold, or a specific atom. All the QSAR models have been thoroughly validated according to the OECD principles. All the QSAR models are statistically very robust (R2 = 0.80-0.87) with high external predictive ability (CCCex = 0.81-0.92). The QSAR analysis reveals that the HAT activity has good correlation with the presence of five membered rings in the molecule.

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

    Science.gov (United States)

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

    2014-03-01

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

  1. Analysis of DoD inkjet printhead performance for printable electronics fabrication using dynamic lumped element modeling and swarm intelligence based optimal prediction

    Institute of Scientific and Technical Information of China (English)

    何茂伟; 孙丽玲; 胡琨元; 朱云龙; 陈瀚宁

    2015-01-01

    The major challenge in printable electronics fabrication is to effectively and accurately control a drop-on-demand (DoD) inkjet printhead for high printing quality. In this work, an optimal prediction model, constructed with the lumped element modeling (LEM) and the artificial bee colony (ABC) algorithm, was proposed to efficiently predict the combination of waveform parameters for obtaining the desired droplet properties. For acquiring higher simulation accuracy, a modified dynamic lumped element model (DLEM) was proposed with time-varying equivalent circuits, which can characterize the nonlinear behaviors of piezoelectric printhead. The proposed method was then applied to investigate the influences of various waveform parameters on droplet volume and velocity of nano-silver ink, and to predict the printing quality using nano-silver ink. Experimental results show that, compared with two-dimension manual search, the proposed optimal prediction model perform efficiently and accurately in searching the appropriate combination of waveform parameters for printable electronics fabrication.

  2. 3d QSAR studies on a series of quinazoline derrivatives as tyrosine kinase (egfr) inhibitor: the k-nearest neighbor molecular field analysis approach.

    Science.gov (United States)

    Noolvi, Malleshappa N; Patel, Harun M

    2010-06-01

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

  3. Molecular field analysis and 3D-quantitative structure-activity relationship study (MFA 3D-QSAR) unveil novel features of bile acid recognition at TGR5.

    Science.gov (United States)

    Macchiarulo, Antonio; Gioiello, Antimo; Thomas, Charles; Massarotti, Alberto; Nuti, Roberto; Rosatelli, Emiliano; Sabbatini, Paola; Schoonjans, Kristina; Auwerx, Johan; Pellicciari, Roberto

    2008-09-01

    Bile acids regulate nongenomic actions through the activation of TGR5, a membrane receptor that is G protein-coupled to the induction of adenylate cyclase. In this work, a training set of 43 bile acid derivatives is used to develop a molecular interaction field analysis (MFA) and a 3D-quantitative structure-activity relationship study (3D-QSAR) of TGR5 agonists. The predictive ability of the resulting model is evaluated using an external set of compounds with known TGR5 activity, and six bile acid derivatives whose unknown TGR5 activity is herein assessed with in vitro luciferase assay of cAMP formation. The results show a good predictive model and indicate a statistically relevant degree of correlation between the TGR5 activity and the molecular interaction fields produced by discrete positions of the bile acid scaffold. This information is instrumental to extend on a quantitative basis the current structure-activity relationships of bile acids as TGR5 modulators and will be fruitful to design new potent and selective agonists of the receptor.

  4. Elastodynamic analysis of the desmodromic valve train of a racing motorbike engine by means of a combined lumped/finite element model

    Science.gov (United States)

    Rivola, A.; Troncossi, M.; Dalpiaz, G.; Carlini, A.

    2007-02-01

    A combined lumped/finite element model of a portion of the desmodromic valve train of a racing motorbike engine was developed and validated in order to simulate the elastodynamic behaviour of such a particular timing system. The model includes the lumped parameter model of the belt transmission that drives the camshafts, the finite element model of the camshafts, and the lumped parameter model of two cam-valve mechanisms (one for each camshaft). The procedure to validate the model, based on experimental tests carried out on a test bench described here, is presented and discussed. The comparison between the numerical results and the experimental data shows that the effectiveness of the model is satisfactorily achieved. It will be possible, in a further study, to add the other cam-valve mechanisms and the missing external forces, in order to obtain a complete system model. Some possible applications of the presented model are provided in order to show how the overall model could be employed to perform both design optimisation and diagnostics.

  5. 3D pharmacophore mapping using 4D QSAR analysis for the cytotoxicity of lamellarins against human hormone-dependent T47D breast cancer cells.

    Science.gov (United States)

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

    2009-10-01

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

  6. Benchmarking Variable Selection in QSAR.

    Science.gov (United States)

    Eklund, Martin; Norinder, Ulf; Boyer, Scott; Carlsson, Lars

    2012-02-01

    Variable selection is important in QSAR modeling since it can improve model performance and transparency, as well as reduce the computational cost of model fitting and predictions. Which variable selection methods that perform well in QSAR settings is largely unknown. To address this question we, in a total of 1728 benchmarking experiments, rigorously investigated how eight variable selection methods affect the predictive performance and transparency of random forest models fitted to seven QSAR datasets covering different endpoints, descriptors sets, types of response variables, and number of chemical compounds. The results show that univariate variable selection methods are suboptimal and that the number of variables in the benchmarked datasets can be reduced with about 60 % without significant loss in model performance when using multivariate adaptive regression splines MARS and forward selection.

  7. The Structure and Specific Property Analysis of the Lumped Packing-Seal%集装式填料密封结构与特性分析

    Institute of Scientific and Technical Information of China (English)

    李多民

    2001-01-01

    This aper analyzes the structure and disadvantage of the traditional packing -seal,and introduces the structure,the working priniple and characteristics of a neq type of lumped acking seal.%本文分析了传统填料密封结构存在的不足,介绍了一种新型的集装式填料密封结构,并较为详细地论述了其结构、工作原理以及性能特点。

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

    Science.gov (United States)

    Ghosh, P; Bagchi, M C

    2009-01-01

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

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

    Science.gov (United States)

    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.

  10. Lumped-parameter Model of a Bucket Foundation

    DEFF Research Database (Denmark)

    Andersen, Lars; Ibsen, Lars Bo; Liingaard, Morten

    2009-01-01

    As an alternative to gravity footings or pile foundations, offshore wind turbines at shallow water can be placed on a bucket foundation. The present analysis concerns the development of consistent lumped-parameter models for this type of foundation. The aim is to formulate a computationally effic...

  11. A rapidly growing lid lump

    Science.gov (United States)

    Koay, Su-Yin; Lee, Richard M H; Hugkulstone, Charles; Rodrigues, Ian Aureliano Stephen

    2014-01-01

    A 97-year-old woman presented with a 5-month history of a rapidly growing, painless, left upper eyelid lesion. Examination revealed a large vascularised, ulcerated nodule on the left upper lid, causing significant ptosis. Wide local excision of the lesion was performed and the wound was left to heal by secondary intention. Histology and immunohistochemistry of the lesion confirmed a diagnosis of Merkel cell carcinoma, a rare primary malignancy of the eyelid which has significant morbidity and mortality. Although uncommon, this diagnosis should always be considered in any patient with a rapidly growing lid lump. In view of the patient's age, known dementia and family wishes, the patient was managed conservatively, with no further investigations performed. She was due to be followed up in clinic on a regular basis, but has since died from other causes. PMID:25123568

  12. Lump corrections for radioactive waste assay.

    Science.gov (United States)

    Miller, T J

    2009-09-01

    Previous studies have shown that automated radioactive waste assay techniques, such as segmented gamma scanner (SGS) and automated qualitative and quantitative (AQ2), have severely underestimated fissile material due to either the malfunction or absence of appropriate lump correction routines. This paper examines the application of manual techniques, such as Monte Carlo N particle (MCNP) and spectral non-destructive assay platform (SNAP) software, to lump corrections in plutonium (Pu), enriched uranium (EU) and depleted uranium (DU) waste streams. Excellent results have been obtained when comparing MCNP with SNAP and applying the SNAP lump correction routine to a range of simulated and typical wastes containing various Pu and EU lump sizes. It has been concluded that the need for lump corrections was relatively rare and usually apparent from abnormal gamma ray peak area ratios, since most AWE waste streams are only lightly shielded.

  13. A 3D-QSAR-driven approach to binding mode and affinity prediction

    DEFF Research Database (Denmark)

    Tosco, Paolo; Balle, Thomas

    2012-01-01

    A method for predicting the binding mode of a series of ligands is proposed. The procedure relies on three-dimensional quantitative structure-activity relationships (3D-QSAR) and does not require structural knowledge of the binding site. Candidate alignments are automatically built and ranked...... according to a consensus scoring function. 3D-QSAR analysis based on the selected binding mode enables affinity prediction of new drug candidates having less than 10 rotatable bonds....

  14. Pre-processing in AI based Prediction of QSARs

    CERN Document Server

    Patri, Om Prasad

    2009-01-01

    Machine learning, data mining and artificial intelligence (AI) based methods have been used to determine the relations between chemical structure and biological activity, called quantitative structure activity relationships (QSARs) for the compounds. Pre-processing of the dataset, which includes the mapping from a large number of molecular descriptors in the original high dimensional space to a small number of components in the lower dimensional space while retaining the features of the original data, is the first step in this process. A common practice is to use a mapping method for a dataset without prior analysis. This pre-analysis has been stressed in our work by applying it to two important classes of QSAR prediction problems: drug design (predicting anti-HIV-1 activity) and predictive toxicology (estimating hepatocarcinogenicity of chemicals). We apply one linear and two nonlinear mapping methods on each of the datasets. Based on this analysis, we conclude the nature of the inherent relationships betwee...

  15. Application of lumped-parameter models

    Energy Technology Data Exchange (ETDEWEB)

    Ibsen, Lars Bo; Liingaard, M.

    2006-12-15

    This technical report concerns the lumped-parameter models for a suction caisson with a ratio between skirt length and foundation diameter equal to 1/2, embedded into an viscoelastic soil. The models are presented for three different values of the shear modulus of the subsoil. Subsequently, the assembly of the dynamic stiffness matrix for the foundation is considered, and the solution for obtaining the steady state response, when using lumped-parameter models is given. (au)

  16. Ligand-based pharmacophore modeling; atom-based 3D-QSAR analysis and molecular docking studies of phosphoinositide-dependent kinase-1 inhibitors

    Directory of Open Access Journals (Sweden)

    P Kirubakaran

    2012-01-01

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

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

    Science.gov (United States)

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

    2002-01-01

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

  18. Uncovering and testing the fuzzy clusters based on lumped Markov chain in complex network.

    Science.gov (United States)

    Jing, Fan; Jianbin, Xie; Jinlong, Wang; Jinshuai, Qu

    2013-01-01

    Identifying clusters, namely groups of nodes with comparatively strong internal connectivity, is a fundamental task for deeply understanding the structure and function of a network. By means of a lumped Markov chain model of a random walker, we propose two novel ways of inferring the lumped markov transition matrix. Furthermore, some useful results are proposed based on the analysis of the properties of the lumped Markov process. To find the best partition of complex networks, a novel framework including two algorithms for network partition based on the optimal lumped Markovian dynamics is derived to solve this problem. The algorithms are constructed to minimize the objective function under this framework. It is demonstrated by the simulation experiments that our algorithms can efficiently determine the probabilities with which a node belongs to different clusters during the learning process and naturally supports the fuzzy partition. Moreover, they are successfully applied to real-world network, including the social interactions between members of a karate club.

  19. QSAR analysis of substituted benzylamino- and heterocyclylmethylamino-carbodithioate derivatives of 4-(3H)-quinazolinone using CoMFA and SCORE2.0

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Thymidylate synthase (TS) is a critical enzyme for DNA biosynthesis and many nonclassical lipophilic antifolates targeting this enzyme are quite efficient and encouraging as antitumor drugs. In this paper, the binding model of 14 antifolates of substituted benzylamino- and heterocyclylmethylamino- carbodithioate derivatives of 4-(3H)-quinazolinone with TS is examined using molecular simulation methods――FlexiDock and SCORE2.0. The resulting conformation and orientation of these antifolates are directly applied to CoMFA study. The robust QSAR model, its three-dimensional contour map, and binding score of these antifolates derived from SCORE2.0 provide guidelines for structural optimization of current antifolates. The experiment indicates that deletion of cancer chemopreventive structure of dithiocarbamate is unfavorable for interaction between TS and antifolates.

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

    Science.gov (United States)

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

    2016-08-15

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

  1. Analysing grouping of nucleotides in DNA sequences using lumped processes constructed from Markov chains.

    Science.gov (United States)

    Guédon, Yann; d'Aubenton-Carafa, Yves; Thermes, Claude

    2006-03-01

    The most commonly used models for analysing local dependencies in DNA sequences are (high-order) Markov chains. Incorporating knowledge relative to the possible grouping of the nucleotides enables to define dedicated sub-classes of Markov chains. The problem of formulating lumpability hypotheses for a Markov chain is therefore addressed. In the classical approach to lumpability, this problem can be formulated as the determination of an appropriate state space (smaller than the original state space) such that the lumped chain defined on this state space retains the Markov property. We propose a different perspective on lumpability where the state space is fixed and the partitioning of this state space is represented by a one-to-many probabilistic function within a two-level stochastic process. Three nested classes of lumped processes can be defined in this way as sub-classes of first-order Markov chains. These lumped processes enable parsimonious reparameterizations of Markov chains that help to reveal relevant partitions of the state space. Characterizations of the lumped processes on the original transition probability matrix are derived. Different model selection methods relying either on hypothesis testing or on penalized log-likelihood criteria are presented as well as extensions to lumped processes constructed from high-order Markov chains. The relevance of the proposed approach to lumpability is illustrated by the analysis of DNA sequences. In particular, the use of lumped processes enables to highlight differences between intronic sequences and gene untranslated region sequences.

  2. Holographic QSAR of environmental estrogens

    Institute of Scientific and Technical Information of China (English)

    WANG; Xiaodong; XIAO; Qianfen; CUI; Shihai; LIU; Shushen

    2005-01-01

    Experimental and epidemiological studies suggest that some man-made and naturally occurring chemicals related to the environment have the potential to interrupt normal functioning of the endocrine systems of humans and wildlife. These chemicals, termed EDCs (Endocrine disrupting Chemicals), pose serious threats to the reproductive capability of humans and wildlife. Because of the structural diversity and various types, development of structure-based rapid screening methodologies is important and necessary for the assessment of the environmental pollutants. In this paper molecular hologram based QSAR models were developed with the combinatory application of partial least square (PLS) regression for a large diverse set of 105 environmental estrogens. Quantitatively predictive models were developed based on only molecular structures, which can be used for the accurate prediction of estrogenicity to rapidly screen potential environmental endocrine disrupting chemicals.

  3. Application of lumped-parameter models

    DEFF Research Database (Denmark)

    Ibsen, Lars Bo; Liingaard, Morten

    This technical report concerns the lumped-parameter models for a suction caisson with a ratio between skirt length and foundation diameter equal to 1/2, embedded into an viscoelastic soil. The models are presented for three different values of the shear modulus of the subsoil (section 1.1). Subse...

  4. Sonomammographic Evaluation AND Characterization of Breast Lumps

    Directory of Open Access Journals (Sweden)

    Umesh Shah

    2015-12-01

    Full Text Available Introduction: Modern breast USG is an established, ideal and accurate tool for the investigation and characterization of breast lumps. It also compliments X-ray mammography in further evaluation and diagnosis of breast masses and thus avoids unnecessary breast surgeries in benign conditions. We present a case series of 64 patients with ultrasound findings in various breast lumps and pathologies. Aims and Objective: In this study we planned to evaluate and characterize breast lumps with USG examination. Material and Method: The present study was conducted in the Department of Radio-diagnosis, GMERS, Patan. Patients under study were referred from the department of Surgery, medicine and gynaecology and obstetrics. Patients included for study were evaluated by Clinical and Ultrasound examination. Histopathological confirmation was done in all the cases by FNAC/ excision biopsy. Result: On examination distribution of lesions was found to be Fibroadenoma (31.1%, Breast cyst (20.7%, Intraductal papilloma (5.2%, Lipoma (3.4%, Breast abscess (3.4%, Galactocele (3.4%, Cystosarcoma phyllodes (3.4%, Hamartoma/ Fibroadenlipoma (3.4% and Fat necrosis (3.4%, Invasive ductal carcinoma (17.4%, Invasive lobular carcinoma(5.2%. Conclusion: Sonomammography is a very dynamic and powerful tool for the evaluation of lumps. It considerably improves the visualization and evaluation of tumors in radiodense breasts as well it improves the specifi city of mammography when used to complement X-ray mammography. [Natl J Med Res 2015; 5(4.000: 316-318

  5. 3D-QSAR and docking studies of arylmethylamine-based DPP IV inhibitors

    Directory of Open Access Journals (Sweden)

    Chaoyi Jiang

    2012-08-01

    Full Text Available The present work was focused on the study of the three-dimensional (3D structural requirements for the highly potent bioactivity of dipeptidyl peptidase (DPP IV's inhibitor. At first, molecular dynamic and mechanic (MD/MM simulations were performed to research the conformations of the potent DPP IV's inhibitor 5-(aminomethyl-6-(2,4-dichlorophenyl-2-(3,5-dimethoxy-phenylpyrimidin-4-amine. Using the MD/MM-determined molecular conformers as templates, the 3D quantitative structure activity relationship (QSAR studies were carried out based on a set of arylmethylamine DPP IV inhibitors with the comparative molecular field analysis (CoMFA approach. The best 3D-QSAR model was constructed with good statistic values of rcv2 and R2 using PLS analyses (CoMFA: rcv2=0.660, R2=0.953. The generated 3D-QSAR model was proved to be reliable by internal and external validations. Docking studies were further performed to analyze the interaction mode between the highly potent or low potent arylmethylamine derivatives and DPP IV. Our flexible docking results also confirmed the possible bioactive conformation obtained from the 3D-QSAR model, of arylmethylamine-based DPP IV inhibitors. The 3D-QSAR model may provide information of pharmacophoric features for further design and optimization of new scaffold compounds with high inhibitory activity to DPP IV.

  6. 22 CFR 19.13-1 - Lump-sum credit.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Lump-sum credit. 19.13-1 Section 19.13-1... THE FOREIGN SERVICE RETIREMENT AND DISABILITY SYSTEM § 19.13-1 Lump-sum credit. “Lump-sum credit” is the compulsory and special contributions to a participant's or former participant's credit in the Fund...

  7. 42 CFR 411.46 - Lump-sum payments.

    Science.gov (United States)

    2010-10-01

    ... Covered Under Workers' Compensation § 411.46 Lump-sum payments. (a) Lump-sum commutation of future benefits. If a lump-sum compensation award stipulates that the amount paid is intended to compensate the... payment of workers' compensation benefits, medical expenses incurred after the date of the settlement are...

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

    Science.gov (United States)

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

    2014-01-01

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

  9. 3D-QSAR analysis on broad-spectrum arenavirus inhibitors%广谱沙粒病毒抑制剂的3D-QSAR分析

    Institute of Scientific and Technical Information of China (English)

    杨银凤; 王斌; 王景辉; 李燕; 杨凌

    2014-01-01

    沙粒病毒(Arenaviruses)遍布全球,其中的拉沙热病毒可引起致命的拉沙热.通过应用比较分子场分析(CoMFA)和比较相似性指数分析法(CoMSIA)对47个广谱沙粒病毒抑制剂进行了三维定量构效关系(3D-QSAR)分析.使用立体场、静电场、疏水场和氢键受体场组合获得最优模型CoMSIA的统计结果为Q2=0.518,Rncv2=0.972,Rpre2=0.911,说明该模型的可靠性和较好预测能力.此外,模型等势线图直观地解释了分子结构与其活性的关系,为进一步设计新型高效的沙粒病毒抑制剂提供了理论依据.

  10. Estimation of the hydrophobicity of 2,4-diphenyl-1,3-oxazoline analogs and QSAR analysis of their ovicidal activity against Tetranychus [corrected] urticae.

    Science.gov (United States)

    Minakuchi, Chieka; Suzuki, Junji; Toda, Kazuya; Akamatsu, Miki; Nakagawa, Yoshiaki

    2006-08-01

    Partition coefficients of six 2-phenyl-1,3-oxazoline congeners containing 2-I, 2-NO2, 2-CF3, 2,6-(CH3)2, 2,6-F2, and 2-F-6-Cl substitutions on the phenyl moiety were measured in a 1-octanol/water system using the flask-shaking method. The effect on the hydrophobicity (LogP) of substituents on the phenyl moiety of 2-phenyl-1,3-oxazolines linearly correlated with that of benzamide congeners. logP values of other 2-(substituted phenyl)-1,3-oxazoline analogs were empirically estimated from the corresponding substituted benzamides. The ovicidal activity of 2-(substituted phenyl)-4-phenyl-1,3-oxazoline analogs against the two-spotted spider mite Tetranychus [corrected] urticae was quantitatively analyzed using the classical QSAR (Hansch-Fujita) method. Results showed that ovicidal activity increases with hydrophobicity. The introduction of inductive electron-withdrawing groups at ortho-positions increased ovicidal activity, but addition of steric bulk was unfavorable. Substitution at either the meta- or para-position was detrimental to the acaricidal activity.

  11. Simplified molecular input-line entry system and International Chemical Identifier in the QSAR analysis of styrylquinoline derivatives as HIV-1 integrase inhibitors.

    Science.gov (United States)

    Toropova, Alla P; Toropov, Andrey A; Benfenati, Emilio; Gini, Giuseppina

    2011-05-01

    The simplified molecular input-line entry system (SMILES) and IUPAC International Chemical Identifier (InChI) were examined as representations of the molecular structure for quantitative structure-activity relationships (QSAR), which can be used to predict the inhibitory activity of styrylquinoline derivatives against the human immunodeficiency virus type 1 (HIV-1). Optimal SMILES-based descriptors give a best model with n = 26, r(2) = 0.6330, q(2) = 0.5812, s = 0.502, F = 41 for the training set and n = 10, r(2) = 0.7493, r(pred)(2) = 0.6235, R(m)(2) = 0.537, s = 0.541, F = 24 for the validation set. Optimal InChI-based descriptors give a best model with n = 26, r(2) = 0.8673, q(2) = 0.8456, s = 0.302, F = 157 for the training set and n = 10, r(2) = 0.8562, r(pred)(2) = 0.7715, R(m)(2) = 0.819, s = 0.329, F = 48 for the validation set. Thus, the InChI-based model is preferable. The described SMILES-based and InChI-based approaches have been checked with five random splits into the training and test sets. © 2011 John Wiley & Sons A/S.

  12. Lumped and distributed passive networks a generalized and advanced viewpoint

    CERN Document Server

    Wohlers, M Ronald; Declaris, Nicholas

    1969-01-01

    Lumped and Distributed Passive Networks: A Generalized and Advanced Viewpoint considers the mathematical study of a subset of passive linear operators. This five-chapter focuses on the questions of analysis and representation of such operators and illustrates the results of these analyses by obtaining some of the limitations that are imposed on the performance of passive systems. The first two chapters deal with the structure of general linear passive operators. These chapters specifically look into the theory of distributions, called generalized functions. The third and fourth chapters illust

  13. QSAR study and VolSurf characterization of anti-HIV quinolone library

    Science.gov (United States)

    Filipponi, Enrica; Cruciani, Gabriele; Tabarrini, Oriana; Cecchetti, Violetta; Fravolini, Arnaldo

    2001-03-01

    Antiviral quinolones are promising compounds in the search for new therapeutically effective agents for the treatment of AIDS. To rationalize the SAR for this new interesting class of anti-HIV derivatives, we performed a 3D-QSAR study on a library of 101 6-fluoro and 6-desfluoroquinolones, taken either from the literature or synthesized by us. The chemometric procedure involved a fully semiempirical minimization of the molecular structures by the AMSOL program, which takes into account the solvatation effect, and their 3D characterization by the VolSurf/GRID program. The QSAR analysis, based on PCA and PLS methods, shows the key structural features responsible for the antiviral activity.

  14. 2D/3D-QSAR comparative study on mutagenicity of nitroaromatics

    Institute of Scientific and Technical Information of China (English)

    WANG Xiaodong; LIN Zhifen; YIN Daqiang; LIU Shushen; WANG Liansheng

    2005-01-01

    Nitroaromatics are typical toxic organic pollutants and are ubiquitous in environment with diverse structures. They are widely used in many industries and formed during many natural and anthropogenic processes. Most of these pollutants are potentially carcinogenic and the assessment and prediction of the mutagenicity of nitroaromatics are of great interest. In this paper the structure-mutagenicity relationships of 219 nitroaromatics are investigated by molecular orbital theory based classic structure-activity relationships and comparative molecular field analysis (CoMFA). A comparison is undertaken in respect of the interpretation of mechanism and predictive ability for these two categories of QSAR approaches and highly predictive QSAR models have been developed.

  15. IMPROVEMENT OF FLUID PIPE LUMPED PARAMETER MODEL

    Institute of Scientific and Technical Information of China (English)

    Kong Xiaowu; Wei Jianhua; Qiu Minxiu; Wu Genmao

    2004-01-01

    The traditional lumped parameter model of fluid pipe is introduced and its drawbacks are pointed out.Furthermore, two suggestions are put forward to remove these drawbacks.Firstly, the structure of equivalent circuit is modified, and then the evaluation of equivalent fluid resistance is change to take the frequency-dependent friction into account.Both simulation and experiment prove that this model is precise to characterize the dynamic behaviors of fluid in pipe.

  16. QSAR and 3D-QSAR studies of the diacyl-hydrazine derivatives containing furan rings based on the density functional theory

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    QSAR studies of 27 diacyl-hydrazine derivatives containing furan rings were conducted and compared with the DFT method and AM1-MOPAC method.q2 values of 0.61 and 0.40 validated the predictability and reliability of eq.(5) from the DFT method were higher than those of eq.(6) from the AM1-MOPAC method.The DFT-optimized conformations and ESP-fitting charges of the target compounds were also used for 3D-QSAR analysis,including CoMFA and CoMSIA.The leave-one-out cross-validation correlation coefficient and the good correlation between the predicted and experimental activities of excluded test compounds revealed that CoMFA and CoMSIA models were robust.The QSAR results were consistent with the 3D-QSAR results,indicating that the electrostatic and hydrophobic properties of the target compounds were significant to the biological activity.These models are useful tools for predicting the larvicidal activities of new compounds and designing new specific insect growth regulators.

  17. Observations of gravity-capillary lump interactions

    CERN Document Server

    Masnadi, Naeem

    2016-01-01

    In this experimental study, we investigate the interaction of gravity-capillary solitary waves generated by two surface pressure sources moving side by side at constant speed. The nonlinear response of a water surface to a single source moving at a speed just below the minimum phase speed of linear gravity-capillary waves in deep water ($c_{min}\\approx23$ cm s$^{-1}$) consists of periodic generation of pairs of three-dimensional solitary waves (or lumps) in a V-shaped pattern downstream of the source. In the reference frame of the laboratory, these unsteady lumps propagate in a direction oblique to the motion of the source. In the present experiments, the strength of the two sources is adjusted to produce nearly identical responses and the free surface deformations are visualized using photography-based techniques. The first lumps generated by the two sources move in intersecting directions that make a half angle of approximately 15 degrees and collide in the center-plane between the sources. A steep depressi...

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

    Science.gov (United States)

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

    2016-03-01

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

  19. QSAR modeling: um novo pacote computacional open source para gerar e validar modelos QSAR QSAR modeling: a new open source computational package to generate and validate QSAR models

    Directory of Open Access Journals (Sweden)

    João Paulo A. Martins

    2013-01-01

    Full Text Available QSAR modeling is a novel computer program developed to generate and validate QSAR or QSPR (quantitative structure- activity or property relationships models. With QSAR modeling, users can build partial least squares (PLS regression models, perform variable selection with the ordered predictors selection (OPS algorithm, and validate models by using y-randomization and leave-N-out cross validation. An additional new feature is outlier detection carried out by simultaneous comparison of sample leverage with the respective Studentized residuals. The program was developed using Java version 6, and runs on any operating system that supports Java Runtime Environment version 6. The use of the program is illustrated. This program is available for download at lqta.iqm.unicamp.br.

  20. Predictive QSAR modeling of phosphodiesterase 4 inhibitors.

    Science.gov (United States)

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

    2012-02-01

    A series of diverse organic compounds, phosphodiesterase type 4 (PDE-4) inhibitors, have been modeled using a QSAR-based approach. 48 QSAR models were compared by following the same procedure with different combinations of descriptors and machine learning methods. QSAR methodologies used random forests and associative neural networks. The predictive ability of the models was tested through leave-one-out cross-validation, giving a Q² = 0.66-0.78 for regression models and total accuracies Ac=0.85-0.91 for classification models. Predictions for the external evaluation sets obtained accuracies in the range of 0.82-0.88 (for active/inactive classifications) and Q² = 0.62-0.76 for regressions. The method showed itself to be a potential tool for estimation of IC₅₀ of new drug-like candidates at early stages of drug development. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2016-12-01

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

  2. QSAR analysis of a series of 2-aryl(heteroaryl)-2,5-dihydropyrazolo[4,3-c]quinolin-3-(3H)-ones using piecewise hyper-sphere modeling by particle swarm optimization

    Energy Technology Data Exchange (ETDEWEB)

    Lin Li [State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082 (China); Lin Weiqi [State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082 (China); Jiang Jianhui [State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082 (China); Zhou Yanping [State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082 (China); Shen Guoli [State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082 (China); Yu Ruqin [State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082 (China)]. E-mail: rqyu@hnu.cn

    2005-11-03

    In the present work, we employed piecewise hyper-sphere modeling by particle swarm optimization (PHMPSO) which splits the dataset into subsets with desired linearity in each model for QSAR studies of a series of 2-aryl(heteroaryl)-2,5-dihydropyrazolo[4,3-c]quinolin-3-(3H)-ones (PQs) for their affinity to benzodiazepine receptor (BzR). The results were compared to those obtained by MLR modeling in a single model with the whole data set as well as in submodels based on K-means clustering analysis. It has been clearly shown that electronic descriptors and spatial descriptors play the important roles in the compounds' affinity to BzR. In addition, the molecular density, the Y component of the principal moment of inertia, the magnitude and the Y component of the dipole moment of the molecules can detrimentally affect PQ analogue BzR affinity, while the X component of the dipole moment of the molecules can favorably affect compounds' affinity.

  3. QSAR Investigation on Quinolizidinyl Derivatives in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Ghasem Ghasemi

    2013-01-01

    Full Text Available Sets of quinolizidinyl derivatives of bi- and tri-cyclic (hetero aromatic systems were studied as selective inhibitors. On the pattern, quantitative structure-activity relationship (QSAR study has been done on quinolizidinyl derivatives as potent inhibitors of acetylcholinesterase in alzheimer’s disease (AD. Multiple linear regression (MLR, partial least squares (PLSs, principal component regression (PCR, and least absolute shrinkage and selection operator (LASSO were used to create QSAR models. Geometry optimization of compounds was carried out by B3LYP method employing 6–31 G basis set. HyperChem, Gaussian 98 W, and Dragon software programs were used for geometry optimization of the molecules and calculation of the quantum chemical descriptors. Finally, Unscrambler program was used for the analysis of data. In the present study, the root mean square error of the calibration and R2 using MLR method were obtained as 0.1434 and 0.95, respectively. Also, the R and R2 values were obtained as 0.79, 0.62 from stepwise MLR model. The R2 and mean square values using LASSO method were obtained as 0.766 and 3.226, respectively. The root mean square error of the calibration and R2 using PLS method were obtained as 0.3726 and 0.62, respectively. According to the obtained results, it was found that MLR model is the most favorable method in comparison with other statistical methods and is suitable for use in QSAR models.

  4. Development of multiple QSAR models for consensus predictions and unified mechanistic interpretations of the free-radical scavenging activities of chromone derivatives.

    Science.gov (United States)

    Mitra, Indrani; Saha, Achintya; Roy, Kunal

    2012-05-01

    Antioxidants are important defenders of the human body against nocive free radicals, which are the causative agents of most life-threatening diseases. The immense biomedicinal utility of antioxidants necessitates the development and design of new synthetic antioxidant molecules. The present report deals with the modeling of a series of chromone derivatives, which was done to provide detailed insight into the main structural fragments that impart antioxidant activity to these molecules. Four different quantitative structure-property relationship (QSAR) techniques, namely 3D pharmacophore mapping, comparative molecular similarity indices analysis (CoMSIA 3D-QSAR), hologram QSAR (HQSAR), and group-based QSAR (G-QSAR) techniques, were employed to obtain statistically significant models with encouraging external predictive potentials. Moreover, the visual contribution maps obtained for the different models signify the importance of different structural features in specific regions of the chromone nucleus. Additionally, the G-QSAR models determine the composite influence of pairs of substituent fragments on the overall antioxidant activity profiles of the molecules. Multiple models with different strategies for assessing structure-activity relationships were applied to reach a unified conclusion regarding the antioxidant mechanism and to provide consensus predictions, which are more reliable than values derived from a single model. The structural information obtained from the various QSAR models developed in the present work can thus be effectively utilized to design and predict the activities of new molecules belonging to the class of chromone derivatives.

  5. Epsilon-Near-Zero Photonics Wires for Mid-Infrared Optical Lumped Circuitry

    CERN Document Server

    Liu, Runyu; Zhong, Yujun; Podolskiy, Viktor; Wasserman, Daniel

    2016-01-01

    There has been recent interest in the development of optical analogues of lumped element circuitry, where optical elements act as effective optical inductors, capacitors, and resistors. Such optical circuitry requires the photonic equivalent of electrical wires, structures able carry optical frequency signals to and from the lumped circuit elements while simultaneously maintaining signal carrier wavelengths much larger than the size of the lumped elements. Here we demonstrate the design, fabrication, and characterization of hybrid metal/doped-semiconductor 'photonic wires' operating at optical frequencies with effective indices of propagation near-zero. Our samples are characterized by polarization and angle-dependent FTIR spectroscopy and modeled by finite element methods and rigorous coupled wave analysis. We demonstrate coupling to such photonic wires from free space, and show the effective wavelength of the excited mode to be approximately an order of magnitude larger than the free-space wavelength of our...

  6. Virtual Screening and Molecular Design Based on Hierarchical Qsar Technology

    Science.gov (United States)

    Kuz'min, Victor E.; Artemenko, A. G.; Muratov, Eugene N.; Polischuk, P. G.; Ognichenko, L. N.; Liahovsky, A. V.; Hromov, A. I.; Varlamova, E. V.

    This chapter is devoted to the hierarchical QSAR technology (HiT QSAR) based on simplex representation of molecular structure (SiRMS) and its application to different QSAR/QSPR tasks. The essence of this technology is a sequential solution (with the use of the information obtained on the previous steps) of the QSAR paradigm by a series of enhanced models based on molecular structure description (in a specific order from 1D to 4D). Actually, it's a system of permanently improved solutions. Different approaches for domain applicability estimation are implemented in HiT QSAR. In the SiRMS approach every molecule is represented as a system of different simplexes (tetratomic fragments with fixed composition, structure, chirality, and symmetry). The level of simplex descriptors detailed increases consecutively from the 1D to 4D representation of the molecular structure. The advantages of the approach presented are an ability to solve QSAR/QSPR tasks for mixtures of compounds, the absence of the "molecular alignment" problem, consideration of different physical-chemical properties of atoms (e.g., charge, lipophilicity), and the high adequacy and good interpretability of obtained models and clear ways for molecular design. The efficiency of HiT QSAR was demonstrated by its comparison with the most popular modern QSAR approaches on two representative examination sets. The examples of successful application of the HiT QSAR for various QSAR/QSPR investigations on the different levels (1D-4D) of the molecular structure description are also highlighted. The reliability of developed QSAR models as the predictive virtual screening tools and their ability to serve as the basis of directed drug design was validated by subsequent synthetic, biological, etc. experiments. The HiT QSAR is realized as the suite of computer programs termed the "HiT QSAR" software that so includes powerful statistical capabilities and a number of useful utilities.

  7. QSAR Study of Sucrose and Guanidine Derivatives

    African Journals Online (AJOL)

    NICO

    design, but there have been several applications of QSAR to the taste properties of ... by selection of relevant grid points by the genetic algorithm method to ... The geometry optimization of all the derivatives and evalu- ation of values of the ... form of the solution to the quantum mechanical equation as expressed in the ...

  8. Lumped elements for RF and microwave circuits

    CERN Document Server

    Bahl, Inder

    2003-01-01

    Due to the unprecedented growth in wireless applications over the past decade, development of low-cost solutions for RF and microwave communication systems has become of great importance. This practical new book is the first comprehensive treatment of lumped elements, which are playing a critical role in the development of the circuits that make these cost-effective systems possible. The books offers you an in-depth understanding of the different types of RF and microwave circuit elements, including inductors, capacitors, resistors, transformers, via holes, airbridges, and crossovers. Support

  9. 3D-QSAR Study of 7,8-Dialkyl-1,3-diaminopyrrolo-[3,2-f]Quinazolines with Anticancer Activity as DHFR Inhibitors

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  10. GWDC Wins the Lekhwair Drilling Contract on a Lump Lump Sum Basis in Oman

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ GWDC (Great Wall Drilling Company Ltd.) has become the first Chinese drilling contractor to win a contract on a lump sum basis in PDO (Petroleum Development Oman) to carry out a major strategic drilling campaign in Lekhwair, Oman. The Lekhwair Drilling Campaign Contract was signed in August, 2005 following acceptance of the award by PDO.

  11. MRI、超声及钼靶在乳腺肿块大小测量中的比较%A Comparative Analysis of MRI, Ultrasonography and Molybdenum Target Mammography in the Measurement of Breast Lump Size

    Institute of Scientific and Technical Information of China (English)

    安静; 夏玉军

    2016-01-01

    Objective To comparatively analyze the accuracy of MRI, ultrasound and mammography in the measurement of lump size in patients with breast cancer. Methods 51 cases of breast tumor patients (53 lesions) who underwent diagnosis and treatment for breast tumors from January 2014 to June 2014 in our hospital were selected as research objects. All the selected patients underwent preoperative mammography, ultrasound, and MRI examination to measure the size of breast lumps. The corresponding data was recorded and compared with postoperative pathological results. The accuracy of the three methods in determining the lump size was compared. Results The difference between the maximum cross-sectional diameter of breast lumps obtained from mammography, ultrasound, and MRI measurements and the results obtained by actual measurement of pathological specimens was≤1 cm in 10 cases ( 27.8%), 20 cases ( 55.6%) , and 24 cases ( 66.7%) respectively. Conclusion The accuracy of MRI in the measurement of breast lump size was higher than the accuracy of ultrasound and mammography. MRI is a realiable examination method in the preoperative assessment of breast tumor size.%目的:对比分析MRI、超声及钼靶测量乳腺肿块大小的准确性。方法选取2014年1月~2014年6月在本院就诊的51例乳腺肿物患者(53个病灶)为研究对象,所有患者于术前均通过钼靶、超声及MRI检查测量了肿块大小,记录相应数据,并与术后病理结果进行对比,比较3种方法测量肿块大小的准确性。结果钼靶、超声、MRI测得的乳腺肿块横截面最大径与病理标本的实际测量值差值≤1 cm者分别有10例(27.8%)、20例(55.6%)、24例(66.7%)。结论MRI检查测量乳腺肿块大小的准确性高于钼靶和超声检查,是术前准确评估乳腺肿块大小的可靠检查手段。

  12. Structure Modification Toward Applicability Domain of a QSAR/QSPR Model Considering Activity/Property.

    Science.gov (United States)

    Ochi, Shoki; Miyao, Tomoyuki; Funatsu, Kimito

    2017-08-16

    In drug and material design, the activity and property values of the designed chemical structures can be predicted by quantitative structure-activity and structure-property relationship (QSAR/QSPR) models. When a QSAR/QSPR model is applied to chemical structures, its applicability domain (AD) must be considered. The predicted activity/property values are only reliable for chemical structures inside the AD. Chemical structures outside the AD are usually neglected, as the predicted values are unreliable. The purpose of this study is to develop a methodology for obtaining novel chemical structures with the desired activity or property based on a QSAR/QSPR model by making use of the neglected structures. We propose a structure modification strategy for the AD that considers the activity and property simultaneously. The AD is defined by a one-class support vector machine and the structure modification is guided by a partial derivative of the AD model and matched molecular pairs analysis. Three proof-of-concept case studies generate novel chemical structures inside the AD that exhibit preferable activity/property values according to the QSAR/QSPR model. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Science.gov (United States)

    Gramatica, Paola; Cassani, Stefano; Chirico, Nicola

    2014-05-15

    A database of environmentally hazardous chemicals, collected and modeled by QSAR by the Insubria group, is included in the updated version of QSARINS, software recently proposed for the development and validation of QSAR models by the genetic algorithm-ordinary least squares method. In this version, a module, named QSARINS-Chem, includes several datasets of chemical structures and their corresponding endpoints (physicochemical properties and biological activities). The chemicals are accessible in different ways (CAS, SMILES, names and so forth) and their three-dimensional structure can be visualized. Some of the QSAR models, previously published by our group, have been redeveloped using the free online software for molecular descriptor calculation, PaDEL-Descriptor. The new models can be easily applied for future predictions on chemicals without experimental data, also verifying the applicability domain to new chemicals. The QSAR model reporting format (QMRF) of these models is also here downloadable. Additional chemometric analyses can be done by principal component analysis and multicriteria decision making for screening and ranking chemicals to prioritize the most dangerous. Copyright © 2014 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2013-06-01

    Quantitative structure-property/activity relationships (QSPRs/QSARs) are a tool to predict various endpoints for various substances. The "classic" QSPR/QSAR analysis is based on the representation of the molecular structure by the molecular graph. However, simplified molecular input-line entry system (SMILES) gradually becomes most popular representation of the molecular structure in the databases available on the Internet. Under such circumstances, the development of molecular descriptors calculated directly from SMILES becomes attractive alternative to "classic" descriptors. The CORAL software (http://www.insilico.eu/coral) is provider of SMILES-based optimal molecular descriptors which are aimed to correlate with various endpoints. We analyzed data set on nanoparticles uptake in PaCa2 pancreatic cancer cells. The data set includes 109 nanoparticles with the same core but different surface modifiers (small organic molecules). The concept of a QSAR as a random event is suggested in opposition to "classic" QSARs which are based on the only one distribution of available data into the training and the validation sets. In other words, five random splits into the "visible" training set and the "invisible" validation set were examined. The SMILES-based optimal descriptors (obtained by the Monte Carlo technique) for these splits are calculated with the CORAL software. The statistical quality of all these models is good. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. AutoWeka: toward an automated data mining software for QSAR and QSPR studies.

    Science.gov (United States)

    Nantasenamat, Chanin; Worachartcheewan, Apilak; Jamsak, Saksiri; Preeyanon, Likit; Shoombuatong, Watshara; Simeon, Saw; Mandi, Prasit; Isarankura-Na-Ayudhya, Chartchalerm; Prachayasittikul, Virapong

    2015-01-01

    In biology and chemistry, a key goal is to discover novel compounds affording potent biological activity or chemical properties. This could be achieved through a chemical intuition-driven trial-and-error process or via data-driven predictive modeling. The latter is based on the concept of quantitative structure-activity/property relationship (QSAR/QSPR) when applied in modeling the biological activity and chemical properties, respectively, of compounds. Data mining is a powerful technology underlying QSAR/QSPR as it harnesses knowledge from large volumes of high-dimensional data via multivariate analysis. Although extremely useful, the technicalities of data mining may overwhelm potential users, especially those in the life sciences. Herein, we aim to lower the barriers to access and utilization of data mining software for QSAR/QSPR studies. AutoWeka is an automated data mining software tool that is powered by the widely used machine learning package Weka. The software provides a user-friendly graphical interface along with an automated parameter search capability. It employs two robust and popular machine learning methods: artificial neural networks and support vector machines. This chapter describes the practical usage of AutoWeka and relevant tools in the development of predictive QSAR/QSPR models. The software is freely available at http://www.mt.mahidol.ac.th/autoweka.

  16. QSAR models based on quantum topological molecular similarity.

    Science.gov (United States)

    Popelier, P L A; Smith, P J

    2006-07-01

    A new method called quantum topological molecular similarity (QTMS) was fairly recently proposed [J. Chem. Inf. Comp. Sc., 41, 2001, 764] to construct a variety of medicinal, ecological and physical organic QSAR/QSPRs. QTMS method uses quantum chemical topology (QCT) to define electronic descriptors drawn from modern ab initio wave functions of geometry-optimised molecules. It was shown that the current abundance of computing power can be utilised to inject realistic descriptors into QSAR/QSPRs. In this article we study seven datasets of medicinal interest : the dissociation constants (pK(a)) for a set of substituted imidazolines , the pK(a) of imidazoles , the ability of a set of indole derivatives to displace [(3)H] flunitrazepam from binding to bovine cortical membranes , the influenza inhibition constants for a set of benzimidazoles , the interaction constants for a set of amides and the enzyme liver alcohol dehydrogenase , the natriuretic activity of sulphonamide carbonic anhydrase inhibitors and the toxicity of a series of benzyl alcohols. A partial least square analysis in conjunction with a genetic algorithm delivered excellent models. They are also able to highlight the active site, of the ligand or the molecule whose structure determines the activity. The advantages and limitations of QTMS are discussed.

  17. {sup 14}C chronology of the oldest Scandinavian church in use. An AMS/PIXE study of lime lump carbonate in the mortar

    Energy Technology Data Exchange (ETDEWEB)

    Lindroos, Alf, E-mail: alf.lindroos@abo.fi [Geology and Mineralogy, Department of Natural Sciences, Åbo Akademi University (Finland); Art History, Faculty of Art, Åbo Akademi University (Finland); Ranta, Heikki [Diocese of Lund, Church of Sweden (Sweden); Heinemeier, Jan [AMS " 1" 4C Dating Laboratory, Department of Physics and Astronomy, University of Aarhus (Denmark); Lill, Jan-Olof [Accelerator Laboratory, Turku PET Centre, Åbo Akademi University (Finland)

    2014-07-15

    Mortar dating was applied to newly revealed, original mortar in the church of Dalby in Scania, southern Sweden which is considered to be the oldest still standing church in Scandinavia. Small white lime lumps were sampled by chipping from the supporting pillars in the interior of the church. Special emphasis was in sampling lime lumps because the church is situated in the Scania limestone area and aggregate limestone contamination was anticipated in the bulk mortars. Earlier studies have, however, shown that lime lumps do not contain aggregate material but only possible limestone rests from incomplete calcination. The sampled material was prepared for radiocarbon AMS dating. The carbonate in the lime lumps was hydrolyzed according to the sequential leaching technique developed for the Århus {sup 14}C laboratory in Denmark. Prior to the hydrolysis the lime lumps were examined for dead-carbon contamination using a stereo microscope and cathodoluminescence. The lime lumps displayed heterogeneous carbonate luminescence. This is, however, common and it was not considered a problem because carbonate growth in changing pH/Eh conditions often leads to changing luminescence colors. Two lumps had little dead carbon contamination and an early second millennium {sup 14}C signature. One lump, however, seemed to be heavily contaminated with dead carbon. Since the sample passed the microscopic screening, the leftovers of the lump was subjected to PIXE analysis and compared with the other two lumps. The well-defined, early 2nd millennium {sup 14}C age of the lime lumps of this particular church is an important contribution to the discussion on stone church chronology in Scandinavia.

  18. A QSAR model for predicting rejection of emerging contaminants (pharmaceuticals, endocrine disruptors) by nanofiltration membranes.

    Science.gov (United States)

    Yangali-Quintanilla, Victor; Sadmani, Anwar; McConville, Megan; Kennedy, Maria; Amy, Gary

    2010-01-01

    A quantitative structure activity relationship (QSAR) model has been produced for predicting rejection of emerging contaminants (pharmaceuticals, endocrine disruptors, pesticides and other organic compounds) by polyamide nanofiltration (NF) membranes. Principal component analysis, partial least square regression and multiple linear regressions were used to find a general QSAR equation that combines interactions between membrane characteristics, filtration operating conditions and compound properties for predicting rejection. Membrane characteristics related to hydrophobicity (contact angle), salt rejection, and surface charge (zeta potential); compound properties describing hydrophobicity (log K(ow), log D), polarity (dipole moment), and size (molar volume, molecular length, molecular depth, equivalent width, molecular weight); and operating conditions namely flux, pressure, cross flow velocity, back diffusion mass transfer coefficient, hydrodynamic ratio (J(o)/k), and recovery were identified as candidate variables for rejection prediction. An experimental database produced by the authors that accounts for 106 rejection cases of emerging contaminants by NF membranes as result of eight experiments with clean and fouled membranes (NF-90, NF-200) was used to produce the QSAR model. Subsequently, using the QSAR model, rejection predictions were made for external experimental databases. Actual rejections were compared against predicted rejections and acceptable R(2) correlation coefficients were found (0.75 and 0.84) for the best models. Additionally, leave-one-out cross-validation of the models achieved a Q(2) of 0.72 for internal validation. In conclusion, a unified general QSAR equation was able to predict rejections of emerging contaminants during nanofiltration; moreover the present approach is a basis to continue investigation using multivariate analysis techniques for understanding membrane rejection of organic compounds.

  19. In vitro mutagenicity and genotoxicity study of a number of short-chain chlorinated hydrocarbons using the micronucleus test and the alkaline single cell gel electrophoresis technique (Comet assay) in human lymphocytes: a structure-activity relationship (QSAR) analysis of the genotoxic and cytotoxic potential.

    Science.gov (United States)

    Tafazoli, M; Baeten, A; Geerlings, P; Kirsch-Volders, M

    1998-03-01

    Using the micronucleus (MN) test and the alkaline single cell gel electrophoresis (Comet) assay, potential mutagenicity (MN formation), genotoxicity (DNA breakage capacity) and cytotoxicity (cell proliferation reduction) of five chlorinated hydrocarbons (carbon tetrachloride, hexachloroethane, 1,2-dichloroethane, 1-chlorohexane and 2,3-dichlorobutane) have been evaluated in isolated human lymphocytes. With the MN test a low but statistically significant mutagenic activity was detected for all tested substances (except 2,3-dichlorobutane) with one out of the two donors and in the presence or absence of an exogenous metabolic activation system (S9 mix). However, at the concentration ranges tested none of the positive compounds induced a clear dose-dependent mutagenic effect. The Comet assay detected a strong DNA damaging effect for 1-chlorohexane, 2,3-dichlorobutane and 1,2-dichloroethane, but not for carbon tetrachloride and hexachloroethane. The influence of metabolism on the genotoxic activity of the chemicals was more clear in the Comet assay than in the MN test. The experimental genotoxicity and cytotoxicity data obtained in this study, together with data on five more related chemicals previously investigated, and their physico-chemical descriptors or electronic parameters have been used for QSAR analysis. The QSAR analysis high-lighted that the toxicity of the tested compounds was influenced by different parameters, like lipophilicity (logP), electron donor ability (charge) and longest carbon-chlorine (LBC-Cl) bond length. In addition, steric parameters, like molar refractivity (MR) and LBC-Cl, and electronic parameters, like ELUMO (energy of the lowest unoccupied molecular orbital, indicating electrophilicity), were predominant factors discriminating genotoxins from non-genotoxins in the presence but not in the absence of S9 mix. Although a limited number of compounds have been examined and cytotoxicity and genotoxicity were identified in two different

  20. Random vibrations of linear viscoelastic beams with lumped masses

    Science.gov (United States)

    Dinca, F.; Sireteanu, T.

    1974-01-01

    A method is presented of determining the mean square transversal deflection of an isotropic and homogeneous linear viscoelastic beam having a certain number of lengthwise distributed lumped masses. It is assumed that the beam is acted upon by a stationary random process uniformly distributed along the beam. The method is useful in vibration level control by means of additional lumped masses.

  1. 3D-QSAR modelling dataset of bioflavonoids for predicting the potential modulatory effect on P-glycoprotein activity

    Directory of Open Access Journals (Sweden)

    Pathomwat Wongrattanakamon

    2016-12-01

    Full Text Available The data is obtained from exploring the modulatory activities of bioflavonoids on P-glycoprotein function by ligand-based approaches. Multivariate Linear-QSAR models for predicting the induced/inhibitory activities of the flavonoids were created. Molecular descriptors were initially used as independent variables and a dependent variable was expressed as pFAR. The variables were then used in MLR analysis by stepwise regression calculation to build the linear QSAR data. The entire dataset consisted of 23 bioflavonoids was used as a training set. Regarding the obtained MLR QSAR model, R of 0.963, R2=0.927, Radj2=0.900, SEE=0.197, F=33.849 and q2=0.927 were achieved. The true predictabilities of QSAR model were justified by evaluation with the external dataset (Table 4. The pFARs of representative flavonoids were predicted by MLR QSAR modelling. The data showed that internal and external validations may generate the same conclusion.

  2. On burning a lump of coal

    Science.gov (United States)

    Alonso-Serrano, Ana; Visser, Matt

    2016-06-01

    Burning something, (e.g. the proverbial lump of coal, or an encyclopaedia for that matter), in a blackbody furnace leads to an approximately Planck emission spectrum with an average entropy/information transfer of approximately 3.9 ± 2.5 bits per emitted photon. This quantitative and qualitative result depends only on the underlying unitarity of the quantum physics of burning, combined with the statistical mechanics of blackbody radiation. The fact that the utterly standard and unitarity preserving process of burning something (in fact, burning anything) nevertheless has an associated entropy/information budget, and the quantitative size of that entropy/information budget, is a severely under-appreciated feature of standard quantum statistical physics.

  3. Dark lump excitations in superfluid Fermi gases

    Institute of Scientific and Technical Information of China (English)

    Xu Yan-Xia; Duan Wen-Shan

    2012-01-01

    We study the linear and nonlinear properties of two-dimensional matter-wave pulses in disk-shaped superfluid Fermi gases.A Kadomtsev Petviashvili I (KPI) solitary wave has been realized for superfluid Fermi gases in the limited cases of Bardeen-Cooper-Schrieffer (BCS) regime,Bose-Einstein condensate (BEC) regime,and unitarity regime.Onelump solution as well as one-line soliton solutions for the KPI equation are obtained,and two-line soliton solutions with the same amplitude are also studied in the limited cases.The dependence of the lump propagating velocity and the sound speed of two-dimensional superfluid Fermi gases on the interaction parameter are investigated for the limited cases of BEC and unitarity.

  4. On burning a lump of coal

    CERN Document Server

    Alonso-Serrano, Ana

    2015-01-01

    Burning something, (e.g. the proverbial lump of coal, or an encyclopaedia for that matter), in a blackbody furnace leads to an approximately Planck emission spectrum with an average entropy/information transfer of approximately $3.9 \\pm 2.5$ bits per emitted photon. This quantitative and qualitative result depends only on the underlying unitarity of the quantum physics of burning, combined with the statistical mechanics of blackbody radiation. The fact that the utterly standard and unitarity preserving process of burning something (in fact, burning anything) nevertheless *has* an associated entropy/information budget, and the quantitative *size* of that entropy/information budget, is a severely under-appreciated feature of standard quantum statistical physics.

  5. QSAR modeling: um novo pacote computacional open source para gerar e validar modelos QSAR

    Directory of Open Access Journals (Sweden)

    João Paulo A. Martins

    2013-01-01

    Full Text Available QSAR modeling is a novel computer program developed to generate and validate QSAR or QSPR (quantitative structure- activity or property relationships models. With QSAR modeling, users can build partial least squares (PLS regression models, perform variable selection with the ordered predictors selection (OPS algorithm, and validate models by using y-randomization and leave-N-out cross validation. An additional new feature is outlier detection carried out by simultaneous comparison of sample leverage with the respective Studentized residuals. The program was developed using Java version 6, and runs on any operating system that supports Java Runtime Environment version 6. The use of the program is illustrated. This program is available for download at lqta.iqm.unicamp.br.

  6. LUMPED: a Visual Basic code of lumped-parameter models for mean residence time analyses of groundwater systems

    Science.gov (United States)

    Ozyurt, N. N.; Bayari, C. S.

    2003-02-01

    A Microsoft ® Visual Basic 6.0 (Microsoft Corporation, 1987-1998) code of 15 lumped-parameter models is presented for the analysis of mean residence time in aquifers. Groundwater flow systems obeying plug and exponential flow models and their combinations of parallel or serial connection can be simulated by these steady-state models which may include complications such as bypass flow and dead volume. Each model accepts tritium, krypton-85, chlorofluorocarbons (CFC-11, CFC-12 and CFC-113) and sulfur hexafluoride (SF 6) as environmental tracer. Retardation of gas tracers in the unsaturated zone and their degradation in the flow system may also be accounted for. The executable code has been tested to run under Windows 95 or higher operating systems. The results of comparisons between other comparable codes are discussed and the limitations are indicated.

  7. The Danish (Q)SAR Database Update Project

    DEFF Research Database (Denmark)

    Nikolov, Nikolai Georgiev; Dybdahl, Marianne; Abildgaard Rosenberg, Sine

    2013-01-01

    , carcinogenicity and others), each of them available for 185,000 organic substances. The database has been available online since 2005 (http://qsar.food.dtu.dk). A major update project for the Danish (Q)SAR database is under way, with a new online release planned in the beginning of 2015. The updated version...

  8. (Q)SAR: A Tool for the Toxicologist.

    Science.gov (United States)

    Steinbach, Thomas; Gad-McDonald, Samantha; Kruhlak, Naomi; Powley, Mark; Greene, Nigel

    2015-01-01

    A continuing education (CE) course at the 2014 American College of Toxicology annual meeting covered the topic of (Quantitative) Structure-Activity Relationships [(Q)SAR]. The (Q)SAR methodologies use predictive computer modeling based on predefined rules to describe the relationship between chemical structure and a chemical's associated biological activity or statistical tools to find correlations between biologic activity and the molecular structure or properties of a compound. The (Q)SAR has applications in risk assessment, drug discovery, and regulatory decision making. Pressure within industry to reduce the cost of drug development and societal pressure for government regulatory agencies to produce more accurate and timely risk assessment of drugs and chemicals have necessitated the use of (Q)SAR. Producing a high-quality (Q)SAR model depends on many factors including the choice of statistical methods and descriptors, but first and foremost the quality of the data input into the model. Understanding how a (Q)SAR model is developed and applied is critical to the successful use of such a tool. The CE session covered the basic principles of (Q)SAR, practical applications of these computational models in toxicology, how regulatory agencies use and interpret (Q)SAR models, and potential pitfalls of using them.

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

    Science.gov (United States)

    Saini, V; Kumar, A

    2014-01-01

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

  10. Molecular docking, MM/GBSA and 3D-QSAR studies on EGFR inhibitors

    Indian Academy of Sciences (India)

    RAJU BATHINI; SREE KANTH SIVAN; SABIHA FATIMA; VIJJULATHA MANGA

    2016-07-01

    Epidermal growth factor receptor (EGFR) is the first growth factor receptor proposed as a target for cancer therapy. Molecular modeling protocols like molecular docking, molecular mechanics/generalized born surface area (MM/GBSA) calculations and three dimensional-quantitative structure activity relationship(3D-QSAR) studies were performed on 45 molecules to understand the structural requirements for EGFR tyrosine kinase inhibitors. Conformation for all the molecules obtained from molecular docking were used as is for 3D-QSAR analysis. Comparative molecular field analysis (CoMFA) and comparative molecular similarityindices analysis (CoMSIA) models were obtained by performing partial least square analysis on 35 training molecules and these models were validated using 10 test moleucles. The models showed good statistical results in terms of r², q² loo and r² pred values. Information rendered from 3D-QSAR model and sitemap analysis was used to optimize lead molecule to design prospective inhibitors. Improvement in EGFR binding affinity can be achieved by substitutional modification on phenyl ring attached to alkynyl group with bulkier hydrogen bond donor and acceptor substituents that can increase favourable interaction with the receptor.

  11. Lump Solution of (2+1)-Dimensional Boussinesq Equation

    Science.gov (United States)

    Ma, Hong-Cai; Deng, Ai-Ping

    2016-05-01

    A class of lump solutions of (2+1)-dimensional Boussinesq equation are obtained with the help of Maple by using Hirota bilinear method. Some contour plots with different determinant values are sequentially made to show that the corresponding lump solution tends to zero when the determinant approaches zero. The particular lump solutions with specific values of the involved parameters are plotted, as illustrative examples. Supported by the National Natural Science Foundation of China under Grant No. 10647112 and the Fund of Science and Technology Commission of Shanghai Municipality under Grant No. ZX201307000014

  12. Optimal Component Lumping: problem formulation and solution techniques

    DEFF Research Database (Denmark)

    Lin, Bao; Leibovici, Claude F.; Jørgensen, Sten Bay

    2008-01-01

    to determine the lumping scheme. Given an objective function defined with a linear weighting rule, an optimal lumping problem is formulated as a mixed integer nonlinear programming (MINLP) problem both in discrete and in continuous settings. A reformulation of the original problem is also presented, which...... significantly reduces the number of independent variables. The application to a system with 144 components demonstrates that the optimal lumping problem can be efficiently solved with a stochastic optimization method, Tabu Search (TS) algorithm. The case study also reveals that the discrete formulation...

  13. Lump solutions to the BKP equation by symbolic computation

    Science.gov (United States)

    Yang, Jing-Yun; Ma, Wen-Xiu

    2016-09-01

    Lump solutions are rationally localized in all directions in the space. A general class of lump solutions to the (2+1)-dimensional B-Kadomtsev-Petviashvili (BKP) equation is presented through symbolic computation with Maple. The Hirota bilinear form of the equation is the starting point in the computation process. Like the KP equation, the resulting lump solutions contain six arbitrary parameters. Two of the parameters are due to the translation invariances of the BKP equation with the independent variables, and the other four need to satisfy a nonzero determinant condition and the positivity condition, which guarantee analyticity and rational localization of the solutions.

  14. Biological activities of triazine derivatives. Combining DFT and QSAR results

    Directory of Open Access Journals (Sweden)

    Majdouline Larif

    2017-02-01

    Full Text Available In order to investigate the relationship between activities and structures, a 3D-QSAR study is applied to a set of 43 molecules based on triazines. This study was conducted using the principal component analysis (PCA method, the multiple linear regression method (MLR and the artificial neural network (ANN. The predicted values of activities are in good agreement with the experimental results. The artificial neural network (ANN techniques, considering the relevant descriptors obtained from the MLR, showed a correlation coefficient of 0.9 with an 8-3-1 ANN model which is a good result. As a result of quantitative structure–activity relationships, we found that the model proposed in this study is constituted of major descriptors used to describe these molecules. The obtained results suggested that the proposed combination of several calculated parameters could be useful to predict the biological activity of triazine derivatives.

  15. Exploring the QSAR's predictive truthfulness of the novel N-tuple discrete derivative indices on benchmark datasets.

    Science.gov (United States)

    Martínez-Santiago, O; Marrero-Ponce, Y; Vivas-Reyes, R; Rivera-Borroto, O M; Hurtado, E; Treto-Suarez, M A; Ramos, Y; Vergara-Murillo, F; Orozco-Ugarriza, M E; Martínez-López, Y

    2017-05-01

    Graph derivative indices (GDIs) have recently been defined over N-atoms (N = 2, 3 and 4) simultaneously, which are based on the concept of derivatives in discrete mathematics (finite difference), metaphorical to the derivative concept in classical mathematical analysis. These molecular descriptors (MDs) codify topo-chemical and topo-structural information based on the concept of the derivative of a molecular graph with respect to a given event (S) over duplex, triplex and quadruplex relations of atoms (vertices). These GDIs have been successfully applied in the description of physicochemical properties like reactivity, solubility and chemical shift, among others, and in several comparative quantitative structure activity/property relationship (QSAR/QSPR) studies. Although satisfactory results have been obtained in previous modelling studies with the aforementioned indices, it is necessary to develop new, more rigorous analysis to assess the true predictive performance of the novel structure codification. So, in the present paper, an assessment and statistical validation of the performance of these novel approaches in QSAR studies are executed, as well as a comparison with those of other QSAR procedures reported in the literature. To achieve the main aim of this research, QSARs were developed on eight chemical datasets widely used as benchmarks in the evaluation/validation of several QSAR methods and/or many different MDs (fundamentally 3D MDs). Three to seven variable QSAR models were built for each chemical dataset, according to the original dissection into training/test sets. The models were developed by using multiple linear regression (MLR) coupled with a genetic algorithm as the feature wrapper selection technique in the MobyDigs software. Each family of GDIs (for duplex, triplex and quadruplex) behaves similarly in all modelling, although there were some exceptions. However, when all families were used in combination, the results achieved were quantitatively

  16. Nonlinearly Coupled Superconducting Lumped Element Resonators

    Science.gov (United States)

    Collodo, Michele C.; Potočnik, Anton; Rubio Abadal, Antonio; Mondal, Mintu; Oppliger, Markus; Wallraff, Andreas

    We study SQUID-mediated tunable coupling between two superconducting on-chip resonators in the microwave frequency range. In this circuit QED implementation, we employ lumped-element type resonators, which consist of Nb thin film structured into interdigitated finger shunt capacitors and meander inductors. A SQUID, functioning as flux dependent and intrinsically nonlinear inductor, is placed as a coupling element together with an interdigitated capacitor between the two resonators (cf. A. Baust et al., Phys Rev. B 91 014515 (2015)). We perform a spectroscopic measurement in a dilution refrigerator and find the linear photon hopping rate between the resonators to be widely tunable as well as suppressible for an appropriate choice of parameters, which is made possible due to the interplay of inductively and capacitively mediated coupling. Vanishing linear coupling promotes nonlinear effects ranging from onsite- to cross-Kerr interaction. A dominating cross-Kerr interaction related to this configuration is notable, as it induces a unique quantum state. In the course of analog quantum simulations, such elementary building blocks can serve as a precursor for more complex geometries and thus pave the way to a number of novel quantum phases of light

  17. Unified QSAR approach to antimicrobials. Part 3: first multi-tasking QSAR model for input-coded prediction, structural back-projection, and complex networks clustering of antiprotozoal compounds.

    Science.gov (United States)

    Prado-Prado, Francisco J; González-Díaz, Humberto; de la Vega, Octavio Martinez; Ubeira, Florencio M; Chou, Kuo-Chen

    2008-06-01

    Several pathogen parasite species show different susceptibilities to different antiparasite drugs. Unfortunately, almost all structure-based methods are one-task or one-target Quantitative Structure-Activity Relationships (ot-QSAR) that predict the biological activity of drugs against only one parasite species. Consequently, multi-tasking learning to predict drugs activity against different species by a single model (mt-QSAR) is vitally important. In the two previous works of the present series we reported two single mt-QSAR models in order to predict the antimicrobial activity against different fungal (Bioorg. Med. Chem.2006, 14, 5973-5980) or bacterial species (Bioorg. Med. Chem.2007, 15, 897-902). These mt-QSARs offer a good opportunity (unpractical with ot-QSAR) to construct drug-drug similarity Complex Networks and to map the contribution of sub-structures to function for multiple species. These possibilities were unattended in our previous works. In the present work, we continue this series toward other important direction of chemotherapy (antiparasite drugs) with the development of an mt-QSAR for more than 500 drugs tested in the literature against different parasites. The data were processed by Linear Discriminant Analysis (LDA) classifying drugs as active or non-active against the different tested parasite species. The model correctly classifies 212 out of 244 (87.0%) cases in training series and 207 out of 243 compounds (85.4%) in external validation series. In order to illustrate the performance of the QSAR for the selection of active drugs we carried out an additional virtual screening of antiparasite compounds not used in training or predicting series; the model recognized 97 out of 114 (85.1%) of them. We also give the procedures to construct back-projection maps and to calculate sub-structures contribution to the biological activity. Finally, we used the outputs of the QSAR to construct, by the first time, a multi-species Complex Networks of

  18. Metaplastic breast carcinoma presenting as benign breast lump

    Directory of Open Access Journals (Sweden)

    Ashesh Jha

    2017-01-01

    Full Text Available A 38-year-old female presented with the left breast lump for 6 months. Physical examination revealed 11 cm × 7 cm mobile lump in the left breast without any axillary or supraclavicular lymphadenopathy. Mammographically it appeared as benign breast lump (breast imaging reporting and Data System-II. Fine needle aspiration cytology and Tru-cut biopsy were not able to differentiate between benign or malignant nature of this breast lump. For better characterization of this lesion, lumpectomy was performed, which revealed malignant tumor with squamous differentiation along with areas of ductal carcinoma in situ and the inferior margin was not free. For proper locoregional control, left modified radical mastectomy was performed. Postoperative period was uneventful. Final biopsy report of the mastectomy specimen was negative for any residual tumor, and axillary lymph nodes were not involved.

  19. 全数字化乳腺摄影不典型乳腺肿块的X线征象分析%The X-ray features analysis of the atypical breast lumps in full field digital mammography

    Institute of Scientific and Technical Information of China (English)

    孙艳莉

    2015-01-01

    目的:分析36例不典型乳腺肿块的影像学表现,提高影像学诊断水平。方法随机抽取2010年8月~2014年8月,经手术病理证实的乳腺不典型肿块36例,回顾性分析其数字乳腺摄影的影像学表现。结果36例43个肿块,术前诊断BI‐RADSⅡ类5例,BI‐RADSⅢ类17例,BI‐RADSⅣ类14例。其中12例纤维腺瘤(5例多发)因腺体较丰富,肿块与腺体重叠,边缘显示不清,表现为等密度肿块;5例脂肪瘤及2例错构瘤主要位于皮下脂肪层及退化不全的乳腺内,肿块与腺体组织分解不清,表现为与周围组织等密度肿块;4例硬化性腺病及2例慢性炎性病变,表现为稍高密度不均匀肿块;11例乳腺癌分别表现为星状影(2例)、结构扭曲(5例)和非对称密度影(4例),其中3例非对称密度影伴钙化。结论不典型乳腺肿块数字乳腺摄影诊断常较困难,密切结合临床触诊,充分运用特殊体位摄影及图像后处理功能,对可疑病变及时进行穿刺活检或外科手术切除活检,可大幅提高不典型乳腺肿块,尤其是不典型乳腺癌的检出率和诊断符合率。%Objective To analyze the imaging findings of 36 cases of atypical breast lumpsinorder to further improve the level of imaging diagnosis of the atypical breast lumps ,especially the breast cancer .Methods Extract randomly 36 cases of atypical breast lumps confirmed by surgery pathology with complete information from August in 2010 to August in 2014 ,and analyze retrospectively their imaging findings with full field digital mammography .Results 43 lumps in 36 ca‐ses were found and diagnosed before operation ,including BI‐RADSⅡ 5 cases ,BI‐RADS Ⅲ 17 cases ,BI‐RADS Ⅳ 14 ca‐ses .12 cases of fibro adenoma (5 cases were frequentil multiple) hand no clear edge because their gland was rich and the bump and gland were lapped ,showed isopycnic lump ,5 cases lipoma and 2 cases

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

    Science.gov (United States)

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

    2012-08-01

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

  1. Organic Micropollutants Removal from Water by Oxidation and Other Processes:QSAR Models, Decision Support System and Hybrids of Processes

    KAUST Repository

    Sudhakaran, Sairam

    2013-08-01

    The presence of organic micropollutants (OMPs) in water is of great environmental concern. OMPs such as endocrine disruptors and certain pharmaceuticals have shown alarming effects on aquatic life. OMPs are included in the priority list of contaminants in several government directorate frameworks. The low levels of OMPs concentration (ng/L to μg/L) force the use of sophisticated analytical instruments. Although, the techniques to detect OMPs are progressing, the focus of current research is only on limited, important OMPs due to the high amount of time, cost and effort involved in analyzing them. Alternatively, quantitative structure activity relationship (QSAR) models help to screen processes and propose appropriate options without considerable experimental effort. QSAR models are well-established in regulatory bodies as a method to screen toxic chemicals. The goal of the present thesis was to develop QSAR models for OMPs removal by oxidation. Apart from the QSAR models, a decision support system (DSS) based on multi-criteria analysis (MCA) involving socio-economic-technical and sustainability aspects was developed. Also, hybrids of different water treatment processes were studied to propose a sustainable water treatment train for OMPs removal. In order to build the QSAR models, the ozone/hydroxyl radical rate constants or percent removals of the OMPs were compiled. Several software packages were used to 5 compute the chemical properties of OMPs and perform statistical analyses. For DSS, MCA was used since it allows the comparison of qualitative (non-monetary, non-metric) and quantitative criteria (e.g., costs). Quadrant plots were developed to study the hybrid of natural and advanced water treatment processes. The QSAR models satisfied both chemical and statistical criteria. The DSS resulted in natural treatment and ozonation as the preferred processes for OMPs removal. The QSAR models can be used as a screening tool for OMPs removal by oxidation. Moreover, the

  2. QSAR Models for the Prediction of Plasma Protein Binding

    Directory of Open Access Journals (Sweden)

    Zeshan Amin

    2013-02-01

    Full Text Available Introduction: The prediction of plasma protein binding (ppb is of paramount importance in the pharmacokinetics characterization of drugs, as it causes significant changes in volume of distribution, clearance and drug half life. This study utilized Quantitative Structure – Activity Relationships (QSAR for the prediction of plasma protein binding. Methods: Protein binding values for 794 compounds were collated from literature. The data was partitioned into a training set of 662 compounds and an external validation set of 132 compounds. Physicochemical and molecular descriptors were calculated for each compound using ACD labs/logD, MOE (Chemical Computing Group and Symyx QSAR software packages. Several data mining tools were employed for the construction of models. These included stepwise regression analysis, Classification and Regression Trees (CART, Boosted trees and Random Forest. Results: Several predictive models were identified; however, one model in particular produced significantly superior prediction accuracy for the external validation set as measured using mean absolute error and correlation coefficient. The selected model was a boosted regression tree model which had the mean absolute error for training set of 13.25 and for validation set of 14.96. Conclusion: Plasma protein binding can be modeled using simple regression trees or multiple linear regressions with reasonable model accuracies. These interpretable models were able to identify the governing molecular factors for a high ppb that included hydrophobicity, van der Waals surface area parameters, and aromaticity. On the other hand, the more complicated ensemble method of boosted regression trees produced the most accurate ppb estimations for the external validation set.

  3. Nanomaterials - the Next Great Challenge for Qsar Modelers

    Science.gov (United States)

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

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

  4. A PLS QSAR analysis using 3D generated aromatic descriptors of principal property type: Application to some dopamine D2 benzamide antagonists

    Science.gov (United States)

    Norinder, Ulf

    1993-12-01

    A simple and computationally nonintensive technique based on principal component analysis of 3D fields to derive theoretical descriptors is presented. The descriptors are then applied to a quantitative structure-activity relationship study on some dopamine D2 antagonists of benzamide type.

  5. MEMS 3-DoF gyroscope design, modeling and simulation through equivalent circuit lumped parameter model

    Energy Technology Data Exchange (ETDEWEB)

    Mian, Muhammad Umer, E-mail: umermian@gmail.com; Khir, M. H. Md.; Tang, T. B. [Department of Electrical and Electronic Engineering, Universiti Teknologi PETRONAS, Tronoh, Perak (Malaysia); Dennis, John Ojur [Department of Fundamental & Applied Sciences, Universiti Teknologi PETRONAS, Tronoh, Perak (Malaysia); Riaz, Kashif; Iqbal, Abid [Faculty of Electronics Engineering, GIK Institute of Engineering Sciences and Technology, Topi, Khyber Pakhtunkhaw (Pakistan); Bazaz, Shafaat A. [Department of Computer Science, Center for Advance Studies in Engineering, Islamabad (Pakistan)

    2015-07-22

    Pre-fabrication, behavioural and performance analysis with computer aided design (CAD) tools is a common and fabrication cost effective practice. In light of this we present a simulation methodology for a dual-mass oscillator based 3 Degree of Freedom (3-DoF) MEMS gyroscope. 3-DoF Gyroscope is modeled through lumped parameter models using equivalent circuit elements. These equivalent circuits consist of elementary components which are counterpart of their respective mechanical components, used to design and fabricate 3-DoF MEMS gyroscope. Complete designing of equivalent circuit model, mathematical modeling and simulation are being presented in this paper. Behaviors of the equivalent lumped models derived for the proposed device design are simulated in MEMSPRO T-SPICE software. Simulations are carried out with the design specifications following design rules of the MetalMUMPS fabrication process. Drive mass resonant frequencies simulated by this technique are 1.59 kHz and 2.05 kHz respectively, which are close to the resonant frequencies found by the analytical formulation of the gyroscope. The lumped equivalent circuit modeling technique proved to be a time efficient modeling technique for the analysis of complex MEMS devices like 3-DoF gyroscopes. The technique proves to be an alternative approach to the complex and time consuming couple field analysis Finite Element Analysis (FEA) previously used.

  6. MEMS 3-DoF gyroscope design, modeling and simulation through equivalent circuit lumped parameter model

    Science.gov (United States)

    Mian, Muhammad Umer; Dennis, John Ojur; Khir, M. H. Md.; Riaz, Kashif; Iqbal, Abid; Bazaz, Shafaat A.; Tang, T. B.

    2015-07-01

    Pre-fabrication, behavioural and performance analysis with computer aided design (CAD) tools is a common and fabrication cost effective practice. In light of this we present a simulation methodology for a dual-mass oscillator based 3 Degree of Freedom (3-DoF) MEMS gyroscope. 3-DoF Gyroscope is modeled through lumped parameter models using equivalent circuit elements. These equivalent circuits consist of elementary components which are counterpart of their respective mechanical components, used to design and fabricate 3-DoF MEMS gyroscope. Complete designing of equivalent circuit model, mathematical modeling and simulation are being presented in this paper. Behaviors of the equivalent lumped models derived for the proposed device design are simulated in MEMSPRO T-SPICE software. Simulations are carried out with the design specifications following design rules of the MetalMUMPS fabrication process. Drive mass resonant frequencies simulated by this technique are 1.59 kHz and 2.05 kHz respectively, which are close to the resonant frequencies found by the analytical formulation of the gyroscope. The lumped equivalent circuit modeling technique proved to be a time efficient modeling technique for the analysis of complex MEMS devices like 3-DoF gyroscopes. The technique proves to be an alternative approach to the complex and time consuming couple field analysis Finite Element Analysis (FEA) previously used.

  7. Triazoloquinazolines as Human A3 Adenosine Receptor Antagonists: A QSAR Study

    Directory of Open Access Journals (Sweden)

    Dae-Sil Lee

    2006-11-01

    Full Text Available Multiple linear regression analysis was performed on the quantitative structure-activity relationships (QSAR of the triazoloquinazoline adenosine antagonists for human A3receptors. The data set used for the QSAR analysis encompassed the activities of 33triazoloquinazoline derivatives and 72 physicochemical descriptors. A template moleculewas derived using the known molecular structure for one of the compounds when bound tothe human A2B receptor, in which the amide bond was in a cis-conformation. All the testcompounds were aligned to the template molecule. In order to identify a reasonable QSARequation to describe the data set, we developed a multiple linear regression program thatexamined every possible combination of descriptors. The QSAR equation derived from thisanalysis indicates that the spatial and electronic effects is greater than that of hydrophobiceffects in binding of the antagonists to the human A3 receptor. It also predicts that a largesterimol length parameter is advantageous to activity, whereas large sterimol widthparameters and fractional positive partial surface areas are nonadvatageous.

  8. QSAR for Photodegradation Activity of Polycyclic Aromatic Hydrocarbons in Aqueous Systems

    Institute of Scientific and Technical Information of China (English)

    XU Xiang; LI Xianguo

    2014-01-01

    The relationship between chemical structures and photodegradation activity of 12 PAHs is studied using DFT and HF methods, and stepwise multiple linear regression analysis method. The equilibrium geometries and vibration frequency have been investigated by considering Solvent effects using a selfconsistent reaction field based on the polarizable continuum model. With DFT and HF methods, different quantum chemical structural descriptors are obtained by quantum chemical calculation and the results with DFT method are better for QSAR model. It is concluded that the photodegradation activity is closely related to its molecular structure. In the regression analysis, the main factors affecting photodegradation rate include the energy of the highest occupied orbital EHOMO and the number of six-carbon benzene ring N1, and the QSAR model successfully established is logkb=6.046 + 54.830EHOMO +0.272N1. Statistical evaluation of the developed QSAR shows that the relationships are statistically significant and the model has good predictive ability. EHOMO is the most important factor influcing the photodegradation of PAHs, because the higher EHOMO is, the more easily electron will be excited and the more easily molecular will be degraded. Comparison of the photodegradation of PAHs with their biodegradation shows that the committed step of biodegradation is that the effects of microorganisms make the chemical bond break, while in the committed step of photodegradation PAHs eject electrons.

  9. A QSAR study and molecular design of benzothiazole derivatives as potent anticancer agents

    Institute of Scientific and Technical Information of China (English)

    CHEN JinCan; QIAN Li; SHEN Yong; CHEN LanMei; ZHENG KangCheng

    2008-01-01

    A quantitative structure-activity relationship (QSAR) of a series of benzothiazole derivatives showing a potent and selective cytotoxicity against a tumorigenic cell line has been studied by using the density functional theory (DFT), molecular mechanics (MM+) and statistical methods, and the QSAR equation was established via a correlation analysis and a stepwise regression analysis.A new scheme deter-mining outliers by "leave-one-out" (LOO) cross-validation coefficient (q2n-1) was suggested and suc-cessfully used.In the established optimal equation (excluding two outliers), the steric parameter (MRR) and the net charge (QFR) of the first atom of the substituent (R), as well as the square of hydrophobic parameter (IgP)2 of the whole molecule, are the main independent factors contributing to the anticancer activities of the compounds.The fitting correlation coefficient (R2) and the cross-validation coefficient (q2) values are 0.883 and 0.797, respectively.It indicates that this model has a significantly statistical quality and an excellent prediction ability.Based on the QSAR studies, 4 new compounds with high predicted anticancer activities have been theoretically designed and they are expected to be confirmed experimentally.

  10. A QSAR study and molecular design of benzothiazole derivatives as potent anticancer agents

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A quantitative structure-activity relationship (QSAR) of a series of benzothiazole derivatives showing a potent and selective cytotoxicity against a tumorigenic cell line has been studied by using the density functional theory (DFT), molecular mechanics (MM+) and statistical methods, and the QSAR equation was established via a correlation analysis and a stepwise regression analysis. A new scheme determining outliers by "leave-one-out" (LOO) cross-validation coefficient (q2n-i) was suggested and successfully used. In the established optimal equation (excluding two outliers), the steric parameter (MRR) and the net charge (QFR) of the first atom of the substituent (R), as well as the square of hydrophobic parameter (lgP)2 of the whole molecule, are the main independent factors contributing to the anticancer activities of the compounds. The fitting correlation coefficient (R2) and the cross-validation coefficient (q2) values are 0.883 and 0.797, respectively. It indicates that this model has a significantly statistical quality and an excellent prediction ability. Based on the QSAR studies, 4 new compounds with high predicted anticancer activities have been theoretically designed and they are expected to be confirmed experimentally.

  11. Towards interoperable and reproducible QSAR analyses: Exchange of datasets

    Directory of Open Access Journals (Sweden)

    Spjuth Ola

    2010-06-01

    Full Text Available Abstract Background QSAR is a widely used method to relate chemical structures to responses or properties based on experimental observations. Much effort has been made to evaluate and validate the statistical modeling in QSAR, but these analyses treat the dataset as fixed. An overlooked but highly important issue is the validation of the setup of the dataset, which comprises addition of chemical structures as well as selection of descriptors and software implementations prior to calculations. This process is hampered by the lack of standards and exchange formats in the field, making it virtually impossible to reproduce and validate analyses and drastically constrain collaborations and re-use of data. Results We present a step towards standardizing QSAR analyses by defining interoperable and reproducible QSAR datasets, consisting of an open XML format (QSAR-ML which builds on an open and extensible descriptor ontology. The ontology provides an extensible way of uniquely defining descriptors for use in QSAR experiments, and the exchange format supports multiple versioned implementations of these descriptors. Hence, a dataset described by QSAR-ML makes its setup completely reproducible. We also provide a reference implementation as a set of plugins for Bioclipse which simplifies setup of QSAR datasets, and allows for exporting in QSAR-ML as well as old-fashioned CSV formats. The implementation facilitates addition of new descriptor implementations from locally installed software and remote Web services; the latter is demonstrated with REST and XMPP Web services. Conclusions Standardized QSAR datasets open up new ways to store, query, and exchange data for subsequent analyses. QSAR-ML supports completely reproducible creation of datasets, solving the problems of defining which software components were used and their versions, and the descriptor ontology eliminates confusions regarding descriptors by defining them crisply. This makes is easy to join

  12. Insight into the structural requirement of substituted quinazolinone biphenyl acylsulfonamides derivatives as Angiotensin II AT1 receptor antagonist: 2D and 3D QSAR approach

    Directory of Open Access Journals (Sweden)

    Mukesh C. Sharma

    2014-01-01

    Full Text Available A series of 19 molecules substituted quinazolinone biphenyl acylsulfonamides derivatives displaying variable inhibition of Angiotensin II receptor AT1 activity were selected to develop models for establishing 2D and 3D QSAR. The compounds in the selected series were characterized by spatial, molecular and electro topological descriptors using QSAR module of Molecular Design Suite (VLife MDS™ 3.5. The best 2D QSAR model was selected, having correlation coefficient r2 (0.8056 and cross validated squared correlation coefficient q2 (0.6742 with external predictive ability of pred_r2 0.7583 coefficient of correlation of predicted data set (pred_r2se 0.2165. The results obtained from QSAR studies could be used in designing better Ang II activity among the congeners in future. The optimum QSAR model showed that the parameters SsssCHE index, SddCE-index, T_2_Cl_4, and SssNHE-index contributed in the model. 3D QSAR analysis by kNN-molecular field analysis approach developed based on principles of the k-nearest neighbor method combined with Genetic algorithms, stepwise forward variable selection approach; a leave-one-out cross-validated correlation coefficient (q2 of 0.6516 and a non-cross-validated correlation coefficient (r2 of 0.8316 and pred_r2 0.6954 were obtained. Contour maps using this approach showed that steric, electrostatic, and hydrophobic field effects dominantly determine binding affinities. The information rendered by 3D QSAR models may lead to a better understanding of structural requirements of Angiotensin II receptor and can help in the design of novel potent antihypertensive molecules.

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

    Science.gov (United States)

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

    2014-10-01

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

  14. Support vector machine applied in QSAR modelling

    Institute of Scientific and Technical Information of China (English)

    MEI Hu; ZHOU Yuan; LIANG Guizhao; LI Zhiliang

    2005-01-01

    Support vector machine (SVM), partial least squares (PLS), and Back-Propagation artificial neural network (ANN) were employed to establish QSAR models of 2 dipeptide datasets. In order to validate predictive capabilities on external dataset of the resulting models, both internal and external validations were performed. The division of dataset into both training and test sets was carried out by D-optimal design. The results showed that support vector machine (SVM) behaved well in both calibration and prediction. For the dataset of 48 bitter tasting dipeptides (BTD), the results obtained by support vector regression (SVR) were superior to that by PLS in both calibration and prediction. When compared with BP artificial neural network, SVR showed less calibration power but more predictive capability. For the dataset of angiotensin-converting enzyme (ACE) inhibitors, the results obtained by support vector machine (SVM) regression were equivalent to those by PLS and BP artificial neural network. In both datasets, SVR using linear kernel function behaved well as that using radial basis kernel function. The results showed that there is wide prospect for the application of support vector machine (SVM) into QSAR modeling.

  15. A new structure-based QSAR method affords both descriptive and predictive models for phosphodiesterase-4 inhibitors.

    Science.gov (United States)

    Dong, Xialan; Zheng, Weifan

    2008-11-06

    We describe the application of a new QSAR (quantitative structure-activity relationship) formalism to the analysis and modeling of PDE-4 inhibitors. This new method takes advantage of the X-ray structural information of the PDE-4 enzyme to characterize the small molecule inhibitors. It calculates molecular descriptors based on the matching of their pharmacophore feature pairs with those (the reference) of the target binding pocket. Since the reference is derived from the X-ray crystal structures of the target under study, these descriptors are target-specific and easy to interpret. We have analyzed 35 indole derivative-based PDE-4 inhibitors where Partial Least Square (PLS) analysis has been employed to obtain the predictive models. Compared to traditional QSAR methods such as CoMFA and CoMSIA, our models are more robust and predictive measured by statistics for both the training and test sets of molecules. Our method can also identify critical pharmacophore features that are responsible for the inhibitory potency of the small molecules. Thus, this structure-based QSAR method affords both descriptive and predictive models for phosphodiesterase-4 inhibitors. The success of this study has also laid a solid foundation for systematic QSAR modeling of the PDE family of enzymes, which will ultimately contribute to chemical genomics research and drug discovery targeting the PDE enzymes.

  16. Is conformation a fundamental descriptor in QSAR? A case for halogenated anesthetics

    Science.gov (United States)

    Guimarães, Maria C; Duarte, Mariene H; Silla, Josué M

    2016-01-01

    Summary An intriguing question in 3D-QSAR lies on which conformation(s) to use when generating molecular descriptors (MD) for correlation with bioactivity values. This is not a simple task because the bioactive conformation in molecule data sets is usually unknown and, therefore, optimized structures in a receptor-free environment are often used to generate the MD´s. In this case, a wrong conformational choice can cause misinterpretation of the QSAR model. The present computational work reports the conformational analysis of the volatile anesthetic isoflurane (2-chloro-2-(difluoromethoxy)-1,1,1-trifluoroethane) in the gas phase and also in polar and nonpolar implicit and explicit solvents to show that stable minima (ruled by intramolecular interactions) do not necessarily coincide with the bioconformation (ruled by enzyme induced fit). Consequently, a QSAR model based on two-dimensional chemical structures was built and exhibited satisfactory modeling/prediction capability and interpretability, then suggesting that these 2D MD´s can be advantageous over some three-dimensional descriptors. PMID:27340468

  17. 3D-QSAR and molecular docking studies on HIV protease inhibitors

    Science.gov (United States)

    Tong, Jianbo; Wu, Yingji; Bai, Min; Zhan, Pei

    2017-02-01

    In order to well understand the chemical-biological interactions governing their activities toward HIV protease activity, QSAR models of 34 cyclic-urea derivatives with inhibitory HIV were developed. The quantitative structure activity relationship (QSAR) model was built by using comparative molecular similarity indices analysis (CoMSIA) technique. And the best CoMSIA model has rcv2, rncv2 values of 0.586 and 0.931 for cross-validated and non-cross-validated. The predictive ability of CoMSIA model was further validated by a test set of 7 compounds, giving rpred2 value of 0.973. Docking studies were used to find the actual conformations of chemicals in active site of HIV protease, as well as the binding mode pattern to the binding site in protease enzyme. The information provided by 3D-QSAR model and molecular docking may lead to a better understanding of the structural requirements of 34 cyclic-urea derivatives and help to design potential anti-HIV protease molecules.

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

    Directory of Open Access Journals (Sweden)

    Swapnil Chavan

    2014-10-01

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

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

    Science.gov (United States)

    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.

  20. Ultrashort spatiotemporal optical solitons in quadratic nonlinear media: Generation of line and lump solitons from few-cycle input pulses

    CERN Document Server

    Leblond, Hervé; Mihalache, Dumitru; 10.1103/PHYSREVA.80.053812

    2011-01-01

    By using a powerful reductive perturbation technique, or a multiscale analysis, a generic Kadomtsev-Petviashvili evolution equation governing the propagation of femtosecond spatiotemporal optical solitons in quadratic nonlinear media beyond the slowly varying envelope approximation is put forward. Direct numerical simulations show the formation, from adequately chosen few-cycle input pulses, of both stable line solitons (in the case of a quadratic medium with normal dispersion) and of stable lumps (for a quadratic medium with anomalous dispersion). Besides, a typical example of the decay of the perturbed unstable line soliton into stable lumps for a quadratic nonlinear medium with anomalous dispersion is also given.

  1. QSARs for Plasma Protein Binding: Source Data and Predictions

    Data.gov (United States)

    U.S. Environmental Protection Agency — The dataset has all of the information used to create and evaluate 3 independent QSAR models for the fraction of a chemical unbound by plasma protein (Fub) for...

  2. Prediction of acute mammalian toxicity using QSAR methods: a case study of sulfur mustard and its breakdown products.

    Science.gov (United States)

    Ruiz, Patricia; Begluitti, Gino; Tincher, Terry; Wheeler, John; Mumtaz, Moiz

    2012-07-27

    Predicting toxicity quantitatively, using Quantitative Structure Activity Relationships (QSAR), has matured over recent years to the point that the predictions can be used to help identify missing comparison values in a substance's database. In this manuscript we investigate using the lethal dose that kills fifty percent of a test population (LD₅₀) for determining relative toxicity of a number of substances. In general, the smaller the LD₅₀ value, the more toxic the chemical, and the larger the LD₅₀ value, the lower the toxicity. When systemic toxicity and other specific toxicity data are unavailable for the chemical(s) of interest, during emergency responses, LD₅₀ values may be employed to determine the relative toxicity of a series of chemicals. In the present study, a group of chemical warfare agents and their breakdown products have been evaluated using four available rat oral QSAR LD₅₀ models. The QSAR analysis shows that the breakdown products of Sulfur Mustard (HD) are predicted to be less toxic than the parent compound as well as other known breakdown products that have known toxicities. The QSAR estimated break down products LD₅₀ values ranged from 299 mg/kg to 5,764 mg/kg. This evaluation allows for the ranking and toxicity estimation of compounds for which little toxicity information existed; thus leading to better risk decision making in the field.

  3. A DFT-based toxicity QSAR study of aromatic hydrocarbons to Vibrio fischeri: Consideration of aqueous freely dissolved concentration.

    Science.gov (United States)

    Wang, Ying; Yang, Xianhai; Wang, Juying; Cong, Yi; Mu, Jingli; Jin, Fei

    2016-05-05

    In the present study, quantitative structure-activity relationship (QSAR) techniques based on toxicity mechanism and density functional theory (DFT) descriptors were adopted to develop predictive models for the toxicity of alkylated and parent aromatic hydrocarbons to Vibrio fischeri. The acute toxicity data of 17 aromatic hydrocarbons from both literature and our experimental results were used to construct QSAR models by partial least squares (PLS) analysis. With consideration of the toxicity process, the partition of aromatic hydrocarbons between water phase and lipid phase and their interaction with the target biomolecule, the optimal QSAR model was obtained by introducing aqueous freely dissolved concentration. The high statistical values of R(2) (0.956) and Q(CUM)(2) (0.942) indicated that the model has good goodness-of-fit, robustness and internal predictive power. The average molecular polarizability (α) and several selected thermodynamic parameters reflecting the intermolecular interactions played important roles in the partition of aromatic hydrocarbons between the water phase and biomembrane. Energy of the highest occupied molecular orbital (E(HOMO)) was the most influential descriptor which dominated the toxicity of aromatic hydrocarbons through the electron-transfer reaction with biomolecules. The results demonstrated that the adoption of freely dissolved concentration instead of nominal concentration was a beneficial attempt for toxicity QSAR modeling of hydrophobic organic chemicals.

  4. Quantitative Structure-Activity Relationships (QSARs) - Applications and Methodology

    Science.gov (United States)

    Cronin, Mark T. D.

    The aim of this introduction is to describe briefly the applications and methodologies involved in (Q)SAR and relate these to the various chapters in this volume. This chapter gives the reader an overview of how, why and where in silico methods, including (Q)SAR, have been utilized to predict endpoints as diverse as those from pharmacology and toxicology. It provides an illustration of how all the various topics in this book interweave to form a single coherent area of science.

  5. Rigorous theoretical derivation of lumped models to transmission line systems

    Institute of Scientific and Technical Information of China (English)

    Zhao Jixiang

    2012-01-01

    By virtue of the negative electric parameter concept,i.e.negative lumped resistance,inductance,conductance and capacitance (N-RLGC),the lumped equivalent models of transmission line systems,including the circuit model,two-port π-network and T-network,are given.We start from the N-segment-ladder-like equivalent networks composed distributed parameters,and achieve the input impedance in the form of a continued fraction.Utilizing the continued fraction theory,the expressions of input impedance are obtained under three kinds of extreme cases,i.e.the load impedances are equal to zero,infinity and characteristic impedance,respectively.When the number of segment N is limited to infinity,they are transformed to lumped elements.Comparison between the distributed model and lumped model of transmission lines,the expression of tanh yd,which is the key term in the transmission line equations,are obtained by RLGC,furthermore,according to input admittance,admittance matrix and ABCD matrix of transmission lines,the lumped equivalent circuit models,π-networks and T-networks have been given.The models are verified in the frequency and time domain,respectively,showing that the models are accurate and efficient.

  6. LUMPED Unsteady: a Visual Basic ® code of unsteady-state lumped-parameter models for mean residence time analyses of groundwater systems

    Science.gov (United States)

    Ozyurt, N. Nur; Bayari, C. Serdar

    2005-04-01

    A Microsoft ® Visual Basic 6.0 (Microsoft Corporation, 1987-1998) code of 9 lumped-parameter models of unsteady flow is presented for the analysis of mean residence time in aquifers. Groundwater flow systems obeying plug and well-mixed flow models and their combinations in parallel or serial connection can be simulated by the code. Models can use tritium, tritiugenic He-3, oxygen-18, deuterium, krypton-85, chlorofluorocarbons (CFC-11, CFC-12 and CFC-113) and sulfur hexafluoride (SF 6) as the environmental tracers. The executable code runs under all 32-bit Windows operating systems. Details of the code are explained and its limitations are indicated.

  7. Multipotent cholinesterase/monoamine oxidase inhibitors for the treatment of Alzheimer’s disease: design, synthesis, biochemical evaluation, ADMET, molecular modeling, and QSAR analysis of novel donepezil-pyridyl hybrids

    Directory of Open Access Journals (Sweden)

    Bautista-Aguilera OM

    2014-10-01

    BuChE. Concerning human monoamine oxidase (hMAO A inhibition, only DPH9 and 5 proved active, compound DPH9 being the most potent (IC50 [MAO A] =5,700±2,100 nM. For hMAO B, only DPHs 13 and 14 were moderate inhibitors, and compound DPH14 was the most potent (IC50 [MAO B] =3,950±940 nM. Molecular modeling of inhibitor DPH14 within EeAChE showed a binding mode with an extended conformation, interacting simultaneously with both catalytic and peripheral sites of EeAChE thanks to a linker of appropriate length. Absortion, distribution, metabolism, excretion and toxicity analysis showed that structures lacking phenyl-substituent show better druglikeness profiles; in particular, DPHs13–15 showed the most suitable absortion, distribution, metabolism, excretion and toxicity properties. Novel donepezil-pyridyl hybrid DPH14 is a potent, moderately selective hAChE and selective irreversible hMAO B inhibitor which might be considered as a promising compound for further development for the treatment of AD. Keywords: donepezil-pyridyl hybrids, ChE, MAO, 3D-QSAR, molecular modeling, ADMET

  8. Do Lumped-Parameter Models Provide the Correct Geometrical Damping?

    DEFF Research Database (Denmark)

    Andersen, Lars

    This paper concerns the formulation of lumped-parameter models for rigid footings on homogenous or stratified soil. Such models only contain a few degrees of freedom, which makes them ideal for inclusion in aero-elastic codes for wind turbines and other models applied to fast evaluation of struct......This paper concerns the formulation of lumped-parameter models for rigid footings on homogenous or stratified soil. Such models only contain a few degrees of freedom, which makes them ideal for inclusion in aero-elastic codes for wind turbines and other models applied to fast evaluation...... response during excitation and the geometrical damping related to free vibrations of a hexagonal footing. The optimal order of a lumped-parameter model is determined for each degree of freedom, i.e. horizontal and vertical translation as well as torsion and rocking. In particular, the necessity of coupling...... between horizontal sliding and rocking is discussed....

  9. Systematic lumping of complex tropospheric chemical mechanisms using a time-scale based approach

    Directory of Open Access Journals (Sweden)

    L. E. Whitehouse

    2004-07-01

    Full Text Available This paper presents a formal method of species lumping that can be applied automatically to intermediate compounds within detailed and complex tropospheric chemical reaction schemes. The method is based on grouping species with reference to their chemical lifetimes and reactivity structures. A method for determining the forward and reverse transformations between individual and lumped compounds is developed. Preliminary application to the Leeds Master Chemical Mechanism (MCMv2.0 has led to the removal of 734 species and 1777 reactions from the scheme, with minimal degradation of accuracy across a wide range of test trajectories relevant to polluted tropospheric conditions. The lumped groups are seen to relate to groups of peroxy acyl nitrates, nitrates, carbonates, oxepins, substituted phenols, oxeacids and peracids with similar lifetimes and reaction rates with OH. In combination with other reduction techniques, such as sensitivity analysis and the application of the quasi-steady state approximation (QSSA, a reduced mechanism has been developed that contains 35% of the number of species and 40% of the number of reactions compared to the full mechanism. This has led to a speed up of a factor of 8 in terms of computer calculation time within box model simulations.

  10. Exact Modeling of Cardiovascular System Using Lumped Method

    CERN Document Server

    Ghasemalizadeh, Omid; Firoozabadi, Bahar; Hassani, Kamran

    2014-01-01

    Electrical analogy (Lumped method) is an easy way to model human cardiovascular system. In this paper Lumped method is used for simulating a complete model. It describes a 36-vessel model and cardiac system of human body with details that could show hydrodynamic parameters of cardiovascular system. Also this paper includes modeling of pulmonary, atrium, left and right ventricles with their equivalent circuits. Exact modeling of right and left ventricles pressure increases the accuracy of our simulation. In this paper we show that a calculated pressure for aorta from our complex circuit is near to measured pressure by using advanced medical instruments.

  11. Fundamentals of electromagnetics 1 internal behavior of lumped elements

    CERN Document Server

    Voltmer, David

    2007-01-01

    This book is the first of two volumes which have been created to provide an understanding of the basic principles and applications of electromagnetic fields for electrical engineering students. Fundamentals of Electromagnetics Vol 1: Internal Behavior of Lumped Elements focuses upon the DC and low-frequency behavior of electromagnetic fields within lumped elements. The properties of electromagnetic fields provide the basis for predicting the terminal characteristics of resistors, capacitors, and inductors. The properties of magnetic circuits are included as well. For slightly higher frequencie

  12. 氯代苯胺对斑马鱼的急性毒性的电性拓扑研究%QSAR Analysis of Acute Toxicity of Chloroanilines to Zebra-Fish

    Institute of Scientific and Technical Information of China (English)

    唐自强; 冯长君

    2012-01-01

    基于拓扑理论计算了7种氯代苯胺分子的Kier和Hall的原子类型电性拓扑状态指数(E1).通过多元线性回归和最佳变量子集回归方法建立了氯代苯胺对斑马鱼急性毒性(pLC50)与其电性拓扑状态指数的最佳二元定量构效关系(QSAR)模型,其传统判定系数(R2)为0.978,逐一剔除法(LOO)的交互验证系数(Q2)为0.964.根据统计学观点,该模型具有良好的稳健性及预测能力,用该模型给出的估算值和实验值非常接近,优于相关文献的计算结果.从进入该QSAR模型的2个电性拓扑状态指数(E9,E26)可见,所建的数学方程显示芳环内=C<及硝基中氮原子(=N≤)是影响其pLC50的主要结构因素.%On the basis of topological method, Kier and Hall's atom-type electro-topologicai state indices (Et) of seven chloroanilines compounds were calculated, and Ef was used to describe the structure of chloroanilines. By using the multiple linear regression and Leaps-and-Bounds regression, a QSAR model was set up depicting the relationship between and the acute toxicity (pLC60) of chloroanilines to zebra-fish. Research with the optimal two-parameter QSAR model developed in this paper demonstrated that the model was highly reliable and of good predictive ability from the view-point of statistics. According to the parameters in the model) E9 and E36), it could be seen that the characteristics of molecular structure, such as the structural fragments =C < in the aromatic ring and = N ≤ , were the major factors affecting the acute toxicity(pLC50).

  13. QSAR STUDY TO PREDICT ANTI-AMOEBIC ACTIVITIES OF PYRAZOLINE AND DIOXAZOLE DERIVATIVES WITH THE HELP OF PM5-BASED DESCRIPTORS

    Directory of Open Access Journals (Sweden)

    Anil K. Srivastava et al

    2012-09-01

    Full Text Available In quest of better anti-amoebic agents, quantitative structure-activity relationship (QSAR studies were performed on a series of pyrazoline & dioxazoles derivatives with the help of PM5 calculations and geometry optimizations using CAChe software. Multiple Linear Regression (MLR analysis was performed to derive QSAR models using the descriptors, molecular weight (MW, conformation minimum energy (ɛ, HOMO energy (HOMO, shape index, basic kappa second order (k2, absolute hardness (h, electronegativity (c, electrophilicity index (ω, molar volume (MV, molar refractivity (MR, LogP (LP, parachor (Pc and solvent accessibility surface area (SASA. The QSAR models equations of anti-amoebic agents have been developed by using maximum of seven descriptors, in which conformation minimum energy, shape index, molar volume and parchor were present have good predictive powers of correlation coefficients. These models can successfully predict the anti-amoebic activity of any newly discovered pyrazoline and dioxazole derivatives which can later be tested in laboratory.

  14. Do Lumped-Parameter Models Provide the Correct Geometrical Damping?

    DEFF Research Database (Denmark)

    Andersen, Lars

    2007-01-01

    This paper concerns the formulation of lumped-parameter models for rigid footings on homogenous or stratified soil with focus on the horizontal sliding and rocking. Such models only contain a few degrees of freedom, which makes them ideal for inclusion in aero-elastic codes for wind turbines...

  15. Leaks, Lumps, and Lines: Stigma and Women's Bodies

    Science.gov (United States)

    Chrisler, Joan C.

    2011-01-01

    Women's bodies have often been positioned in art and popular culture as monstrous or defiled and women's bodily products (e.g., menstrual fluid, breast milk) as disgusting. This framing has led to the stigmatization of aspects of women's bodies (e.g., leaking fluids, lumps of fat, and lines in the skin that indicate aging), especially those…

  16. Reduction in thermal conductivity of BiSbTe lump

    Science.gov (United States)

    Ahmad, Kaleem; Wan, C.; Al-Eshaikh, M. A.; Kadachi, A. N.

    2017-03-01

    In this work, systematic investigations on the thermal conductivities of BiSbTe lump, microstructured pristine BiSbTe bulk and single wall carbon nanotubes (SWCNTs)/BiSbTe bulk nanocomposites were performed. BiSbTe lumps were crushed to form a coarse powder (200 µm) and effect of particle size reduction on the effective thermal conductivity of BiSbTe (200 µm) bulk were analyzed. For further reduction in the conductivity, a two pronged strategy has been employed. First, additional refinement of BiSbTe (200 µm) were performed through ball milling in an inert environment. Second, SWCNTs in 0.75, and 1.0 vol% were distributed uniformly in the fine BiSbTe ball milled powder. The results showed that the effective thermal conductivities decrease with the reduction in the particle size from lump to BiSbTe (200 µm) bulk as well as with the addition of SWCNTs accompanied by further refinement of BiSbTe particles. The significant reduction in thermal conductivities of the lump was achieved for pure BiSbTe (200 µm) bulk and 0.75 vol% of SWCNTs/BiSbTe composite. This can be ascribed to the enhanced phonon scattering by the grain boundaries between the nanostructured BiSbTe particles as well as the interfaces between BiSbTe and the low dimensional carbon nanotubes.

  17. Do Lumped-Parameter Models Provide the Correct Geometrical Damping?

    DEFF Research Database (Denmark)

    Andersen, Lars

    2007-01-01

    This paper concerns the formulation of lumped-parameter models for rigid footings on homogenous or stratified soil with focus on the horizontal sliding and rocking. Such models only contain a few degrees of freedom, which makes them ideal for inclusion in aero-elastic codes for wind turbines...

  18. Reduction in thermal conductivity of BiSbTe lump

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, Kaleem [King Saud University, Sustainable Energy Technologies Center, College of Engineering, PO Box 800, Riyadh (Saudi Arabia); Wan, C. [Tsinghua University, State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Beijing (China); Al-Eshaikh, M.A.; Kadachi, A.N. [King Saud University, Research Center, College of Engineering, PO Box 800, Riyadh (Saudi Arabia)

    2017-03-15

    In this work, systematic investigations on the thermal conductivities of BiSbTe lump, microstructured pristine BiSbTe bulk and single wall carbon nanotubes (SWCNTs)/BiSbTe bulk nanocomposites were performed. BiSbTe lumps were crushed to form a coarse powder (200 μm) and effect of particle size reduction on the effective thermal conductivity of BiSbTe (200 μm) bulk were analyzed. For further reduction in the conductivity, a two pronged strategy has been employed. First, additional refinement of BiSbTe (200 μm) were performed through ball milling in an inert environment. Second, SWCNTs in 0.75, and 1.0 vol% were distributed uniformly in the fine BiSbTe ball milled powder. The results showed that the effective thermal conductivities decrease with the reduction in the particle size from lump to BiSbTe (200 μm) bulk as well as with the addition of SWCNTs accompanied by further refinement of BiSbTe particles. The significant reduction in thermal conductivities of the lump was achieved for pure BiSbTe (200 μm) bulk and 0.75 vol% of SWCNTs/BiSbTe composite. This can be ascribed to the enhanced phonon scattering by the grain boundaries between the nanostructured BiSbTe particles as well as the interfaces between BiSbTe and the low dimensional carbon nanotubes. (orig.)

  19. Experimental realization of optical lumped nanocircuits at infrared wavelengths.

    Science.gov (United States)

    Sun, Yong; Edwards, Brian; Alù, Andrea; Engheta, Nader

    2012-01-29

    The integration of radiofrequency electronic methodologies on micro- as well as nanoscale platforms is crucial for information processing and data-storage technologies. In electronics, radiofrequency signals are controlled and manipulated by 'lumped' circuit elements, such as resistors, inductors and capacitors. In earlier work, we theoretically proposed that optical nanostructures, when properly designed and judiciously arranged, could behave as nanoscale lumped circuit elements--but at optical frequencies. Here, for the first time we experimentally demonstrate a two-dimensional optical nanocircuit at mid-infrared wavelengths. With the guidance of circuit theory, we design and fabricate arrays of Si3N4 nanorods with specific deep subwavelength cross-sections, quantitatively evaluate their equivalent impedance as lumped circuit elements in the mid-infrared regime, and by Fourier transform infrared spectroscopy show that these nanostructures can indeed function as two-dimensional optical lumped circuit elements. We further show that the connections among nanocircuit elements, in particular whether they are in series or in parallel combination, can be controlled by the polarization of impinging optical signals, realizing the notion of 'stereo-circuitry' in metatronics-metamaterials-inspired optical circuitry.

  20. Lump Sum Moving Cost and Aggregate Office Space Use

    NARCIS (Netherlands)

    G. Romijn

    1997-01-01

    textabstractWhen firms decide to change office space use, in many instances this involves relocation. Relocation involves sizable costs to the firm that can to a large extent be characterized as lump sum, i.e. independent of the change in demand. In this paper we propose and solve a model of the

  1. Lump Sum Moving Cost and Aggregate Office Space Use

    NARCIS (Netherlands)

    G. Romijn

    1997-01-01

    textabstractWhen firms decide to change office space use, in many instances this involves relocation. Relocation involves sizable costs to the firm that can to a large extent be characterized as lump sum, i.e. independent of the change in demand. In this paper we propose and solve a model of the dem

  2. Seleção de variáveis em QSAR Variable selection in QSAR

    Directory of Open Access Journals (Sweden)

    Márcia Miguel Castro Ferreira

    2002-05-01

    Full Text Available The process of building mathematical models in quantitative structure-activity relationship (QSAR studies is generally limited by the size of the dataset used to select variables from. For huge datasets, the task of selecting a given number of variables that produces the best linear model can be enormous, if not unfeasible. In this case, some methods can be used to separate good parameter combinations from the bad ones. In this paper three methodologies are analyzed: systematic search, genetic algorithm and chemometric methods. These methods have been exposed and discussed through practical examples.

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

    Science.gov (United States)

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

    2013-10-01

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

  4. 5 CFR 838.734 - Payment of lump-sum awards by survivor annuity.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Payment of lump-sum awards by survivor... Orders Awarding Former Spouse Survivor Annuities Payment Procedures § 838.734 Payment of lump-sum awards by survivor annuity. OPM will not honor court orders awarding lump-sum payments (other than the...

  5. Predicting antiprotozoal activity of benzyl phenyl ether diamine derivatives through QSAR multi-target and molecular topology.

    Science.gov (United States)

    Garcia-Domenech, Ramon; Zanni, Riccardo; Galvez-Llompart, Maria; Galvez, Jorge

    2015-05-01

    Multi-target QSAR is a novel approach that can predict simultaneously the activity of a given chemical compound on different pharmacological targets. In this work, we have used molecular topology and statistical tools such as multilinear regression analysis and artificial neural networks, to achieve a multi-target QSAR model capable to predict the antiprotozoal activity of a group of benzyl phenyl ether diamine derivatives. The activity was related to three parasites with a high prevalence rate in humans: Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani. The multi-target model showed a high regression coefficient (R(2) = 0.9644 and R(2) = 0.9235 for training and test sets, respectively) and a low standard error of estimate (SEE = 0.279). Model validation was performed with an external test (R(2) = 0.9001) and a randomization analysis. Finally, the model was applied to the search of potential new active compounds.

  6. QSAR MODELING OF ANTIBACTERIAL ACTIVITY OF SOME BENZIMIDAZOLE DERIVATIVES

    Directory of Open Access Journals (Sweden)

    SANJA O. PODUNAVAC-KUZMANOVIĆ

    2011-03-01

    Full Text Available A quantitative structure-activity relationship (QSAR study has been carried out for a training set of 12 benzimidazole derivatives to correlate and predict the antibacterial activity of studied compounds against Gram-negative bacteria Pseudomonas aeruginosa. Multiple linear regression was used to select the descriptors and to generate the best prediction model that relates the structural features to inhibitory activity. The predictivity of the model was estimated by cross-validation with the leave-one-out method. Our results suggest a QSAR model based on the following descriptors: parameter of lipophilicity (logP and hydration energy (HE. Good agreement between experimental and predicted inhibitory values, obtained in the validation procedure, indicated the good quality of the generated QSAR model.

  7. On the development and validation of QSAR models.

    Science.gov (United States)

    Gramatica, Paola

    2013-01-01

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

  8. QSAR Studies of 6-Amino Uracil Base Analogues: A Thymidine Phosphorylase Inhibitor in Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Surya Prakash B. N. Gupta

    2008-01-01

    Full Text Available A novel series of 6-amino uracil base analogue were synthesized. QSAR study was used to relate the selective nonsubstrate inhibitory activity of 6-amino uracil base analogue with various physicochemical descriptors. Stepwise multiple regression analysis was performed to find out the correlation between various physicochemical descriptors and biological activity of the compounds by using Openstat 2 version 6.5.1 and valstat statistical software. Out of the several equations developed, the best equation having the highest significance was selected for further study. The equation is able to explain 60% of total variance and are more than 95% significant as revealed by the F value.

  9. QSAR STUDY OF SALICYLANILIDES DERIVATIVES AGAINST VARIOUS MYCOBACTERILAL STRAIN AT AM1 SEMI EMPIRICAL LEVEL

    Directory of Open Access Journals (Sweden)

    Supratim Ray

    2012-04-01

    Full Text Available A QSAR study was performed by quantum chemical calculation only at the AM1 semi empirical levels to calculate the Mulliken’s charges and dipole moment of common atoms for 30 salicylanilides compounds with antimycobacterial activity against Mycobacterium tuberculosis and Mycobacterium kansasii. Stepwise regression analysis is used as statistical tool. The model developed for Mycobacterium tuberculosis indicates the importance of halide substitutions at meta and para position of the phenyl ring attached to carboxamide group towards antitubercular activity. The model developed for Mycobacterium kansasii shows the importance of oxygen atom and carbonyl group of the ester linkage of salicylanilides for activity.

  10. QSAR Methods to Screen Endocrine Disruptors

    Directory of Open Access Journals (Sweden)

    Nicola Porta

    2016-08-01

    Full Text Available The identification of endocrine disrupting chemicals (EDCs is one of the important goals of environmental chemical hazard screening. We report on in silico methods addressing toxicological studies about EDCs with a special focus on the application of QSAR models for screening purpose. Since Estrogen-like (ER activity has been extensively studied, the majority of the available models are based on ER-related endpoints. Some of these models are here reviewed and described. As example for their application, we screen an assembled dataset of candidate substitutes for some known EDCs belonging to the chemical classes of phthalates, bisphenols and parabens, selected considering their toxicological relevance and broad application, with the general aim of preliminary assessing their ED potential. The goal of the substitution processes is to advance inherently safer chemicals and products, consistent with the principles of green chemistry. Results suggest that the integration of a family of different models accounting for different endpoints can be a convenient way to describe ED as properly as possible and allow also both to increase the confidence of the predictions and to maximize the probability that most active compounds are correctly found.

  11. coral Software: QSAR for Anticancer Agents.

    Science.gov (United States)

    Benfenati, Emilio; Toropov, Andrey A; Toropova, Alla P; Manganaro, Alberto; Gonella Diaza, Rodolfo

    2011-06-01

    CORrelations And Logic (coral at http://www.insilico.eu/coral) is freeware aimed at establishing a quantitative structure - property/activity relationships (QSPR/QSAR). Simplified molecular input line entry system (SMILES) is used to represent the molecular structure. In fact, symbols in SMILES nomenclatures are indicators of the presence of defined molecular fragments. By means of the calculation with Monte Carlo optimization of the so called correlation weights (contributions) for the above-mentioned molecular fragments, one can define optimal SMILES-based descriptors, which are correlated with an endpoint for the training set. The predictability of these descriptors for an external validation set can be estimated. A collection of SMILES-based models of anticancer activity of 1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridines for different splits into training and validation set which are calculated with the coral are examined and discussed. Good performance has been obtained for three splits: the r(2) ranged between 0.778 and 0.829 for the sub-training set, between 0.828 and 0.933 for the calibration set, and between 0.807 and 0.931 for the validation set. © 2011 John Wiley & Sons A/S.

  12. QSAR based docking studies of marine algal anticancer compounds as inhibitors of protein kinase B (PKBβ).

    Science.gov (United States)

    Davis, G Dicky John; Vasanthi, A Hannah Rachel

    2015-08-30

    Marine algae are prolific source of bioactive secondary metabolites and are found to be active against different cancer cell lines. QSAR studies will explicate the significance of a particular class of descriptor in eliciting anticancer activity against a cancer type. Marine algal compounds showing anticancer activity against six different cancer cell lines namely MCF-7, A431, HeLa, HT-29, P388 and A549 taken from Seaweed metabolite database were subjected to comprehensive QSAR modeling studies. A hybrid-GA (genetic algorithm) optimization technique for descriptor space reduction and multiple linear regression analysis (MLR) approach was used as fitness functions. Cell lines HeLa and MCF-7 showed good statistical quality (R(2)∼0.75, Q(2)∼0.65) followed by A431, HT29 and P388 cell lines with reasonable statistical values (R(2)∼0.70, Q(2)∼0.60). The models developed were interpretable, with good statistical and predictive significance. Molecular descriptor analyses revealed that Baumann's alignment-independent topological descriptors had a major role in variation of activity along with other descriptors. Incidentally, earlier QSAR analysis on a variety of chemically diverse PKBα inhibitors revealed Baumann's alignment-independent topological descriptors that differentiated the molecules binding to Protein kinase B (PKBα) kinase or PH domain, hence a docking study of two crystal structures of PKBβ was performed for identification of novel ATP-competitive inhibitors of PKBβ. Five compounds had a good docking score and Callophycin A showed better ligand efficiency than other PKBβ inhibitors. Furthermore in silico pharmacokinetic and toxicity studies also showed that Callophycin A had a high drug score (0.85) compared to the other inhibitors. These results encourages discovering novel inhibitors for cancer therapeutic targets by screening metabolites from marine algae.

  13. 4D-QSAR: Perspectives in Drug Design

    Directory of Open Access Journals (Sweden)

    Carolina H. Andrade

    2010-05-01

    Full Text Available Drug design is a process driven by innovation and technological breakthroughs involving a combination of advanced experimental and computational methods. A broad variety of medicinal chemistry approaches can be used for the identification of hits, generation of leads, as well as to accelerate the optimization of leads into drug candidates. The quantitative structure–activity relationship (QSAR formalisms are among the most important strategies that can be applied for the successful design new molecules. This review provides a comprehensive review on the evolution and current status of 4D-QSAR, highlighting present challenges and new opportunities in drug design.

  14. An ensemble model of QSAR tools for regulatory risk assessment.

    Science.gov (United States)

    Pradeep, Prachi; Povinelli, Richard J; White, Shannon; Merrill, Stephen J

    2016-01-01

    Quantitative structure activity relationships (QSARs) are theoretical models that relate a quantitative measure of chemical structure to a physical property or a biological effect. QSAR predictions can be used for chemical risk assessment for protection of human and environmental health, which makes them interesting to regulators, especially in the absence of experimental data. For compatibility with regulatory use, QSAR models should be transparent, reproducible and optimized to minimize the number of false negatives. In silico QSAR tools are gaining wide acceptance as a faster alternative to otherwise time-consuming clinical and animal testing methods. However, different QSAR tools often make conflicting predictions for a given chemical and may also vary in their predictive performance across different chemical datasets. In a regulatory context, conflicting predictions raise interpretation, validation and adequacy concerns. To address these concerns, ensemble learning techniques in the machine learning paradigm can be used to integrate predictions from multiple tools. By leveraging various underlying QSAR algorithms and training datasets, the resulting consensus prediction should yield better overall predictive ability. We present a novel ensemble QSAR model using Bayesian classification. The model allows for varying a cut-off parameter that allows for a selection in the desirable trade-off between model sensitivity and specificity. The predictive performance of the ensemble model is compared with four in silico tools (Toxtree, Lazar, OECD Toolbox, and Danish QSAR) to predict carcinogenicity for a dataset of air toxins (332 chemicals) and a subset of the gold carcinogenic potency database (480 chemicals). Leave-one-out cross validation results show that the ensemble model achieves the best trade-off between sensitivity and specificity (accuracy: 83.8 % and 80.4 %, and balanced accuracy: 80.6 % and 80.8 %) and highest inter-rater agreement [kappa (κ): 0

  15. Lump Solutions for the (3+1)-Dimensional Kadomtsev-Petviashvili Equation

    Science.gov (United States)

    Liu, De-Yin; Tian, Bo; Xie, Xi-Yang

    2016-12-01

    In this article, we investigate the lump solutions for the Kadomtsev-Petviashvili equation in (3+1) dimensions that describe the dynamics of plasmas or fluids. Via the symbolic computation, lump solutions for the (3+1)-dimensional Kadomtsev-Petviashvili equation are derived based on the bilinear forms. The conditions to guarantee analyticity and rational localisation of the lump solutions are presented. The lump solutions contain eight parameters, two of which are totally free, and the other six of which need to satisfy the presented conditions. Plots with particular choices of the involved parameters are made to show the lump solutions and their energy distributions.

  16. Lumping procedure for a kinetic model of catalytic naphtha reforming

    Directory of Open Access Journals (Sweden)

    H. M. Arani

    2009-12-01

    Full Text Available A lumping procedure is developed for obtaining kinetic and thermodynamic parameters of catalytic naphtha reforming. All kinetic and deactivation parameters are estimated from industrial data and thermodynamic parameters are calculated from derived mathematical expressions. The proposed model contains 17 lumps that include the C6 to C8+ hydrocarbon range and 15 reaction pathways. Hougen-Watson Langmuir-Hinshelwood type reaction rate expressions are used for kinetic simulation of catalytic reactions. The kinetic parameters are benchmarked with several sets of plant data and estimated by the SQP optimization method. After calculation of deactivation and kinetic parameters, plant data are compared with model predictions and only minor deviations between experimental and calculated data are generally observed.

  17. Breast Lumps in a Teaching Hospital: A 5 Year Study

    Directory of Open Access Journals (Sweden)

    Chiragkumar L Prajapati

    2014-02-01

    The clinical diagnosis were breast cancer in 260 patients (47.3%, fibroadenoma in 175 (31.8%, fibrocystic changes in 67 (12.2% patients; the others were benign diseases. Histopathology, done in 294 patients, revealed 161(54.8%, 56(19.0% and 46(15.6% patients having invasive cancer, fibroadenoma, and fibrocystic changes respectively. Conclusion: Breast lump was the most common presenting complaint with most patients not presenting early. Fewer lumps are discovered by breast self examination. The finding of fibroadenoma as the most common of the benign lesions is similar to that reported by other researchers in India and other parts of the world. [Natl J Med Res 2014; 4(1.000: 65-67

  18. 5-Lump kinetic model for gas oil catalytic cracking

    Energy Technology Data Exchange (ETDEWEB)

    Ancheyta-Juarez, Jorge; Aguilar-Rodriguez, Enrique [Instituto Mexicano del Petroleo, Eje Central Lazaro Cardenas 152, Mexico 07730 DF (Mexico); Lopez-Isunza, Felipe [Universidad Autonoma Metropolitana-Iztapalapa, Mexico 09340 DF (Mexico)

    1999-02-22

    A new 5-lump kinetic model is proposed to describe the gas oil catalytic cracking (FCC) process. The model contains eight kinetic constants, including one for catalyst deactivation, taking into account LPG (combined C{sub 3}-C{sub 4}), dry gas (C{sub 2} and lighter) and coke yields separately from other lumps (unconverted gas oil and gasoline). Apparent activation energies were determined from experiments obtained in a microactivity reactor (MAT) at temperatures: 480C, 500C and 520C; for a catalyst-to-oil ratio of 5 using vacuum gas oil and equilibrium catalyst, both recovered from an industrial FCC unit. Product yields predicted by this model show good agreement with experimental data

  19. 7-lump kinetic model for residual oil catalytic cracking

    Institute of Scientific and Technical Information of China (English)

    XU Ou-guan; SU Hong-ye; MU Sheng-jing; CHU Jian

    2006-01-01

    In this paper a novel 7-lump kinetic model is proposed to describe residual oil catalytic cracking, in which coke is lumped separately for accurate prediction. The reactor block is modeled as a combination of an ideal pipe flow reactor (PFR)and a continuously stirred tank reactor (CSTR). Unit factors are designed to correct the deviation between model predictions and practical plant data and tuned by modified Levenberg-Marquardt algorithm. The parameters estimated are reliable and good agreement between the model predictions and plant observations is observed. The model helps us get good insight into the performance of an industrial riser reactor that would be useful for optimization of residual oil catalytic cracking.

  20. Strangulated double omental hernia presenting as an epigastric lump.

    Science.gov (United States)

    Mukherjee, Ramanuj; Paira, Susil Kumar; Ghosh, Parthasarathi; Halder, Sandip K; Roy, Bipradas; Ray, Debasis; Mukherjee, Saibal Kumar

    2012-09-01

    Internal herniations constitute one of the relatively uncommon surgical emergencies. Among them double omental hernia with bowel strangulation is very rare and is a major diagnostic challenge. A case of a strangulated double omental hernia in a 42-year-old female patient is reported. The patient presented with a painful tender epigastric lump.There was a diagnostic dilemma. CT scan was followed by laparotomy which revealed a strangulated double omental hernia.

  1. Idiopathic Granulomatous Mastitis: A Clinical Puzzle in Breast Lump Cases.

    Science.gov (United States)

    Nath, Vivek G; Sahoo, Rakesh; Sahoo, Avinash; Barad, Jithendra Kumar; Arun, K A

    2017-06-01

    Idiopathic granulomatous mastitis (IGM) is a rare benign disease, characterized by chronic inflammation and granulomatous disease process. A middle aged lady with breast lump for six months with equivocal mammographic and ultrasound results underwent lumpectomy and biopsy. Ruling out all other possible granulomatous diseases and malignancy, a diagnosis of IGM was made. IGM becomes clinically significant as it closely mimics carcinoma breast and some inflammatory and infectious pathology.

  2. Idiopathic Granulomatous Mastitis: A Clinical Puzzle in Breast Lump Cases

    OpenAIRE

    Nath, Vivek G; sahoo, Rakesh; sahoo, Avinash; Barad, Jithendra kumar; Arun, K A

    2017-01-01

    Idiopathic granulomatous mastitis (IGM) is a rare benign disease, characterized by chronic inflammation and granulomatous disease process. A middle aged lady with breast lump for six months with equivocal mammographic and ultrasound results underwent lumpectomy and biopsy. Ruling out all other possible granulomatous diseases and malignancy, a diagnosis of IGM was made. IGM becomes clinically significant as it closely mimics carcinoma breast and some inflammatory and infectious pathology.

  3. Supersymmetric Q-Lumps in the Grassmannian nonlinear sigma models

    CERN Document Server

    Bak, D; Lee, J; Oh, P; Bak, Dongsu; Hahn, Sang-Ok; Lee, Joohan; Oh, Phillial

    2007-01-01

    We construct the N=2 supersymmetric Grassmannian nonlinear sigma model for the massless case and extend it to massive N=2 model by adding an appropriate superpotential. We then study their BPS equations leading to supersymmetric Q-lumps carrying both topological and Noether charges. These solutions are shown to be always time dependent even sometimes involving multiple frequencies. Thus we illustrate explicitly that the time dependence is consistent with remaining supersymmetries of solitons.

  4. Discovery of New Anti-Schistosomal Hits by Integration of QSAR-Based Virtual Screening and High Content Screening.

    Science.gov (United States)

    Neves, Bruno J; Dantas, Rafael F; Senger, Mario R; Melo-Filho, Cleber C; Valente, Walter C G; de Almeida, Ana C M; Rezende-Neto, João M; Lima, Elid F C; Paveley, Ross; Furnham, Nicholas; Muratov, Eugene; Kamentsky, Lee; Carpenter, Anne E; Braga, Rodolpho C; Silva-Junior, Floriano P; Andrade, Carolina Horta

    2016-08-11

    Schistosomiasis is a debilitating neglected tropical disease, caused by flatworms of Schistosoma genus. The treatment relies on a single drug, praziquantel (PZQ), making the discovery of new compounds extremely urgent. In this work, we integrated QSAR-based virtual screening (VS) of Schistosoma mansoni thioredoxin glutathione reductase (SmTGR) inhibitors and high content screening (HCS) aiming to discover new antischistosomal agents. Initially, binary QSAR models for inhibition of SmTGR were developed and validated using the Organization for Economic Co-operation and Development (OECD) guidance. Using these models, we prioritized 29 compounds for further testing in two HCS platforms based on image analysis of assay plates. Among them, 2-[2-(3-methyl-4-nitro-5-isoxazolyl)vinyl]pyridine and 2-(benzylsulfonyl)-1,3-benzothiazole, two compounds representing new chemical scaffolds have activity against schistosomula and adult worms at low micromolar concentrations and therefore represent promising antischistosomal hits for further hit-to-lead optimization.

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

    Science.gov (United States)

    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. Lumped mass modeling of overburden motion during explosive blasting

    Energy Technology Data Exchange (ETDEWEB)

    Schamaun, J. T.

    1981-02-01

    The in situ extraction of oil from most oil shale beds is highly dependent upon explosive fracturing and rubbling of rock in a controlled and predictable manner. Besides the rubbling requirement, it is also important that the surrounding rock remain competent to minimize fluid leakage during processing. For rubbling concepts in which the overburden is explosively lifted to provide the required void in an oil shale zone, an engineering lumped mass model has been devised to describe the motion of the overburden. The model simulates the overburden as an array of interacting lumped masses which are loaded from below with a time-dependent force to approximate the explosive load. Correlation with experimental data obtained from field blasting operations shows that this model will provide an adequate approximation of overburden behavior. The basic features of the model are described in the report along with the correlations with field data. Results from several parametric studies are also presented which were used to aid in blast design. This lumped mass model can be extended to include other parameters and has potential for the study of other related blasting situations.

  7. Dynamics of neutrino lumps in growing neutrino quintessence

    CERN Document Server

    Casas, Santiago; Wetterich, Christof

    2016-01-01

    We investigate the formation and dissipation of large scale neutrino structures in cosmologies where the time evolution of dynamical dark energy is stopped by a growing neutrino mass. In models where the coupling between neutrinos and dark energy grows with the value of the scalar cosmon field, the evolution of neutrino lumps depends on the neutrino mass. For small masses the lumps form and dissolve periodically, leaving only a small backreaction of the neutrino structures on the cosmic evolution. This process heats the neutrinos to temperatures much above the photon temperature such that neutrinos acquire again an almost relativistic equation of state. The present equation of state of the combined cosmon-neutrino fluid is very close to -1. In contrast, for larger neutrino masses the lumps become stable. The highly concentrated neutrino structures entail a large backreaction similar to the case of a constant neutrino-cosmon coupling. A present average neutrino mass of around 0.5 eV seems so far compatible wit...

  8. Lumped parametric model of the human ear for sound transmission.

    Science.gov (United States)

    Feng, Bin; Gan, Rong Z

    2004-09-01

    A lumped parametric model of the human auditoria peripherals consisting of six masses suspended with six springs and ten dashpots was proposed. This model will provide the quantitative basis for the construction of a physical model of the human middle ear. The lumped model parameters were first identified using published anatomical data, and then determined through a parameter optimization process. The transfer function of the middle ear obtained from human temporal bone experiments with laser Doppler interferometers was used for creating the target function during the optimization process. It was found that, among 14 spring and dashpot parameters, there were five parameters which had pronounced effects on the dynamic behaviors of the model. The detailed discussion on the sensitivity of those parameters was provided with appropriate applications for sound transmission in the ear. We expect that the methods for characterizing the lumped model of the human ear and the model parameters will be useful for theoretical modeling of the ear function and construction of the ear physical model.

  9. Preselection of A- and B- modified d-homo lactone and d-seco androstane derivatives as potent compounds with antiproliferative activity against breast and prostate cancer cells - QSAR approach and molecular docking analysis.

    Science.gov (United States)

    Kovačević, Strahinja Z; Podunavac-Kuzmanović, Sanja O; Jevrić, Lidija R; Vukić, Vladimir R; Savić, Marina P; Djurendić, Evgenija A

    2016-10-10

    The problem with trial-and-error approach in organic synthesis of targeted anticancer compounds can be successfully avoided by computational modeling of molecules, docking studies and chemometric tools. It has been proven that A- and B- modified d-homo lactone and d-seco androstane derivatives are compounds with significant antiproliferative activity against estrogen-independent breast adenocarcinoma (ER-, MDA-MB-231) and androgen-independent prostate cancer cells (AR-, PC-3). This paper presents the quantitative structure-activity relationship (QSAR) models based on artificial neural networks (ANNs) which are able to predict whether d-homo lactone and/or d-seco androstane-based compounds will express antiproliferative activity against breast cancer cells (MDA-MB-231) or not. Also, the present paper describes the molecular docking study of 3β-acetoxy-5α,6α-epoxy- (3) and 6α,7α-epoxy-1,4-dien-3-one (24) d-homo lactone androstane derivatives, as well as 4-en-3-one (15) d-seco androstane derivative, which are compounds with strong or moderate antiproliferative activity against prostate cancer cells (PC-3), and compares them with commercially available medicament for prostate cancer - abiraterone. The obtained promising results can be used as guidelines in further syntheses of novel d-homo lactone and d-seco androstane derivatives with antiproliferative activity against breast and prostate cancer cells.

  10. 氯代苯胺对斑马鱼的急性毒性及3D-QSAR分析%Acute Toxicity of Chloroanilines to Zebra Fish and 3D-QSAR Analysis

    Institute of Scientific and Technical Information of China (English)

    李伟民; 尹大强; 李时银; 王学江; 王连生

    2002-01-01

    研究了2-氯-4-硝基苯胺、4-氯-3-硝基苯胺、2-氯-5-硝基苯胺、2,4-二氯苯胺、3,4-二氯苯胺、2,5-二氯苯胺、2,3-二氯苯胺对斑马鱼(Brachydanio rerio)的96 h急性毒性,96 h LC50分别为6.99,2.58,8.63,7.79,6.08,5.23,0.49 mg/L.运用三维定量结构活性相关模型(3D-QSAR)对这些化合物的毒性效应和构效关系进行了分析和评价,估算毒性值与实际观测值相关性较好,相关系数R2=0.907.

  11. 3D-QSAR study of 20 (S)-camptothecin analogs

    Institute of Scientific and Technical Information of China (English)

    Ai-jun LU; Zhen-shan ZHANG; Ming-yue ZHENG; Han-jun ZOU; Xiao-min LUO; Hua-liang JIANG

    2007-01-01

    Aim: To build up a quantitative structure-activity relationship (QSAR) model of20 (S)-camptothecin (CPT) analogs for the prediction of the activity of new CPT analogs for drug design. Methods: A training set of 43 structurally diverse CPT analogs which were inhibitors of topoisomerase Ⅰ were used to construct a quan-titative structure-activity relationship model with a comparative molecular field analysis (CoMFA). The QSAR model was optimized using partial least squares(PLS) analysis. A test set of 10 compounds was evaluated using the model. Results: The CoMFA model was constructed successfully, and a good cross-validated correlation was obtained in which q2 was 0.495. Then, the analysis of the non-cross-validated PLS model in which r2 was 0.935 was built and permitted demonstrations of high predictability for the activities of the 10 CPT analogs in the test set selected in random. Conclusion: The CoMFA model indicated that bulky negative-charged group at position 9, 10 and 11 of CPT would increase activity, but excessively increasing bulky group at position 10 is adverse to inhibi-tory activity; substituents that occupy position 7 with the bulky positive group will enhance the inhibitive activity. The model can be used to design new CPT analogs and understand the mechanism of action.

  12. QSAR, molecular docking studies of thiophene and imidazopyridine derivatives as polo-like kinase 1 inhibitors

    Science.gov (United States)

    Cao, Shandong

    2012-08-01

    The purpose of the present study was to develop in silico models allowing for a reliable prediction of polo-like kinase inhibitors based on a large diverse dataset of 136 compounds. As an effective method, quantitative structure activity relationship (QSAR) was applied using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The proposed QSAR models showed reasonable predictivity of thiophene analogs (Rcv2=0.533, Rpred2=0.845) and included four molecular descriptors, namely IC3, RDF075m, Mor02m and R4e+. The optimal model for imidazopyridine derivatives (Rcv2=0.776, Rpred2=0.876) was shown to perform good in prediction accuracy, using GATS2m and BEHe1 descriptors. Analysis of the contour maps helped to identify structural requirements for the inhibitors and served as a basis for the design of the next generation of the inhibitor analogues. Docking studies were also employed to position the inhibitors into the polo-like kinase active site to determine the most probable binding mode. These studies may help to understand the factors influencing the binding affinity of chemicals and to develop alternative methods for prescreening and designing of polo-like kinase inhibitors.

  13. DFT-based QSAR and QSPR models of several cis-platinum complexes: solvent effect.

    Science.gov (United States)

    Sarmah, Pubalee; Deka, Ramesh C

    2009-06-01

    Cytotoxic activities of cis-platinum complexes against parental and resistant ovarian cancer cell lines were investigated by quantitative structure-activity relationship (QSAR) analysis using density functional theory (DFT) based descriptors. The calculated parameters were found to increase the predictability of each QSAR model with incorporation of solvent effects indicating its importance in studying biological activity. Given the importance of logarithmic n-octanol/water partition coefficient (log P(o/w)) in drug metabolism and cellular uptake, we modeled the log P(o/w) of 24 platinum complexes with different leaving and carrier ligands by the quantitative structure-property relationship (QSPR) analysis against five different concentrations of MeOH using DFT and molecular mechanics derived descriptors. The log P(o/w) values of an additional set of 20 platinum complexes were also modeled with the same descriptors. We investigated the predictability of the model by calculating log P(o/w) of four compounds in the test set and found their predicted values to be in good agreement with the experimental values. The QSPR analyses performed on 24 complexes, combining the training and test sets, also provided significant values for the statistical parameters. The solvent medium played an important role in QSPR analysis by increasing the internal predictive ability of the models.

  14. Dimensionless lumped formulation for performance assessment of adsorbed natural gas storage

    Energy Technology Data Exchange (ETDEWEB)

    da Silva, M.J.M.; Sphaier, L.A. [Laboratory of Theoretical and Applied Mechanics - LMTA/PGMEC, Department of Mechanical Engineering, Universidade Federal Fluminense, Rua Passo da Patria 156, bloco E, sala 216, Niteroi, RJ 24210-240 (Brazil)

    2010-05-15

    Adsorbed natural gas (ANG) has been emerging as an attractive alternative to compressed natural gas or liquefied natural gas, on various circumstances. However, in spite of the advantages associated with ANG over other storage modes, there are some issues that need be properly addressed in order to ensure a viable employment of such alternative. One major problem is that the thermal effects associated with the sorption phenomena tend to diminish the storage capacity, thereby resulting in poorer performance. Hence, in order to design commercially viable storage vessels, the heat and mass transfer mechanisms that occur in these devices must be carefully understood and controlled. With the purpose of improving the understanding of mass and energy transport within ANG vessels, dimensionless groups associated with this problem have been developed in this study, resulting in an innovation to the ANG literature. Along with the dimensionless groups, a lumped-capacitance formulation has been also proposed. Although this type of formulation is limited compared to the multi-dimensional formulations present in the literature, its computational solution is remarkably faster. Numerical solution results using the proposed lumped formulation are compared with those of a previous study, suggesting that the simpler model can be applied to larger process times. The process of charging and discharging ANG vessels was then simulated employing the proposed formulation for different combinations of the developed dimensionless groups. In order to properly assess charge and discharge processes, a performance coefficient was employed. The results show that increasing the heat capacity ratio and dimensionless heat transfer coefficient tend to augment the performance coefficient, whereas an increase in the dimensionless heat of sorption worsens performance. The proposed normalization scheme is applicable to both multi-dimensional and spatially-lumped formulations, thereby facilitating the

  15. MODEL QSAR SENYAWA FLUOROKUINOLON BARU SEBAGAI ZAT ANTIBAKTERI Salmonella thypimurium

    Directory of Open Access Journals (Sweden)

    Eva Vaulina

    2006-11-01

    Full Text Available Modelling of novel Fluoroquinolone derivates as antibacterial compund of Salmonella thypimurium was conducted. The research was done as an initial step in discovering some new Fluoroquinolone compounds which have higher activity to Salmonella thypimurium. There are 16 compunds that use as the material of the research and they already have antibacterial activity data that expressed in Minimal Inhibitory Concentration (MIC, mg/mL. Calculation was performed by semiempirical AM1 method. The QSAR model was determined by multilinear regression analysis, with Log MIC as dependent variable and the independent variables are atomic net charges of C5 (qC5 and C7 (qC7, dipole moment (m, polarizability (a, n-octanol-water coefficien partition (Log P, molecular weight (Mw, and surface area of van der Waals (AvdW. The relationship between Log MIC and the descriptors which performed by statistical analysis is:(Log MIC = -2.119 + 34.541(qC5 – 19.748(qC7 – 0.919polar + 1.170logP + 0.111(Mw – 0.003(Avdw, with n =16, r = 0.907, r2 = 0.822, SD = 0.288, F calc = 6.938, F table = 3.374 , F calc/F table = 2.056 and PRESS = 0.749. The research can obtain the new coumpounds that modified from compound number 16 (etil fluoroquinolone, MIC prediction = 0.0354 mg/mL, (etil fluoroquinlone fosfate, 2.84. 10-19mg/mL, and (isopropyl fluoroquinlone, 0.1085 mg/mL, and compound number 2 (m-nitro fluoroquinolone sulfonat, 1.32. 10-11mg/mL. This results can be suggested to synthesis step

  16. Multiobjective optimization in quantitative structure-activity relationships: deriving accurate and interpretable QSARs.

    Science.gov (United States)

    Nicolotti, Orazio; Gillet, Valerie J; Fleming, Peter J; Green, Darren V S

    2002-11-07

    Deriving quantitative structure-activity relationship (QSAR) models that are accurate, reliable, and easily interpretable is a difficult task. In this study, two new methods have been developed that aim to find useful QSAR models that represent an appropriate balance between model accuracy and complexity. Both methods are based on genetic programming (GP). The first method, referred to as genetic QSAR (or GPQSAR), uses a penalty function to control model complexity. GPQSAR is designed to derive a single linear model that represents an appropriate balance between the variance and the number of descriptors selected for the model. The second method, referred to as multiobjective genetic QSAR (MoQSAR), is based on multiobjective GP and represents a new way of thinking of QSAR. Specifically, QSAR is considered as a multiobjective optimization problem that comprises a number of competitive objectives. Typical objectives include model fitting, the total number of terms, and the occurrence of nonlinear terms. MoQSAR results in a family of equivalent QSAR models where each QSAR represents a different tradeoff in the objectives. A practical consideration often overlooked in QSAR studies is the need for the model to promote an understanding of the biochemical response under investigation. To accomplish this, chemically intuitive descriptors are needed but do not always give rise to statistically robust models. This problem is addressed by the addition of a further objective, called chemical desirability, that aims to reward models that consist of descriptors that are easily interpretable by chemists. GPQSAR and MoQSAR have been tested on various data sets including the Selwood data set and two different solubility data sets. The study demonstrates that the MoQSAR method is able to find models that are at least as good as models derived using standard statistical approaches and also yields models that allow a medicinal chemist to trade statistical robustness for chemical

  17. Efficient dynamic molecular simulation using QSAR model to know inhibition activity in breast cancer medicine

    Science.gov (United States)

    Zharifah, A.; Kusumowardani, E.; Saputro, A.; Sarwinda, D.

    2017-07-01

    According to data from GLOBOCAN (IARC) at 2012, breast cancer was the highest rated of new cancer case by 43.3 % (after controlled by age), with mortality rated as high as 12.9 %. Oncology is a major field which focusing on improving the development of drug and therapeutics cancer in pharmaceutical and biotechnology companies. Nowadays, many researchers lead to computational chemistry and bioinformatic for pharmacophore generation. A pharmacophore describes as a group of atoms in the molecule which is considered to be responsible for a pharmacological action. Prediction of biological function from chemical structure in silico modeling reduces the use of chemical reagents so the risk of environmental pollution decreased. In this research, we proposed QSAR model to analyze the composition of cancer drugs which assumed to be homogenous in character and treatment. Atomic interactions which analyzed are learned through parameters such as log p as descriptors hydrophobic, n_poinas descriptor contour strength and molecular structure, and also various concentrations inhibitor (micromolar and nanomolar) from NCBI drugs bank. The differences inhibitor activity was observed by the presence of IC 50 residues value from inhibitor substances at various concentration. Then, we got a general overview of the state of safety for drug stability seen from its IC 50 value. In our study, we also compared between micromolar and nanomolar inhibitor effect from QSAR model results. The QSAR model analysis shows that the drug concentration with nanomolar is better than micromolar, related with the content of inhibitor substances concentration. This QSAR model got the equation: Log 1/IC50 = (0.284) (±0.195) logP + (0.02) (±0.012) n_poin + (-0.005) (±0.083) Inhibition10.2nanoM + (0.1) (±0.079) Inhibition30.5nanoM + (-0.016) (±0.045) Inhibition91.5nanoM + (-2.572) (±1.570) (n = 13; r = 0.813; r2 = 0.660; s = 0.764; F = 2.720; q2 = 0.660).

  18. Global QSAR models of skin sensitisers for regulatory purposes

    Directory of Open Access Journals (Sweden)

    Price Nick R

    2010-07-01

    Full Text Available Abstract Background The new European Regulation on chemical safety, REACH, (Registration, Evaluation, Authorisation and Restriction of CHemical substances, is in the process of being implemented. Many chemicals used in industry require additional testing to comply with the REACH regulations. At the same time EU member states are attempting to reduce the number of animals used in experiments under the 3 Rs policy, (refining, reducing, and replacing the use of animals in laboratory procedures. Computational techniques such as QSAR have the potential to offer an alternative for generating REACH data. The FP6 project CAESAR was aimed at developing QSAR models for 5 key toxicological endpoints of which skin sensitisation was one. Results This paper reports the development of two global QSAR models using two different computational approaches, which contribute to the hybrid model freely available online. Conclusions The QSAR models for assessing skin sensitisation have been developed and tested under stringent quality criteria to fulfil the principles laid down by the OECD. The final models, accessible from CAESAR website, offer a robust and reliable method of assessing skin sensitisation for regulatory use.

  19. Quantitative structure-activity relationship (QSAR) models for polycyclic aromatic hydrocarbons (PAHs) dissipation in rhizosphere based on molecular structure and effect size

    Energy Technology Data Exchange (ETDEWEB)

    Ma Bin; Chen Huaihai; Xu Minmin; Hayat, Tahir [Zhejiang Provincial Key Laboratory of Subtropical Soil and Plant Nutrition, College of Environmental and Natural Resource Sciences, Zhejiang University, Hangzhou 310029 (China); He Yan, E-mail: yhe2006@zju.edu.c [Zhejiang Provincial Key Laboratory of Subtropical Soil and Plant Nutrition, College of Environmental and Natural Resource Sciences, Zhejiang University, Hangzhou 310029 (China); Xu Jianming, E-mail: jmxu@zju.edu.c [Zhejiang Provincial Key Laboratory of Subtropical Soil and Plant Nutrition, College of Environmental and Natural Resource Sciences, Zhejiang University, Hangzhou 310029 (China)

    2010-08-15

    Rhizoremediation is a significant form of bioremediation for polycyclic aromatic hydrocarbons (PAHs). This study examined the role of molecular structure in determining the rhizosphere effect on PAHs dissipation. Effect size in meta-analysis was employed as activity dataset for building quantitative structure-activity relationship (QSAR) models and accumulative effect sizes of 16 PAHs were used for validation of these models. Based on the genetic algorithm combined with partial least square regression, models for comprehensive dataset, Poaceae dataset, and Fabaceae dataset were built. The results showed that information indices, calculated as information content of molecules based on the calculation of equivalence classes from the molecular graph, were the most important molecular structural indices for QSAR models of rhizosphere effect on PAHs dissipation. The QSAR model, based on the molecular structure indices and effect size, has potential to be used in studying and predicting the rhizosphere effect of PAHs dissipation. - Effect size based on meta-analysis was used for building PAHs dissipation quantitative structure-activity relationship (QSAR) models.

  20. Quantification of contributions of molecular fragments for eye irritation of organic chemicals using QSAR study.

    Science.gov (United States)

    Kar, Supratik; Roy, Kunal

    2014-05-01

    The eye irritation potential of chemicals has largely been evaluated using the Draize rabbit-eye test for a very long time. The Draize eye-irritation data on 38 compounds established by the European Center for Ecotoxicology and Toxicology of Chemicals (ECETOC) has been used in the present quantitative structure-activity relationship (QSAR) analysis in order to predict molar-adjusted eye scores (MES) and determine possible structural requisites and attributes that are primarily responsible for the eye irritation caused by the studied solutes. The developed model was rigorously validated internally as well as externally by applying principles of the Organization for Economic Cooperation and Development (OECD). The test for applicability domain was also carried out in order to check the reliability of the predictions. Important fragments contributing to higher MES values of the solutes were identified through critical analysis and interpretation of the developed model. Considering all the identified structural attributes, one can choose or design safe solutes with low eye irritant properties. The presented approach suggests a model for use in the context of virtual screening of relevant solute libraries. The developed QSAR model can be used to predict existing as well as future chemicals falling within the applicability domain of the model in order to reduce the use of animals.

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

    Science.gov (United States)

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

    2009-12-01

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

  2. Azolium analogues as CDK4 inhibitors: Pharmacophore modeling, 3D QSAR study and new lead drug discovery

    Science.gov (United States)

    Rondla, Rohini; Padma Rao, Lavanya Souda; Ramatenki, Vishwanath; Vadija, Rajender; Mukkera, Thirupathi; Potlapally, Sarita Rajender; Vuruputuri, Uma

    2017-04-01

    The cyclin-dependent kinase 4 (CDK4) enzyme is a key regulator in cell cycle G1 phase progression. It is often overexpressed in variety of cancer cells, which makes it an attractive therapeutic target for cancer treatment. A number of chemical scaffolds have been reported as CDK4 inhibitors in the literature, and in particular azolium scaffolds as potential inhibitors. Here, a ligand based pharmacophore modeling and an atom based 3D-QSAR analyses for a series of azolium based CDK4 inhibitors are presented. A five point pharmacophore hypothesis, i.e. APRRR with one H-bond acceptor (A), one positive cationic feature (P) and three ring aromatic sites (R) is developed, which yielded an atom based 3D-QSAR model that shows an excellent correlation coefficient value- R2 = 0.93, fisher ratio- F = 207, along with good predictive ability- Q2 = 0.79, and Pearson R value = 0.89. The visual inspection of the 3D-QSAR model, with the most active and the least active ligands, demonstrates the favorable and unfavorable structural regions for the activity towards CDK4. The roles of positively charged nitrogen, the steric effect, ligand flexibility, and the substituents on the activity are in good agreement with the previously reported experimental results. The generated 3D QSAR model is further applied as query for a 3D database screening, which identifies 23 lead drug candidates with good predicted activities and diverse scaffolds. The ADME analysis reveals that, the pharmacokinetic parameters of all the identified new leads are within the acceptable range.

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

    Science.gov (United States)

    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

  4. 3D-QSAR Study of Indol-2-yl Ethanones Derivatives as Novel Indoleamine 2,3-Dioxygenase (IDO Inhibitors

    Directory of Open Access Journals (Sweden)

    Kamlendra S. Bhadoriya

    2012-01-01

    Full Text Available 3D-QSAR approach using kNN-MFA was applied to a series of Indol-2-yl ethanones derivatives as novel IDO inhibitors. For the purpose, 22 compounds were used to develop models. To elucidate the structural properties required for IDO inhibitory activity, we report here k-nearest neighbor molecular field analysis (kNN-MFA-based 3D-QSAR model for Indol-2-yl ethanones derivatives as novel IDO inhibitors. Overall model classification accuracy was 76.27% (q2 = 0.7627, representing internal validation in training set and 79.35% (pred_r2 = 0.7935, representing external validation in test set using sphere exclusion and forward as a method of data selection and variable selection, respectively. Contour maps using this approach showed that hydrophobic and steric effects dominantly determine binding affinities. The information rendered by 3D-QSAR model may lead to a better understanding of structural requirements of IDO inhibitors and can help in the design of novel potent molecules.

  5. Combining QSAR modeling and text-mining techniques to link chemical structures and carcinogenic modes of action

    Directory of Open Access Journals (Sweden)

    Georgios Papamokos

    2016-08-01

    Full Text Available There is an increasing need for new reliable non-animal based methods to predict and test toxicity of chemicals. QSAR, a computer-based method linking chemical structures with biological activities, is used in predictive toxicology. In this study we tested the approach to combine QSAR data with literature profiles of carcinogenic modes of action automatically generated by a text-mining tool. The aim was to generate data patterns to identify associations between chemical structures and biological mechanisms related to carcinogenesis. Using these two methods, individually and combined, we evaluated 96 rat carcinogens of the hematopoietic system, liver, lung and skin. We found that skin and lung rat carcinogens were mainly mutagenic, while the group of carcinogens affecting the hematopoietic system and the liver also included a large proportion of non-mutagens. The automatic literature analysis showed that mutagenicity was a frequently reported endpoint in the literature of these carcinogens, however less common endpoints such as immunosuppression and hormonal receptor-mediated effects were also found in connection with some of the carcinogens, results of potential importance for certain target organs. The combined approach, using QSAR and text-mining techniques, could be useful for identifying more detailed information on biological mechanisms and the relation with chemical structures. The method can be particularly useful in increasing the understanding of structure and activity relationships for non-mutagens.

  6. Genotoxicity of quinolones: substituents contribution and transformation products QSAR evaluation using 2D and 3D models.

    Science.gov (United States)

    Li, Min; Wei, Dongbin; Zhao, Huimin; Du, Yuguo

    2014-01-01

    The genotoxicity of 21 quinolones antibiotics was determined using SOS/umu assay. Some quinolones exhibited high genotoxicity, and the chemical substituent on quinolone ring significantly affected genotoxicity. To establish the relationship between genotoxicity and substituent, a 2D-QSAR model based on quantum chemical parameters was developed. Calculation suggested that both steric and electrostatic properties were correlated well with genotoxicity. Furthermore, the specific effect on three key active sites (1-, 7- and 8-positions) of quinolone ring was investigated using a 3D-QSAR (comparative molecular field analysis, CoMFA) method. From our modeling, the genotoxicity increased when substituents had: (1) big volume and/or positive charge at 1-position; (2) negative charge at 7-position; and (3) small volume and/or negative charge at 8-position. The developed QSAR models were applicable to estimate genotoxicity of quinolones antibiotics and their transformation products. It is noted that some of the transformation products exhibited higher genotoxicity comparing to their precursor (e.g., ciprofloxacin). This study provided an alternative way to understand the molecule genotoxicity of quinolones derivatives, as well as to evaluate their potential environmental risks.

  7. Combining QSAR Modeling and Text-Mining Techniques to Link Chemical Structures and Carcinogenic Modes of Action.

    Science.gov (United States)

    Papamokos, George; Silins, Ilona

    2016-01-01

    There is an increasing need for new reliable non-animal based methods to predict and test toxicity of chemicals. Quantitative structure-activity relationship (QSAR), a computer-based method linking chemical structures with biological activities, is used in predictive toxicology. In this study, we tested the approach to combine QSAR data with literature profiles of carcinogenic modes of action automatically generated by a text-mining tool. The aim was to generate data patterns to identify associations between chemical structures and biological mechanisms related to carcinogenesis. Using these two methods, individually and combined, we evaluated 96 rat carcinogens of the hematopoietic system, liver, lung, and skin. We found that skin and lung rat carcinogens were mainly mutagenic, while the group of carcinogens affecting the hematopoietic system and the liver also included a large proportion of non-mutagens. The automatic literature analysis showed that mutagenicity was a frequently reported endpoint in the literature of these carcinogens, however, less common endpoints such as immunosuppression and hormonal receptor-mediated effects were also found in connection with some of the carcinogens, results of potential importance for certain target organs. The combined approach, using QSAR and text-mining techniques, could be useful for identifying more detailed information on biological mechanisms and the relation with chemical structures. The method can be particularly useful in increasing the understanding of structure and activity relationships for non-mutagens.

  8. The Analysis of Structure Effect and Research on QSAR of the Pyrethroid Insecticides%拟除虫菊酯农药的结构效应分析及QSAR研究

    Institute of Scientific and Technical Information of China (English)

    李玲玉; 颜冬云; 王春光; 秦文秀

    2011-01-01

    The increasing societal concern about the safety of pesticide caused by the worldwide use of pyrethroid is now providing strong drivers towards maximising the efficiency of pyredthroid utilisation and the development of new pyrethroids.There is growing recognition that the ultimate goal of achieving efficient and sustainable pyrethroid usage will require greater understanding of its structure-activity relationships.The paper summarized the difference of pyrethroid isomers in the activity/property, and presented the research progress and prospect on QSAR of the pyrethroid insecticides.This article would offer theoretical basis for the study of new pesticides with high efficiency and low toxicity.%拟除虫菊酯类农药的广泛应用引起了全社会对农药安全问题的关注,很大程度上刺激了最大限度地发挥拟除虫菊酯类农药的使用效率和新型拟除虫菊酯类农药的开发.人们越来越认识到保持拟除虫菊酯的高效性与持续攀升的使用量将需要更多地探究其结构一活性效应.综述了不同结构拟除虫菊酯及其异构体的活性/性质差异以及国内外拟除虫菊酯类农药的QSAR研究进展,并对拟除虫菊酯QSAR研究进行了展望,可为新型高效低毒农药的研发提供理论支撑.

  9. Estudos de QSAR 3D para um conjunto de inibidores de butirilcolinesterase humana QSAR 3D studies of a series of human butyrylcholinesterase inhibitors

    Directory of Open Access Journals (Sweden)

    Humberto F. Freitas

    2009-01-01

    Full Text Available Alzheimer's disease (AD is considered the main cause of cognitive decline in adults. The available therapies for AD treatment seek to maintain the activity of cholinergic system through the inhibition of the enzyme acetylcholinesterase. However, butyrylcholinesterase (BuChE can be considered an alternative target for AD treatment. Aiming at developing new BuChE inhibitors, robust QSAR 3D models with high predictive power were developed. The best model presents a good fit (r²=0.82, q²=0.76, with two PCs and high predictive power (r²predict=0.88. Analysis of regression vector shows that steric properties have considerable importance to the inhibition of the BuChE.

  10. The Interplay between QSAR/QSPR Studiesand Partial Order Ranking and Formal Concept Analyses

    Directory of Open Access Journals (Sweden)

    Lars Carlsen

    2009-04-01

    Full Text Available The often observed scarcity of physical-chemical and well as toxicological data hampers the assessment of potentially hazardous chemicals released to the environment. In such cases Quantitative Structure-Activity Relationships/Quantitative Structure-Property Relationships (QSAR/QSPR constitute an obvious alternative for rapidly, effectively and inexpensively generatng missing experimental values. However, typically further treatment of the data appears necessary, e.g., to elucidate the possible relations between the single compounds as well as implications and associations between the various parameters used for the combined characterization of the compounds under investigation. In the present paper the application of QSAR/QSPR in combination with Partial Order Ranking (POR methodologies will be reviewed and new aspects using Formal Concept Analysis (FCA will be introduced. Where POR constitutes an attractive method for, e.g., prioritizing a series of chemical substances based on a simultaneous inclusion of a range of parameters, FCA gives important information on the implications associations between the parameters. The combined approach thus constitutes an attractive method to a preliminary assessment of the impact on environmental and human health by primary pollutants or possibly by a primary pollutant well as a possible suite of transformation subsequent products that may be both persistent in and bioaccumulating and toxic.The present review focus on the environmental – and human health impact by residuals of the rocket fuel 1,1-dimethyl- hydrazine (heptyl and its transformation products as an illustrative example.

  11. QSAR Study for Carcinogenic Potency of Aromatic Amines Based on GEP and MLPs

    Directory of Open Access Journals (Sweden)

    Fucheng Song

    2016-11-01

    Full Text Available A new analysis strategy was used to classify the carcinogenicity of aromatic amines. The physical-chemical parameters are closely related to the carcinogenicity of compounds. Quantitative structure activity relationship (QSAR is a method of predicting the carcinogenicity of aromatic amine, which can reveal the relationship between carcinogenicity and physical-chemical parameters. This study accessed gene expression programming by APS software, the multilayer perceptrons by Weka software to predict the carcinogenicity of aromatic amines, respectively. All these methods relied on molecular descriptors calculated by CODESSA software and eight molecular descriptors were selected to build function equations. As a remarkable result, the accuracy of gene expression programming in training and test sets are 0.92 and 0.82, the accuracy of multilayer perceptrons in training and test sets are 0.84 and 0.74 respectively. The precision of the gene expression programming is obviously superior to multilayer perceptrons both in training set and test set. The QSAR application in the identification of carcinogenic compounds is a high efficiency method.

  12. QSAR study of prolylcarboxypeptidase inhibitors by genetic algorithm: Multiple linear regressions

    Indian Academy of Sciences (India)

    Eslam Pourbasheer; Saadat Vahdani; Reza Aalizadeh; Alireza Banaei; Mohammad Reza Ganjali

    2015-07-01

    The predictive analysis based on quantitative structure activity relationships (QSAR) on benzim-idazolepyrrolidinyl amides as prolylcarboxypeptidase (PrCP) inhibitors was performed. Molecules were represented by chemical descriptors that encode constitutional, topological, geometrical, and electronic structure features. The hierarchical clustering method was used to classify the dataset into training and test subsets. The important descriptors were selected with the aid of the genetic algorithm method. The QSAR model was constructed, using the multiple linear regressions (MLR), and its robustness and predictability were verified by internal and external cross-validation methods. Furthermore, the calculation of the domain of applicability defines the area of reliable predictions. The root mean square errors (RMSE) of the training set and the test set for GA-MLR model were calculated to be 0.176, 0.279 and the correlation coefficients (R2) were obtained to be 0.839, 0.923, respectively. The proposed model has good stability, robustness and predictability when verified by internal and external validation.

  13. Structure-based modelling in reproductive toxicology: (Q)SARs for the placental barrier.

    Science.gov (United States)

    Hewitt, M; Madden, J C; Rowe, P H; Cronin, M T D

    2007-01-01

    The replacement of animal testing for endpoints such as reproductive toxicity is a long-term goal. This study describes the possibilities of using simple (quantitative) structure-activity relationships ((Q)SARs) to predict whether a molecule may cross the placental membrane. The concept is straightforward, if a molecule is not able to cross the placental barrier, then it will not be a reproductive toxicant. Such a model could be placed at the start of any integrated testing strategy. To develop these models the literature was reviewed to obtain data relating to the transfer of molecules across the placenta. A reasonable number of data were obtained and are suitable for the modelling of the ability of a molecule to cross the placenta. Clearance or transfer indices data were sought due to their ability to eliminate inter-placental variation by standardising drug clearance to the reference compound antipyrine. Modelling of the permeability data indicates that (Q)SARs with reasonable statistical fit can be developed for the ability of molecules to cross the placental barrier membrane. Analysis of the models indicates that molecular size, hydrophobicity and hydrogen-bonding ability are molecular properties that may govern the ability of a molecule to cross the placental barrier.

  14. QSAR Study for Carcinogenic Potency of Aromatic Amines Based on GEP and MLPs

    Science.gov (United States)

    Song, Fucheng; Zhang, Anling; Liang, Hui; Cui, Lianhua; Li, Wenlian; Si, Hongzong; Duan, Yunbo; Zhai, Honglin

    2016-01-01

    A new analysis strategy was used to classify the carcinogenicity of aromatic amines. The physical-chemical parameters are closely related to the carcinogenicity of compounds. Quantitative structure activity relationship (QSAR) is a method of predicting the carcinogenicity of aromatic amine, which can reveal the relationship between carcinogenicity and physical-chemical parameters. This study accessed gene expression programming by APS software, the multilayer perceptrons by Weka software to predict the carcinogenicity of aromatic amines, respectively. All these methods relied on molecular descriptors calculated by CODESSA software and eight molecular descriptors were selected to build function equations. As a remarkable result, the accuracy of gene expression programming in training and test sets are 0.92 and 0.82, the accuracy of multilayer perceptrons in training and test sets are 0.84 and 0.74 respectively. The precision of the gene expression programming is obviously superior to multilayer perceptrons both in training set and test set. The QSAR application in the identification of carcinogenic compounds is a high efficiency method. PMID:27854309

  15. CORAL: QSAR models for acute toxicity in fathead minnow (Pimephales promelas).

    Science.gov (United States)

    Toropova, A P; Toropov, A A; Lombardo, A; Roncaglioni, A; Benfenati, E; Gini, G

    2012-05-05

    CORrelation And Logic (CORAL) is a software that generates quantitative structure activity relationships (QSAR) for different endpoints. This study is dedicated to the QSAR analysis of acute toxicity in Fathead minnow (Pimephales promelas). Statistical quality for the external test set is a complex function of the split (into training and test subsets), the number of epochs of the Monte Carlo optimization, and the threshold that is a criterion for dividing the correlation weights into two classes rare (blocked) and not rare (active). Computational experiments with three random splits (data on 568 compounds) indicated that this approach can satisfactorily predict the desired endpoint (the negative decimal logarithm of the 50% lethal concentration, in mmol/L, pLC50). The average correlation coefficients (r2) are 0.675 ± 0.0053, 0.824 ± 0.0242, 0.787 ± 0.0101 for subtraining, calibration, and test set, respectively. The average standard errors of estimation (s) are 0.837 ± 0.021, 0.555 ± 0.047, 0.606 ± 0.049 for subtraining, calibration, and test set, respectively. The CORAL software together with three random splits into subtraining, calibration, and test sets can be downloaded on the Internet (http://www.insilico.eu/coral/). Copyright © 2012 Wiley Periodicals, Inc.

  16. Evaluation of passive autocatalytic recombiners operation efficiency by means of the lumped parameter approach*

    Directory of Open Access Journals (Sweden)

    Bury Tomasz

    2015-06-01

    Full Text Available The problem of hydrogen behavior in containment buildings of nuclear reactors belongs to thermal-hydraulic area. Taking into account the size of systems under consideration and, first of all, safety issues, such type of analyses cannot be done by means of full-scale experiments. Therefore, mathematical modeling and numerical simulations are widely used for these purposes. A lumped parameter approach based code HEPCAL has been elaborated in the Institute of Thermal Technology of the Silesian University of Technology for simulations of pressurized water reactor containment transient response. The VVER-440/213 and European pressurised water reactor (EPR reactors containments are the subjects of analysis within the framework of this paper. Simulations have been realized for the loss-of-coolant accident scenarios with emergency core cooling system failure. These scenarios include core overheating and hydrogen generation. Passive autocatalytic recombiners installed for removal of hydrogen has been taken into account. The operational efficiency of the hydrogen removal system has been evaluated by comparing with an actual hydrogen concentration and flammability limit. This limit has been determined for the three-component mixture of air, steam and hydrogen. Some problems related to the lumped parameter approach application have been also identified.

  17. Dark Lump Excitations in Bose-Einstein Condensates

    Institute of Scientific and Technical Information of China (English)

    黄国翔; 朱善华

    2002-01-01

    Key Laboratory for Optical and Magnetic Resonance Spectroscopy and Department of Physics, East China Normal University, Shanghai 200062We investigate the dynamics of two-dimensional matter-wave pulses in a Bose-Einstein condensate with diskshaped traps. For the case ofrepulsive atom-atom interactions, a Kadomtsev-Petviashvili equation with positive dispersion is derived using the method of multiple scales. The results show that it is possible to excite dark lump-like two-dimensional nonlinear excitations in the Bose-Einstein condensate.

  18. A lumped model for rotational modes in periodic solid composites

    KAUST Repository

    Peng, Pai

    2013-10-01

    We present a lumped model to study the rotational modes in a type of two-dimensional periodic solid composites comprised of a square array of rubber-coated steel cylinders embedded in an epoxy matrix. The model captures the physical essence of rotational modes in such systems for various combinations of material parameters, and, therefore it is able to describe the transition behaviour when the system is gradually adjusted from an elastic metamaterial to an elastic phononic crystal. From the model, we can define a transition zone which separates the typical elastic metamaterials and the phononic crystals.

  19. New equivalent lumped electrical circuit for piezoelectric transformers.

    Science.gov (United States)

    Gonnard, Paul; Schmitt, P M; Brissaud, Michel

    2006-04-01

    A new equivalent circuit is proposed for a contour-vibration-mode piezoelectric transformer (PT). It is shown that the usual lumped equivalent circuit derived from the conventional Mason approach is not accurate. The proposed circuit, built on experimental measurements, makes an explicit difference between the elastic energies stored respectively on the primary and secondary parts. The experimental and theoretical resonance frequencies with the secondary in open or short circuit are in good agreement as well as the output "voltage-current" characteristic and the optimum efficiency working point. This circuit can be extended to various PT configurations and appears to be a useful tool for modeling electronic devices that integrate piezoelectric transformers.

  20. Implementation of Lumped Plasticity Models and Developments in an Object Oriented Nonlinear Finite Element Code

    Science.gov (United States)

    Segura, Christopher L.

    Numerical simulation tools capable of modeling nonlinear material and geometric behavior are important to structural engineers concerned with approximating the strength and deformation capacity of a structure. While structures are typically designed to behave linear elastic when subjected to building code design loads, exceedance of the linear elastic range is often an important consideration, especially with regards to structural response during hazard level events (i.e. earthquakes, hurricanes, floods), where collapse prevention is the primary goal. This thesis addresses developments made to Mercury, a nonlinear finite element program developed in MATLAB for numerical simulation and in C++ for real time hybrid simulation. Developments include the addition of three new constitutive models to extend Mercury's lumped plasticity modeling capabilities, a constitutive driver tool for testing and implementing Mercury constitutive models, and Mercury pre and post-processing tools. Mercury has been developed as a tool for transient analysis of distributed plasticity models, offering accurate nonlinear results on the material level, element level, and structural level. When only structural level response is desired (collapse prevention), obtaining material level results leads to unnecessarily lengthy computational time. To address this issue in Mercury, lumped plasticity capabilities are developed by implementing two lumped plasticity flexural response constitutive models and a column shear failure constitutive model. The models are chosen for implementation to address two critical issues evident in structural testing: column shear failure and strength and stiffness degradation under reverse cyclic loading. These tools make it possible to model post-peak behavior, capture strength and stiffness degradation, and predict global collapse. During the implementation process, a need was identified to create a simple program, separate from Mercury, to simplify the process of

  1. Asymmetric Flexural-gravity Lumps in Nonuniform Media

    CERN Document Server

    Liang, Yong

    2014-01-01

    Here we show that asymmetric fully-localized flexural-gravity lumps can propagate on the surface of an inviscid and irrotational fluid covered by a variable-thickness elastic material, provided that the thickness varies only in one direction and has a local minimum. We derive and present equations governing the evolution of the envelope of flexural-gravity wave packets allowing the flexing material to have small variations in the transverse (to propagation) direction. We show that the governing equation belongs to the general family of Davey-Stewartson equations, but with an extra term in the surface evolution equation that accounts for the variable thickness of the elastic cover. We then use an iterative Newton-Raphson scheme, with a numerical continuation procedure via Lagrange interpolation, in a search to find fully-localized solutions of this system of equations. We show that if the elastic sheet thickness has (at least) a local minimum, flexural-gravity lumps can propagate near the minimum thickness, an...

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

    Science.gov (United States)

    Gramatica, Paola; Sangion, Alessandro

    2016-06-27

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

  3. A primer on QSAR/QSPR modeling fundamental concepts

    CERN Document Server

    Roy, Kunal; Das, Rudra Narayan

    2015-01-01

    This brief goes back to basics and describes the Quantitative structure-activity/property relationships (QSARs/QSPRs) that represent predictive models derived from the application of statistical tools correlating biological activity (including therapeutic and toxic) and properties of chemicals (drugs/toxicants/environmental pollutants) with descriptors representative of molecular structure and/or properties. It explains how the sub-discipline of Cheminformatics is used for many applications such as risk assessment, toxicity prediction, property prediction and regulatory decisions apart from drug discovery and lead optimization. The authors also present, in basic terms, how QSARs and related chemometric tools are extensively involved in medicinal chemistry, environmental chemistry and agricultural chemistry for ranking of potential compounds and prioritizing experiments. At present, there is no standard or introductory publication available that introduces this important topic to students of chemistry and phar...

  4. New autocorrelation topological indexes and their application in QSAR study

    Institute of Scientific and Technical Information of China (English)

    WANG Peng; YANG Lei; CHEN Chun-yun; GAO Da-wen; LONG Ming-ce

    2005-01-01

    Considering the problems of classical structure parameters that existed in the study of quantitative structure activity relationship (QSAR). Two new groups of autocorrelation topological indexes V(t), E(t),P(t) and A(t), B(t), C(t), D(t) were developed on the basis of molecular topology and autocorrelation function in mathematics. The first group were obtained from Van der Waals volume, electronegativity and topological vertex degree; and the second group were obtained from the different combination of topological vertex degree. Corresponding softwares of ATIJP and ATITP have been developed for calculating these two new groups of indexes. Better results have been obtained from the application of these indexes in QSAR study.

  5. Review on lazy learning regressors and their applications in QSAR.

    Science.gov (United States)

    Kulkarni, Abhijit J; Jayaraman, Valadi K; Kulkarni, Bhaskar D

    2009-05-01

    Building accurate quantitative structure-activity relationships (QSAR) is important in drug design, environmental modeling, toxicology, and chemical property prediction. QSAR methods can be utilized to solve mainly two types of problems viz., pattern recognition, (or classification) where output is discrete (i.e. class information), e.g., active or non-active molecule, binding or non-binding molecule etc., and function approximation, (i.e. regression) where the output is continuous (e.g., actual activity prediction). The present review deals with the second type of problem (regression) with specific attention to one of the most effective machine learning procedures, viz. lazy learning. The methodologies of the algorithm along with the relevant technical information are discussed in detail. We also present three real-life case studies to briefly outline the typical characteristics of the modeling formalism.

  6. A Lumped Thermal Model Including Thermal Coupling and Thermal Boundary Conditions for High Power IGBT Modules

    DEFF Research Database (Denmark)

    Bahman, Amir Sajjad; Ma, Ke; Blaabjerg, Frede

    2017-01-01

    Detailed thermal dynamics of high power IGBT modules are important information for the reliability analysis and thermal design of power electronic systems. However, the existing thermal models have their limits to correctly predict these complicated thermal behavior in the IGBTs: The typically used...... thermal distribution under long-term studies. Meanwhile the boundary conditions for the thermal analysis are modeled and included, which can be adapted to different real field applications of power electronic converters. Finally, the accuracy of the proposed thermal model is verified by FEM simulations...... thermal model based on one-dimensional RC lumps have limits to provide temperature distributions inside the device, moreover some variable factors in the real-field applications like the cooling and heating conditions of the converter cannot be adapted. On the other hand, the more advanced three...

  7. A Lumped Thermal Model Including Thermal Coupling and Thermal Boundary Conditions for High Power IGBT Modules

    DEFF Research Database (Denmark)

    Bahman, Amir Sajjad; Ma, Ke; Blaabjerg, Frede

    2017-01-01

    Detailed thermal dynamics of high power IGBT modules are important information for the reliability analysis and thermal design of power electronic systems. However, the existing thermal models have their limits to correctly predict these complicated thermal behavior in the IGBTs: The typically used...... thermal distribution under long-term studies. Meanwhile the boundary conditions for the thermal analysis are modeled and included, which can be adapted to different real-field applications of power electronic converters. Finally, the accuracy of the proposed thermal model is verified by FEM simulations...... thermal model based on one-dimensional RC lumps have limits to provide temperature distributions inside the device, moreover some variable factors in the real-field applications like the cooling and heating conditions of the converter cannot be adapted. On the other hand, the more advanced three...

  8. Systematic reduction of complex tropospheric chemical mechanisms, Part II: Lumping using a time-scale based approach

    Directory of Open Access Journals (Sweden)

    L. E. Whitehouse

    2004-01-01

    Full Text Available This paper presents a formal method of species lumping that can be applied automatically to intermediate compounds within detailed and complex tropospheric chemical reaction schemes. The method is based on grouping species with reference to their chemical lifetimes and reactivity structures. A method for determining the forward and reverse transformations between individual and lumped compounds is developed. Preliminary application to the Leeds Master Chemical Mechanism (MCMv2.0 has led to the removal of 734 species and 1777 reactions from the scheme, with minimal degradation of accuracy across a wide range of test trajectories relevant to polluted tropospheric conditions. The lumped groups are seen to relate to groups of peroxy acyl nitrates, nitrates, carbonates, oxepins, substituted phenols, oxeacids and peracids with similar lifetimes and reaction rates with OH. In combination with other reduction techniques, such as sensitivity analysis and the application of the quasi-steady state approximation (QSSA, a reduced mechanism has been developed that contains 35% of the number of species and 40% of the number of reactions compared to the full mechanism. This has led to a speed up of a factor of 8 in terms of computer calculation time within box model simulations.

  9. Comparative Study of Core Needle Biopsy and Fine Needle Aspiration Cytology in Palpable Breast Lumps: Scenario in Developing Nations.

    Science.gov (United States)

    Tikku, Gargi; Umap, Pradeep

    2016-01-01

    The purpose of this study was to evaluate the utility of core needle biopsy as a diagnostic tool for palpable breast lumps in developing countries as compared to fine needle aspiration cytology. All patients attending the surgery outpatient department with palpable breast lumps were subjected to fine needle aspiration cytology and core needle biopsy by the same operator in a single session. Fine needle aspiration cytology was performed by the standard technique. Core needle biopsy was done freehand using a 14G manual core biopsy needle. Reporting categories of the two techniques were taken from the standard National Health Service Breast Screening Programme criteria and were compared with the final histopathology results. A total of 107 patients underwent fine needle aspiration cytology and core needle biopsy simultaneously. Histopathology was available for 85 cases. Statistical analysis of fine needle aspiration cytology and core needle biopsy showed no significant difference between the diagnoses offered by core needle biopsy and histopathology while there was a significant difference between fine needle aspiration cytology and histopathology diagnoses. Core needle biopsy detected more breast carcinomas as compared to fine needle aspiration cytology with a sensitivity 95.83% as opposed to 64.58%. Though both the techniques were equally specific (100%), Core needle biopsy was able to correctly categorize borderline / inadequate lesions into definitely benign and malignant categories. We suggest that core needle biopsy should be preferred over fine needle aspiration cytology for the diagnosis of palpable breast lumps with fine needle aspiration cytology being reserved for definitely benign lesions.

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

    Science.gov (United States)

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

    2012-03-01

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

  11. QSAR Models for P-450 (2D6) Substrate Activity

    DEFF Research Database (Denmark)

    Ringsted, Tine; Nikolov, Nikolai Georgiev; Jensen, Gunde Egeskov;

    2009-01-01

    activity relationship (QSAR) modelling systems. They cross validated (leave-groups-out) with concordances of 71%, 81% and 82%, respectively. Discrete organic European Inventory of Existing Commercial Chemical Substances (EINECS) chemicals were screened to predict an approximate percentage of CYP 2D6...... substrates. These chemicals are potentially present in the environment. The biological importance of the CYP 2D6 and the use of the software mentioned above were discussed....

  12. Alert-QSAR. Implications for Electrophilic Theory of Chemical Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Vasile Ostafe

    2011-08-01

    Full Text Available Given the modeling and predictive abilities of quantitative structure activity relationships (QSARs for genotoxic carcinogens or mutagens that directly affect DNA, the present research investigates structural alert (SA intermediate-predicted correlations ASA of electrophilic molecular structures with observed carcinogenic potencies in rats (observed activity, A = Log[1/TD50], i.e., ASA=f(X1SA,X2SA,.... The present method includes calculation of the recently developed residual correlation of the structural alert models, i.e., ARASA=f(A-ASA,X1SA,X2SA,... . We propose a specific electrophilic ligand-receptor mechanism that combines electronegativity with chemical hardness-associated frontier principles, equality of ligand-reagent electronegativities and ligand maximum chemical hardness for highly diverse toxic molecules against specific receptors in rats. The observed carcinogenic activity is influenced by the induced SA-mutagenic intermediate effect, alongside Hansch indices such as hydrophobicity (LogP, polarizability (POL and total energy (Etot, which account for molecular membrane diffusion, ionic deformation, and stericity, respectively. A possible QSAR mechanistic interpretation of mutagenicity as the first step in genotoxic carcinogenesis development is discussed using the structural alert chemoinformation and in full accordance with the Organization for Economic Co-operation and Development QSAR guidance principles.

  13. Alert-QSAR. Implications for Electrophilic Theory of Chemical Carcinogenesis

    Science.gov (United States)

    Putz, Mihai V.; Ionaşcu, Cosmin; Putz, Ana-Maria; Ostafe, Vasile

    2011-01-01

    Given the modeling and predictive abilities of quantitative structure activity relationships (QSARs) for genotoxic carcinogens or mutagens that directly affect DNA, the present research investigates structural alert (SA) intermediate-predicted correlations ASA of electrophilic molecular structures with observed carcinogenic potencies in rats (observed activity, A = Log[1/TD50], i.e., ASA=f(X1SA,X2SA,…)). The present method includes calculation of the recently developed residual correlation of the structural alert models, i.e., ARASA=f(A−ASA,X1SA,X2SA,…). We propose a specific electrophilic ligand-receptor mechanism that combines electronegativity with chemical hardness-associated frontier principles, equality of ligand-reagent electronegativities and ligand maximum chemical hardness for highly diverse toxic molecules against specific receptors in rats. The observed carcinogenic activity is influenced by the induced SA-mutagenic intermediate effect, alongside Hansch indices such as hydrophobicity (LogP), polarizability (POL) and total energy (Etot), which account for molecular membrane diffusion, ionic deformation, and stericity, respectively. A possible QSAR mechanistic interpretation of mutagenicity as the first step in genotoxic carcinogenesis development is discussed using the structural alert chemoinformation and in full accordance with the Organization for Economic Co-operation and Development QSAR guidance principles. PMID:21954348

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

    Science.gov (United States)

    Papa, Ester; Battaini, Francesca; Gramatica, Paola

    2005-02-01

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

  15. Thermal analysis of hydro-pneumatic suspension system for dumper based on a lumped-parameter thermal model%基于集中参数热模型法的自卸车油气悬架系统热分析

    Institute of Scientific and Technical Information of China (English)

    黄夏旭; 申焱华; 杨珏; 张文明

    2013-01-01

    lumped components. Each component has a thermal storage and interconnections to neighbor components through a linear mesh of thermal resistances. The heat is generated by oil flows through the damping orifices and nitrogen compression. Then, based on the gas state equation and thermodynamic theory, the nonlinear equations of the thermal model are established, which originally contain the heat capacity of the cylinder, the piston, and the oil. The simulation analysis is carried out under the model. The results show that, except for the oil in the bottom of the piston rod, while considering the thermal capacitance of the cylinder and piston, the temperature of the suspension system rises slower than if those capacitances are ignored. A validation experiment is performed to confirm the predicted results. The oil temperature in the initial stage of the experiment decreased first and then increased, which is different from the calculated value's monotonically upward trend. This may be caused by the fact that the oil from the static to flow requires a certain amount of energy in the initial stage of the experiment, while the external input of energy is shortage. Due to the measurement error, the lack of detail in lumped element division, and some other reasons, there are some differences between the experimental data and calculated values, but the tendencies of the experimental and calculated temperature rise of the suspension system are the similar. The comparison results show that the proposed model can describe the thermodynamic state of the hydro-pneumatic suspension more accurately than previous methods. The thermal capacitance of the cylinder and piston will increase the hysteresis effect of temperature changes.

  16. Evaluation of the Use of QSARS for Priority Setting and Risk Assessment.

    Science.gov (United States)

    Feijtel, T C

    1995-09-01

    Abstract Impending changes in EEC legislation have accelerated the need to define the principles and practical considerations of the use of QSARs in priority setting and risk assessment. It is important to delineate the limitations of this approach and to review whether and how this information should be used in the risk assessment. The value and limitations of QSARs for use in priority setting and risk assessment will not be discussed in detail since the European Chemical Industry Ecology and Toxicology Centre (ECETOC) has only recently established a Task Force to tackle this issue. The terms of reference of the Task Force are: (1) compare the predictions obtained with QSARs to measured data using ECETOC databases and other sources of data and comment on the validity and applicability of such QSARs; (2) identify and review software packages which are available for accessing and using appropriate QSARs; (3) identify those aspects of environmental distribution, fate and effects where the further development of QSARs is desirable and feasible; and (4) provide a scientific basis for ECETOC's contribution to the activities of the European Chemicals Bureau (ECB) in this area. In this short paper, only an initial and personal evaluation is made of when and where to use QSARs in the priority setting and risk assessment process within the regulatory framework. Some critical remarks and suggestions are provided to guide future developments and integration of QSARs in the risk assessment process.

  17. The lumping of heat transfer parameters in cooled packed beds: effect of the bed entry

    NARCIS (Netherlands)

    Westerink, E.J.; Gerner, J.W.; Gerner, J.W.; Westerterp, K.R.; van der Wal, S.

    1993-01-01

    The lumping of the heat transfer parameters of the one- and the two-dimensional pseudo-homogeneous model of a cooled fixed bed were compared. It appeared that the lumping of the two-dimensional parameters, being the effective radial conductivity h-eff and the heat transfer coefficient at the wall (a

  18. 5 CFR 550.1206 - Refunding a lump-sum payment.

    Science.gov (United States)

    2010-01-01

    ... section. (c) An employee who is reemployed in a position that has no leave system to which annual leave... ADMINISTRATION (GENERAL) Lump-Sum Payment for Accumulated and Accrued Annual Leave § 550.1206 Refunding a lump... leave under 5 U.S.C. 5551 is reemployed in the Federal service prior to the end of the period covered...

  19. 5 CFR 847.702 - Lump-sum payments and refunds.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Lump-sum payments and refunds. 847.702... payments and refunds. (a) Employee contributions with interest which are transferred to the Fund under subpart E of this part are included in any lump-sum credit or unexpended balance payable to the...

  20. An Analytical Study of Power Line Effect on UTP Cable using Lumped Circuit Components

    Directory of Open Access Journals (Sweden)

    Mitamoni Sarma

    2013-11-01

    Full Text Available The paper defines the term electrical noise with its types. Electromagnetic Interference (EMI, which is one type of electrical noise, is also defined and general techniques used for controlling EMI are described. Networking cables are affected by the EMI effect caused by a nearby power cable and data transmission through Unshielded Twisted Pair (UTP cable, which is the mostly effected cable by EMI, may be degraded for it. Today, UTP cable is the most popular networking cable supporting 10G Ethernet. The most common effective methods for reduction of EMI effect on UTP cable, physical separation and use of shielding are described. EMI is caused by coupling mechanisms between source of interference and receptor. The two types of couplings are capacitive coupling and inductive coupling. The paper analyses and models the two couplings using lumped circuit components and electric circuit analysis considering power cable as the source of interference and networking cable as the receptor circuit of EMI.

  1. Estimation of Radiated Fields of Small Horizontal Submodules Based on a Lumped-Element Model

    Directory of Open Access Journals (Sweden)

    M. Leone

    2006-12-01

    Full Text Available A novel approach to the estimation of radiated electric field of small horizontal submodules is presented. The principle idea is to describe the radiating submodule-on-motherboard structure with a lumped-element equivalent circuit which includes both the geometrical and the electrical parameters. The electromagnetic emission from the structure is approximated by the radiation characteristics of a Hertzian dipole driven by the antenna voltage resulting from the connector equivalent circuit. Therefore, no time consuming numerical field simulations are needed to evaluate the radiated electric field. Instead, a fast frequency circuit analysis with e.g. PSPICE is sufficient. Moreover, this modeling approach provides a clear insight concerning the influence of geometrical and electrical parameters with respect to radiated emissions. Finally, the computational solutions are compared with experimental results, demonstrating a good correspondence regarding engineering purposes.

  2. Development of Lumped Element Kinetic Inductance Detectors for NIKA

    CERN Document Server

    Roesch, M; Bideaud, A; Boudou, N; Calvo, M; Cruciani, A; Doyle, S; Leduc, H G; Monfardini, A; Swenson, L; Leclercq, S; Mauskopf, P; Schuster, K F

    2012-01-01

    Lumped-element kinetic inductance detectors(LEKIDs) have recently shown considerable promise as direct absorption mm-wavelength detectors for astronomical applications. One major research thrust within the N\\'eel Iram Kids Array (NIKA) collaboration has been to investigate the suitability of these detectors for deployment at the 30-meter IRAM telescope located on Pico Veleta in Spain. Compared to microwave kinetic inductance detectors (MKID), using quarter wavelength resonators, the resonant circuit of a LEKID consists of a discrete inductance and capacitance coupled to a feedline. A high and constant current density distribution in the inductive part of these resonators makes them very sensitive. Due to only one metal layer on a silicon substrate, the fabrication is relatively easy. In order to optimize the LEKIDs for this application, we have recently probed a wide variety of individual resonator and array parameters through simulation and physical testing. This included determining the optimal feed-line co...

  3. Lumped Mass Modeling for Local-Mode-Suppressed Element Connectivity

    DEFF Research Database (Denmark)

    Joung, Young Soo; Yoon, Gil Ho; Kim, Yoon Young

    2005-01-01

    for the standard element density method. Local modes are artificial, numerical modes resulting from the intrinsic modeling technique of the topology optimization method. Even with existing local mode controlling techniques, the convergence of the topology optimization of vibrating structures, especially...... experiencing large structural changes, appears to be still poor. In ECP, the nodes of the domain-discretizing elements are connected by zero-length one-dimensional elastic links having varying stiffness. For computational efficiency, every elastic link is now assumed to have two lumped masses at its ends......For successful topology design optimization of crashworthy “continuum” structures, unstable element-free and local vibration mode-free transient analyses should be ensured. Among these two issues, element instability was shown to be overcome if a recently-developed formulation, the element...

  4. Recursive modular modelling methodology for lumped-parameter dynamic systems.

    Science.gov (United States)

    Orsino, Renato Maia Matarazzo

    2017-08-01

    This paper proposes a novel approach to the modelling of lumped-parameter dynamic systems, based on representing them by hierarchies of mathematical models of increasing complexity instead of a single (complex) model. Exploring the multilevel modularity that these systems typically exhibit, a general recursive modelling methodology is proposed, in order to conciliate the use of the already existing modelling techniques. The general algorithm is based on a fundamental theorem that states the conditions for computing projection operators recursively. Three procedures for these computations are discussed: orthonormalization, use of orthogonal complements and use of generalized inverses. The novel methodology is also applied for the development of a recursive algorithm based on the Udwadia-Kalaba equation, which proves to be identical to the one of a Kalman filter for estimating the state of a static process, given a sequence of noiseless measurements representing the constraints that must be satisfied by the system.

  5. Lumped model for rotational modes in phononic crystals

    KAUST Repository

    Peng, Pai

    2012-10-16

    We present a lumped model for the rotational modes induced by the rotational motion of individual scatterers in two-dimensional phononic crystals comprised of square arrays of solid cylindrical scatterers in solid hosts. The model provides a physical interpretation of the origin of the rotational modes, reveals the important role played by the rotational motion in determining the band structure, and reproduces the dispersion relations in a certain range. The model increases the possibilities of manipulating wave propagation in phononic crystals. In particular, expressions derived from the model for eigenfrequencies at high symmetry points unambiguously predict the presence of a new type of Dirac-like cone at the Brillouin center, which is found to be the result of accidental degeneracy of the rotational and dipolar modes.

  6. Metastatic uterine leiomyosarcoma presenting as a breast lump.

    LENUS (Irish Health Repository)

    Sibartie, S

    2009-01-31

    BACKGROUND: It is uncommon to encounter a breast metastasis from an extramammary malignancy and even rarer from a uterine leiomyosarcoma. AIMS: We describe the third case report in the medical literature of a breast metastasis from a uterine leiomyosarcoma. METHODS: We report the management of a 56-year-old patient who presented with a breast lump 3 years after hysterectomy for a fibroid uterus. We conducted a literature review of breast leiomyosarcomas. RESULTS: The excision of the breast mass revealed a low-grade leiomyosarcoma. Radiographic examinations demonstrated metastases to the lung, liver, pelvis and bone. Retrospective pathology review of her uterus identified a small focus of leiomyosarcoma. She received chemotherapy and palliative radiotherapy but passed away within few months. CONCLUSION: Metastasis to the breast from a non-breast primary is generally a sign of disseminated disease and; thus, a poor prognostic indicator.

  7. Granulomatous Mastitis: A Rare Cause of Male Breast Lump

    Science.gov (United States)

    Al Manasra, Abdel Rahman A.; Al-Hurani, Mohammad F.

    2016-01-01

    Background Mastitis is a common benign disorder of the female breast. It is frequently associated with tenderness, swelling and nipple discharge. We are describing an extremely rare case of an idiopathic granulomatous mastitis in the male breast. Only 1 previous case was reported. Case Report A 29-year-old male patient presented with a hard, painless lump in the right breast of 2 weeks duration. The patient underwent surgical excision with margin. The histopathologic findings were consistent with granulomatous mastitis. The case was reported as idiopathic granulomatous mastitis after exclusion of all known causes of the disease. Conclusion Granulomatous mastitis is rare in females and extremely rare in male breast tissue. Since this disease mimics breast cancer in its clinical picture and radiologic findings are usually not conclusive, surgical excision is recommended in all cases. PMID:27721777

  8. Simulation of FCC Riser Reactor Based on Ten Lump Model

    Directory of Open Access Journals (Sweden)

    Debashri Paul

    2015-07-01

    Full Text Available The ten lump strategy and reaction schemes are based on the concentration of the various stocks i.e., paraffins, naphthenes, aromatic and aromatic substituent groups (paraffinic and napthenic groups attached to aromatic rings. The developed model has been studied using C++ programming language using Runge-Kutta Fehlberg mathematical method. At a space time of 4.5 s, the gasoline yield is predicted to be 72 mass % and 67 mass % for naphthenic and paraffinic feedstock respectively. Type of feed determines the yield of gasoline and coke. A highly naphthenic charge stock has given the greatest yield of gasoline among naphthenic, paraffinic and aromatic charge stock. In addition to this, effect of space time and temperature on the yield of coke and gasoline and conversion of gas oil has been presented. Also, the effect of catalyst to oil ratio is also taken in studies.

  9. Lumped mass formulations for modeling flexible body systems

    Science.gov (United States)

    Rampalli, Rajiv

    1989-01-01

    The efforts of Mechanical Dynamics, Inc. in obtaining a general formulation for flexible bodies in a multibody setting are discussed. The efforts being supported by MDI, both in house and externally are summarized. The feasibility of using lumped mass approaches to modeling flexibility in a multibody dynamics context is examined. The kinematics and kinetics for a simple system consisting of two rigid bodies connected together by an elastic beam are developed in detail. Accuracy, efficiency and ease of use using this approach are some of the issues that are then looked at. The formulation is then generalized to a superelement containing several nodes and connecting several bodies. Superelement kinematics and kinetics equations are developed. The feasibility and effectiveness of the method is illustrated by the use of some examples illustrating phenomena common in the context of spacecraft motions.

  10. Granulocytic Sarcoma Presenting as a Palpable Breast Lump

    Science.gov (United States)

    Fernandes Vieira, Victor; Vo, Quoc Duy; Bouquet de la Jolinière, Jean; Khomsi, Fathi; Feki, Anis; Hoogewoud, Henri-Marcel

    2017-01-01

    We report the case of a 45-year-old woman who palpated a voluminous painless lump in the superior outer quadrant of her left breast. Her past medical history revealed an acute myeloid leukemia (AML) treated and considered in remission 1 month prior to this discovery. Imaging work-up by mammogram, US, and MRI showed multiples masses suspect of malignancy in both breasts. US-guided needle biopsy was performed in the palpable mass and in one of the multiple lesions located in the right breast. Histologic findings were compatible with a granulocytic sarcoma in both breasts, which was considered as a relapse of the AML treated a few months earlier. PMID:28168190

  11. Effects of Nonlinearities on Induced Voltages across Lumped Devices

    Directory of Open Access Journals (Sweden)

    Ziya Mazloom

    2011-01-01

    Full Text Available There have been many studies on induced currents and voltages along overhead conductors due to lightning flashes. In most of these studies lumped loads and components are connected only as line terminations [1]-[4]. In studies where series and shunt connected components are connected along the lines the effects of nonlinear components and effects are disregarded [5]-[8]. This is not always correct as nonlinear effects will introduce high frequencies in the system and affect the current and voltage wave distribution. In this paper the effects of series and shunt components and nonlinear phenomenon on a system representative of the Swedish electrified railway system will be investigated. It is seen how introduction of different linear and nonlinear components affect the propagating voltage wave forms.

  12. Hierarchical QSAR technology based on the Simplex representation of molecular structure.

    Science.gov (United States)

    Kuz'min, V E; Artemenko, A G; Muratov, E N

    2008-01-01

    This article is about the hierarchical quantitative structure-activity relationship technology (HiT QSAR) based on the Simplex representation of molecular structure (SiRMS) and its application for different QSAR/QSP(property)R tasks. The essence of this technology is a sequential solution (with the use of the information obtained on the previous steps) to the QSAR problem by the series of enhanced models of molecular structure description [from one dimensional (1D) to four dimensional (4D)]. It is a system of permanently improved solutions. In the SiRMS approach, every molecule is represented as a system of different simplexes (tetratomic fragments with fixed composition, structure, chirality and symmetry). The level of simplex descriptors detailing increases consecutively from the 1D to 4D representation of the molecular structure. The advantages of the approach reported here are the absence of "molecular alignment" problems, consideration of different physical-chemical properties of atoms (e.g. charge, lipophilicity, etc.), the high adequacy and good interpretability of obtained models and clear ways for molecular design. The efficiency of the HiT QSAR approach is demonstrated by comparing it with the most popular modern QSAR approaches on two representative examination sets. The examples of successful application of the HiT QSAR for various QSAR/QSPR investigations on the different levels (1D-4D) of the molecular structure description are also highlighted. The reliability of developed QSAR models as predictive virtual screening tools and their ability to serve as the base of directed drug design was validated by subsequent synthetic and biological experiments, among others. The HiT QSAR is realized as a complex of computer programs known as HIT QSAR: software that also includes a powerful statistical block and a number of useful utilities.

  13. Hierarchical QSAR technology based on the Simplex representation of molecular structure

    Science.gov (United States)

    Kuz'min, V. E.; Artemenko, A. G.; Muratov, E. N.

    2008-06-01

    This article is about the hierarchical quantitative structure-activity relationship technology (HiT QSAR) based on the Simplex representation of molecular structure (SiRMS) and its application for different QSAR/QSP(property)R tasks. The essence of this technology is a sequential solution (with the use of the information obtained on the previous steps) to the QSAR problem by the series of enhanced models of molecular structure description [from one dimensional (1D) to four dimensional (4D)]. It is a system of permanently improved solutions. In the SiRMS approach, every molecule is represented as a system of different simplexes (tetratomic fragments with fixed composition, structure, chirality and symmetry). The level of simplex descriptors detailing increases consecutively from the 1D to 4D representation of the molecular structure. The advantages of the approach reported here are the absence of "molecular alignment" problems, consideration of different physical-chemical properties of atoms (e.g. charge, lipophilicity, etc.), the high adequacy and good interpretability of obtained models and clear ways for molecular design. The efficiency of the HiT QSAR approach is demonstrated by comparing it with the most popular modern QSAR approaches on two representative examination sets. The examples of successful application of the HiT QSAR for various QSAR/QSPR investigations on the different levels (1D-4D) of the molecular structure description are also highlighted. The reliability of developed QSAR models as predictive virtual screening tools and their ability to serve as the base of directed drug design was validated by subsequent synthetic and biological experiments, among others. The HiT QSAR is realized as a complex of computer programs known as HiT QSAR software that also includes a powerful statistical block and a number of useful utilities.

  14. QSAR studies of bioconcentration factors of polychlorinated biphenyls (PCBs) using DFT, PCS and CoMFA.

    Science.gov (United States)

    Liu, Hui; Liu, Hongxia; Sun, Ping; Wang, Zunyao

    2014-11-01

    The bioconcentration factors (BCFs) of 58 polychlorinated biphenyls (PCBs) were modeled by quantitative structure-activity relationship (QSAR) using density functional theory (DFT), the position of Cl substitution (PCS) and comparative molecular field analysis (CoMFA) methods. All the models were robust and predictive, and especially, the best CoMFA model was significant with a correlation coefficient (R(2)) of 0.926, a cross-validation correlation coefficient (Q(2)) of 0.821 and a root mean square error estimated (RMSE) of 0.235. The results indicate that the electrostatic descriptors play a more significant role in BCFs of PCBs. Additionally, a test set was used to compare the predictive ability of our models to others, and results show that our CoMFA model present the lowest RMSE. Thus, the models obtain in this work can be used to predict the BCFs of remaining 152 PCBs without available experimental values.

  15. QSAR and SAR studies on the reduction of some aromatic nitro compounds by xanthine oxidase.

    Science.gov (United States)

    Thakur, Mamta; Thakur, Abhilash; Balasubramanian, Krishnan

    2006-01-01

    This work describes QSAR and SAR studies on the reduction of 27 aromatic nitro compounds by xanthine oxidase using both distance-based topological indices and quantum molecular descriptors along with indicator parameters. The application of a multiple linear regression analysis indicated that a combination of distance-based topological indices with the ad hoc molecular descriptors and the indicator parameters yielded a statistically significant model for the activity, log K (the reduction of aromatic nitro compounds by xanthine oxidase). The final selection of a potential aromatic nitro compound for the reduction by xanthine oxidase is made by quantum molecular modeling. We have found that, among the various parameters, the quantum Mulliken charge parameters on the fourth atom or para position relative to the nitro group correlated best with the activity.

  16. Synthesis, fungicidal activity, and QSAR of a series of 2-dichlorophenyl-3-triazolylpropyl ethers.

    Science.gov (United States)

    Arnoldi, A; Carzaniga, R; Morini, G; Merlini, L; Farina, G

    2000-06-01

    A series of new alkyl and arylalkyl ethers of 2-(2, 4-dichlorophenyl)-3-(1H-1,2,4-triazol-1-yl)propanol, related to the fungicide tetraconazole, were synthesized and tested in vitro or in vivo against seven common pathogens in comparison with tetraconazole. In vitro, most of them exhibited a broad spectrum of activity and an efficacy of the same order of magnitude of the standard, but the activity was influenced by the nature of the substituents. A QSAR study showed that lipophilicity is a major positive parameter in affecting the activity; the second relevant parameter is mu, whereas geometrical descriptors indicate that linear and narrow substituents are more suitable than wide ones. In in vivo assays some compounds had good activity on bean rust, either protective or curative. Sterol analysis showed that the mechanism of action is due to inhibition of 14alpha-demethylase.

  17. 3D-QSAR study on phenoxy-alkylamine compounds of a 1-adrenoceptor antagonist

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The study of three-dimensional quantitative structure-activityrelationship (3D-QSAR) of DDPH and its derivatives that have been known with their activity parameters has been developed using the comparative molecular field analysis (CoMFA) method. Here, (+)-DDPH crystal structure was selected as the active conformation model and comparisons between the influences of different charge calculation methods and grid setup were conducted. The coefficients of cross-validation (q2 ) and regression (r2) are 0.481 and 0.997, respectively. The standard error (SE) is 0.102. The research result suggests that the steric field makes more contributions to the activity than the electrostatic field. This model can help us not only in improving our understanding of the receptor-ligand interactions, but also in predicting the activity of derivatives and designing new compounds with better potency.

  18. A DFT-based QSAR study on inhibition of human dihydrofolate reductase.

    Science.gov (United States)

    Karabulut, Sedat; Sizochenko, Natalia; Orhan, Adnan; Leszczynski, Jerzy

    2016-11-01

    Diaminopyrimidine derivatives are frequently used as inhibitors of human dihydrofolate reductase, for example in treatment of patients whose immune system are affected by human immunodeficiency virus. Forty-seven dicyclic and tricyclic potential inhibitors of human dihydrofolate reductase were analyzed using the quantitative structure-activity analysis supported by DFT-based and DRAGON-based descriptors. The developed model yielded an RMSE deviation of 1.1 a correlation coefficient of 0.81. The prediction set was characterized by R(2)=0.60 and RMSE=3.59. Factors responsible for inhibition process were identified and discussed. The resulting model was validated via cross validation and Y-scrambling procedure. From the best model, we found several mass-related descriptors and Sanderson electronegativity-related descriptors that have the best correlations with the investigated inhibitory concentration. These descriptors reflect results from QSAR studies based on characteristics of human dihydrofolate reductase inhibitors.

  19. Patient-specific parameter estimation in single-ventricle lumped circulation models under uncertainty.

    Science.gov (United States)

    Schiavazzi, Daniele E; Baretta, Alessia; Pennati, Giancarlo; Hsia, Tain-Yen; Marsden, Alison L

    2017-03-01

    Computational models of cardiovascular physiology can inform clinical decision-making, providing a physically consistent framework to assess vascular pressures and flow distributions, and aiding in treatment planning. In particular, lumped parameter network (LPN) models that make an analogy to electrical circuits offer a fast and surprisingly realistic method to reproduce the circulatory physiology. The complexity of LPN models can vary significantly to account, for example, for cardiac and valve function, respiration, autoregulation, and time-dependent hemodynamics. More complex models provide insight into detailed physiological mechanisms, but their utility is maximized if one can quickly identify patient specific parameters. The clinical utility of LPN models with many parameters will be greatly enhanced by automated parameter identification, particularly if parameter tuning can match non-invasively obtained clinical data. We present a framework for automated tuning of 0D lumped model parameters to match clinical data. We demonstrate the utility of this framework through application to single ventricle pediatric patients with Norwood physiology. Through a combination of local identifiability, Bayesian estimation and maximum a posteriori simplex optimization, we show the ability to automatically determine physiologically consistent point estimates of the parameters and to quantify uncertainty induced by errors and assumptions in the collected clinical data. We show that multi-level estimation, that is, updating the parameter prior information through sub-model analysis, can lead to a significant reduction in the parameter marginal posterior variance. We first consider virtual patient conditions, with clinical targets generated through model solutions, and second application to a cohort of four single-ventricle patients with Norwood physiology. Copyright © 2016 John Wiley & Sons, Ltd.

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

    Science.gov (United States)

    Sivan, Sree Kanth; Manga, Vijjulatha

    2010-06-01

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

  1. Effect of ambient temperature on species lumping for total organic gases in gasoline exhaust emissions

    Science.gov (United States)

    Roy, Anirban; Choi, Yunsoo

    2017-03-01

    Volatile organic compound (VOCs) emissions from sources often need to be compressed or "lumped" into species classes for use in emissions inventories intended for air quality modeling. This needs to be done to ensure computational efficiency. The lumped profiles are usually reported for one value of ambient temperature. However, temperature-specific detailed profiles have been constructed in the recent past - the current study investigates how the lumping of species from those profiles into different atmospheric chemistry mechanisms is affected by temperature, considering three temperatures (-18 °C, -7 °C and 24 °C). The mechanisms considered differed on the assumptions used for lumping: CB05 (carbon bond type), SAPRC (ozone formation potential) and RACM2 (molecular surrogate and reactivity weighting). In this space, four sub-mechanisms for SAPRC were considered. Scaling factors were developed for each lumped model species and mechanism in terms of moles of lumped species per unit mass. Species which showed a direct one-to-one mapping (SAPRC/RACM2) reported scaling factors that were unchanged across mechanisms. However, CB05 showed different trends since one compound often is mapped onto multiple model species, out of which the paraffinic double bond (PAR) is predominant. Temperature-dependent parameterizations for emission factors pertaining to each lumped species class and mechanism were developed as part of the study. Here, the same kind of model species showed varying lumping parameters across the different mechanisms. These differences could be attributed to differing approaches in lumping. The scaling factors and temperature-dependent parameterizations could be used to update emissions inventories such as MOVES or SMOKE for use in chemical transport modeling.

  2. Combined 3D-QSAR modeling and molecular docking study on multi-acting quinazoline derivatives as HER2 kinase inhibitors.

    Science.gov (United States)

    Mirzaie, Sako; Monajjemi, Majid; Hakhamaneshi, Mohammad Saeed; Fathi, Fardin; Jamalan, Mostafa

    2013-01-01

    A series of new quinazoline derivatives has been recently reported as potent multi-acting histone deacetylase (HDAC), epidermal growth factor receptor (EGFR), and human epidermal growth factor receptor 2 (HER2) inhibitors. HER2 is one of the major targets for the treatment of breast cancer and other carcinomas. Three-dimensional structure-activity relationship (3D-QSAR) is a well-known technique, which is used to drug design and development. This technique is used for quantitatively predicting the interaction between a molecule and the active site of a specific target. For each 3D-QSAR study, a three-dimensional model is created from a large curve fit to find a fitting between computational descriptors and biological activity. This model could be used as a predictive tool in drug design. The best model has the highest correlation between theoretical and experimental data. Self-Organizing Molecular Field Analysis (SOMFA), a grid-based and alignment-dependent 3D-QSAR method, is employed to study the correlation between the molecular properties and HER2 inhibitory potency of the quinazoline derivatives. Before presentation of inhibitor structures to SOMFA study, conformation of inhibitors was determined by AutoDock4, HyperChem and AutoDock Vina, separately. Overall, six independent models were produced and evaluated by the statistical partial least square (PLS) analysis. Among the several generated 3D-QSARs, the best model was selected on the basis of its statistical significance and predictive potential. The model derived from the superposition of docked conformation with AutoDock Vina with reasonable cross-validated q(2) (0.767), non cross-validated r(2) (0.815) and F-test (97.22) values showed a desirable predictive capability. Analysis of SOMFA model could provide some useful information in the design of novel HER2 kinase inhibitors with better spectrum of activity.

  3. Per- and polyfluoro toxicity (LC(50) inhalation) study in rat and mouse using QSAR modeling.

    Science.gov (United States)

    Bhhatarai, Barun; Gramatica, Paola

    2010-03-15

    Fully or partially fluorinated compounds, known as per- and polyfluorinated chemicals are widely distributed in the environment and released because of their use in different household and industrial products. Few of these long chain per- and polyfluorinated chemicals are classified as emerging pollutants, and their environmental and toxicological effects are unveiled in the literature. This has diverted the production of long chain compounds, considered as more toxic, to short chains, but concerns regarding the toxicity of both types of per- and polyfluorinated chemicals are alarming. There are few experimental data available on the environmental behavior and toxicity of these compounds, and moreover, toxicity profiles are found to be different for the types of animals and species used. Quantitative structure-activity relationship (QSAR) is applied to a combination of short and long chain per- and polyfluorinated chemicals, for the first time, to model and predict the toxicity on two species of rodents, rat (Rattus) and mouse (Mus), by modeling inhalation (LC(50)) data. Multiple linear regression (MLR) models using the ordinary-least-squares (OLS) method, based on theoretical molecular descriptors selected by genetic algorithm (GA), were used for QSAR studies. Training and prediction sets were prepared a priori, and these sets were used to derive statistically robust and predictive (both internally and externally) models. The structural applicability domain (AD) of the model was verified on a larger set of per- and polyfluorinated chemicals retrieved from different databases and journals. The descriptors involved, the similarities, and the differences observed between models pertaining to the toxicity related to the two species are discussed. Chemometric methods such as principal component analysis (PCA) and multidimensional scaling (MDS) were used to select most toxic compounds from those within the AD of both models, which will be subjected to experimental tests

  4. QSAR models for anti-androgenic effect - a preliminary study

    DEFF Research Database (Denmark)

    Jensen, Gunde Egeskov; Nikolov, Nikolai Georgiev; Wedebye, Eva Bay;

    2011-01-01

    of the model for a particular application, balance of training sets, domain definition, and cut-offs for prediction interpretation should also be taken into account. Different descriptors in the modelling systems are illustrated with hydroxyflutamide and dexamethasone as examples (a non-steroid and a steroid......Three modelling systems (MultiCase (R), LeadScope (R) and MDL (R) QSAR) were used for construction of androgenic receptor antagonist models. There were 923-942 chemicals in the training sets. The models were cross-validated (leave-groups-out) with concordances of 77-81%, specificity of 78...

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

    Science.gov (United States)

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

    2008-04-01

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

  6. Synthesis, antimicrobial evaluation and QSAR studies of gallic acid derivatives

    Directory of Open Access Journals (Sweden)

    Anurag Khatkar

    2017-05-01

    Full Text Available A series of gallic acid derivatives (1–33 was synthesized and characterized by physicochemical and spectral means. The synthesized compounds were evaluated in vitro for their antimicrobial activity against different Gram positive and Gram negative bacterial and fungal strains by the tube dilution method. Results of antimicrobial screening indicated that compound 6 was the most active antimicrobial agent (pMICam = 1.92 μM/mL. The results of QSAR studies demonstrated that antibacterial, antifungal and overall antimicrobial activities of synthesized gallic acid derivatives were governed by the electronic parameters, cosmic total energy (Cos E. and nuclear energy (Nu. E..

  7. Synthesis of lumped models from N-port scattering parameter data

    Science.gov (United States)

    Rautio, James C.

    1994-03-01

    A closed form technique is described which allows the synthesis of an N-node lumped network from N-port scattering parameter (S-parameter) data. The synthesis is appropriate for networks where N is very large, for example, high speed digital interconnect networks. The resulting lumped model can be used in SPICE and other simulators. The synthesis is valid for any structure that is small with respect to wavelength. Thus it is also appropriate for synthesizing lumped models of simple discontinuities, such as step junctions and cross junctions. A description of the theory and several examples are provided.

  8. A correction technique for the dispersive effects of mass lumping for transport problems

    KAUST Repository

    Guermond, Jean-Luc

    2013-01-01

    This paper addresses the well-known dispersion effect that mass lumping induces when solving transport-like equations. A simple anti-dispersion technique based on the lumped mass matrix is proposed. The method does not require any non-trivial matrix inversion and has the same anti-dispersive effects as the consistent mass matrix. A novel quasi-lumping technique for P2 finite elements is introduced. Higher-order extensions of the method are also discussed. © 2012 Elsevier B.V.

  9. Optimization of lumping schemes for plane square quadratic finite element in elastodynamics

    Directory of Open Access Journals (Sweden)

    Kolman R.

    2007-10-01

    Full Text Available The effectiveness of explicit direct time-integration methods is conditioned by using diagonal mass matrix which entails significant computational savings and storage advantages. In recent years many procedures that produced diagonally lumped mass matrices were developed. For example, the row sum method and diagonal scaling method (HRZ procedure can be mentioned. In this paper, the dispersive properties of different lumping matrices with variable mass distribution for the plane square 8-node serendipity elements are investigated. The dispersion diagrams for such lumping matrices are derived for various Courant numbers, wavelengths and the directions of wave propagation.

  10. Development of a Mathematical Lumped Parameters Model for the Heat Transfer Performance of a Solar Collector

    Directory of Open Access Journals (Sweden)

    G. Iordanou

    2011-10-01

    Full Text Available This work describes the developed of a lumped parameter model and demonstrates its practical application. The lumped parameter mathematical model is a useful instrument to be used for rapid determination of design dimensions and operational performance of solar collectors at the designing stage. Such model which incorporates data from relevant Computational Fluid Dynamics design and experimental investigations can provide an acceptable accuracy in predictions and can be used as an effective design tool. A computer algorithm validates the lumped parameter model via a window environment program.

  11. lumpR 2.0.0: an R package facilitating landscape discretisation for hillslope-based hydrological models

    Science.gov (United States)

    Pilz, Tobias; Francke, Till; Bronstert, Axel

    2017-08-01

    The characteristics of a landscape pose essential factors for hydrological processes. Therefore, an adequate representation of the landscape of a catchment in hydrological models is vital. However, many of such models exist differing, amongst others, in spatial concept and discretisation. The latter constitutes an essential pre-processing step, for which many different algorithms along with numerous software implementations exist. In that context, existing solutions are often model specific, commercial, or depend on commercial back-end software, and allow only a limited or no workflow automation at all. Consequently, a new package for the scientific software and scripting environment R, called lumpR, was developed. lumpR employs an algorithm for hillslope-based landscape discretisation directed to large-scale application via a hierarchical multi-scale approach. The package addresses existing limitations as it is free and open source, easily extendible to other hydrological models, and the workflow can be fully automated. Moreover, it is user-friendly as the direct coupling to a GIS allows for immediate visual inspection and manual adjustment. Sufficient control is furthermore retained via parameter specification and the option to include expert knowledge. Conversely, completely automatic operation also allows for extensive analysis of aspects related to landscape discretisation. In a case study, the application of the package is presented. A sensitivity analysis of the most important discretisation parameters demonstrates its efficient workflow automation. Considering multiple streamflow metrics, the employed model proved reasonably robust to the discretisation parameters. However, parameters determining the sizes of subbasins and hillslopes proved to be more important than the others, including the number of representative hillslopes, the number of attributes employed for the lumping algorithm, and the number of sub-discretisations of the representative hillslopes.

  12. Ricci magnetic geodesic motion of vortices and lumps

    CERN Document Server

    Alqahtani, L S

    2014-01-01

    Ricci magnetic geodesic (RMG) motion in a k\\"ahler manifold is the analogue of geodesic motion in the presence of a magnetic field proportional to the ricci form. It has been conjectured to model low-energy dynamics of vortex solitons in the presence of a Chern-Simons term, the k\\"ahler manifold in question being the $n$-vortex moduli space. This paper presents a detailed study of RMG motion in soliton moduli spaces, focusing on the cases of hyperbolic vortices and spherical $\\mathbb{C}P^1$ lumps. It is shown that RMG flow localizes on fixed point sets of groups of holomorphic isometries, but that the flow on such submanifolds does not, in general, coincide with their intrinsic RMG flow. For planar vortices, it is shown that RMG flow differs from an earlier reduced dynamics proposed by Kim and Lee, and that the latter flow is ill-defined on the vortex coincidence set. An explicit formula for the metric on the whole moduli space of hyperbolic two-vortices is computed (extending an old result of Strachan's), an...

  13. Finding and testing network communities by lumped Markov chains.

    Science.gov (United States)

    Piccardi, Carlo

    2011-01-01

    Identifying communities (or clusters), namely groups of nodes with comparatively strong internal connectivity, is a fundamental task for deeply understanding the structure and function of a network. Yet, there is a lack of formal criteria for defining communities and for testing their significance. We propose a sharp definition that is based on a quality threshold. By means of a lumped Markov chain model of a random walker, a quality measure called "persistence probability" is associated to a cluster, which is then defined as an "α-community" if such a probability is not smaller than α. Consistently, a partition composed of α-communities is an "α-partition." These definitions turn out to be very effective for finding and testing communities. If a set of candidate partitions is available, setting the desired α-level allows one to immediately select the α-partition with the finest decomposition. Simultaneously, the persistence probabilities quantify the quality of each single community. Given its ability in individually assessing each single cluster, this approach can also disclose single well-defined communities even in networks that overall do not possess a definite clusterized structure.

  14. Pressure pulsation in roller pumps: a validated lumped parameter model.

    Science.gov (United States)

    Moscato, Francesco; Colacino, Francesco M; Arabia, Maurizio; Danieli, Guido A

    2008-11-01

    During open-heart surgery roller pumps are often used to keep the circulation of blood through the patient body. They present numerous key features, but they suffer from several limitations: (a) they normally deliver uncontrolled pulsatile inlet and outlet pressure; (b) blood damage appears to be more than that encountered with centrifugal pumps. A lumped parameter mathematical model of a roller pump (Sarns 7000, Terumo CVS, Ann Arbor, MI, USA) was developed to dynamically simulate pressures at the pump inlet and outlet in order to clarify the uncontrolled pulsation mechanism. Inlet and outlet pressures obtained by the mathematical model have been compared with those measured in various operating conditions: different rollers' rotating speed, different tube occlusion rates, and different clamping degree at the pump inlet and outlet. Model results agree with measured pressure waveforms, whose oscillations are generated by the tube compression/release mechanism during the rollers' engaging and disengaging phases. Average Euclidean Error (AEE) was 20mmHg and 33mmHg for inlet and outlet pressure estimates, respectively. The normalized AEE never exceeded 0.16. The developed model can be exploited for designing roller pumps with improved performances aimed at reducing the undesired pressure pulsation.

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

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Baiyang, E-mail: poplar_chen@hotmail.com [Harbin Institute of Technology Shenzhen Graduate School, Shenzhen Key Laboratory of Water Resource Utilization and Environmental Pollution Control, Shenzhen 518055 (China); Zhang, Tian [Harbin Institute of Technology Shenzhen Graduate School, Shenzhen Key Laboratory of Water Resource Utilization and Environmental Pollution Control, Shenzhen 518055 (China); Bond, Tom [Department of Civil and Environmental Engineering, Imperial College, London SW7 2AZ (United Kingdom); Gan, Yiqun [Harbin Institute of Technology Shenzhen Graduate School, Shenzhen Key Laboratory of Water Resource Utilization and Environmental Pollution Control, Shenzhen 518055 (China)

    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.

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

    Science.gov (United States)

    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.

  17. 2D-QSAR and 3D-QSAR/CoMSIA Studies on a Series of (R)-2-((2-(1H-Indol-2-yl)ethyl)amino)-1-Phenylethan-1-ol with Human β₃-Adrenergic Activity.

    Science.gov (United States)

    Apablaza, Gastón; Montoya, Luisa; Morales-Verdejo, Cesar; Mellado, Marco; Cuellar, Mauricio; Lagos, Carlos F; Soto-Delgado, Jorge; Chung, Hery; Pessoa-Mahana, Carlos David; Mella, Jaime

    2017-03-05

    The β₃ adrenergic receptor is raising as an important drug target for the treatment of pathologies such as diabetes, obesity, depression, and cardiac diseases among others. Several attempts to obtain selective and high affinity ligands have been made. Currently, Mirabegron is the only available drug on the market that targets this receptor approved for the treatment of overactive bladder. However, the FDA (Food and Drug Administration) in USA and the MHRA (Medicines and Healthcare products Regulatory Agency) in UK have made reports of potentially life-threatening side effects associated with the administration of Mirabegron, casting doubts on the continuity of this compound. Therefore, it is of utmost importance to gather information for the rational design and synthesis of new β₃ adrenergic ligands. Herein, we present the first combined 2D-QSAR (two-dimensional Quantitative Structure-Activity Relationship) and 3D-QSAR/CoMSIA (three-dimensional Quantitative Structure-Activity Relationship/Comparative Molecular Similarity Index Analysis) study on a series of potent β₃ adrenergic agonists of indole-alkylamine structure. We found a series of changes that can be made in the steric, hydrogen-bond donor and acceptor, lipophilicity and molar refractivity properties of the compounds to generate new promising molecules. Finally, based on our analysis, a summary and a regiospecific description of the requirements for improving β₃ adrenergic activity is given.

  18. 2D-QSAR and 3D-QSAR/CoMSIA Studies on a Series of (R-2-((2-(1H-Indol-2-ylethylamino-1-Phenylethan-1-ol with Human β3-Adrenergic Activity

    Directory of Open Access Journals (Sweden)

    Gastón Apablaza

    2017-03-01

    Full Text Available The β3 adrenergic receptor is raising as an important drug target for the treatment of pathologies such as diabetes, obesity, depression, and cardiac diseases among others. Several attempts to obtain selective and high affinity ligands have been made. Currently, Mirabegron is the only available drug on the market that targets this receptor approved for the treatment of overactive bladder. However, the FDA (Food and Drug Administration in USA and the MHRA (Medicines and Healthcare products Regulatory Agency in UK have made reports of potentially life-threatening side effects associated with the administration of Mirabegron, casting doubts on the continuity of this compound. Therefore, it is of utmost importance to gather information for the rational design and synthesis of new β3 adrenergic ligands. Herein, we present the first combined 2D-QSAR (two-dimensional Quantitative Structure-Activity Relationship and 3D-QSAR/CoMSIA (three-dimensional Quantitative Structure-Activity Relationship/Comparative Molecular Similarity Index Analysis study on a series of potent β3 adrenergic agonists of indole-alkylamine structure. We found a series of changes that can be made in the steric, hydrogen-bond donor and acceptor, lipophilicity and molar refractivity properties of the compounds to generate new promising molecules. Finally, based on our analysis, a summary and a regiospecific description of the requirements for improving β3 adrenergic activity is given.

  19. Hologram QSAR Studies of Antiprotozoal Activities of Sesquiterpene Lactones

    Directory of Open Access Journals (Sweden)

    Gustavo H. G. Trossini

    2014-07-01

    Full Text Available Infectious diseases such as trypanosomiasis and leishmaniasis are considered neglected tropical diseases due the lack for many years of research and development into new drug treatments besides the high incidence of mortality and the lack of current safe and effective drug therapies. Natural products such as sesquiterpene lactones have shown activity against T. brucei and L. donovani, the parasites responsible for these neglected diseases. To evaluate structure activity relationships, HQSAR models were constructed to relate a series of 40 sesquiterpene lactones (STLs with activity against T. brucei, T. cruzi, L. donovani and P. falciparum and also with their cytotoxicity. All constructed models showed good internal (leave-one-out q2 values ranging from 0.637 to 0.775 and external validation coefficients (r2test values ranging from 0.653 to 0.944. From HQSAR contribution maps, several differences between the most and least potent compounds were found. The fragment contribution of PLS-generated models confirmed the results of previous QSAR studies that the presence of α,β-unsatured carbonyl groups is fundamental to biological activity. QSAR models for the activity of these compounds against T. cruzi, L. donovani and P. falciparum are reported here for the first time. The constructed HQSAR models are suitable to predict the activity of untested STLs.

  20. Hologram QSAR studies of antiprotozoal activities of sesquiterpene lactones.

    Science.gov (United States)

    Trossini, Gustavo H G; Maltarollo, Vinícius G; Schmidt, Thomas J

    2014-07-18

    Infectious diseases such as trypanosomiasis and leishmaniasis are considered neglected tropical diseases due the lack for many years of research and development into new drug treatments besides the high incidence of mortality and the lack of current safe and effective drug therapies. Natural products such as sesquiterpene lactones have shown activity against T. brucei and L. donovani, the parasites responsible for these neglected diseases. To evaluate structure activity relationships, HQSAR models were constructed to relate a series of 40 sesquiterpene lactones (STLs) with activity against T. brucei, T. cruzi, L. donovani and P. falciparum and also with their cytotoxicity. All constructed models showed good internal (leave-one-out q2 values ranging from 0.637 to 0.775) and external validation coefficients (r2test values ranging from 0.653 to 0.944). From HQSAR contribution maps, several differences between the most and least potent compounds were found. The fragment contribution of PLS-generated models confirmed the results of previous QSAR studies that the presence of α,β-unsatured carbonyl groups is fundamental to biological activity. QSAR models for the activity of these compounds against T. cruzi, L. donovani and P. falciparum are reported here for the first time. The constructed HQSAR models are suitable to predict the activity of untested STLs.

  1. Use of molecular modeling, docking, and 3D-QSAR studies for the determination of the binding mode of benzofuran-3-yl-(indol-3-yl)maleimides as GSK-3beta inhibitors.

    Science.gov (United States)

    Kim, Ki Hwan; Gaisina, Irina; Gallier, Franck; Holzle, Denise; Blond, Sylvie Y; Mesecar, Andrew; Kozikowski, Alan P

    2009-12-01

    Molecular modeling and docking studies along with three-dimensional quantitative structure relationships (3D-QSAR) studies have been used to determine the correct binding mode of glycogen synthase kinase 3beta (GSK-3beta) inhibitors. The approaches of comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) are used for the 3D-QSAR of 51 substituted benzofuran-3-yl-(indol-3-yl)maleimides as GSK-3beta inhibitors. Two binding modes of the inhibitors to the binding site of GSK-3beta are investigated. The binding mode 1 yielded better 3D-QSAR correlations using both CoMFA and CoMSIA methodologies. The three-component CoMFA model from the steric and electrostatic fields for the experimentally determined pIC(50) values has the following statistics: R(2)(cv) = 0.386 nd SE(cv) = 0.854 for the cross-validation, and R(2) = 0.811 and SE = 0.474 for the fitted correlation. F (3,47) = 67.034, and probability of R(2) = 0 (3,47) = 0.000. The binding mode suggested by the results of this study is consistent with the preliminary results of X-ray crystal structures of inhibitor-bound GSK-3beta. The 3D-QSAR models were used for the estimation of the inhibitory potency of two additional compounds.

  2. Use of Molecular Modelling, Docking, and 3D-QSAR Studies for the Determination of the Binding Mode of 3-Benzofuranyl-4-indolyl-maleimides as GSK-3β Inhibitors

    Science.gov (United States)

    Kim, Ki Hwan; Gaisina, Irina; Gallier, Franck; Holzle, Denise; Blond, Sylvie Y.; Mesecar, Andrew; Kozikowski, Alan P.

    2010-01-01

    Molecular modelling and docking studies along with three-dimensional quantitative structure relationships (3D-QSAR) studies have been used to determine the correct binding mode of glycogen synthase kinase 3β (GSK-3β) inhibitors. The approaches of Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Index Analysis (CoMSIA) are used for the 3D-QSAR of 51 substituted 3-benzofuranyl-4-indolyl-maleimides as GSK-3β inhibitors. Two binding modes of the inhibitors to the binding site of GSK-3β are investigated. The binding mode 1 yielded better 3D-QSAR correlations using both CoMFA and CoMSIA methodologies. The three-component CoMFA model from the steric and electrostatic fields for the experimentally determined pIC50 values has the following statistics: R2(cv) = 0.386 and SE(cv) = 0.854 for the cross-validation, and R2 = 0.811 and SE = 0.474 for the fitted correlation. F (3,47) = 67.034, and Probability.of R2 = 0 (3,47) = 0.000. The binding mode suggested by the results of this study is consistent with the preliminary results of X-ray crystal structures of inhibitor-bound GSK-3β. The 3D-QSAR models were used for the estimation of the inhibitory potency of two additional compounds. PMID:19440740

  3. Performance Prediction of Two-Phase Geothermal Reservoir using Lumped Parameter Model

    Science.gov (United States)

    Nurlaela, F.; Sutopo

    2016-09-01

    Many studies have been conducted to simulate performance of low-temperature geothermal reservoirs using lumped parameter method. Limited work had been done on applying non-isothermal lumped parameter models to higher temperature geothermal reservoirs. In this study, the lumped parameter method was applied to high-temperature two phase geothermal reservoirs. The model couples both energy and mass balance equations thus can predict temperature, pressure and fluid saturation changes in the reservoir as a result of production, reinjection of water, and/or natural recharge. This method was validated using reservoir simulation results of TOUGH2. As the results, the two phase lumped parameter model simulation without recharge shows good matching, however reservoir model with recharge condition show quite good conformity.

  4. Application of Biologically-Based Lumping To Investigate the Toxicological Interactions of a Complex Gasoline Mixture

    Science.gov (United States)

    People are often exposed to complex mixtures of environmental chemicals such as gasoline, tobacco smoke, water contaminants, or food additives. However, investigators have often considered complex mixtures as one lumped entity. Valuable information can be obtained from these exp...

  5. Ultrabroadband Microwave Metamaterial Absorber Based on Electric SRR Loaded with Lumped Resistors

    Science.gov (United States)

    Zhao, Jingcheng; Cheng, Yongzhi

    2016-10-01

    An ultrabroadband microwave metamaterial absorber (MMA) based on an electric split-ring resonator (ESRR) loaded with lumped resistors is presented. Compared with an ESRR MMA, the composite MMA (CMMA) loaded with lumped resistors offers stronger absorption over an extremely extended bandwidth. The reflectance simulated under different substrate loss conditions indicates that incident electromagnetic (EM) wave energy is mainly consumed by the lumped resistors. The simulated surface current and power loss density distributions further illustrate the mechanism underlying the observed absorption. Further simulation results indicate that the performance of the CMMA can be tuned by adjusting structural parameters of the ESRR and lumped resistor parameters. We fabricated and measured MMA and CMMA samples. The CMMA yielded below -10 dB reflectance from 4.4 GHz to 18 GHz experimentally, with absorption bandwidth and relative bandwidth of 13.6 GHz and 121.4%, respectively. This ultrabroadband microwave absorber has potential applications in the electromagnetic energy harvesting and stealth fields.

  6. Novel amino acids indices based on quantum topological molecular similarity and their application to QSAR study of peptides.

    Science.gov (United States)

    Hemmateenejad, Bahram; Yousefinejad, Saeed; Mehdipour, Ahmad Reza

    2011-04-01

    A new source of amino acid (AA) indices based on quantum topological molecular similarity (QTMS) descriptors has been proposed for use in QSAR study of peptides. For each bond of the chemical structure of AA, eight electronic properties were calculated using the approaches of bond critical point and theory of atom in molecule. Thus, for each molecule a data matrix of QTMS descriptors (having information from both topology and electronic features) were calculated. Using four different criterion based on principal component analysis of the QTMS data matrices, four different sets of AA indices were generated. The indices were used as the input variables for QSAR study (employing genetic algorithm-partial least squares) of three peptides' data sets, namely, angiotensin-converting enzyme inhibitors, bactericidal peptides and the peptides binding to the HLA-A*0201 molecule. The obtained models had better prediction ability or a comparable one with respect to the previously reported models. In addition, by using the proposed indices and analysis of the variable important in projection, the active site of the peptides which plays a significant role in the biological activity of interest, was identified.

  7. Otitis media and a neck lump--current diagnostic challenges for Paragonimus-like trematode infections.

    Science.gov (United States)

    Schuster, H; Agada, F O; Anderson, A R; Jackson, R S; Blair, D; McGann, H; Kelly, G

    2007-02-01

    A 29 year-old Nigerian studying in the UK presented with a neck lump and otitis media. Paragonimus-like trematode eggs were found in the neck lump aspirate. Morphologically these eggs resembled Paragonimus uterobilateralis or Achillurbainia congolensis. We favoured the diagnosis of achillurbainiasis over extrapulmonary paragonimiasis on the basis of clinical features and because we could not amplify DNA sequences using PCR primers specific for Paragonimus species. We discuss current diagnostic challenges for this rare parasitic infection.

  8. Some error estimates for the lumped mass finite element method for a parabolic problem

    KAUST Repository

    Chatzipantelidis, P.

    2012-01-01

    We study the spatially semidiscrete lumped mass method for the model homogeneous heat equation with homogeneous Dirichlet boundary conditions. Improving earlier results we show that known optimal order smooth initial data error estimates for the standard Galerkin method carry over to the lumped mass method whereas nonsmooth initial data estimates require special assumptions on the triangulation. We also discuss the application to time discretization by the backward Euler and Crank-Nicolson methods. © 2011 American Mathematical Society.

  9. The deformed conifold as a geometry on the space of unit charge CP^1 lumps

    CERN Document Server

    Speight, J M

    2001-01-01

    The strong structural similarity between the deformed conifold of Candelas and de la Ossa (a noncompact Calabi-Yau manifold) and the moduli space of unit charge CP^1 lumps equipped with its L^2 metric is pointed out. This allows one to reinterpret certain recent results on D3 branes in terms of lump dynamics, and to deduce certain curvature properties of the deformed conifold.

  10. Lumped modeling with circuit elements for nonreciprocal magnetoelectric tunable band-pass filter

    Science.gov (United States)

    Li, Xiao-Hong; Zhou, Hao-Miao; Zhang, Qiu-shi; Hu, Wen-Wen

    2016-11-01

    This paper presents a lumped equivalent circuit model of the nonreciprocal magnetoelectric tunable microwave band-pass filter. The reciprocal coupled-line circuit is based on the converse magnetoelectric effect of magnetoelectric composites, includes the electrical tunable equivalent factor of the piezoelectric layer, and is established by the introduced lumped elements, such as radiation capacitance, radiation inductance, and coupling inductance, according to the transmission characteristics of the electromagnetic wave and magnetostatic wave in an inverted-L-shaped microstrip line and ferrite slab. The nonreciprocal transmission property of the filter is described by the introduced T-shaped circuit containing controlled sources. Finally, the lumped equivalent circuit of a nonreciprocal magnetoelectric tunable microwave band-pass filter is given and the lumped parameters are also expressed. When the deviation angles of the ferrite slab are respectively 0° and 45°, the corresponding magnetoelectric devices are respectively a reciprocal device and a nonreciprocal device. The curves of S parameter obtained by the lumped equivalent circuit model and electromagnetic simulation are in good agreement with the experimental results. When the deviation angle is between 0° and 45°, the maximum value of the S parameter predicted by the lumped equivalent circuit model is in good agreement with the experimental result. The comparison results of the paper show that the lumped equivalent circuit model is valid. Further, the effect of some key material parameters on the performance of devices is predicted by the lumped equivalent circuit model. The research can provide the theoretical basis for the design and application of nonreciprocal magnetoelectric tunable devices. Project supported by the National Natural Science Foundation of China (Grant Nos. 11172285, 11472259, and 11302217) and the Natural Science Foundation of Zhejiang Province, China (Grant No. LR13A020002).

  11. Predicting chemically-induced skin reactions. Part II: QSAR models of skin permeability and the relationships between skin permeability and skin sensitization

    Energy Technology Data Exchange (ETDEWEB)

    Alves, Vinicius M. [Laboratory of Molecular Modeling and Design, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO 74605-220 (Brazil); Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Muratov, Eugene [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Laboratory of Theoretical Chemistry, A.V. Bogatsky Physical–Chemical Institute NAS of Ukraine, Odessa 65080 (Ukraine); Fourches, Denis [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Strickland, Judy; Kleinstreuer, Nicole [ILS/Contractor supporting the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), P.O. Box 13501, Research Triangle Park, NC 27709 (United States); Andrade, Carolina H. [Laboratory of Molecular Modeling and Design, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO 74605-220 (Brazil); Tropsha, Alexander, E-mail: alex_tropsha@unc.edu [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States)

    2015-04-15

    Skin permeability is widely considered to be mechanistically implicated in chemically-induced skin sensitization. Although many chemicals have been identified as skin sensitizers, there have been very few reports analyzing the relationships between molecular structure and skin permeability of sensitizers and non-sensitizers. The goals of this study were to: (i) compile, curate, and integrate the largest publicly available dataset of chemicals studied for their skin permeability; (ii) develop and rigorously validate QSAR models to predict skin permeability; and (iii) explore the complex relationships between skin sensitization and skin permeability. Based on the largest publicly available dataset compiled in this study, we found no overall correlation between skin permeability and skin sensitization. In addition, cross-species correlation coefficient between human and rodent permeability data was found to be as low as R{sup 2} = 0.44. Human skin permeability models based on the random forest method have been developed and validated using OECD-compliant QSAR modeling workflow. Their external accuracy was high (Q{sup 2}{sub ext} = 0.73 for 63% of external compounds inside the applicability domain). The extended analysis using both experimentally-measured and QSAR-imputed data still confirmed the absence of any overall concordance between skin permeability and skin sensitization. This observation suggests that chemical modifications that affect skin permeability should not be presumed a priori to modulate the sensitization potential of chemicals. The models reported herein as well as those developed in the companion paper on skin sensitization suggest that it may be possible to rationally design compounds with the desired high skin permeability but low sensitization potential. - Highlights: • It was compiled the largest publicly-available skin permeability dataset. • Predictive QSAR models were developed for skin permeability. • No concordance between skin

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

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiaolin [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210046 (China); Ye, Li [Suzhou NeuPharma Co.,Ltd, Suzhou 215123 (China); Wang, Xiaoxiang [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210046 (China); Wang, Xinzhou [Suzhou NeuPharma Co.,Ltd, Suzhou 215123 (China); Liu, Hongling [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210046 (China); Zhu, Yongliang [Suzhou NeuPharma Co.,Ltd, Suzhou 215123 (China); Yu, Hongxia, E-mail: hongxiayu01@yahoo.com.cn [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210046 (China)

    2012-12-15

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

  13. Insight into the interactions between novel isoquinolin-1,3-dione derivatives and cyclin-dependent kinase 4 combining QSAR and molecular docking.

    Directory of Open Access Journals (Sweden)

    Junxia Zheng

    Full Text Available Several small-molecule CDK inhibitors have been identified, but none have been approved for clinical use in the past few years. A new series of 4-[(3-hydroxybenzylamino-methylene]-4H-isoquinoline-1,3-diones were reported as highly potent and selective CDK4 inhibitors. In order to find more potent CDK4 inhibitors, the interactions between these novel isoquinoline-1,3-diones and cyclin-dependent kinase 4 was explored via in silico methodologies such as 3D-QSAR and docking on eighty-one compounds displaying potent selective activities against cyclin-dependent kinase 4. Internal and external cross-validation techniques were investigated as well as region focusing, bootstraping and leave-group-out. A training set of 66 compounds gave the satisfactory CoMFA model (q2 = 0.695, r2 = 0.947 and CoMSIA model (q2 = 0.641, r2 = 0.933. The remaining 15 compounds as a test set also gave good external predictive abilities with r2pred values of 0.875 and 0.769 for CoMFA and CoMSIA, respectively. The 3D-QSAR models generated here predicted that all five parameters are important for activity toward CDK4. Surflex-dock results, coincident with CoMFA/CoMSIA contour maps, gave the path for binding mode exploration between the inhibitors and CDK4 protein. Based on the QSAR and docking models, twenty new potent molecules have been designed and predicted better than the most active compound 12 in the literatures. The QSAR, docking and interactions analysis expand the structure-activity relationships of constrained isoquinoline-1,3-diones and contribute towards the development of more active CDK4 subtype-selective inhibitors.

  14. Elaborate ligand-based modeling coupled with multiple linear regression and k nearest neighbor QSAR analyses unveiled new nanomolar mTOR inhibitors.

    Science.gov (United States)

    Khanfar, Mohammad A; Taha, Mutasem O

    2013-10-28

    The mammalian target of rapamycin (mTOR) has an important role in cell growth, proliferation, and survival. mTOR is frequently hyperactivated in cancer, and therefore, it is a clinically validated target for cancer therapy. In this study, we combined exhaustive pharmacophore modeling and quantitative structure-activity relationship (QSAR) analysis to explore the structural requirements for potent mTOR inhibitors employing 210 known mTOR ligands. Genetic function algorithm (GFA) coupled with k nearest neighbor (kNN) and multiple linear regression (MLR) analyses were employed to build self-consistent and predictive QSAR models based on optimal combinations of pharmacophores and physicochemical descriptors. Successful pharmacophores were complemented with exclusion spheres to optimize their receiver operating characteristic curve (ROC) profiles. Optimal QSAR models and their associated pharmacophore hypotheses were validated by identification and experimental evaluation of several new promising mTOR inhibitory leads retrieved from the National Cancer Institute (NCI) structural database. The most potent hit illustrated an IC50 value of 48 nM.

  15. Development of TLSER model and QSAR model for predicting partition coefficients of hydrophobic organic chemicals between low density polyethylene film and water.

    Science.gov (United States)

    Liu, Huihui; Wei, Mengbi; Yang, Xianhai; Yin, Cen; He, Xiao

    2017-01-01

    Partition coefficients are vital parameters for measuring accurately the chemicals concentrations by passive sampling devices. Given the wide use of low density polyethylene (LDPE) film in passive sampling, we developed a theoretical linear solvation energy relationship (TLSER) model and a quantitative structure-activity relationship (QSAR) model for the prediction of the partition coefficient of chemicals between LDPE and water (Kpew). For chemicals with the octanol-water partition coefficient (log Kow) coefficient (R(2)) and cross-validated coefficient (Q(2)). In order to further explore the theoretical mechanisms involved in the partition process, a QSAR model with four descriptors (MLOGP (Moriguchi octanol-water partition coeff.), P_VSA_s_3 (P_VSA-like on I-state, bin 3), Hy (hydrophilic factor) and NssO (number of atoms of type ssO)) was established, and statistical analysis indicated that the model had satisfactory goodness-of-fit, robustness and predictive ability. For chemicals with log KOW>8, a TLSER model with Vx and a QSAR model with MLOGP as descriptor were developed. This is the first paper to explore the models for highly hydrophobic chemicals. The applicability domain of the models, characterized by the Euclidean distance-based method and Williams plot, covered a large number of structurally diverse chemicals, which included nearly all the common hydrophobic organic compounds. Additionally, through mechanism interpretation, we explored the structural features those governing the partition behavior of chemicals between LDPE and water.

  16. Structural features of substituted triazole-linked chalcone derivatives as antimalarial activities against D10 strains ofPlasmodium falciparum:A QSAR approach

    Institute of Scientific and Technical Information of China (English)

    Mukesh C. Sharma

    2015-01-01

    A quantitative structure–activity relationship (QSAR) was performed to analyze antimalarial activities against the D10 strains ofPlasmodium falciparum of triazole-linked chalcone and dienone hybrid derivatives using partial least squares regression coupled with stepwise forward–backward variable selection method. QSAR analyses were performed on the available IC50 D10 strains ofPlasmodium falciparum data based on theoretical molecular descriptors. The QSAR model developed gave good predictive correlation coefficient (r2) of 0.8994, significant cross validated correlation coefficient (q2) of 0.7689,r2 for external test set(p2)redr of 0.8256, coefficient of correlation of predicted data set)(p2sered,r of 0.3276. The model shows that antimalarial activity is greatly affected by donor and electron-withdrawing substituents. The study implicates that chalcone and dienone rings should have strong donor and electron-withdrawing substituents as they increase the activity of chalcone. Results show that the predictive ability of the model is satisfactory, and it can be used for designing similar group of antimalarial compounds. The findings derived from this analysis along with other molecular modeling studies will be helpful in designing of the new potent antimalarial activity of clinical utility.

  17. On the interaction of gravity-capillary lumps in deep water

    Science.gov (United States)

    Masnadi, Naeem; Duncan, James

    2016-11-01

    The nonlinear response of a water surface to a pressure source moving at a speed just below the minimum phase speed of linear gravity-capillary waves in deep water (cmin = 23 . 1 cm/s) consists of periodic generation of pairs of three-dimensional solitary waves (lumps) in a V-shaped pattern downstream of the source. In the reference frame of the laboratory, these unsteady lumps propagate in a direction oblique to the motion of the source and are damped by viscosity. In the current study, the interaction of lumps generated by two equal strength pressure sources moving side by side in parallel straight lines is investigated experimentally via photography-based techniques. The first lump generated by each source, collides with the lump from the other source in the center-plane of the two sources. It is observed that a steep depression is formed during the collision. Soon after the collision, this depression radiates energy in the form of small-amplitude radial waves. After the radiation, a quasi-stable pattern is formed with several rows of localized depressions that are qualitatively similar to lumps but exhibit periodic oscillations in depth, similar to a "breather". The shape of the wave pattern and the period of oscillations depend strongly on the distance between the soures.

  18. Lumped conceptual hydrological model for Purna river basin, India

    Indian Academy of Sciences (India)

    V D Loliyana; P L Patel

    2015-12-01

    In present study, a lumped conceptual hydrological model, NAM (MIKE11), is calibrated while optimizing the runoff simulations on the basis of minimization of percentage water balance (% WBL) and root mean square error (RMSE) using measured stream flow data of eight years from 1991 to 1998 for Yerli catchment (area = 15,701 km2) of upper Tapi basin, Maharashtra in Western India. The sensitivity of runoff volume and peak-runoff has been undertaken with reference to nine NAM parameters using the data of calibration period. The runoff volume and peak-runoff have been found to be highly sensitive with reference to maximum water content in root zone storage (Lmax) and overland flow coefficient (CQOF) respectively. On the other hand, runoff volume is found to be moderately sensitive with maximum water content in surface storage (Umax). The calibrated model has been validated for independent stream flow data of Yerli gauging site for years 2001–2004, and Gopalkheda gauging site for years 1991–1998 and 2001–2004. The model performance has been assessed using statistical performance indices, and compared the same with their yardsticks suggested in published literature. The simulated results demonstrated that calibrated model is able to simulate hydrographs satisfactorily for Yerli (NSE = 0.86–0.88, r = 0.93–0.96, EI = 1.05–1.12) as well as Gopalkheda subcatchments (NSE = 0.76–0.92 and r = 0.88–0.96, EI = 0.89–0.91) at monthly time scale. The model also performs reasonably well in simulating the annual hydrographs at daily time scale. The calibrated model may be useful in prediction of water yield and flooding conditions in the Purna catchment.

  19. Methods for reliability and uncertainty assessment and for applicability evaluations of classification- and regression-based QSARs.

    Science.gov (United States)

    Eriksson, Lennart; Jaworska, Joanna; Worth, Andrew P; Cronin, Mark T D; McDowell, Robert M; Gramatica, Paola

    2003-01-01

    This article provides an overview of methods for reliability assessment of quantitative structure-activity relationship (QSAR) models in the context of regulatory acceptance of human health and environmental QSARs. Useful diagnostic tools and data analytical approaches are highlighted and exemplified. Particular emphasis is given to the question of how to define the applicability borders of a QSAR and how to estimate parameter and prediction uncertainty. The article ends with a discussion regarding QSAR acceptability criteria. This discussion contains a list of recommended acceptability criteria, and we give reference values for important QSAR performance statistics. Finally, we emphasize that rigorous and independent validation of QSARs is an essential step toward their regulatory acceptance and implementation. PMID:12896860

  20. Methods for reliability and uncertainty assessment and for applicability evaluations of classification- and regression-based QSARs.

    Science.gov (United States)

    Eriksson, Lennart; Jaworska, Joanna; Worth, Andrew P; Cronin, Mark T D; McDowell, Robert M; Gramatica, Paola

    2003-08-01

    This article provides an overview of methods for reliability assessment of quantitative structure-activity relationship (QSAR) models in the context of regulatory acceptance of human health and environmental QSARs. Useful diagnostic tools and data analytical approaches are highlighted and exemplified. Particular emphasis is given to the question of how to define the applicability borders of a QSAR and how to estimate parameter and prediction uncertainty. The article ends with a discussion regarding QSAR acceptability criteria. This discussion contains a list of recommended acceptability criteria, and we give reference values for important QSAR performance statistics. Finally, we emphasize that rigorous and independent validation of QSARs is an essential step toward their regulatory acceptance and implementation.

  1. Calculation of PDS-XADS core closed-loop transfer function by using feedback with the lumped-model

    Energy Technology Data Exchange (ETDEWEB)

    Moghassem, Alireza; Payirandeh, Ali; Abbaspour, Ali [Islamic Azad Univ., Tehran (Iran, Islamic Republic of). Nuclear Engineering Dept.

    2016-03-15

    In this paper, the PDS-XADS LBE-cooled core open-loop transfer function was calculated by considering the source importance in point-kinetic equations. For this purpose, the overall-feedback transfer function was calculated considering the lumped-model for 14-steps of subcritical levels. Following effects were considered in three steps: 1. Doppler broadening, fuel expansion, coolant density and structure expansion, 2. Delayed-reactivity and void-worth inserted to prior step, 3. Severe-accident condition, inserted to prior steps. The linear stability analysis was modeled by using the Bode diagrams, Nyquist stability criterion and Nichols chart in MATLAB for each subcritical level and six groups of delayed neutrons. For optimized subcritical level determination, a conservative severe accident was considered. According to calculation results and analysis, the PDS-XADS core is stable and in optimized subcritical level, has the higher safety margin. The results are in good agreement with SIMMER-III code and main neutronic results. The optimized subcritical level by using the lumped-model is 0.97687.

  2. Comparative study of four QSAR models of aromatic compounds to aquatic organisms

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Quantitative structure-activity relationships (QSARs) were developed for 43 aromatic compounds toxicity to Photobacterium phosphoreum and Daphnia magna based on four methods: octanol/water partition coefficient, linear solvation energy relationship, molecular connectivity index and group contribution. Through the evaluation of four QSAR methods, LSER was proved to be the best. And it applied to the widest range of chemicals with the greatest accuracy.

  3. QSAR models for reproductive toxicity and endocrine disruption in regulatory use - a preliminary investigation

    DEFF Research Database (Denmark)

    Jensen, Gunde Egeskov; Niemela, J.R.; Wedebye, Eva Bay

    2008-01-01

    the new legislation. This article focuses on a screening exercise by use of our own and commercial QSAR models for identification of possible reproductive toxicants. Three QSAR models were used for reproductive toxicity for the endpoints teratogenic risk to humans (based on animal tests, clinical data...... for humans owing to possible developmental toxic effects: Xn (Harmful) and R63 (Possible risk of harm to the unborn child). The chemicals were also screened in three models for endocrine disruption....

  4. AutoGPA-Based 3D-QSAR Modeling and Molecular Docking Study on Factor Xa Inhibitors as Anticoagulant Agents

    Directory of Open Access Journals (Sweden)

    Guo Fang Yuan

    2016-01-01

    Full Text Available The three-dimensional-quantitative structure activity relationship (3D-QSAR studies were performed on a series of direct factor Xa (FXa inhibitors using AutoGPA-based modeling method in this paper. A training set of 38 molecules and a test set containing 10 molecules were used to build the 3D-QSAR model and validate the derived model, respectively. The developed model with correlation coefficients (r2 of 0.8564 and cross-validated correlation coefficients (q2 of 0.6721 were validated by an external test set of 10 molecules with predicted correlation coefficient (rpred2 of 0.6077. Docking study of FXa inhibitors and FXa active site was performed to check the induced pharmacophore query and comparative molecular field analysis (CoMFA contour maps using MOE2012.10. It was proved to be coincidence with the interaction information between ligand and FXa active site and was rendered to provide a useful tool to improve FXa inhibitors.

  5. Support vector machine for SAR/QSAR of phenethyl-amines

    Institute of Scientific and Technical Information of China (English)

    Bing NIU; Wen-cong LU; Shan-sheng YANG; Yu-dong CAI; Guo-zheng LI

    2007-01-01

    Aim: To discriminate 32 phenethyl-amines between antagonists and agonists,and predict the activities of these compounds. Methods: The support vectormachine (SVM) is employed to investigate the structure-activity relationship(SAR)/quantitative structure-activity relationship (QSAR) of phenethyl-aminesbased on molecular descriptors. Results: By using the leave-one-out cross-vali-dation (LOOCV) test, 1 optimal SAR and 2 optimal QSAR models for agonists andantagonists were attained. The accuracy of prediction for the classification ofphenethyl-amines by using the LOOCV test is 91.67%, and the accuracy of predic-tion for the classification of phenethyl-amines by using the independent test is100%; the results are better than those of the Fisher, the artificial neural network(ANN), and the K-nearest neighbor models for this real world data. The RMSE(root mean square error)of antagonists' QSAR model is 0.5881, and the RMSE ofagonists' QSAR model is 0.4779, which are better than those of the multiple linearregression, partial least squares, and ANN models for this real world data.Conclusion: The SVM can be used to investigate the SAR and QSAR of phenethyl-amines and could be a promising tool in the field of SAR/QSAR research.

  6. New free Danish online (Q)SAR predictions database with >600,000 substances

    DEFF Research Database (Denmark)

    Wedebye, Eva Bay; Dybdahl, Marianne; Reffstrup, Trine Klein

    by regulators and industry. A lot of progress in (Q)SAR model development, application and documentation has been made since the publication in 2005. A new and completely rebuild online (Q)SAR predictions database was therefore published in November 2015 at http://qsar.food.dtu.dk. The number of chemicals...... in the database has been expanded from 185,000 to >600,000. As far as possible all organic single constituent substances that were pre-registered under REACH have been included in the new structure set. The new Danish (Q)SAR Database includes estimates from more than 200 (Q)SARs covering a wide range of hazardous......-scale screenings. The online interface to the database allows for advanced combination of searches as well as sorting functions on chemical similarity. Negotiations are underway with the OECD to integrate the new database with the OECD (Q)SAR Application Toolbox. The database was developed by the DTU National Food...

  7. Lumped Parameter Modeling as a Predictive Tool for a Battery Status Monitor

    Energy Technology Data Exchange (ETDEWEB)

    Jon P. Christophersen; Chester G. Motloch; Chinh D. Ho; John L. Morrison; Ronald C. Fenton; Vincent S. Battaglia; Tien Q. Duong

    2003-10-01

    The Advanced Technology Development Program is currently evaluating the performance of the second generation of lithium-ion cells (i.e., Gen 2 cells). Both the Gen 2 Baseline and Variant C cells are tested in accordance with the cell-specific test plan, and are removed at roughly equal power fade increments and sent for destructive diagnostic analysis. The diagnostic laboratories did not need all test cells for analysis, and returned five spare cells to the Idaho National Engineering and Environmental Laboratory (INEEL). INEEL used these cells for special pulse testing at various duty cycles, amplitudes, and durations to investigate the usefulness of the lumped parameter model (LPM) as a predictive tool in a battery status monitor (BSM). The LPM is a simplified linear model that accurately predicts the voltage response during certain pulse conditions. A database of parameter trends should enable dynamic predictions of state-of-charge and state-of-health conditions during in-vehicle pulsing. This information could be used by the BSM to provide accurate information to the vehicle control system.

  8. Parameter Identification on Lumped Parameters of the Hydraulic Engine Mount Model

    Directory of Open Access Journals (Sweden)

    Li Qian

    2016-01-01

    Full Text Available Hydraulic Engine Mounts (HEM are important vibration isolation components with compound structure in the vehicle powertrain mounting system. They have the characteristic that large damping and high dynamic stiffness in the high frequency region, and small damping and low dynamic stiffness in the low frequency region, which can meet the requirements of the vehicle powertrain mounting system better. The method to identify the lumped parameters of the HEM is not only the necessary work for the analysis and calculation in dynamic performance and can also provide the theory for the performance optimization and structure optimization of product in the future. The parameter identification method based on coupled fluid-structure interaction (FSI and finite element analysis (FEA was established in this study to identify the equivalent piston area of the rubber spring, the volume stiffness of the upper chamber, as well as the inertia coefficient and damping coefficient of the liquid through the inertia track. The simulated dynamic characteristic curves of the HEM with the parameters identified are in accordance with the measured dynamic characteristic curves well.

  9. EVALUATION OF BREAST LUMPS BY ULTRASONOGRAPHY: A STUDY IN RURAL TEACHING INSTITUTION

    Directory of Open Access Journals (Sweden)

    Monu

    2014-07-01

    Full Text Available To find the sensitivity, specificity and positive predictive value of ultrasound in detection of palpable breast lumps and to correlate the findings of ultrasound with the findings of fine needle aspiration cytology (FNAC, or histopathology. Ultrasonagraphic evaluation of 50 palpable breast lumps was done in our institute from January 2011 to February 2012. Diagnosis was made considering four features of the lumps i.e. shape, margins, width: AP ratio and echogenicity. Diagnosis was confirmed by fine needle aspiration cytology or histopathology. The sensitivity of ultrasound in detection of palpable breast lumps was 84%. The incidence of breast lumps was highest in the age group of 20-39 years (60%. Lump alone was the presentation in 88% of the cases. 64% of the lumps were present in outer upper quadrant of the breast. The sensitivity, specificity and positive predictive value of ultrasound in fibroadenoma of the breast was 88.88%, 94.7% and 91.2% respectively. The sensitivity for carcinoma of the breast was 84.61% and for cystic masses it was 100%. The ultrasound features that most reliably characterized breast masses as benign were round or oval shape (93.33% were benign, circumscribed margins (89.28% were benign and width: AP ratio >1.4 (87.09% were benign. Features that characterized masses as malignant were irregular shape (75% were malignant, non-circumscribed margins (57.14% were malignant and width: AP ratio ≤1.4 (63.63% were malignant.Ultrasound is a useful tool in differentiation of cystic from solid masses of the breast. It is useful in young females and pregnant women where mammography is not advisable. However its role in diagnosis of carcinoma of the breast needs further evaluation before it can be used for screening of carcinoma breast.

  10. Prediction of Halocarbon Toxicity from Structure: A Hierarchical QSAR Approach

    Energy Technology Data Exchange (ETDEWEB)

    Gute, B D; Balasubramanian, K; Geiss, K; Basak, S C

    2003-04-11

    Mathematical structural invariants and quantum theoretical descriptors have been used extensively in quantitative structure-activity relationships (QSARs) for the estimation of pharmaceutical activities, biological properties, physicochemical properties, and the toxicities of chemicals. Recently our research team has explored the relative importance of various levels of chemodescriptors, i.e., topostructural, topochemical, geometrical, and quantum theoretical descriptors, in property estimation. This study examines the contribution of chemodescriptors ranging from topostructural to quantum theoretic calculations up to the Gaussian STO-3G level in the prediction of the toxicity of a set of twenty halocarbons. We also report the results of experimental cell-level toxicity studies on these twenty halocarbons to validate our models.

  11. Synthesis, antimicrobial evaluation and QSAR studies of propionic acid derivatives

    Directory of Open Access Journals (Sweden)

    Sanjiv Kumar

    2017-02-01

    Full Text Available A series of Schiff bases (1–17 and esters (18–24 of propionic acid was synthesized in appreciable yield and characterized by physicochemical as well as spectral means. The synthesized compounds were evaluated in vitro for their antimicrobial activity against Gram-positive bacteria Staphylococcus aureus, Bacillus subtilis, Gram negative bacterium Escherichia coli and fungal strains Candida albicans and Aspergillus niger by tube dilution method. Results of antimicrobial screening indicated that besides having good antibacterial activity, the synthesized compounds also displayed appreciable antifungal activity and compound 10 emerged as the most active antifungal agent (pMICca and pMICan = 1.93. The results of QSAR studies demonstrated that antibacterial, antifungal and overall antimicrobial activities of synthesized propionic acid derivatives were governed by the topological parameters, Kier’s alpha first order shape index (κα1 and valence first order molecular connectivity index (1χv.

  12. On QSAR Study of Stereoselectivity for Wittig Reaction

    Institute of Scientific and Technical Information of China (English)

    CHEN Zhi-Tao; ZHOU Peng; LI Gen-Rong; LI Zhi-Liang

    2006-01-01

    Molecular structures of reactants were characterized by molecular electronegativity distance vector (VHMED) considering hydrogen association. A reasonable molecular modeling equation with 4-parameters was achieved for quantitative structure-property/activity relationship (QSPR/QSAR) by stepwise multiple regression (SMR) that the variable was introduced item by item in significant level order. A high correlation coefficient (R = 0.980) demonstrates that the mo- del is able to well express a quantitative relation between stereoselectivity and the reactant struc- tures as quantitative structure-reactivity/stereoselectivity relationship (QSRR/QSSR). The multiple correlation coefficient (RCV = 0.964) was tested through cross-validation with the leave-one-out (LOO) procedure. The above results show that the model possesses high estimation stability and good prediction ability between the amount of both cis and trans isomers in products and reactants.

  13. Synthesis,QSAR Study and Optimization of Propiophenone Oxime Derivatives

    Institute of Scientific and Technical Information of China (English)

    CHEN Liang; YU Fei; LIU Bin; YUAN Liping; YAO Jianhua; HUANG Ying; XlE Wei; CAO Jin; NI Changchun; SHEN Zhou; LI Xiuli; ZHANG Yibin; SHEN Tianxiang

    2009-01-01

    A method combining chemical and biological experiments and computer-aided molecular design was used to optimize lead compounds with inhibiting activity against Sphaerotheca fuliginea. 44 propiophenone oxime deriva-tives were synthesized by 3-amino-1-arylpropan-1-one oxime and halohydrocarbon. The results of biological test showed that most of these compounds had inhibiting activity against Sphaerothecafuliginea. QSAR study was done based on the experimental data of the 44 compounds. CoMFA ( γcv2, S and γ2 are 0.577, 0.258 and 0.962, respec-tively) and CoMSIA ( γcv2, S and γ2 are 0.583, 0.343 and 0.932 respectively) models were contributed and employed to design three new lead compounds whose prediction carcinogenic and mutagenic toxicities show impossibility. The performances of the two models are satisfied because the test results showed that their prediction activity and observed activity are corresponding.

  14. Molecular design and QSARs/QSPRs with molecular descriptors family.

    Science.gov (United States)

    Bolboacă, Sorana D; Jäntschi, Lorentz; Diudea, Mircea V

    2013-06-01

    The aim of the present paper is to present the methodology of the molecular descriptors family (MDF) as an integrative tool in molecular modeling and its abilities as a multivariate QSAR/QSPR modeling tool. An algorithm for extracting useful information from the topological and geometrical representation of chemical compounds was developed and integrated to calculate MDF members. The MDF methodology was implemented and the software is available online (http://l.academicdirect.org/Chemistry/SARs/MDF_SARs/). This integrative tool was developed in order to maximize performance, functionality, efficiency and portability. The MDF methodology is able to provide reliable and valid multiple linear regression models. Furthermore, in many cases, the MDF models were better than the published results in the literature in terms of correlation coefficients (statistically significant Steiger's Z test at a significance level of 5%) and/or in terms of values of information criteria and Kubinyi function. The MDF methodology developed and implemented as a platform for investigating and characterizing quantitative relationships between the chemical structure and the activity/property of active compounds was used on more than 50 study cases. In almost all cases, the methodology allowed obtaining of QSAR/QSPR models improved in explanatory power of structure-activity and structure-property relationships. The algorithms applied in the computation of geometric and topological descriptors (useful in modeling physicochemical or biological properties of molecules) and those used in searching for reliable and valid multiple linear regression models certain enrich the pool of low-cost low-time drug design tools.

  15. QSAR modeling of mono- and bis-quaternary ammonium salts that act as antagonists at neuronal nicotinic acetylcholine receptors mediating dopamine release.

    Science.gov (United States)

    Zheng, Fang; Bayram, Ersin; Sumithran, Sangeetha P; Ayers, Joshua T; Zhan, Chang-Guo; Schmitt, Jeffrey D; Dwoskin, Linda P; Crooks, Peter A

    2006-05-01

    Back-propagation artificial neural networks (ANNs) were trained on a dataset of 42 molecules with quantitative IC50 values to model structure-activity relationships of mono- and bis-quaternary ammonium salts as antagonists at neuronal nicotinic acetylcholine receptors (nAChR) mediating nicotine-evoked dopamine release. The ANN QSAR models produced a reasonable level of correlation between experimental and calculated log(1/IC50) (r2=0.76, r(cv)2=0.64). An external test for the models was performed on a dataset of 18 molecules with IC50 values >1 microM. Fourteen of these were correctly classified. Classification ability of various models, including self-organizing maps (SOM), for all 60 molecules was also evaluated. A detailed analysis of the modeling results revealed the following relative contributions of the used descriptors to the trained ANN QSAR model: approximately 44.0% from the length of the N-alkyl chain attached to the quaternary ammonium head group, approximately 20.0% from Moriguchi octanol-water partition coefficient of the molecule, approximately 13.0% from molecular surface area, approximately 12.6% from the first component shape directional WHIM index/unweighted, approximately 7.8% from Ghose-Crippen molar refractivity, and 2.6% from the lowest unoccupied molecular orbital energy. The ANN QSAR models were also evaluated using a set of 13 newly synthesized compounds (11 biologically active antagonists and two biologically inactive compounds) whose structures had not been previously utilized in the training set. Twelve among 13 compounds were predicted to be active which further supports the robustness of the trained models. Other insights from modeling include a structural modification in the bis-quinolinium series that involved replacing the 5 and/or 8 as well as the 5' and/or 8' carbon atoms with nitrogen atoms, predicting inactive compounds. Such data can be effectively used to reduce synthetic and in vitro screening activities by eliminating

  16. QSAR studies on triazole derivatives as sglt inhibitors via CoMFA and CoMSIA

    Science.gov (United States)

    Zhi, Hui; Zheng, Junxia; Chang, Yiqun; Li, Qingguo; Liao, Guochao; Wang, Qi; Sun, Pinghua

    2015-10-01

    Forty-six sodium-dependent glucose cotransporters-2 (SGLT-2) inhibitors with hypoglycemic activity were selected to develop three-dimensional quantitative structure-activity relationship (3D-QSAR) using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models. A training set of 39 compounds were used to build up the models, which were then evaluated by a series of internal and external cross-validation techniques. A test set of 7 compounds was used for the external validation. The CoMFA model predicted a q2 value of 0.792 and an r2 value of 0.985. The best CoMSIA model predicted a q2 value of 0.633 and an r2 value of 0.895 based on a combination of steric, electrostatic, hydrophobic and hydrogen-bond acceptor effects. The predictive correlation coefficients of CoMFA and CoMSIA models were 0.872 and 0.839, respectively. The analysis of the contour maps from each model provided insight into the structural requirements for the development of more active sglt inhibitors, and on the basis of the models 8 new sglt inhibitors were designed and predicted.

  17. Lumped parameter analytic modeling and behavioral simulation of a 3-DOF MEMS gyro-accelerometer

    Science.gov (United States)

    Verma, Payal; Arya, Sandeep K.; Gopal, Ram

    2015-12-01

    A new analytical model of a 3-degree-of-freedom (3-DOF) gyro-accelerometer system consisting of a 1-DOF drive and 2-DOF sense modes is presented. The model constructs lumped differential equations associated with each DOF of the system by vector analysis. The coupled differential equations thus established are solved analytically for their responses in both the time and frequency domains. Considering these frequency response equations, novel device design concepts are derived by forcing the sense phase to zero, which leads to a certain relationship between the structural frequencies, thereby causing minimization of the damping effect on the performance of the system. Furthermore, the feasibility of the present gyro-accelerometer structure is studied using a unique discriminatory scheme for the detection of both gyro action and linear acceleration at their events. This scheme combines the formulated settled transient solution of the gyro-accelerometer with the processes of synchronous demodulation and filtration, which leads to the in-phase and quadrature components of the system's output signal. These two components can be utilized in the detection of angular motion and linear acceleration. The obtained analytical results are validated by simulation in a MATLAB/Simulink environment, and it is found that the results are in excellent agreement with each other.

  18. [Hybrid and uncemented hip arthroplasty: Contribution margin in the German lump sum reimbursement system].

    Science.gov (United States)

    Hanstein, Tim; Kumpe, O; Mittelmeier, W; Skripitz, R

    2015-08-01

    The economization of inpatient care began when lump sum reimbursement was introduced into the hospital sector. Since then, total hip arthroplasty (THA) has experienced a rapid development in terms of annual procedures and the optimization of the clinical pathway. Therefore, it is obvious to highlight THA as one of the most common procedures in the German health care system. In this work, the two most common techniques for the fixation of THA are investigated with regard to their cost structure and their influence on the clinical result. In Germany, uncemented and hybrid fixation are used for THA. In this study we investigated the differences in material costs, the duration of surgery, and the length of stay. For each fixation technique a retrospective cost analysis was carried out, based on the data from the treatment documentation of the University Hospital for Orthopedics, Rostock (OUK). The mean values of the parameters and expenses have been reviewed with descriptive statistics for differences. With regard to total costs and the contribution margin there was no statistically significant difference. Although there are differences in individual cost areas, in total costs, cost advantages and disadvantages cancel each other out. Thus, from an economic perspective no particular technique can be recommended.

  19. Lump Solutions and Interaction Phenomenon for (2+1)-Dimensional Sawada-Kotera Equation

    Science.gov (United States)

    Huang, Li-Li; Chen, Yong

    2017-05-01

    In this paper, a class of lump solutions to the (2+1)-dimensional Sawada-Kotera equation is studied by searching for positive quadratic function solutions to the associated bilinear equation. To guarantee rational localization and analyticity of the lumps, some sufficient and necessary conditions are presented on the parameters involved in the solutions. Then, a completely non-elastic interaction between a lump and a stripe of the (2+1)-dimensional Sawada-Kotera equation is obtained, which shows a lump solution is drowned or swallowed by a stripe soliton. Finally, 2-dimensional curves, 3-dimensional plots and density plots with particular choices of the involved parameters are presented to show the dynamic characteristics of the obtained lump and interaction solutions. Supported by the Global Change Research Program of China under Grant No. 2015CB953904, National Natural Science Foundation of China under Grant Nos. 11675054 and 11435005, Outstanding Doctoral Dissertation Cultivation Plan of Action under Grant No. YB2016039, and Shanghai Collaborative Innovation Center of Trustworthy Software for Internet of Things under Grant No. ZF1213

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

    Directory of Open Access Journals (Sweden)

    Stålring Jonna C

    2011-07-01

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

  1. An integrated approach with new strategies for QSAR models and lead optimization.

    Science.gov (United States)

    Hsu, Hui-Hui; Hsu, Yen-Chao; Chang, Li-Jen; Yang, Jinn-Moon

    2017-03-14

    Computational drug design approaches are important for shortening the time and reducing the cost for drug discovery and development. Among these methods, molecular docking and quantitative structure activity relationship (QSAR) play key roles for lead discovery and optimization. Here, we propose an integrated approach with core strategies to identify the protein-ligand hot spots for QSAR models and lead optimization. These core strategies are: 1) to generate both residue-based and atom-based interactions as the features; 2) to identify compound common and specific skeletons; and 3) to infer consensus features for QSAR models. We evaluated our methods and new strategies on building QSAR models of human acetylcholinesterase (huAChE). The leave-one-out cross validation values q (2) and r (2) of our huAChE QSAR model are 0.82 and 0.78, respectively. The experimental results show that the selected features (resides/atoms) are important for enzymatic functions and stabling the protein structure by forming key interactions (e.g., stack forces and hydrogen bonds) between huAChE and its inhibitors. Finally, we applied our methods to arthrobacter globiformis histamine oxidase (AGHO) which is correlated to heart failure and diabetic. Based on our AGHO QSAR model, we identified a new substrate verified by bioassay experiments for AGHO. These results show that our methods and new strategies can yield stable and high accuracy QSAR models. We believe that our methods and strategies are useful for discovering new leads and guiding lead optimization in drug discovery.

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

    Science.gov (United States)

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

    2014-05-19

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

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

    Science.gov (United States)

    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.

  4. 3D-QSAR studies on chromone derivatives as HIV-1 protease inhibitors

    Science.gov (United States)

    Ungwitayatorn, Jiraporn; Samee, Weerasak; Pimthon, Jutarat

    2004-02-01

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

  5. QSAR for Predicting Biodegradation Rates of Polycyclic Aromatic Hydrocarbons in Aqueous Systems

    Institute of Scientific and Technical Information of China (English)

    XU Xiang; LI Xian-Guo

    2012-01-01

    The relationship between chemical structures and biodegradation rates (k b) of 22 polycyclic aromatic hydrocarbons (PAHs) was studied using density functional theory (DFT) and stepwise multiple linear regression analysis (SMLR) method.The equilibrium geometries and vibration frequency have been investigated at the B3LYP/6-31+G(d,p) level by thinking Solvent effects using a selfconsistent reaction field (SCRF) based on the polarizable continuum model (PCM).It was concluded that the biodegradation rate was closely related to its molecular structure,and there is one high correlation coefficient between the in-plane bending vibration frequency of the conjugated ring of PAHs (Freq) and k b.By means of regression analysis,the main factors affecting the biodegradation rate were obtained and the equation of quantitative structure-activity relationship (QSAR) was successfully established kb =-0.653+0.001Freq+0.068CQ+0.049N1.Statistical evaluation of the developed QSAR showed that the relationships were statistically significant and the model had good predictive ability.The fact that a bending frequency is more important than the HOMO or LUMO energies in predicting k b suggests that the bending of benzene ring might play an important role in the enzymatic catalysis of the initial oxidation step.

  6. Combined Pharmacophore Modeling, 3D-QSAR, Homology Modeling and Docking Studies on CYP11B1 Inhibitors

    Directory of Open Access Journals (Sweden)

    Rui Yu

    2015-01-01

    Full Text Available The mitochondrial cytochrome P450 enzymes inhibitor steroid 11β-hydroxylase (CYP11B1 can decrease the production of cortisol. Therefore, these inhibitors have an effect in the treatment of Cushing’s syndrome. A pharmacophore model generated by Genetic Algorithm with Linear Assignment for Hypermolecular Alignment of Datasets (GALAHAD was used to align the compounds and perform comparative molecular field analysis (CoMFA with Q2 = 0.658, R2 = 0.959. The pharmacophore model contained six hydrophobic regions and one acceptor atom, and electropositive and bulky substituents would be tolerated at the A and B sites, respectively. A three-dimensional quantitative structure-activity relationship (3D-QSAR study based on the alignment with the atom root mean square (RMS was applied using comparative molecular field analysis (CoMFA with Q2 = 0.666, R2 = 0.978, and comparative molecular similarity indices analysis (CoMSIA with Q2 = 0.721, R2 = 0.972. These results proved that all the models have good predictability of the bioactivities of inhibitors. Furthermore, the QSAR models indicated that a hydrogen bond acceptor substituent would be disfavored at the A and B groups, while hydrophobic groups would be favored at the B site. The three-dimensional (3D model of the CYP11B1 was generated based on the crystal structure of the CYP11B2 (PDB code 4DVQ. In order to probe the ligand-binding modes, Surflex-dock was employed to dock CYP11B1 inhibitory compounds into the active site of the receptor. The docking result showed that the imidazolidine ring of CYP11B1 inhibitors form H bonds with the amino group of residue Arg155 and Arg519, which suggested that an electronegative substituent at these positions could enhance the activities of compounds. All the models generated by GALAHAD QSAR and Docking methods provide guidance about how to design novel and potential drugs for Cushing’s syndrome treatment.

  7. Investigations and design of pyridine-2-carboxylic acid thiazol-2-ylamide analogs as methionine aminopeptidase inhibitors using 3D-QSAR and molecular docking

    DEFF Research Database (Denmark)

    Hauser, Alexander Sebastian

    2014-01-01

    -dimensional quantitative structure–activity relationship (3D-QSAR) studies were carried out on a series of pyridine-2-carboxylic acid thiazol-2-ylamide-based MetAP inhibitors using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. The models were...... complexes, four new pyridine-2-carboxylic acid thiazol-2-ylamide analogs were designed. These analogs exhibit significantly better predicted activity than the reported molecules. The present work has implications for the development of novel antibiotics as potent MetAP inhibitors....

  8. Cytological and Pathological Correlation of FNAC in Assessing Breast Lumps and Axillary Lymph Node Swellings in a Public Sector Hospital in India

    Directory of Open Access Journals (Sweden)

    Vasu Reddy Challa

    2013-01-01

    Full Text Available Background. Breast lumps have varied pathology, and there are different techniques to prove the diagnosis. The aim of the present study is to analyze the role of fine needle aspiration cytology (FNAC of the breast lesions at our center. Methods. We had retrospectively analysed 854 patients who underwent FNAC for primary breast lumps and 190 patients who underwent FNAC for an axillary lymph node in the year 2010. Results. Of 854 patients, histological correlation was available in 723 patients. The analysis was done for 812 patients as medical records were not available for 42 patients. FNAC was false negative in seven cases; 2 cases of phyllodes were reported as fibroadenoma, and 5 cases of carcinoma were diagnosed as atypical hyperplasia. The sensitivity, specificity, and false negative value of FNAC in diagnosing breast lumps were 99% (715/723, 100%, and 1%, respectively. Of 190 patients for whom FNAC was performed for axilla, 170 had proven to have axillary lymph node metastases, and the rest had reactive hyperplasia or inflammatory cells. Conclusions. FNAC is rapid, accurate, outpatient based, and less complicated procedure and helps in diagnosis of breast cancer, benign diseases, and axillary involvement in experienced hands with less chance of false results.

  9. Profile-QSAR: a novel meta-QSAR method that combines activities across the kinase family to accurately predict affinity, selectivity, and cellular activity.

    Science.gov (United States)

    Martin, Eric; Mukherjee, Prasenjit; Sullivan, David; Jansen, Johanna

    2011-08-22

    Profile-QSAR is a novel 2D predictive model building method for kinases. This "meta-QSAR" method models the activity of each compound against a new kinase target as a linear combination of its predicted activities against a large panel of 92 previously studied kinases comprised from 115 assays. Profile-QSAR starts with a sparse incomplete kinase by compound (KxC) activity matrix, used to generate Bayesian QSAR models for the 92 "basis-set" kinases. These Bayesian QSARs generate a complete "synthetic" KxC activity matrix of predictions. These synthetic activities are used as "chemical descriptors" to train partial-least squares (PLS) models, from modest amounts of medium-throughput screening data, for predicting activity against new kinases. The Profile-QSAR predictions for the 92 kinases (115 assays) gave a median external R²(ext) = 0.59 on 25% held-out test sets. The method has proven accurate enough to predict pairwise kinase selectivities with a median correlation of R²(ext) = 0.61 for 958 kinase pairs with at least 600 common compounds. It has been further expanded by adding a "C(k)XC" cellular activity matrix to the KxC matrix to predict cellular activity for 42 kinase driven cellular assays with median R²(ext) = 0.58 for 24 target modulation assays and R²(ext) = 0.41 for 18 cell proliferation assays. The 2D Profile-QSAR, along with the 3D Surrogate AutoShim, are the foundations of an internally developed iterative medium-throughput screening (IMTS) methodology for virtual screening (VS) of compound archives as an alternative to experimental high-throughput screening (HTS). The method has been applied to 20 actual prospective kinase projects. Biological results have so far been obtained in eight of them. Q² values ranged from 0.3 to 0.7. Hit-rates at 10 uM for experimentally tested compounds varied from 25% to 80%, except in K5, which was a special case aimed specifically at finding "type II" binders, where none of the compounds were predicted to be

  10. Pharmacophore Identification and QSAR Studies on Substituted Benzoxazinone as Antiplatelet Agents: kNN-MFA Approach.

    Science.gov (United States)

    Choudhari, Prafulla B; Bhatia, Manish S; Jadhav, Swapnil D

    2012-01-01

    The three-dimensional quantitative structure-activity relationship (3D-QSAR) and pharmacophore identification studies on 28 substituted benzoxazinone derivatives as antiplatelet agents have been carried out. Multiple linear regression (MLR) method was applied for QSAR model development considering training and test set approaches with various feature selection methods. Stepwise (SW), simulated annealing (SA) and genetic algorithm (GA) were applied to derive QSAR models which were further validated for statistical significance and predictive ability by internal and external validation. The results of pharmacophore identification studies showed that hydrogen bond accepters, aromatic and hydrophobic, are the important features for antiplatelet activity. The selected best 3D kNN-MFA model A has a training set of 23 molecules and test set of 5 molecules with validation (q(2)) and cross validation (pred_r(2)) values 0.9739 and 0.8217, respectively. Additionally, the selected best 3D QSAR (MLR) model B has a training set of 23 molecules and test set of 5 molecules with validation (r(2)) and cross validation (pred_r(2)) values of 0.9435 and 0.7663, respectively, and four descriptors at the grid points S_123, E_407, E_311 and H_605. The information rendered by 3D-QSAR models may lead to a better understanding and designing of novel potent antiplatelet molecules.

  11. Performance of Deep and Shallow Neural Networks, the Universal Approximation Theorem, Activity Cliffs, and QSAR.

    Science.gov (United States)

    Winkler, David A; Le, Tu C

    2017-01-01

    Neural networks have generated valuable Quantitative Structure-Activity/Property Relationships (QSAR/QSPR) models for a wide variety of small molecules and materials properties. They have grown in sophistication and many of their initial problems have been overcome by modern mathematical techniques. QSAR studies have almost always used so-called "shallow" neural networks in which there is a single hidden layer between the input and output layers. Recently, a new and potentially paradigm-shifting type of neural network based on Deep Learning has appeared. Deep learning methods have generated impressive improvements in image and voice recognition, and are now being applied to QSAR and QSAR modelling. This paper describes the differences in approach between deep and shallow neural networks, compares their abilities to predict the properties of test sets for 15 large drug data sets (the kaggle set), discusses the results in terms of the Universal Approximation theorem for neural networks, and describes how DNN may ameliorate or remove troublesome "activity cliffs" in QSAR data sets. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Monte Carlo method based QSAR modeling of maleimide derivatives as glycogen synthase kinase-3β inhibitors.

    Science.gov (United States)

    Živković, Jelena V; Trutić, Nataša V; Veselinović, Jovana B; Nikolić, Goran M; Veselinović, Aleksandar M

    2015-09-01

    The Monte Carlo method was used for QSAR modeling of maleimide derivatives as glycogen synthase kinase-3β inhibitors. The first QSAR model was developed for a series of 74 3-anilino-4-arylmaleimide derivatives. The second QSAR model was developed for a series of 177 maleimide derivatives. QSAR models were calculated with the representation of the molecular structure by the simplified molecular input-line entry system. Two splits have been examined: one split into the training and test set for the first QSAR model, and one split into the training, test and validation set for the second. The statistical quality of the developed model is very good. The calculated model for 3-anilino-4-arylmaleimide derivatives had following statistical parameters: r(2)=0.8617 for the training set; r(2)=0.8659, and r(m)(2)=0.7361 for the test set. The calculated model for maleimide derivatives had following statistical parameters: r(2)=0.9435, for the training, r(2)=0.9262 and r(m)(2)=0.8199 for the test and r(2)=0.8418, r(av)(m)(2)=0.7469 and ∆r(m)(2)=0.1476 for the validation set. Structural indicators considered as molecular fragments responsible for the increase and decrease in the inhibition activity have been defined. The computer-aided design of new potential glycogen synthase kinase-3β inhibitors has been presented by using defined structural alerts.

  13. Molecular modeling-driven approach for identification of Janus kinase 1 inhibitors through 3D-QSAR, docking and molecular dynamics simulations.

    Science.gov (United States)

    Itteboina, Ramesh; Ballu, Srilata; Sivan, Sree Kanth; Manga, Vijjulatha

    2017-10-01

    Janus kinase 1 (JAK 1) belongs to the JAK family of intracellular nonreceptor tyrosine kinase. JAK-signal transducer and activator of transcription (JAK-STAT) pathway mediate signaling by cytokines, which control survival, proliferation and differentiation of a variety of cells. Three-dimensional quantitative structure activity relationship (3 D-QSAR), molecular docking and molecular dynamics (MD) methods was carried out on a dataset of Janus kinase 1(JAK 1) inhibitors. Ligands were constructed and docked into the active site of protein using GLIDE 5.6. Best docked poses were selected after analysis for further 3 D-QSAR analysis using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methodology. Employing 60 molecules in the training set, 3 D-QSAR models were generate that showed good statistical reliability, which is clearly observed in terms of r(2)ncv and q(2)loo values. The predictive ability of these models was determined using a test set of 25 molecules that gave acceptable predictive correlation (r(2)Pred) values. The key amino acid residues were identified by means of molecular docking, and the stability and rationality of the derived molecular conformations were also validated by MD simulation. The good consonance between the docking results and CoMFA/CoMSIA contour maps provides helpful clues about the reasonable modification of molecules in order to design more efficient JAK 1 inhibitors. The developed models are expected to provide some directives for further synthesis of highly effective JAK 1 inhibitors.

  14. Integration of QSAR models for bioconcentration suitable for REACH

    Energy Technology Data Exchange (ETDEWEB)

    Gissi, Andrea [Laboratory of Chemistry and Environmental Toxicology, IRCCS - Istituto di Ricerche Farmacologiche “Mario Negri”, via Giuseppe La Masa 19, 20156 Milan (Italy); Dipartimento di Farmacia — Scienze del Farmaco, Università degli Studi di Bari “Aldo Moro”, via Orabona 4, I-70125 Bari (Italy); Nicolotti, Orazio; Carotti, Angelo; Gadaleta, Domenico [Dipartimento di Farmacia — Scienze del Farmaco, Università degli Studi di Bari “Aldo Moro”, via Orabona 4, I-70125 Bari (Italy); Lombardo, Anna [Laboratory of Chemistry and Environmental Toxicology, IRCCS - Istituto di Ricerche Farmacologiche “Mario Negri”, via Giuseppe La Masa 19, 20156 Milan (Italy); Benfenati, Emilio, E-mail: benfenati@marionegri.it [Laboratory of Chemistry and Environmental Toxicology, IRCCS - Istituto di Ricerche Farmacologiche “Mario Negri”, via Giuseppe La Masa 19, 20156 Milan (Italy)

    2013-07-01

    QSAR (Quantitative Structure Activity Relationship) models can be a valuable alternative method to replace or reduce animal test required by REACH. In particular, some endpoints such as bioconcentration factor (BCF) are easier to predict and many useful models have been already developed. In this paper we describe how to integrate two popular BCF models to obtain more reliable predictions. In particular, the herein presented integrated model relies on the predictions of two among the most used BCF models (CAESAR and Meylan), together with the Applicability Domain Index (ADI) provided by the software VEGA. Using a set of simple rules, the integrated model selects the most reliable and conservative predictions and discards possible outliers. In this way, for the prediction of the 851 compounds included in the ANTARES BCF dataset, the integrated model discloses a R{sup 2} (coefficient of determination) of 0.80, a RMSE (Root Mean Square Error) of 0.61 log units and a sensitivity of 76%, with a considerable improvement in respect to the CAESAR (R{sup 2} = 0.63; RMSE = 0.84 log units; sensitivity 55%) and Meylan (R{sup 2} = 0.66; RMSE = 0.77 log units; sensitivity 65%) without discarding too many predictions (118 out of 851). Importantly, considering solely the compounds within the new integrated ADI, the R{sup 2} increased to 0.92, and the sensitivity to 85%, with a RMSE of 0.44 log units. Finally, the use of properly set safety thresholds applied for monitoring the so called “suspicious” compounds, which are those chemicals predicted in proximity of the border normally accepted to discern non-bioaccumulative from bioaccumulative substances, permitted to obtain an integrated model with sensitivity equal to 100%. - Highlights: • Applying two independent QSAR models for bioconcentration factor increases the prediction. • The concordance of the models is an important component of the integration. • The measurement of the applicability domain improves the

  15. A numerical study on a lumped-parameter model and a CFD code coupling for the analysis of the loss of coolant accident in a reactor containment; Etude numerique 0D-multiD pour l'analyse de perte de refrigerant dans une enceinte de confinement d'un reacteur nucleaire

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Y.J.

    2005-12-15

    In the case of PWR severe accident (Loss of Coolant Accident, LOCA), the inner containment ambient properties such as temperature, pressure and gas species concentrations due to the released steam condensation are the main factors that determine the risk. For this reason, their distributions should be known accurately, but the complexity of the geometry and the computational costs are strong limitations to conduct full three-dimensional numerical simulations. An alternative approach is presented in this thesis, namely, the coupling between a lumped-parameter model and a CFD. The coupling is based on the introduction of a 'heat transfer function' between both models and it is expected that large decreases in the CPU-costs may be achieved. First of all, wall condensation models, such as the Uchida or the Chilton-Colburn models which are implemented in the code CAST3M/TONUS, are investigated. They are examined through steady-state calculations by using the code TONUS-0D, based on lumped parameter models. The temperature and the pressure within the inner containment are compared with those reported in the archival literature. In order to build the 'heat transfer function', natural convection heat transfer is then studied by using the code CAST3M for a partitioned cavity which represents a simplified geometry of the reactor containment. At a first step, two-dimensional natural convection heat transfer without condensation is investigated only. Either the incompressible-Boussinesq fluid flow model or the asymptotic low Mach model are considered for solving the time dependent conservation equations. The SUPG finite element method and the implicit scheme are applied for the numerical discretization. The computed results are qualified by the second-order Richardson extrapolation method which allows obtaining the so-called 'Exact values', i.e. grid size independent values. The computations are also validated through non-partitioned cavity case

  16. QSAR study of heparanase inhibitors activity using artificial neural networks and Levenberg-Marquardt algorithm.

    Science.gov (United States)

    Jalali-Heravi, M; Asadollahi-Baboli, M; Shahbazikhah, P

    2008-03-01

    A linear and non-linear quantitative structure-activity relationship (QSAR) study is presented for modeling and predicting heparanase inhibitors' activity. A data set that consisted of 92 derivatives of 2,3-dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid, furanyl-1,3-thiazol-2-yl and benzoxazol-5-yl acetic acids is used in this study. Among a large number of descriptors, four parameters classified as physico-chemical, topological and electronic indices are chosen using stepwise multiple regression technique. The artificial neural networks (ANNs) model shows superiority over the multiple linear regressions (MLR) by accounting 87.9% of the variances of antiviral potency of the heparanase inhibitors. This paper focuses on investigating the role of weight update functions in developing ANNs. Levenberg-Marquardt (L-M) algorithm shows a better performance compared with basic back propagation (BBP) and conjugate gradient (CG) algorithms. The accuracy of 4-3-1 L-M ANN model was illustrated using leave-one-out (LOO), leave-multiple-out (LMO) cross-validations and Y-randomization. The mean effect of descriptors and sensitivity analysis show that log P is the most important parameter affecting the inhibitory behavior of the molecules.

  17. Cytotoxic activity evaluation and QSAR study of chromene-based chalcones.

    Science.gov (United States)

    Firoozpour, Loghman; Edraki, Najmeh; Nakhjiri, Maryam; Emami, Saeed; Safavi, Maliheh; Ardestani, Sussan Kabudanian; Khoshneviszadeh, Mehdi; Shafiee, Abbas; Foroumadi, Alireza

    2012-12-01

    Chalcone and chromene motifs are synthetic or naturally occurring scaffolds with significant cytotoxic profile. Two types of novel regioisomeric chromene-chalcone hybrids, namely 1-(6-chloro or 6-methoxy-2H-chromen-3-yl)-3-phenylprop-2-en-1-one (Type A) and 3-(6-chloro or 6-methoxy-2H-chromen-3-yl)-1-phenylprop-2-en-1-one (Type B), both with different substituents on the phenyl ring attached to propenone linkage, have been evaluated for their cytotoxic activity against breast cancer cell lines (MCF-7 and MDA-MB-231). The results indicate that type A of chromene-chalcones demonstrated better cytotoxic profile than type B especially in MDA-MB-231 cell line. In addition, the growth inhibitory activity of most of the target compounds is higher than Etoposide as a reference drug. QSAR analysis of these novel compounds demonstrated that topological and geometrical parameters are among the important descriptors that influence the cytotoxic activity profile of compounds.

  18. Synthesis, algal inhibition activities and QSAR studies of novel gramine compounds containing ester functional groups

    Institute of Scientific and Technical Information of China (English)

    LI Xia; YU Liangmin; JIANG Xiaohui; XIA Shuwei; ZHAO Haizhou

    2009-01-01

    2,5,6-Tribromo-l-methylgramine (TBG), isolated from bryozoan Zoobotryon pellucidum was shown to be very efficient in preventing recruitment of larval settlement. In order to improve the compatibility of TBG and its analogues with other ingredients in antifouling paints, structural modification of TBG was focused mainly on halogen substitution and N-substitution. Two halogen-substitute gramines and their derivatives which contain ester functional groups at N-position of gramines were synthesized. Algal inhibition activities of the synthesized compounds against algae Nitzschia closterium were evaluated and the Median Effective Concentration (EC50) range was 1.06-6.74 μg ml-1. Compounds that had a long chain ester group exhibited extremely high antifouling activity. Quantitive Structure Activity Relationship (QSAR) studies with multiple linear regression analysis were applied to find correlation between different calculated molecular descriptors and biological activity of the synthesized compounds. The results show that the toxicity (log (1/EC50)) is correlated well with the partition coefficient log P. Thus, these products have potential function as antifouling agents.

  19. Evaluation and QSAR modeling on multiple endpoints of estrogen activity based on different bioassays.

    Science.gov (United States)

    Liu, Huanxiang; Papa, Ester; Gramatica, Paola

    2008-02-01

    There is a great need for an effective means of rapidly assessing endocrine-disrupting activity, especially estrogen-simulating activity, due to the large number of chemicals that have serious adverse effects on the environment. Many approaches using a variety of biological screening assays are used to identify endocrine disrupting chemicals. The present investigation analyzes the consistency and peculiarity of information from different experimental assays collected from a literature survey, by studying the correlation of the different endpoints. In addition, the activity values of more widely used selected bioassays have been combined by principle components analysis (PCA) to build one cumulative endpoint, the estrogen activity index (EAI), for priority setting to identify chemicals most likely possessing estrogen activity for early entry into screening. This index was then modeled using only a few theoretical molecular descriptors. The constructed MLR-QSAR model has been statistically validated for its predictive power, and can be proposed as a preliminary evaluative method to screen/prioritize estrogens according to their integrated estrogen activity, just starting from molecular structure.

  20. Sensitivity Analysis of QSAR Models for Assessing Novel Military Compounds

    Science.gov (United States)

    2009-01-01

    isopropylamino-2,4,6-triazine BP boiling point BTTN butanetriol trinitrate CAS Chemical Abstract Service DDE dichlorodiphenyldichloroethylene DNNC...pasted into the input screen, or obtained from a linked file of CAS ( Chemical Abstract System) numbers. The EPI Suite interface screen also permits...environment. A similarity search based on molecular formula was performed using SciFinder of Chemical Abstract Service in Columbus, OH (SciFinder 2007

  1. Clinical subtypes and genetic heterogeneity: of lumping and splitting in Parkinson disease.

    Science.gov (United States)

    von Coelln, Rainer; Shulman, Lisa M

    2016-12-01

    Recent studies on clinical, genetic and pathological heterogeneity of Parkinson disease have renewed the old debate whether we should think of Parkinson disease as one disease with variations, or as a group of independent diseases that happen to present with similar phenotypes. Here, we provide an overview of where the debate is coming from, and how recent findings in clinical subtyping, genetics and clinico-pathological correlation have shaped this controversy over the last few years. New and innovative clinical diagnostic criteria for Parkinson disease have been proposed and await validation. Studies using functional imaging or wearable biosensors, as well as biomarker studies, provide new support for the validity of the traditional clinical subtypes of Parkinson disease (tremor-dominant versus akinetic-rigid or postural instability/gait difficulty). A recent cluster analysis (as unbiased data-driven approach to subtyping) included a wide spectrum of nonmotor variables, and showed correlation of the proposed subtypes with disease progression in a longitudinal analysis. New genetic factors contributing to Parkinson disease susceptibility continue to be identified, including rare mutations causing monogenetic disease, common variants with small effect size and risk factors (like mutations in the gene for glucocerebrosidase) that fall in between the two other categories. Recent studies show some limited correlation between genetic factors and clinical heterogeneity. Despite some variations in patterns of pathology, Lewy bodies are still the hallmark of Parkinson disease, including the vast majority of genetic subgroups. Evidence of clinical, genetic and pathological heterogeneity of Parkinson disease continues to emerge, but clearly defined subtypes that hold up in more than one of these domains remain elusive. For research to identify such subtypes, splitting is likely the way forward; until then, for clinical practice, lumping remains the more pragmatic approach.

  2. 3D-QSAR Studies on a Series of Dihydroorotate Dehydrogenase Inhibitors: Analogues of the Active Metabolite of Leflunomide

    Directory of Open Access Journals (Sweden)

    Hong-Guang Du

    2011-05-01

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

  3. Exploring QSARs of the interaction of flavonoids with GABA (A) receptor using MLR, ANN and SVM techniques.

    Science.gov (United States)

    Deeb, Omar; Shaik, Basheerulla; Agrawal, Vijay K

    2014-10-01

    Quantitative Structure-Activity Relationship (QSAR) models for binding affinity constants (log Ki) of 78 flavonoid ligands towards the benzodiazepine site of GABA (A) receptor complex were calculated using the machine learning methods: artificial neural network (ANN) and support vector machine (SVM) techniques. The models obtained were compared with those obtained using multiple linear regression (MLR) analysis. The descriptor selection and model building were performed with 10-fold cross-validation using the training data set. The SVM and MLR coefficient of determination values are 0.944 and 0.879, respectively, for the training set and are higher than those of ANN models. Though the SVM model shows improvement of training set fitting, the ANN model was superior to SVM and MLR in predicting the test set. Randomization test is employed to check the suitability of the models.

  4. Chemosensitizing acridones: in vitro calmodulin dependent cAMP phosphodiesterase inhibition, docking, pharmacophore modeling and 3D QSAR studies.

    Science.gov (United States)

    Rajendra Prasad, V V S; Deepak Reddy, G; Appaji, D; Peters, G J; Mayur, Y C

    2013-03-01

    Calmodulin inhibitors have proved to play a significant role in sensitizing MDR cancer cells by interfering with cellular drug accumulation. The present investigation focuses on the evaluation of in vitro inhibitory efficacy of chloro acridones against calmodulin dependent cAMP phosphodiesterase (PDE1c). Moreover, molecular docking of acridones was performed with PDE1c in order to identify the possible protein ligand interactions and results thus obtained were compared with in vitro data. In addition an efficient pharmacophore model was developed from a set of 38 chemosensitizing acridones effective against doxorubicin resistant (HL-60/DX) cancer cell lines. Pharmacophoric features such as one hydrogen bond acceptor, one hydrophobic region, a positive ion group and three aromatic rings i.e., AHPRRR have been identified. Ligand based 3D-QSAR was also performed by employing partial least square regression analysis.

  5. A novel vector of topological and structural information for amino acids and its QSAR applications for peptides and analogues

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A new descriptor, called vector of topological and structural information for coded and noncoded amino acids (VTSA), was derived by principal component analysis (PCA) from a matrix of 66 topological and structural variables of 134 amino acids. The VTSA vector was then applied into two sets of peptide quantitative structure-activity relationships or quantitative sequence-activity modelings (QSARs/ QSAMs). Molded by genetic partial least squares (GPLS), support vector machine (SVM), and immune neural network (INN), good results were obtained. For the datasets of 58 angiotensin converting en-zyme inhibitors (ACEI) and 89 elastase substrate catalyzed kinetics (ESCK) , the R2, cross-validation R2, and root mean square error of estimation (RMSEE) were as follows: ACEI, R2cu≥0.82, Q2cu≥0.77, Ermse≤0.44 (GPLS+SVM); ESCK, R2cu≥0.84, Q2cu≥0.82, Ermse≤0.20 (GPLS+INN), respectively.

  6. 3D QSAR modeling of 4-nerolidylcatechol derivatives and virtual screening for identification of potent plasmodium inhibitor

    Directory of Open Access Journals (Sweden)

    Dhrubajyoti Gogoi

    2014-08-01

    Full Text Available The present study was aim to develop a three dimensional quantitative structure–activity relationships (3D QSAR model based on the structure of 4-nerolidylcatechol (IC50=0.67 µM, a novel plant derived Plasmodium inhibitor and its derivatives for identification of efficient antimalarial lead. A statisti-cally validated Partial Least-Squares (PLS based Molecular Field Analysis (MFA model was built up using the training set of eight 4-nerolidylcatechol derivatives and their diverse conformers. A statistically reliable model with good predictive power (cross-validated correlation coefficient q2=0.769 was obtained. Hence, the generated model was used to screen a library of 30,000 compounds of chembridge database (http://www.chembridge.com. Results of drug likeness prediction and ADMET study has suggested six compounds as potential antimalarial/plasmodial lead.

  7. A novel QSAR model of Salmonella mutagenicity and its application in the safety assessment of drug impurities

    Energy Technology Data Exchange (ETDEWEB)

    Valencia, Antoni; Prous, Josep; Mora, Oscar [Prous Institute for Biomedical Research, Rambla de Catalunya, 135, 3-2, Barcelona 08008 (Spain); Sadrieh, Nakissa [Office of Pharmaceutical Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993-0002 (United States); Valerio, Luis G., E-mail: luis.valerio@fda.hhs.gov [Office of Pharmaceutical Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993-0002 (United States)

    2013-12-15

    As indicated in ICH M7 draft guidance, in silico predictive tools including statistically-based QSARs and expert analysis may be used as a computational assessment for bacterial mutagenicity for the qualification of impurities in pharmaceuticals. To address this need, we developed and validated a QSAR model to predict Salmonella t. mutagenicity (Ames assay outcome) of pharmaceutical impurities using Prous Institute's Symmetry℠, a new in silico solution for drug discovery and toxicity screening, and the Mold2 molecular descriptor package (FDA/NCTR). Data was sourced from public benchmark databases with known Ames assay mutagenicity outcomes for 7300 chemicals (57% mutagens). Of these data, 90% was used to train the model and the remaining 10% was set aside as a holdout set for validation. The model's applicability to drug impurities was tested using a FDA/CDER database of 951 structures, of which 94% were found within the model's applicability domain. The predictive performance of the model is acceptable for supporting regulatory decision-making with 84 ± 1% sensitivity, 81 ± 1% specificity, 83 ± 1% concordance and 79 ± 1% negative predictivity based on internal cross-validation, while the holdout dataset yielded 83% sensitivity, 77% specificity, 80% concordance and 78% negative predictivity. Given the importance of having confidence in negative predictions, an additional external validation of the model was also carried out, using marketed drugs known to be Ames-negative, and obtained 98% coverage and 81% specificity. Additionally, Ames mutagenicity data from FDA/CFSAN was used to create another data set of 1535 chemicals for external validation of the model, yielding 98% coverage, 73% sensitivity, 86% specificity, 81% concordance and 84% negative predictivity. - Highlights: • A new in silico QSAR model to predict Ames mutagenicity is described. • The model is extensively validated with chemicals from the FDA and the public domain.

  8. Inductive QSAR Descriptors. Distinguishing Compounds with Antibacterial Activity by Artificial Neural Networks

    Directory of Open Access Journals (Sweden)

    Artem Cherkasov

    2005-01-01

    Full Text Available Abstract: On the basis of the previous models of inductive and steric effects, ‘inductive’ electronegativity and molecular capacitance, a range of new ‘inductive’ QSAR descriptors has been derived. These molecular parameters are easily accessible from electronegativities and covalent radii of the constituent atoms and interatomic distances and can reflect a variety of aspects of intra- and intermolecular interactions. Using 34 ‘inductive’ QSAR descriptors alone we have been able to achieve 93% correct separation of compounds with- and without antibacterial activity (in the set of 657. The elaborated QSAR model based on the Artificial Neural Networks approach has been extensively validated and has confidently assigned antibacterial character to a number of trial antibiotics from the literature.

  9. Recent advances in QSAR-based identification and design of anti-tubercular agents.

    Science.gov (United States)

    Nidhi; Siddiqi, Mohammad Imran

    2014-01-01

    Increasing worldwide incidence and the advent of multi drug resistant and extensively drug resistant tuberculosis raise the need of new drugs for the treatment of tuberculosis soon. To meet the required pace QSAR-based rational approaches may prove fruitful as they render rapid and cost-efficient design and optimization of new drug candidates. This review presents a comprehensive overview of QSAR studies reported for newer anti-tubercular agents including nitroimidazoles, fluoroquinolones, quinoxalines, carboxamides and other classes of molecules. The article includes review of 2D and 3D-QSAR approaches and the recent trend of integration of these methods with virtual screening using 3D pharmacophore and molecular docking approaches for the identification and design of novel anti-tubercular agents.

  10. 3D-QSAR Study on Apicidin Inhibit Histone Deacetylase

    Institute of Scientific and Technical Information of China (English)

    陈海峰; 康九红; 李强; 曾宝珊; 姚小军; 范波涛; 袁身刚; Panay,A.; Doucet,J.P.

    2003-01-01

    For Histone Deacetylase (HDAC) Inhibitor, four 3D-QSAR models for four types of different activities, were constructed.The cross-valldated q2 value of CoMFA Model 1 is 0.624 and the noncross-validated r2 value is 0.939. The cross-validated q2 value of Model 2 for training set is 0.652 and the noncross-validated r2 value is 0.963. The cross-validated q2 value for Model 3 is 0.713, with noncross-validated r2 value 0.947. The crossvalidated q2 value for Model 4 is 0.566 with noncross-validated r2 value 0.959. Their predicted abilities were validated by different test sets which did not include in training set. Then the relationship between substituents and activities was analyzed by using these models and the main influence elements in different positions (positions 8 and 14) were found. The polar donor electron group of position 8 could increase the activity of inhibition of HDAC, because it could form chelation with the catalytic Zn. Suitable bulk and positive groups at position 14 are favorable to anti-HDAC activity. These models could web interpret the relationship between inhibition activity and apicidin structure affording us important information for structurebased drug design.

  11. Antibacterial activities, DFT and QSAR studies of quinazolinone compounds

    Directory of Open Access Journals (Sweden)

    A. G. Al-Sehemi

    2016-08-01

    Full Text Available The quinazolinone compounds (1 and 2 in this work were examined for their in vitro antibacterial activities against gram-positive (Staphylococcus aureus and gram-negative bacteria (Klebsiella pneumonia, Proteus bacilli and Shigella flexneri. Compared to the reference antibiotic chloramphenicol, these compounds showed high antibacterial activities against studied strains with inhibition zones observation. The ground state geometries have been optimized by using density functional theory (DFT at B3LYP/6-31G* level of theory. The absorption spectra have been calculated by using time dependent density functional theory (TDDFT with and without solvent. The effect of different functionals (B3LYP, MPW1PW91, and PBE1PBE on the absorption wavelengths has been studied. The ionization potential (IP, electron affinity (EA, energy gap (Egap, electronegativity (χ, hardness (η, electrophilicity (ω, softness (S and electrophilicity index (ωi were computed and discussed. The nonlinear optical (NLO properties vary by changing the theory (DFT to HF or functional (B3LYP to CAM-B3LYP. The physicochemical parameters have been studied by quantitative structure–activity relationship (QSAR. The computed properties of investigated compounds have been compared with the Chloramphenicol as well as available experimental data.

  12. QSAR Accelerated Discovery of Potent Ice Recrystallization Inhibitors.

    Science.gov (United States)

    Briard, Jennie G; Fernandez, Michael; De Luna, Phil; Woo, Tom K; Ben, Robert N

    2016-05-24

    Ice recrystallization is the main contributor to cell damage and death during the cryopreservation of cells and tissues. Over the past five years, many small carbohydrate-based molecules were identified as ice recrystallization inhibitors and several were shown to reduce cryoinjury during the cryopreservation of red blood cells (RBCs) and hematopoietic stems cells (HSCs). Unfortunately, clear structure-activity relationships have not been identified impeding the rational design of future compounds possessing ice recrystallization inhibition (IRI) activity. A set of 124 previously synthesized compounds with known IRI activities were used to calibrate 3D-QSAR classification models using GRid INdependent Descriptors (GRIND) derived from DFT level quantum mechanical calculations. Partial least squares (PLS) model was calibrated with 70% of the data set which successfully identified 80% of the IRI active compounds with a precision of 0.8. This model exhibited good performance in screening the remaining 30% of the data set with 70% of active additives successfully recovered with a precision of ~0.7 and specificity of 0.8. The model was further applied to screen a new library of aryl-alditol molecules which were then experimentally synthesized and tested with a success rate of 82%. Presented is the first computer-aided high-throughput experimental screening for novel IRI active compounds.

  13. Literature Review of (Q)SAR Modelling of Nanomaterial Toxicity.

    Science.gov (United States)

    Oksel, Ceyda; Ma, Cai Y; Liu, Jing J; Wilkins, Terry; Wang, Xue Z

    2017-01-01

    Despite the clear benefits that nanotechnology can bring to various sectors of industry, there are serious concerns about the potential health risks associated with engineered nanomaterials (ENMs), intensified by the limited understanding of what makes ENMs toxic and how to make them safe. As the use of ENMs for commercial purposes and the number of workers/end-users being exposed to these materials on a daily basis increases, the need for assessing the potential adverse effects of multifarious ENMs in a time- and cost-effective manner becomes more apparent. One strategy to alleviate the problem of testing a large number and variety of ENMs in terms of their toxicological properties is through the development of computational models that decode the relationships between the physicochemical features of ENMs and their toxicity. Such data-driven models can be used for hazard screening, early identification of potentially harmful ENMs and the toxicity-governing physicochemical properties, and accelerating the decision-making process by maximising the use of existing data. Moreover, these models can also support industrial, regulatory and public needs for designing inherently safer ENMs. This chapter is mainly concerned with the investigation of the applicability of (quantitative) structure-activity relationship ((Q)SAR) methods to modelling of ENMs' toxicity. It summarizes the key components required for successful application of data-driven toxicity prediction techniques to ENMs, the published studies in this field and the current limitations of this approach.

  14. Prediction of PAH mutagenicity in human cells by QSAR classification.

    Science.gov (United States)

    Papa, E; Pilutti, P; Gramatica, P

    2008-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants of high environmental concern. The experimental data of a mutagenicity test on human B-lymphoblastoid cells (alternative to the Ames bacterial test) for a set of 70 oxo-, nitro- and unsubstituted PAHs, detected in particulate matter (PM), were modelled by Quantitative Structure-Activity Relationships (QSAR) classification methods (k-NN, k-Nearest Neighbour, and CART, Classification and Regression Tree) based on different theoretical molecular descriptors selected by Genetic Algorithms. The best models were validated for predictivity both externally and internally. For external validation, Self Organizing Maps (SOM) were applied to split the original data set. The best models, developed on the training set alone, show good predictive performance also on the prediction set chemicals (sensitivity 69.2-87.1%, specificity 62.5-87.5%). The classification of PAHs according to their mutagenicity, based only on a few theoretical molecular descriptors, allows a preliminary assessment of the human health risk, and the prioritisation of these compounds.

  15. Understanding human rhinovirus infections in terms of QSAR.

    Science.gov (United States)

    Verma, Rajeshwar P; Hansch, Corwin

    2007-03-01

    The human rhinoviruses (HRVs) are the single most important cause of common colds. The widespread nature of this affliction, the economic consequences, and the well-known impracticality of vaccine development due to the large number of HRV serotypes (>100) have justified the search for chemotherapeutic agents. The interest in the application of quantitative structure-activity relationships has steadily increased in recent decades and we hope it may be useful in the search for anti-HRV agents. In the present paper, we have discussed the inhibition of various six compound series against HRV-1A, -1B, -2, -9, -14, -21, -22, -25, -64, and -89 by the formulation of a total number of 14 QSAR. Hydrophobicity is found to be one of the most important determinants of activity. Parabolic correlation with the hydrophobic parameter (Eq. ) is an encouraging example, where the optimal hydrophobicity is well defined. We believe that this may be the predictive model to narrow the synthetic challenges in order to yield very specific HRV-2 inhibitors. On the basis of this model, we have predicted eleven compounds (I-1 to I-11) that may be the next synthetic target. The proposed molecules (I-1 to I-11) also fulfill the conditions of Lipinski's "rule of five".

  16. QSAR study of acetylcholinesterase inhibitors for Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Somaye Setakeh

    2016-06-01

    Full Text Available Alzheimer’s disease (AD is an incapacitating neurodegenerative disease that slowly destroys brain cells. This disease progressively compromises both memory and cognition, culminating in a state of full dependence and dementia. Currently, AD is the main cause of dementia in the elderly and its prevalence in the developed world is increasing rapidly. Classic drugs, such as acetylcholinesterase inhibitors (AChEIs, fail to decline disease progression and display several side effects that reduce patient’s adhesion to pharmacotherapy. The past decade has witnessed an increasing focus on the search for novel AChEIs and new putative enzymatic targets for AD, like β –and γ -secretases, sirtuins, caspase proteins and glycogen syntheses kinase-3 (GSK-3. Genetic algorithm (GA, artificial neural network (ANN, Imperialist Competitive Algorithm (ICA, multiple linear regression (MLR, was used to create QSAR models. According to the obtained results, GA-ANN model was the most favorable method toward the other statistical methods. For this purpose, ab initio geometry optimization was performed at B3LYP level with a known basis set at 6-31G(d. R and R2 values of the GA-stepwise MLR model were obtained as 0.89 and 0.80.

  17. Lumped Parameter Modeling for Rapid Vibration Response Prototyping and Test Correlation for Electronic Units

    Science.gov (United States)

    Van Dyke, Michael B.

    2013-01-01

    Present preliminary work using lumped parameter models to approximate dynamic response of electronic units to random vibration; Derive a general N-DOF model for application to electronic units; Illustrate parametric influence of model parameters; Implication of coupled dynamics for unit/board design; Demonstrate use of model to infer printed wiring board (PWB) dynamics from external chassis test measurement.

  18. 5 CFR 838.1010 - Court orders or decrees preventing payment of lump sums.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Court orders or decrees preventing payment of lump sums. 838.1010 Section 838.1010 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT... Affecting Civil Service Retirement Benefits § 838.1010 Court orders or decrees preventing payment of...

  19. Miniature wideband filter based on coupled-line sections and quasi-lumped element resonator

    DEFF Research Database (Denmark)

    Zhurbenko, Vitaliy; Krozer, Viktor; Meincke, Peter

    2007-01-01

    A new design of a wideband bandpass filter is proposed, based on coupled-line sections and quasi-lumped element resonator, taking advantage of the last one to introduce two transmission zeros and suppress a spurious response. The proposed filter demonstrates significantly improved characteristics...

  20. New triangular mass-lumped finite elements of degree six for wave propagation

    NARCIS (Netherlands)

    Mulder, W.A.

    2013-01-01

    Mass-lumped continuous finite elements allow for explicit time stepping with the second-order wave equation if the resulting integration weights are positive and provide sufficient accuracy. To meet these requirements on triangular and tetrahedral meshes, the construction of continuous finite elemen

  1. School-based management in the Netherlands: the educational consequences of lump-sum funding

    NARCIS (Netherlands)

    Karsten, S.; Meijer, J.

    1999-01-01

    Important changes are taking place in the ways schools are funded in a large number of countries. In by far the majority of cases, these changes involve more freedom at the school level to decide how money should be spent. The Netherlands has had lump-sum funding in vocational secondary education si

  2. Simulation of hydrogen deflagration experiment – Benchmark exercise with lumped-parameter codes

    Energy Technology Data Exchange (ETDEWEB)

    Kljenak, Ivo, E-mail: ivo.kljenak@ijs.si [Jožef Stefan Institute, Jamova cesta 39, SI-1000 Ljubljana (Slovenia); Kuznetsov, Mikhail, E-mail: mike.kuznetsov@kit.edu [Karlsruhe Institute of Technology, Kaiserstraße 12, 76131 Karlsruhe (Germany); Kostka, Pal, E-mail: kostka@nubiki.hu [NUBIKI Nuclear Safety Research Institute, Konkoly-Thege Miklós út 29-33, 1121 Budapest (Hungary); Kubišova, Lubica, E-mail: lubica.kubisova@ujd.gov.sk [Nuclear Regulatory Authority of the Slovak Republic, Bajkalská 27, 82007 Bratislava (Slovakia); Maltsev, Mikhail, E-mail: maltsev_MB@aep.ru [JSC Atomenergoproekt, 1, st. Podolskykh Kursantov, Moscow (Russian Federation); Manzini, Giovanni, E-mail: giovanni.manzini@rse-web.it [Ricerca sul Sistema Energetico, Via Rubattino 54, 20134 Milano (Italy); Povilaitis, Mantas, E-mail: mantas.p@mail.lei.lt [Lithuania Energy Institute, Breslaujos g.3, 44403 Kaunas (Lithuania)

    2015-03-15

    Highlights: • Blind and open simulations of hydrogen combustion experiment in large-scale containment-like facility with different lumped-parameter codes. • Simulation of axial as well as radial flame propagation. • Confirmation of adequacy of lumped-parameter codes for safety analyses of actual nuclear power plants. - Abstract: An experiment on hydrogen deflagration (Upward Flame Propagation Experiment – UFPE) was proposed by the Jozef Stefan Institute (Slovenia) and performed in the HYKA A2 facility at the Karlsruhe Institute of Technology (Germany). The experimental results were used to organize a benchmark exercise for lumped-parameter codes. Six organizations (JSI, AEP, LEI, NUBIKI, RSE and UJD SR) participated in the benchmark exercise, using altogether four different computer codes: ANGAR, ASTEC, COCOSYS and ECART. Both blind and open simulations were performed. In general, all the codes provided satisfactory results of the pressure increase, whereas the results of the temperature show a wider dispersal. Concerning the flame axial and radial velocities, the results may be considered satisfactory, given the inherent simplification of the lumped-parameter description compared to the local instantaneous description.

  3. Lumped Approximation of a Transmission Line with an Alternative Geometric Discretization

    NARCIS (Netherlands)

    Lopezlena, Ricardo; Scherpen, Jacquelien M.A.

    2004-01-01

    An electromagnetic one-dimensional transmission line represented in a distributed port-Hamiltonian form is lumped into a chain of subsystems which preserve the port-Hamiltonian structure with inputs and outputs in collocated form. The procedure is essentially an adaptation of the procedure for discr

  4. Receptor-based modeling and 3D-QSAR for a quantitative production of the butyrylcholinesterase inhibitors based on genetic algorithm.

    Science.gov (United States)

    Zaheer-ul, Haq; Uddin, Reaz; Yuan, Hongbin; Petukhov, Pavel A; Choudhary, M Iqbal; Madura, Jeffry D

    2008-05-01

    Three-dimensional quantitative structure-activity relationship (3D-QSAR) models have been constructed using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) for a series of structurally related steroidal alkaloids as butyrylcholinesterase (BuChE) inhibitors. Docking studies were employed to position the inhibitors into the BuChE active site to determine the most probable binding mode. The strategy was to explore multiple inhibitor conformations in producing a more reliable 3D-QSAR model. These multiple conformations were derived using the FlexS program. The conformation selection step for CoMFA was done by genetic algorithm. The genetic algorithm based CoMFA approach was found to be the best. Both CoMFA and CoMSIA yielded significant cross-validated q(2) values of 0.701 and 0.627 and the r(2) values of 0.979 and 0.982, respectively. These statistically significant models were validated by a test set of five compounds. Comparison of CoMFA and CoMSIA contour maps helped to identify structural requirements for the inhibitors and serves as a basis for the design of the next generation of the inhibitor analogues. The results demonstrate that the combination of ligand-based and receptor-based modeling with use of a genetic algorithm is a powerful approach to build 3D-QSAR models. These data can be used for the lead optimization process with respect to inhibition enhancement which is important for the drug discovery and development for Alzheimer's disease.

  5. QSAR Models for Thyroperoxidase Inhibition and Screening of U.S. and EU Chemical Inventories

    DEFF Research Database (Denmark)

    Abildgaard Rosenberg, Sine; D. Watt, Eric; Judson, Richard S.

    2017-01-01

    Thyroperoxidase (TPO) is the enzyme that synthesizes thyroid hormones (THs). TPO inhibition by chemicals can result in decreased TH levels and developmental neurotoxicity, and therefore identification of TPO inhibition is of high relevance in safety evaluation of chemicals. In the present study, we...... to QSAR1. Of the substances predicted within QSAR2’s applicability domain, 8,790 (19.3%) REACH substances and 7,166 (19.0%) U.S. EPA substances, respectively, were predicted to be TPO inhibitors. A case study on butyl hydroxyanisole (BHA), which is extensively used as an antioxidant, was included...

  6. A comparative QSAR study on the estrogenic activities of persistent organic pollutants by PLS and SVM

    Directory of Open Access Journals (Sweden)

    Fei Li

    2015-11-01

    Full Text Available Quantitative structure-activity relationships (QSARs were determined using partial least square (PLS and support vector machine (SVM. The predicted values by the final QSAR models were in good agreement with the corresponding experimental values. Chemical estrogenic activities are related to atomic properties (atomic Sanderson electronegativities, van der Waals volumes and polarizabilities. Comparison of the results obtained from two models, the SVM method exhibited better overall performances. Besides, three PLS models were constructed for some specific families based on their chemical structures. These predictive models should be useful to rapidly identify potential estrogenic endocrine disrupting chemicals.

  7. QSAR-3D/CoMFA em compostos imídicos com atividade antinociceptiva

    Directory of Open Access Journals (Sweden)

    Maria Elena Walter

    2013-01-01

    Full Text Available Imide compounds have shown biological activity. These compounds can be easily synthesized with good yields. The objective of this paper was the rational planning of imides and sulfonamides with antinociceptive activity using the 3D-QSAR/CoMFA approach. The studies were performed using two data sets. The first set consisted of 39 cyclic imides while the second set consisted of 39 imides and 15 sulfonamides. The 3D- QSAR/CoMFA models have shown that the steric effect is important for the antinociceptive activity of imide and sulphonamide compounds. Ten new compounds with improved potential antinociceptive activity have been proposed by de novo design leapfrog simulations.

  8. The index of ideality of correlation: A criterion of predictability of QSAR models for skin permeability?

    Science.gov (United States)

    Toropova, Alla P; Toropov, Andrey A

    2017-05-15

    New criterion of the predictive potential of quantitative structure-property/activity relationships (QSPRs/QSARs) is suggested. This criterion is calculated with utilization of the correlation coefficient between experimental and calculated values of endpoint for the calibration set, with taking into account the positive and negative dispersions between experimental and calculated values. The utilization of this criterion improves the predictive potential of QSAR models of dermal permeability coefficient, logKp (cm/h). Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Lumped-equivalent circuit model for multi-stage cascaded magnetoelectric dual-tunable bandpass filter

    Institute of Scientific and Technical Information of China (English)

    张秋实; 朱锋杰; 周浩淼

    2015-01-01

    A lumped-equivalent circuit model of a novel magnetoelectric tunable bandpass filter, which is realized in the form of multi-stage cascading between a plurality of magnetoelectric laminates, is established in this paper for convenient analysis. The multi-stage cascaded filter is degraded to the coupling microstrip filter with only one magnetoelectric laminate and then compared with the existing experiment results. The comparison reveals that the insertion loss curves predicted by the degraded circuit model are in good agreement with the experiment results and the predicted results of the electromagnetic field simulation, thus the validity of the model is verified. The model is then degraded to the two-stage cascaded magneto-electric filter with two magnetoelectric laminates. It is revealed that if the applied external bias magnetic or electric fields on the two magnetoelectric laminates are identical, then the passband of the filter will drift under the changed external field; that is to say, the filter has the characteristics of external magnetic field tunability and electric field tunability. If the applied external bias magnetic or electric fields on two magnetoelectric laminates are different, then the passband will disappear so that the switching characteristic is achieved. When the same magnetic fields are applied to the laminates, the passband bandwidth of the two-stage cascaded magnetoelectric filter with two magnetoelectric laminates becomes nearly doubled in comparison with the passband filter which contains only one magnetoelectric laminate. The bandpass effect is also improved obviously. This research will provide a theoretical basis for the design, preparation, and application of a new high performance magnetoelectric tunable microwave device.

  10. Assessment of health risks due to arsenic from iron ore lumps in a beach setting.

    Science.gov (United States)

    Swartjes, Frank A; Janssen, Paul J C M

    2016-09-01

    In 2011, an artificial hook-shaped peninsula of 128ha beach area was created along the Dutch coast, containing thousands of iron ore lumps, which include arsenic from natural origin. Elemental arsenic and inorganic arsenic induce a range of toxicological effects and has been classified as proven human carcinogens. The combination of easy access to the beach and the presence of arsenic raised concern about possible human health effects by the local authorities. The objective of this study is therefore to investigate human health risks from the presence of arsenic-containing iron ore lumps in a beach setting. The exposure scenarios underlying the human health-based risk limits for contaminated land in The Netherlands, based on soil material ingestion and a residential setting, are not appropriate. Two specific exposure scenarios related to the playing with iron ore lumps on the beach ('sandcastle building') are developed on the basis of expert judgement, relating to children in the age of 2 to 12years, i.e., a worst case exposure scenario and a precautionary scenario. Subsequently, exposure is calculated by the quantification of the following factors: hand loading, soil-mouth transfer effectivity, hand-mouth contact frequency, contact surface, body weight and the relative oral bioavailability factor. By lack of consensus on a universal reference dose for arsenic for use in the stage of risk characterization, three different types of assessments have been evaluated: on the basis of the current Provisional Tolerable Daily Intake (PTWI), on the basis of the Benchmark Dose Lower limit (BMDL), and by a comparison of exposure from the iron ore lumps with background exposure. It is concluded, certainly from the perspective of the conservative exposure assessment, that unacceptable human health risks due to exposure to arsenic from the iron ore lumps are unlikely and there is no need for risk management actions. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. airGRteaching: an R-package designed for teaching hydrology with lumped hydrological models

    Science.gov (United States)

    Thirel, Guillaume; Delaigue, Olivier; Coron, Laurent; Andréassian, Vazken; Brigode, Pierre

    2017-04-01

    discharges, which are updated immediately (a calibration only needs a couple of seconds or less, a simulation is almost immediate). In addition, time series of internal variables, live-visualisation of internal variables evolution and performance statistics are provided. This interface allows for hands-on exercises that can include for instance the analysis by students of: - The effects of each parameter and model components on simulated discharge - The effects of objective functions based on high flows- or low flows-focused criteria on simulated discharge - The seasonality of the model components. References Winston Chang, Joe Cheng, JJ Allaire, Yihui Xie and Jonathan McPherson (2016). shiny: Web Application Framework for R. R package version 0.13.2. https://CRAN.R-project.org/package=shiny Coron L., Thirel G., Perrin C., Delaigue O., Andréassian V., airGR: a suite of lumped hydrological models in an R-package, Environmental Modelling and software, 2017, submitted. Coron, L., Perrin, C. and Michel, C. (2016). airGR: Suite of GR hydrological models for precipitation-runoff modelling. R package version 1.0.3. https://webgr.irstea.fr/airGR/?lang=en. Olivier Delaigue and Laurent Coron (2016). airGRteaching: Tools to simplify the use of the airGR hydrological package by students. R package version 0.0.1. https://webgr.irstea.fr/airGR/?lang=en R Core Team (2016). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL https://www.R-project.org/.

  12. 龙山选煤厂提高块煤产率的方法%Improvement of lump coal yield in Longshan coal preparation plant

    Institute of Scientific and Technical Information of China (English)

    宋景玲

    2014-01-01

    In order to increase the lump coal yield in Longshan coal preparation plant,analyze the raw coal properties.The results show that,the raw coal is medium and high ash,extra low sulfur No.2 anthracite.There is less primary slime and the gangue is harder which is difficult to crush and grind.There is obvious degradation phenomenon.When lump coal ash is above 12%,the raw coal is easy to wash.The analysis of the process flow of coal preparation plant show that,low screening efficiency,frequent collision and high drop distance lead to low lump coal yield.To resolve these problems,replace the drum screen with linear vibrating screen,the raw coal bunker or lump coal point install spiral chute and take other measures to reduce coal breakage.After transformation,the lump coal yield increase by 1. 74%,the medi-um-sized lump coal increase by 0.51%,the small lump coal increase by 1.23%,the plant creates benefits 2.3868×106 yuan per year.%为提高龙山选煤厂块煤产率,分析了原煤性质,说明原煤属中高灰、特低硫的2号无烟煤;原生煤泥较少,矸石较硬,不易破碎解离,有明显泥化现象;块精煤灰分大于12%时,原煤可选性为易选。通过分析选煤厂工艺流程,说明滚筒筛筛分效率低,产品运输转载过程中碰撞溜槽,块煤入仓时摔碎,块煤落煤点较高等是造成选煤厂块煤产率低的主要原因。通过将滚筒筛更换为直线振动筛,在胶带机落煤溜槽内增加防破碎装置或缓冲闸板,在原煤仓内或块煤落煤点安装螺旋溜槽等措施减少块煤破碎。改造后选煤厂块煤产率提高了1.74%,其中精中块提高0.51%,精小块提高1.23%,每年增加经济效益238.68万元。

  13. QSAR Modeling on Benzo[c]phenanthridine Analogues as Topoisomerase I Inhibitors and Anti-cancer Agents

    Directory of Open Access Journals (Sweden)

    Thi-Ngoc-Phuong Huynh

    2012-05-01

    Full Text Available Benzo[c]phenanthridine (BCP derivatives were identified as topoisomerase I (TOP-I targeting agents with pronounced antitumor activity. In this study, hologram-QSAR, 2D-QSAR and 3D-QSAR models were developed for BCPs on topoisomerase I inbibitory activity and cytotoxicity against seven tumor cell lines including RPMI8402, CPT-K5, P388, CPT45, KB3-1, KBV-1and KBH5.0. The hologram, 2D, and 3D-QSAR models were obtained with the square of correlation coefficient R2 = 0.58 − 0.77, the square of the crossvalidation coefficient q2 = 0.41 − 0.60 as well as the external set’s square of predictive correlation coefficient r2 = 0.51 − 0.80. Moreover, the assessment method based on reliability test with confidence level of 95% was used to validate the predictive power of QSAR models and to prevent over-fitting phenomenon of classical QSAR models. Our QSAR model could be applied to design new analogues of BCPs with higher antitumor and topoisomerase I inhibitory activity.

  14. QSAR analyses of organophosphates for insecticidal activity and its in-silico validation using molecular docking study.

    Science.gov (United States)

    Niraj, Ravi Ranjan Kumar; Saini, Vandana; Kumar, Ajit

    2015-11-01

    The present work was carried out to design and develop novel QSAR models using 2D-QSAR and 3D-QSAR with CoMFA methodology for prediction of insecticidal activity of organophosphate (OP) molecules. The models were validated on an entirely different external dataset of in-house generated combinatorial library of OPs, by completely different computational approach of molecular docking against the target AChE protein of Musca domestica. The dock scores were observed to be in good correlation with 2D-QSAR and 3D-QSAR with CoMFA predicted activities and had the correlation coefficients (r(2)) of -0.62 and -0.63, respectively. The activities predicted by 2D-QSAR and 3D-QSAR with CoMFA were also observed to be highly correlated with r(2)=0.82. Also, the combinatorial library molecules were screened for toxicity in non-target organisms and degradability using USEPA-EPI Suite. The work was first step towards computer aided design and development of novel OP pesticide candidates with good insecticidal property but lower toxicity in non-targeted organisms and having biodegradation potential.

  15. Mechanistic Insights into the Binding of Class IIa HDAC Inhibitors toward Spinocerebellar Ataxia Type-2: A 3D-QSAR and Pharmacophore Modeling Approach

    Science.gov (United States)

    Sinha, Siddharth; Goyal, Sukriti; Somvanshi, Pallavi; Grover, Abhinav

    2017-01-01

    Spinocerebellar ataxia (SCA-2) type-2 is a rare neurological disorder among the nine polyglutamine disorders, mainly caused by polyQ (CAG) trinucleotide repeats expansion within gene coding ataxin-2 protein. The expanded trinucleotide repeats within the ataxin-2 protein sequesters transcriptional cofactors i.e., CREB-binding protein (CBP), Ataxin-2 binding protein 1 (A2BP1) leading to a state of hypo-acetylation and transcriptional repression. Histone de-acetylases inhibitors (HDACi) have been reported to restore transcriptional balance through inhibition of class IIa HDAC's, that leads to an increased acetylation and transcription as demonstrated through in-vivo studies on mouse models of Huntington's. In this study, 61 di-aryl cyclo-propanehydroxamic acid derivatives were used for developing three dimensional (3D) QSAR and pharmacophore models. These models were then employed for screening and selection of anti-ataxia compounds. The chosen QSAR model was observed to be statistically robust with correlation coefficient (r2) value of 0.6774, cross-validated correlation coefficient (q2) of 0.6157 and co-relation coefficient for external test set (pred_r2) of 0.7570. A high F-test value of 77.7093 signified the robustness of the model. Two potential drug leads ZINC 00608101 (SEI) and ZINC 00329110 (ACI) were selected after a coalesce procedure of pharmacophore based screening using the pharmacophore model ADDRR.20 and structural analysis using molecular docking and dynamics simulations. The pharmacophore and the 3D-QSAR model generated were further validated for their screening and prediction ability using the enrichment factor (EF), goodness of hit (GH), and receiver operating characteristics (ROC) curve analysis. The compounds SEI and ACI exhibited a docking score of −10.097 and −9.182 kcal/mol, respectively. An evaluation of binding conformation of ligand-bound protein complexes was performed with MD simulations for a time period of 30 ns along with free

  16. Mechanistic Insights into the Binding of Class IIa HDAC Inhibitors toward Spinocerebellar Ataxia Type-2: A 3D-QSAR and Pharmacophore Modeling Approach.

    Science.gov (United States)

    Sinha, Siddharth; Goyal, Sukriti; Somvanshi, Pallavi; Grover, Abhinav

    2016-01-01

    Spinocerebellar ataxia (SCA-2) type-2 is a rare neurological disorder among the nine polyglutamine disorders, mainly caused by polyQ (CAG) trinucleotide repeats expansion within gene coding ataxin-2 protein. The expanded trinucleotide repeats within the ataxin-2 protein sequesters transcriptional cofactors i.e., CREB-binding protein (CBP), Ataxin-2 binding protein 1 (A2BP1) leading to a state of hypo-acetylation and transcriptional repression. Histone de-acetylases inhibitors (HDACi) have been reported to restore transcriptional balance through inhibition of class IIa HDAC's, that leads to an increased acetylation and transcription as demonstrated through in-vivo studies on mouse models of Huntington's. In this study, 61 di-aryl cyclo-propanehydroxamic acid derivatives were used for developing three dimensional (3D) QSAR and pharmacophore models. These models were then employed for screening and selection of anti-ataxia compounds. The chosen QSAR model was observed to be statistically robust with correlation coefficient (r(2)) value of 0.6774, cross-validated correlation coefficient (q(2)) of 0.6157 and co-relation coefficient for external test set (pred_r(2)) of 0.7570. A high F-test value of 77.7093 signified the robustness of the model. Two potential drug leads ZINC 00608101 (SEI) and ZINC 00329110 (ACI) were selected after a coalesce procedure of pharmacophore based screening using the pharmacophore model ADDRR.20 and structural analysis using molecular docking and dynamics simulations. The pharmacophore and the 3D-QSAR model generated were further validated for their screening and prediction ability using the enrichment factor (EF), goodness of hit (GH), and receiver operating characteristics (ROC) curve analysis. The compounds SEI and ACI exhibited a docking score of -10.097 and -9.182 kcal/mol, respectively. An evaluation of binding conformation of ligand-bound protein complexes was performed with MD simulations for a time period of 30 ns along with free

  17. Real external predictivity of QSAR models. Part 2. New intercomparable thresholds for different validation criteria and the need for scatter plot inspection.

    Science.gov (United States)

    Chirico, Nicola; Gramatica, Paola

    2012-08-27

    The evaluation of regression QSAR model performance, in fitting, robustness, and external prediction, is of pivotal importance. Over the past decade, different external validation parameters have been proposed: Q(F1)(2), Q(F2)(2), Q(F3)(2), r(m)(2), and the Golbraikh-Tropsha method. Recently, the concordance correlation coefficient (CCC, Lin), which simply verifies how small the differences are between experimental data and external data set predictions, independently of their range, was proposed by our group as an external validation parameter for use in QSAR studies. In our preliminary work, we demonstrated with thousands of simulated models that CCC is in good agreement with the compared validation criteria (except r(m)(2)) using the cutoff values normally applied for the acceptance of QSAR models as externally predictive. In this new work, we have studied and compared the general trends of the various criteria relative to different possible biases (scale and location shifts) in external data distributions, using a wide range of different simulated scenarios. This study, further supported by visual inspection of experimental vs predicted data scatter plots, has highlighted problems related to some criteria. Indeed, if based on the cutoff suggested by the proponent, r(m)(2) could also accept not predictive models in two of the possible biases (location, location plus scale), while in the case of scale shift bias, it appears to be the most restrictive. Moreover, Q(F1)(2) and Q(F2)(2) showed some problems in one of the possible biases (scale shift). This analysis allowed us to also propose recalibrated, and intercomparable for the same data scatter, new thresholds for each criterion in defining a QSAR model as really externally predictive in a more precautionary approach. An analysis of the results revealed that the scatter plot of experimental vs predicted external data must always be evaluated to support the statistical criteria values: in some cases high

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

    Science.gov (United States)

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

    2014-01-01

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

  19. QSAR as a random event: a case of NOAEL.

    Science.gov (United States)

    Toropova, Alla P; Toropov, Andrey A; Veselinović, Jovana B; Veselinović, Aleksandar M

    2015-06-01

    Quantitative structure-activity relationships (QSAR) for no observed adverse effect levels (NOAEL, mmol/kg/day, in logarithmic units) are suggested. Simplified molecular input line entry systems (SMILES) were used for molecular structure representation. Monte Carlo method was used for one-variable models building up for three different splits into the "visible" training set and "invisible" validation. The statistical quality of the models for three random splits are the following: split 1 n = 180, r (2) = 0.718, q (2) = 0.712, s = 0.403, F = 454 (training set); n = 17, r (2) = 0.544, s = 0.367 (calibration set); n = 21, r (2) = 0.61, s = 0.44, r m (2) = 0.61 (validation set); split 2 n = 169, r (2) = 0.711, q (2) = 0.705, s = 0.409, F = 411 (training set); n = 27, r (2) = 0.512, s = 0.461 (calibration set); n = 22, r (2) = 0.669, s = 0.360, r m (2) = 0.63 (validation set); split 3 n = 172, r (2) = 0.679, q (2) = 0.672, s = 0.420, F = 360 (training set); n = 19, r (2) = 0.617, s = 0.582 (calibration set); n = 21, r (2) = 0.627, s = 0.367, r m (2) = 0.54 (validation set). All models are built according to OCED principles.

  20. Prospective study of fine needle aspiration cytology of clinically palpable breast lump with histopathological correlation

    Directory of Open Access Journals (Sweden)

    Ashwin K. Hebbar

    2013-06-01

    Full Text Available Background and objectives: This study was conducted to compare the diagnostic accuracy of fine needle aspiration cytology in differentiating the benign and malignant lesions of palpable breast lump with histopathological correlation and also to study the accuracy of the needle tip localizing the tumor during fine needle aspiration cytology procedure. Methods: Two years prospective study was conducted in our institution and in that 100 patients underwent fine needle aspiration cytology of the palpable breast lump after thorough physical examination. The cytological diagnosis was classified in to 3 groups benign, suspicious and malignant. After this reporting all the patients were later subjected to open/excision biopsy and its histopathological confirmation. Later diagnostic accuracy of cytology reporting was compared with that of histopathology. Accuracy of the needle tip in localizing the tumor in fine needle aspiration cytology was also studied by comparing the normal glandular cell aspirate with tumor cell aspirate. Repeat cytology was carried out before open/excision biopsy if the pathologist reports the cytology slide as “inadequate”. Results: We had accuracy rate of 100% for benign lesion and 93.10% for malignant lesion with false negative rate of 6.9% and false positive rate of zero with fine needle aspiration cytology in the diagnosis of palpable breast lump. The overall sensitivity of fine needle aspiration in diagnosing the palpable breast lump is 93.10%, specificity is 100%, positive predictive value is 100% and negative predictive value is 90.47%. Since inadequate sampling rate is 2% in our study, the accuracy rate of needle tip in localizing the tumor in fine needle aspiration cytology is 98%. Conclusion: Since our diagnostic accuracy rate and predictive values are very high and comparable to any other published series it can be advised that the patients in which fine needle aspiration cytology is unequivocally diagnostic for

  1. CLINICO PATHOLOGICAL STUDY OF BENIGN BREAST LUMP – A HOSPITAL BASED STUDY

    Directory of Open Access Journals (Sweden)

    Anindita

    2016-03-01

    Full Text Available BACKGROUND Despite the fact that in majority of cases the initial symptom of benign breast disease is a lump, which can be easily detected by the patient herself by self-examination they generally present at a very late stage and this poses a great difficulty in their management. Early and appropriate diagnosis of breast disease is of utmost importance. AIM The aim of the study was to find out the relative frequency and commonest site of occurrence of benign breast disorder and their relationship with age, parity, menstrual cycle, and socio-economic status and also to find out the accuracy of investigative procedures in their diagnosis. DESIGN This is a cross sectional, interventional. Hospital based study. MATERIALS AND METHOD This study was done in 58 female patients in the age group 10 yrs. to 55 yrs. presenting with clinically benign breast lumps randomly chosen from outpatient department and indoor wards of The Calcutta Medical Research Institute, Kolkata. After taking an accurate history and proper clinical examination these patients were sequentially studied by radiological methods (Ultrasonography and mammography, fine needle aspiration cytology (FNAC and histopathology of removed specimen. Patients were enquired about their age, chief complaints, menstrual history, and use of oral pill, marital status, parity, lactation and socioeconomic status. RESULTS 79% of the benign breast lumps were found to be between 10–35 years, Fibro adenoma being the commonest one (41.38% and fibrocystic disease the second most common (29.31%. Breast lump were more common among unmarried and nulliparous females (48.27%, commonest site being upper and outer quadrant (38.8%. 69% patients were associated with an abnormal menstrual status. 76% of the cases were accurately diagnosed by clinical examination, 70% by mammography, 88% by FNAC and 84% by ultrasonography. CONCLUSION This clinicopathological study of benign breast lump is a small endeavour on our part

  2. Synthesis, antifungal activity, and QSAR studies of 1,6-dihydropyrimidine derivatives

    Directory of Open Access Journals (Sweden)

    Chirag Rami

    2013-01-01

    Full Text Available Introduction: A practical synthesis of pyrimidinone would be very helpful for chemists because pyrimidinone is found in many bioactive natural products and exhibits a wide range of biological properties. The biological significance of pyrimidine derivatives has led us to the synthesis of substituted pyrimidine. Materials and Methods: With the aim of developing potential antimicrobials, new series of 5-cyano-6-oxo-1,6-dihydro-pyrimidine derivatives namely 2-(5-cyano-6-oxo-4-substituted (aryl-1,6-dihydropyrimidin-2-ylthio-N-substituted (phenyl acetamide (C1-C41 were synthesized and characterized by Fourier transform infrared spectroscopy (FTIR, mass analysis, and proton nuclear magnetic resonance ( 1 H NMR. All the compounds were screened for their antifungal activity against Candida albicans (MTCC, 227. Results and Discussion: Quantitative structure activity relationship (QSAR studies of a series of 1,6-dihydro-pyrimidine were carried out to study various structural requirements for fungal inhibition. Various lipophilic, electronic, geometric, and spatial descriptors were correlated with antifungal activity using genetic function approximation. Developed models were found predictive as indicated by their square of predictive regression values (r 2pred and their internal and external cross-validation. Study reveals that CHI_3_C, Molecular_SurfaceArea, and Jurs_DPSA_1 contributed significantly to the activity along with some electronic, geometric, and quantum mechanical descriptors. Conclusion: A careful analysis of the antifungal activity data of synthesized compounds revealed that electron withdrawing substitution on N-phenyl acetamide ring of 1,6-dihydropyrimidine moiety possess good activity.

  3. MI-QSAR models for prediction of corneal permeability of organic compounds

    Institute of Scientific and Technical Information of China (English)

    Cheng CHEN; Jie YANG

    2006-01-01

    Aim: To derive a theoretical model for the prediction of corneal permeability of miscellaneous organic compounds in drug design. Methods: A training set of 28structurally diverse compounds was used to build up the membrane-interaction quantitative structure-activity relationship (MI-QSAR) models. Intermolecular and intramolecular solute descriptors were computed using molecular mechanics,molecular dynamics simulations and quantum chemistry. The QSAR models were optimized using multidimensional linear regression fitting and a stepwise method.A test set of 8 compounds was evaluated using the models as part of a validation process. Results: Significant MI-QSAR models (R=0.976, S=0.1301, F=70.957) of corneal permeability of organic compounds were constructed. Corneal permeability was found to depend upon the sum of net atomic charges of hydrogen atoms attached to the heteroatoms (N, O), the sum of the absolute values of the net atomic charges of oxygen and nitrogen atoms, the principal moment of inertia (X),the Connolly accessible area and the conformational flexibility of the solute-membrane complex. Conclusion: The MI-QSAR models indicated that the corneal permeability of organic molecules was not only influenced by the organic solutes themselves, but also related to the properties of the solute-membrane complex,that is, the interactions of the molecule with the phospholipid-rich regions of cellular membranes.

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

    NARCIS (Netherlands)

    Zvinavashe, E.; Berg, H. van den; Soffers, A.E.M.F.; Vervoort, J.; Freidig, A.; Murk, A.J.; Rietjens, I.M.C.M.

    2008-01-01

    Quantitative structure-activity relationship (QSAR) models are expected to play a crucial role in reducing the number of animals to be used for toxicity testing resulting from the adoption of the new European Union chemical control system called Registration, Evaluation, and Authorization of Chemica

  5. Beware of R2: simple, unambiguous assessment of the prediction accuracy of QSAR and QSPR models

    OpenAIRE

    Alexander, D. L. J.; Tropsha, A; Winkler, David A.

    2015-01-01

    The statistical metrics used to characterize the external predictivity of a model, i.e., how well it predicts the properties of an independent test set, have proliferated over the past decade. This paper clarifies some apparent confusion over the use of the coefficient of determination, R2, as a measure of model fit and predictive power in QSAR and QSPR modelling.

  6. QSAR study of selective ligands for the thyroid hormone receptor beta.

    Science.gov (United States)

    Liu, Huanxiang; Gramatica, Paola

    2007-08-01

    In this paper, an accurate and reliable QSAR model of 87 selective ligands for the thyroid hormone receptor beta 1 (TRbeta1) was developed, based on theoretical molecular descriptors to predict the binding affinity of compounds with receptor. The structural characteristics of compounds were described wholly by a large amount of molecular structural descriptors calculated by DRAGON. Six most relevant structural descriptors to the studied activity were selected as the inputs of QSAR model by a robust optimization algorithm Genetic Algorithm. The built model was fully assessed by various validation methods, including internal and external validation, Y-randomization test, chemical applicability domain, and all the validations indicate that the QSAR model we proposed is robust and satisfactory. Thus, the built QSAR model can be used to fast and accurately predict the binding affinity of compounds (in the defined applicability domain) to TRbeta1. At the same time, the model proposed could also identify and provide some insight into what structural features are related to the biological activity of these compounds and provide some instruction for further designing the new selective ligands for TRbeta1 with high activity.

  7. 3D-QSAR, molecular docking, and molecular dynamic simulations for prediction of new Hsp90 inhibitors based on isoxazole scaffold.

    Science.gov (United States)

    Abbasi, Maryam; Sadeghi-Aliabadi, Hojjat; Amanlou, Massoud

    2017-05-24

    Heat shock protein 90(Hsp90), as a molecular chaperone, play a crucial role in folding and proper function of many proteins. Hsp90 inhibitors containing isoxazole scaffold are currently being used in the treatment of cancer as tumor suppressers. Here in the present studies, new compounds based on isoxazole scaffold were predicted using a combination of molecular modeling techniques including three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking and molecular dynamic (MD) simulations. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were also done. The steric and electrostatic contour map of CoMFA and CoMSIA were created. Hydrophobic, hydrogen bond donor and acceptor of CoMSIA model also were generated, and new compounds were predicted by CoMFA and CoMSIA contour maps. To investigate the binding modes of the predicted compounds in the active site of Hsp90, a molecular docking simulation was carried out. MD simulations were also conducted to evaluate the obtained results on the best predicted compound and the best reported Hsp90 inhibitors in the 3D-QSAR model. Findings indicate that the predicted ligands were stable in the active site of Hsp90.

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

    Science.gov (United States)

    Rosenbaum, Lars; Dörr, Alexander; Bauer, Matthias R; Boeckler, Frank M; Zell, Andreas

    2013-07-11

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

  9. 2D-QSAR study of fullerene nanostructure derivatives as potent HIV-1 protease inhibitors

    Science.gov (United States)

    Barzegar, Abolfazl; Jafari Mousavi, Somaye; Hamidi, Hossein; Sadeghi, Mehdi

    2017-09-01

    The protease of human immunodeficiency virus1 (HIV-PR) is an essential enzyme for antiviral treatments. Carbon nanostructures of fullerene derivatives, have nanoscale dimension with a diameter comparable to the diameter of the active site of HIV-PR which would in turn inhibit HIV. In this research, two dimensional quantitative structure-activity relationships (2D-QSAR) of fullerene derivatives against HIV-PR activity were employed as a powerful tool for elucidation the relationships between structure and experimental observations. QSAR study of 49 fullerene derivatives was performed by employing stepwise-MLR, GAPLS-MLR, and PCA-MLR models for variable (descriptor) selection and model construction. QSAR models were obtained with higher ability to predict the activity of the fullerene derivatives against HIV-PR by a correlation coefficient (R2training) of 0.942, 0.89, and 0.87 as well as R2test values of 0.791, 0.67and 0.674 for stepwise-MLR, GAPLS-MLR, and PCA -MLR models, respectively. Leave-one-out cross-validated correlation coefficient (R2CV) and Y-randomization methods confirmed the models robustness. The descriptors indicated that the HIV-PR inhibition depends on the van der Waals volumes, polarizability, bond order between two atoms and electronegativities of fullerenes derivatives. 2D-QSAR simulation without needing receptor's active site geometry, resulted in useful descriptors mainly denoting ;C60 backbone-functional groups; and ;C60 functional groups; properties. Both properties in fullerene refer to the ligand fitness and improvement van der Waals interactions with HIV-PR active site. Therefore, the QSAR models can be used in the search for novel HIV-PR inhibitors based on fullerene derivatives.

  10. Estudos de QSAR baseados em dados de atividade biológica obtidos por microcalorimetria: III interação de m-alcoxifenóis e p-hidroxibenzoatos de alquila com Escherichia coli QSAR based on biological microcalorimetry: III interaction of m-alcoxy-phenols and p-hydroxybenzoates with Escherichia coli

    Directory of Open Access Journals (Sweden)

    P. L. O. Volpe

    1997-04-01

    Full Text Available QSAR studies based on flow microcalorimetric bioassay data for interaction of homologous series of m-alkoxyphenols and p-hydroxybenzoates with E. coli cells were carried out applying factorial design. Results for both series showed a linear relationship between log(dosemax and log Po/w. Analysis of these data allows the identification of contributions toward the derived bioactivity from the parent structures (the molecule minus n-CH2 groups present in the side-chain and the lipophilic groups, CH2. These results are discussed with respect to drug quantitative structure-relationship.

  11. A Novel T-Fed 4-Element Quasi-Lumped Resonator Antenna Array

    Directory of Open Access Journals (Sweden)

    S.S. Olokede

    2014-06-01

    Full Text Available In this paper, electrically small corporately T-fed quasi-lumped element resonator antenna array is investigated. The radiating element, a quasi-lumped element resonator is excited by a novel semi hybrid ring-like T-shaped corporate feed network. The characteristics losses due to Ohmic and discontinuities along the feed line which invariably constitutes complex feed structures are mitigated at the instance of the proposed antenna. Technique to implement the compact array with the intent to enhance the gain is presented. The operation dynamics of the feed along with its theoretical explanation is also reported. Findings indicates that the measured gain is 10.97 dBi for antenna of an estate area of about 0.677λ_0 × 1.257λ_0 sq. mm. Valuable insight to the optimum design in terms of compactness, good gain, and ease of fabrication is documented.

  12. Intense deuterium nuclear fusion of pycnodeuterium-lumps coagulated locally within highly deuterated atom clusters

    CERN Document Server

    Yoshiaki, A; Zhang, Y C

    2002-01-01

    Embedded nano-Pd particles of 5 nm in size instantly abundant D-atoms more than 250% in the atomic ratio against Pd-atoms at room temperature when they are kept in D sub 2 gas pressurized to less than 10 atm. In such ultrahigh densities, 2-4 D-atoms can be coagulated inside each octahedral space of Pd lattice (pycnodeuterium-lump). When a stimulation energy such as latticequake causing by ultrasonic wave was supplied to those highly deuterated Pd particles, intense deuterium nuclear fusion (''solid fusion'') was generated there and both excess heat and sup 4 He gas were abundantly produced. Naturally, these facts can not be realized at all in bulk Pd. The results show that the nuclear fusion occurs without any hazardous rays in pycnodeuterium-lumps coagulated locally inside the each cell of the host metal lattice. These unit cells correspond to minimum unit of the solid fusion reactor as a ''Lattice Reactor''. (author)

  13. Study on Lumped Kinetic Model for FDFCC II. Validation and Prediction of Model

    Institute of Scientific and Technical Information of China (English)

    Wu Feiyue; Weng Huixin; Luo Shixian

    2008-01-01

    On the basis of formulating the 9-lump kinetic model for gasoline catalytic upgrading and the 12-lump kinetic model for heavy oil FCC, this paper is aimed at development of a combined kinetic model for a typical FDFCC process after analyzing the coupled relationship and combination of these two models. The model is also verified by using commercial data, the results of which showed that the model can better predict the product yields and their quality, with the relative errors between the main products of the unit and commercial data being less than five percent. Furthermore, the combined model is used to predict and optimize the operating conditions for gasoline riser and heavy oil riser in FDFCC. So this paper can offer some guidance for the processing of FDFCC and is instructive to model research and development of such multi-reactor process and combined process.

  14. A Size Reduction Technique for Mobile Phone PIFA Antennas Using Lumped Inductors

    DEFF Research Database (Denmark)

    Thaysen, Jesper; Jakobsen, Kaj Bjarne

    2005-01-01

    A size reduction technique for the planar inverted-F antenna (PIFA) is presented. An 18 nH lumped inductor is used in addition to a small 0.3 cm3 PIFA. The PIFA is located on dielectric foam, 5 mm above a 40 mm × 100 mm ground plane. It is possible to reduce the center frequency (|S11|min) by 33 ...

  15. Non-Maxwellian probability density function of fibers with lumped polarization mode dispersion elements.

    Science.gov (United States)

    Antonelli, Cristian; Mecozzi, Antonio

    2004-05-15

    We give an analytical expression for the probability density function of the differential group delay for a concatenation of Maxwellian fiber sections and an arbitrary number of lumped elements with constant and isotropically oriented birefringence. When the contribution of the average squared of the constant birefringence elements is a significant fraction of the total, we show that the outage probability can be significantly overestimated if the probability density function of the differential group delay is approximated by a Maxwellian distribution.

  16. UNILOCULAR OMENTAL CYST IN ADULT FEMALE PRESENTING AS HUGE ABDOMINAL LUMP: A RARE CASE REPORT

    Directory of Open Access Journals (Sweden)

    Himansu

    2015-05-01

    Full Text Available Omental cysts are rare entity with a prevalence of 1: 1,000,000 in adults and in 1: 20, 000 in children. We are reporting a case of a 30 year female patient with abdominal lump over epigastrium and left hypochondrium for 6 months; diagnosed on laparotomy as uniloculated omental cyst originating from lesser omentum. Omental cyst is a challenging diagnostic entity with varied presentations and a wide range of differential diagnosis has to be kept in mind.

  17. The Young principle and integration-masked lumped sources of a diffracted field

    Science.gov (United States)

    Urusovskii, I. A.

    2016-11-01

    A methodologically simple modification of the Young principle is proposed for describing diffracted field formation in problems of wave diffraction by the sharp edges of screens and wedges without using Sommerfeld's two-sheeted space. The method of determining the diffracted field constructs the derivative of the field by introducing lumped sources positioned at given scattering edges with subsequent integration of the constructed field along the directions parallel to the wave fronts of the incident plane wave.

  18. Discrete Spectrum of 2 + 1-Dimensional Nonlinear Schrödinger Equation and Dynamics of Lumps

    Directory of Open Access Journals (Sweden)

    Javier Villarroel

    2016-01-01

    Full Text Available We consider a natural integrable generalization of nonlinear Schrödinger equation to 2+1 dimensions. By studying the associated spectral operator we discover a rich discrete spectrum associated with regular rationally decaying solutions, the lumps, which display interesting nontrivial dynamics and scattering. Particular interest is placed in the dynamical evolution of the associated pulses. For all cases under study we find that the relevant dynamics corresponds to a central configuration of a certain N-body problem.

  19. Insights into the interactions between maleimide derivates and GSK3β combining molecular docking and QSAR.

    Directory of Open Access Journals (Sweden)

    Luisa Quesada-Romero

    Full Text Available Many protein kinase (PK inhibitors have been reported in recent years, but only a few have been approved for clinical use. The understanding of the available molecular information using computational tools is an alternative to contribute to this process. With this in mind, we studied the binding modes of 77 maleimide derivates inside the PK glycogen synthase kinase 3 beta (GSK3β using docking experiments. We found that the orientations that these compounds adopt inside GSK3β binding site prioritize the formation of hydrogen bond (HB interactions between the maleimide group and the residues at the hinge region (residues Val135 and Asp133, and adopt propeller-like conformations (where the maleimide is the propeller axis and the heterocyclic substituents are two slanted blades. In addition, quantitative structure-activity relationship (QSAR models using CoMSIA methodology were constructed to explain the trend of the GSK3β inhibitory activities for the studied compounds. We found a model to explain the structure-activity relationship of non-cyclic maleimide (NCM derivatives (54 compounds. The best CoMSIA model (training set included 44 compounds included steric, hydrophobic, and HB donor fields and had a good Q(2 value of 0.539. It also predicted adequately the most active compounds contained in the test set. Furthermore, the analysis of the plots of the steric CoMSIA field describes the elements involved in the differential potency of the inhibitors that can be considered for the selection of suitable inhibitors.

  20. Synthesis, QSAR and anticandidal evaluation of 1,2,3-triazoles derived from naturally bioactive scaffolds.

    Science.gov (United States)

    Irfan, Mohammad; Aneja, Babita; Yadava, Umesh; Khan, Shabana I; Manzoor, Nikhat; Daniliuc, Constantin G; Abid, Mohammad

    2015-03-26

    In the present study, we used eight natural precursors (1a-h) with most of them having promising antimicrobial activities and synthesised their novel 1,2,3-triazole derivatives (3a-h). In the reaction sequences, the precursor compounds (1a-h) were converted to their respective alkyne (2a-h) followed by addition of benzyl azide freshly prepared by the reaction of benzyl bromide with sodium azide using [3 + 2] azide-alkyne cycloaddition strategy. Structural elucidation of all the triazole derivatives was done using FT-IR, (1)H, (13)C NMR, mass and elemental analysis techniques. The single crystal X-ray diffraction for 3d was also recorded. The result of in vitro anticandidal activity performed against three different strains of Candida showed that compound 3e was found superior/comparable to fluconazole (FLC) with IC50 values of 0.044 μg/mL against Candida albicans (ATCC 90028), 12.022 μg/mL against Candida glabrata (ATCC 90030), and 3.60 μg/mL against Candida tropicalis (ATCC 750). Moreover, at their IC50 values, compounds 3e and 3h showed <5% hemolysis which indicates the non-toxic behaviour of these inhibitors. Cytotoxicity assay was also performed on VERO cell line and all the derivatives were found non-toxic up to the concentration of 10.0 μg/mL. The in silico technique of 3D-QSAR was applied to establish structure activity relationship of the synthesized compounds. The results reveal the molecular fragments that play an essential role in improving the anticandidal activity.

  1. Misconceptions about breast lumps and delayed medical presentation in urban breast cancer patients

    Science.gov (United States)

    Rauscher, Garth H; Ferrans, Carol Estwing; Kaiser, Karen; Campbell, Richard; Calhoun, Elizabeth; Warnecke, Richard B.

    2013-01-01

    BACKGROUND Despite current recommendations for women to be screened for breast cancer with mammography every one to two years, less than half of all newly diagnosed breast cancers are initially detected through screening mammography. Prompt medical attention to a new breast symptom can result in earlier stage at diagnosis, yet many patients delay seeking medical care after becoming aware of a breast symptom. METHODS In a population-based study of breast cancer we examined factors potentially associated with patient delay in seeking health care for a breast symptom among 436 symptomatic urban breast cancer patients (146 White, 197 Black and 95 Hispanic). Race/ethnicity, socioeconomic status, health care access and utilization, and misconceptions about the meaning of breast lumps were the key independent variables. RESULTS Sixteen percent of patients reported delaying more than 3 months before seeking medical advice about breast symptoms. Misconceptions about breast lumps, and lacking a regular provider, health insurance and recent preventive care were all associated with prolonged patient delay (p<0.005 for all). Misconceptions were much more common among ethnic minorities and women of lower socioeconomic status. CONCLUSION Reducing patient delay and disparities in delay will require both educating women about the importance of getting breast lumps evaluated in a timely manner, and providing greater access to regular health care. PMID:20200436

  2. An Improved Lumped Parameter Model for a Piezoelectric Energy Harvester in Transverse Vibration

    Directory of Open Access Journals (Sweden)

    Guang-qing Wang

    2014-01-01

    Full Text Available An improved lumped parameter model (ILPM is proposed which predicts the output characteristics of a piezoelectric vibration energy harvester (PVEH. A correction factor is derived for improving the precisions of lumped parameter models for transverse vibration, by considering the dynamic mode shape and the strain distribution of the PVEH. For a tip mass, variations of the correction factor with PVEH length are presented with curve fitting from numerical solutions. The improved governing motion equations and exact analytical solution of the PVEH excited by persistent base motions are developed. Steady-state electrical and mechanical response expressions are derived for arbitrary frequency excitations. Effects of the structural parameters on the electromechanical outputs of the PVEH and important characteristics of the PVEH, such as short-circuit and open-circuit behaviors, are analyzed numerically in detail. Accuracy of the output performances of the ILPM is identified from the available lumped parameter models and the coupled distributed parameter model. Good agreement is found between the analytical results of the ILPM and the coupled distributed parameter model. The results demonstrate the feasibility of the ILPM as a simple and effective means for enhancing the predictions of the PVEH.

  3. Study on Lumped Kinetic Model for FDFCC I. Establishment of Model

    Institute of Scientific and Technical Information of China (English)

    Wu Feiyue; Weng Huixin; Luo Shixian

    2008-01-01

    According to the process features and the reaction mechanism of FDFCC technology, its two reaction subsystems, one for heavy oil riser reactor, the other for gasoline riser reactor, were respectively studied. Correspondingly, a 12-lump kinetic model for heavy oil FCC and a 9-lump kinetic model for gasoline catalytic upgrading were presented. Based on this work, mathematical correlation of the lumps in the feeds and products involved in the reaction subsystems and those of the overall reaction system were analyzed in detail. Then, a combined kinetic model for FDFCC, which was based on the data recovered from a commercial unit, was put forward. The reaction performance embodied by the kinetic constants for the combined model of FDFCC was in accordance with catalytic cracking reaction mechanism. The model-calculated values were close to the data obtained in commercial scale. The model was easy to be applied in practice and could also provide some theoretical groundwork for further research on kinetic model for FDFCC.

  4. Intermittent reservoir daily-inflow prediction using lumped and distributed data multi-linear regression models

    Indian Academy of Sciences (India)

    R B Magar; V Jothiprakash

    2011-12-01

    In this study, multi-linear regression (MLR) approach is used to construct intermittent reservoir daily inflow forecasting system. To illustrate the applicability and effect of using lumped and distributed input data in MLR approach, Koyna river watershed in Maharashtra, India is chosen as a case study. The results are also compared with autoregressive integrated moving average (ARIMA) models. MLR attempts to model the relationship between two or more independent variables over a dependent variable by fitting a linear regression equation. The main aim of the present study is to see the consequences of development and applicability of simple models, when sufficient data length is available. Out of 47 years of daily historical rainfall and reservoir inflow data, 33 years of data is used for building the model and 14 years of data is used for validating the model. Based on the observed daily rainfall and reservoir inflow, various types of time-series, cause-effect and combined models are developed using lumped and distributed input data. Model performance was evaluated using various performance criteria and it was found that as in the present case, of well correlated input data, both lumped and distributed MLR models perform equally well. For the present case study considered, both MLR and ARIMA models performed equally sound due to availability of large dataset.

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

    Science.gov (United States)

    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...

  6. (Q)SAR and other (non) testing data in integrated testing strategies using standardised weight of evidence criteria

    NARCIS (Netherlands)

    Hulzebos, E.M.

    2012-01-01

    De REACH-verordening (Registratie, Evaluatie, Autorisatie en restrictie van Chemische stoffen) uit 2007 biedt een platform voor het gebruik van alternatieven voor dierproeven. Een van die alternatieven is (Q)SAR (kwantitatieve structuuractiviteitsrelatie). Etje Hulzebosch beschrijft hoe deze methode

  7. Nine-Lump Kinetic Study of Catalytic Pyrolysis of Gas Oils Derived from Canadian Synthetic Crude Oil

    Directory of Open Access Journals (Sweden)

    Rui Zhang

    2016-01-01

    Full Text Available Catalytic pyrolysis of gas oils derived from Canadian synthetic crude oil on a kind of zeolite catalyst was conducted in a confined fluidized bed reactor for the production of light olefins. The overall reactants and products were classified into nine species, and a nine-lump kinetic model was proposed to describe the reactions based on appropriate assumptions. This kinetic model had 24 rate constants and a catalyst deactivation constant. The kinetic constants at 620°C, 640°C, 660°C, and 680°C were estimated by means of nonlinear least-square regression method. Preexponential factors and apparent activation energies were then calculated according to the Arrhenius equation. The apparent activation energies of the three feed lumps were lower than those of the intermediate product lumps. The nine-lump kinetic model showed good calculation precision and the calculated yields were close to the experimental ones.

  8. Resonant mode behavior of lumped-resistor-loaded electric-inductive-capacitive resonator and its absorber application

    Directory of Open Access Journals (Sweden)

    Hong-Min Lee

    2013-05-01

    Full Text Available This paper presents investigations into the resonant mode behavior of a lumped-resistor-loaded electric-inductive-capacitive (ELC resonator, which is illuminated with a parallel polarization external electromagnetic wave. An ELC resonator exhibits a negative effective permittivity for both parallel and perpendicular polarizations. In contrast to a common ELC resonator, the lumped-resistor-loaded ELC resonator exhibits a switchable resonant mode behavior, thereby revealing a negative effective permeability. In addition, this resonator exhibits a low quality factor owing to the loaded lumped resistors. A metamaterial absorber, which consists of a lumped-resistor-loaded ELC resonator and a cut-wire strip, is designed to confirm the effectiveness of the resonator.

  9. Theory of Double Ladder Lumped Circuits With Degenerate Band Edge

    CERN Document Server

    Sloan, Jeff; Capolino, Filippo

    2016-01-01

    Conventional periodic LC ladder circuits exhibit a regular band edge between a pass and a stop band. Here for the first time we develop the theory of simple yet unconventional double ladder circuits exhibiting a special degeneracy condition referred to as degenerate band edge (DBE). This special DBE condition is associated with four independent eigenstates of the double ladder that coalesce into a single one when the operative frequency coincides with the DBE one. In particular, we show that double ladder resonators may exhibit giant loaded quality factor near the DBE and stable resonance frequency against load variations. These two properties in the proposed circuit are superior to the analogous properties in single ladder circuits. Our proposed analysis leads to analytic expressions for all circuit quantities thus providing insight into the very complex behavior near points of degeneracy in periodic circuits; and provides a design procedure for the use of such double ladder in practical applications. Intere...

  10. 3-D QSAutogrid/R: an alternative procedure to build 3-D QSAR models. Methodologies and applications.

    Science.gov (United States)

    Ballante, Flavio; Ragno, Rino

    2012-06-25

    Since it first appeared in 1988 3-D QSAR has proved its potential in the field of drug design and activity prediction. Although thousands of citations now exist in 3-D QSAR, its development was rather slow with the majority of new 3-D QSAR applications just extensions of CoMFA. An alternative way to build 3-D QSAR models, based on an evolution of software, has been named 3-D QSAutogrid/R and has been developed to use only software freely available to academics. 3-D QSAutogrid/R covers all the main features of CoMFA and GRID/GOLPE with implementation by multiprobe/multiregion variable selection (MPGRS) that improves the simplification of interpretation of the 3-D QSAR map. The methodology is based on the integration of the molecular interaction fields as calculated by AutoGrid and the R statistical environment that can be easily coupled with many free graphical molecular interfaces such as UCSF-Chimera, AutoDock Tools, JMol, and others. The description of each R package is reported in detail, and, to assess its validity, 3-D QSAutogrid/R has been applied to three molecular data sets of which either CoMFA or GRID/GOLPE models were reported in order to compare the results. 3-D QSAutogrid/R has been used as the core engine to prepare more that 240 3-D QSAR models forming the very first 3-D QSAR server ( www.3d-qsar.com ) with its code freely available through R-Cran distribution.

  11. 36 CFR 223.64 - Appraisal on a lump-sum value or rate per unit of measure basis.

    Science.gov (United States)

    2010-07-01

    ... or rate per unit of measure basis. 223.64 Section 223.64 Parks, Forests, and Public Property FOREST... Contracts Appraisal and Pricing § 223.64 Appraisal on a lump-sum value or rate per unit of measure basis. Timber may be appraised and sold at a lump-sum value or at a rate per unit of measure which rate may be...

  12. QSAR study on maximal inhibition (Imax) of quaternary ammonium antagonists for S-(-)-nicotine-evoked dopamine release from dopaminergic nerve terminals in rat striatum.

    Science.gov (United States)

    Zheng, Fang; McConnell, Matthew J; Zhan, Chang-Guo; Dwoskin, Linda P; Crooks, Peter A

    2009-07-01

    Maximal inhibition (I(max)) of the agonist effect is an important pharmacological property of inhibitors that interact with multiple receptor subtypes that are activated by the same agonist and which elicit the same functional response. This report represents the first QSAR study on a set of 66 mono- and bis-quaternary ammonium salts that act as antagonists at neuronal nicotinic acetylcholine receptors mediating nicotine-evoked dopamine release, conducted using multi-linear regression (MLR) and neural network (NN) analysis with the maximal inhibition (I(max)) values of the antagonists as target values. The statistical results for the generated MLR model were: r(2)=0.89, rmsd=9.01, q(2)=0.83 and loormsd=11.1; the statistical results for the generated NN model were: r(2)=0.89, rmsd=8.98, q(2)=0.83 and loormsd=11.2. The maximal inhibition values of the compounds exhibited a good correlation with the predictions made by the QSAR models developed, which provide a basis for rationalizing selection of compounds for synthesis in the discovery of effective and selective second generation inhibitors of nAChRs mediating nicotine-evoked dopamine release.

  13. 3D-QSAR and Docking Studies of a Series of β-Carboline Derivatives as Antitumor Agents of PLK1

    Directory of Open Access Journals (Sweden)

    Jahan B. Ghasemi

    2014-01-01

    Full Text Available An alignment-free, three dimensional quantitative structure-activity relationship (3D-QSAR analysis has been performed on a series of β-carboline derivatives as potent antitumor agents toward HepG2 human tumor cell lines. A highly descriptive and predictive 3D-QSAR model was obtained through the calculation of alignment-independent descriptors (GRIND descriptors using ALMOND software. For a training set of 30 compounds, PLS analyses result in a three-component model which displays a squared correlation coefficient (r2 of 0.957 and a standard deviation of the error of calculation (SDEC of 0.116. Validation of this model was performed using leave-one-out, q2loo of 0.85, and leave-multiple-out. This model gives a remarkably high r2pred(0.66 for a test set of 10 compounds. Docking studies were performed to investigate the mode of interaction between β-carboline derivatives and the active site of the most probable anticancer receptor, polo-like kinase protein.

  14. Identification of curcumin derivatives as human glyoxalase I inhibitors: A combination of biological evaluation, molecular docking, 3D-QSAR and molecular dynamics simulation studies.

    Science.gov (United States)

    Yuan, Minggui; Luo, Minxian; Song, Yao; Xu, Qiu; Wang, Xiaofeng; Cao, Yi; Bu, Xianzhang; Ren, Yanliang; Hu, Xiaopeng

    2011-02-01

    Several recent developments suggest that the human glyoxalase I (GLO I) is a potential target for anti-tumor drug development. In present study, a series of curcumin derivatives with high inhibitory activity against human GLO I were discovered. Inhibition constant (K(i)) values of compounds 8, 9, 10, 11 and 13 to GLO I are 4.600μM, 2.600μM, 3.200μM, 3.600μM and 3.600μM, respectively. To elucidate the structural features of potent inhibitors, docking-based three-dimensional structure-activity relationship (3D-QSAR) analyses were performed. Satisfactory agreement between experiment and theory suggests that comparative molecular similarity index analysis (CoMSIA) modeling exhibit much better correlation and predictive power. The cross-validated q(2) value is 0.638 while no-validation r(2) value is 0.930. Integrated with docking-based 3D-QSAR CoMSIA modeling, molecular surface property (electrostatic and steric) mapping and molecular dynamics simulation, a set of receptor-ligand binding models and bio-affinity predictive models for rational design of more potent inhibitors of GLO I are established.

  15. Condensing complex atmospheric chemistry mechanisms. 1: The direct constrained approximate lumping (DCAL) method applied to alkane photochemistry

    Energy Technology Data Exchange (ETDEWEB)

    Wang, S.W.; Georgopoulos, P.G. [Environmental and Occupational Health Sciences Inst., Piscataway, NJ (United States); Li, G.; Rabitz, H. [Princeton Univ., NJ (United States). Dept. of Chemistry

    1998-07-01

    Atmospheric chemistry mechanisms are the most computationally intensive components of photochemical air quality simulation models (PAQSMs). The development of a photochemical mechanism, that accurately describes atmospheric chemistry while being computationally efficient for use in PAQSMs, is a difficult undertaking that has traditionally been pursued through semiempirical (diagnostic) lumping approaches. The limitations of these diagnostic approaches are often associated with inaccuracies due to the fact that the lumped mechanisms have typically been optimized to fit the concentration profile of a specific species. Formal mathematical methods for model reduction have the potential (demonstrated through past applications in other areas) to provide very effective solutions to the need for computational efficiency combined with accuracy. Such methods, that can be used to condense a chemical mechanism, include kinetic lumping and domain separation. An application of the kinetic lumping method, using the direct constrained approximately lumping (DCAL) approach, to the atmospheric photochemistry of alkanes is presented in this work. It is shown that the lumped mechanism generated through the application of the DCAL method has the potential to overcome the limitations of existing semiempirical approaches, especially in relation to the consistent and accurate calculation of the time-concentration profiles of multiple species.

  16. QSAR modeling of the antimicrobial activity of peptides as a mathematical function of a sequence of amino acids.

    Science.gov (United States)

    Toropova, Mariya A; Veselinović, Aleksandar M; Veselinović, Jovana B; Stojanović, Dušica B; Toropov, Andrey A

    2015-12-01

    Antimicrobial peptides have emerged as new therapeutic agents for fighting multi-drug-resistant bacteria. However, the process of optimizing peptide antimicrobial activity and specificity using large peptide libraries is both tedious and expensive. Therefore, computational techniques had to be applied for process optimization. In this work, the representation of the molecular structure of peptides (mastoparan analogs) by a sequence of amino acids has been used to establish quantitative structure-activity relationships (QSARs) for their antibacterial activity. The data for the studied peptides were split three times into the training, calibration and test sets. The Monte Carlo method was used as a computational technique for QSAR models calculation. The statistical quality of QSAR for the antibacterial activity of peptides for the external validation set was: n=7, r(2)=0.8067, s=0.248 (split 1); n=6, r(2)=0.8319, s=0.169 (split 2); and n=6, r(2)=0.6996, s=0.297 (split 3). The stated statistical parameters favor the presented QSAR models in comparison to 2D and 3D descriptor based ones. The Monte Carlo method gave a reasonably good prediction for the antibacterial activity of peptides. The statistical quality of the prediction is different for three random splits. However, the predictive potential is reasonably well for all cases. The presented QSAR modeling approach can be an attractive alternative of 3D QSAR at least for the described peptides. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. 2D-QSAR Using MLR and 3D-QSAR Using CoMSIA Studies on the Toxicity of Aromatic Hydrocarbons on Larval Sinonvaculina Constricta

    Institute of Scientific and Technical Information of China (English)

    WANG Cui-Hua; JIANG Mei; LI Xiao-Lin; SHEN Xin-Qiang; YU Hong-Xia; WU Yang

    2012-01-01

    Aromatic hydrocarbons,one of the persistent organic pollutants(POPs),has been usually found in mussels,accumulated for their hard mobility and activities in harbours and estuaries.In this study,based on the 96 hr-LC50 of 12 aromatic hydrocarbons with larval sinonvaculina constricta,three-dimensional quantitative structure-activity relationship(3D-QSAR) technique:comparative molecular similarity indices analysis(CoMSIA) and 2D-QSAR technique:multiple linear regression(MLR) were described to obtain more detailed insight into the structure-activity relationships between the molecular structure and bio-activity.The results show the MLR model based on density functional theory(DFT) calculation carried out at the B3LYP/6-311** level with Gaussian 03 program yielded a very good correlation with a coefficient squared R2 of 0.716 and a cross-validated Q2 of 0.874.The dipole moment and enthalpy,as the thermodynamic parameters,were two important factors influencing pLC50.Correspondingly,CoMSIA based on the partial least-squares(PLS) methodology with steric,electrostatic,hydrophobic,H-bond donor and acceptor fields contributing simultaneously were employed and the values of R2 and the cross validation with leave-One-Out(LOO) Q2LOO were 0.585 and 0.990,respectively,which reveals the structure features,such as the electronegative substituent(nitro-group),hydrophobic groups(the benzene ring) and H-bond(nitro-group),related to the toxicity.The results of 2D-QSAR employing MLR model and 3D-QSAR employing CoMSIA model provide the useful information for predicting the toxicity of other aromatic hydrocarbons by comparing the molecular structures of similar compounds.

  18. Differentiation of AmpC beta-lactamase binders vs. decoys using classification kNN QSAR modeling and application of the QSAR classifier to virtual screening

    Science.gov (United States)

    Hsieh, Jui-Hua; Wang, Xiang S.; Teotico, Denise; Golbraikh, Alexander; Tropsha, Alexander

    2008-09-01

    The use of inaccurate scoring functions in docking algorithms may result in the selection of compounds with high predicted binding affinity that nevertheless are known experimentally not to bind to the target receptor. Such falsely predicted binders have been termed `binding decoys'. We posed a question as to whether true binders and decoys could be distinguished based only on their structural chemical descriptors using approaches commonly used in ligand based drug design. We have applied the k-Nearest Neighbor ( kNN) classification QSAR approach to a dataset of compounds characterized as binders or binding decoys of AmpC beta-lactamase. Models were subjected to rigorous internal and external validation as part of our standard workflow and a special QSAR modeling scheme was employed that took into account the imbalanced ratio of inhibitors to non-binders (1:4) in this dataset. 342 predictive models were obtained with correct classification rate (CCR) for both training and test sets as high as 0.90 or higher. The prediction accuracy was as high as 100% (CCR = 1.00) for the external validation set composed of 10 compounds (5 true binders and 5 decoys) selected randomly from the original dataset. For an additional external set of 50 known non-binders, we have achieved the CCR of 0.87 using very conservative model applicability domain threshold. The validated binary kNN QSAR models were further employed for mining the NCGC AmpC screening dataset (69653 compounds). The consensus prediction of 64 compounds identified as screening hits in the AmpC PubChem assay disagreed with their annotation in PubChem but was in agreement with the results of secondary assays. At the same time, 15 compounds were identified as potential binders contrary to their annotation in PubChem. Five of them were tested experimentally and showed inhibitory activities in millimolar range with the highest binding constant Ki of 135 μM. Our studies suggest that validated QSAR models could complement

  19. QSAR study on estrogenic activity of structurally diverse compounds using generalized regression neural network

    Institute of Scientific and Technical Information of China (English)

    JI Li; WANG XiaoDong; LUO Si; QIN Liang; YANG XvShu; LIU ShuShen; WANG LianSheng

    2008-01-01

    Computer-based quantitative structure-activity relationship (QSAR) model has been becoming a powerful tool in understanding the structural requirements for chemicals to bind the estrogen receptor (ER), designing drugs for human estrogen replacement therapy, and identifying potential estrogenic endocrine disruptors, in this study, a simple yet powerful neural network technique, generalized regression neural network (GRNN) was used to develop a QSAR model based on 131 structurally diverse estrogens (training set). Only nine descriptors calculated solely from the molecular structures of compounds selected by objective and subjective feature selections were used as inputs of the GRNN model. The predictive power of the built model was found to be comparable to that of the more traditional techniques but requiring significantly easy implementation and a shorter computation-time. The obtained result indicates that the proposed GRNN model is robust and satisfactory, and can provide a feasible and practical tool for the rapid screening of the estrogenic activity of organic compounds.

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

    Science.gov (United States)

    Gramatica, P; Pilutti, P; Papa, E

    2007-01-01

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

  1. MEDV-13 for QSAR Studies on the COX-2 Inhibition by In domethacin Amides and Esters

    Institute of Scientific and Technical Information of China (English)

    LIU,Shu-Shen (刘树深); YIN,Chun-Sheng(印春生); SHI,Yun-Yu(施蕴渝); CAI,Shao-Xi(蔡绍皙); LI,Zhi-Liang(李志良)

    2001-01-01

    A molecular electronegativity distance vector based on 13 atomic types (MEDV-13), is a descriptor for predicting the biological activities of molecules based on the quantitative structure-activity relationship (QSAR). The MEDV-13 with 91 descriptors is employed to describe the structures of a series of selective cydooxygenase-2 (COX-2) inhibitors inchuding 16 indomethacin and its amide and ester derivatives (ImAE). A principal component regression (PCR) is used to derive a QSAR model relating the biological activities expressed by pIC50 values to the MEDV-13. With the number of principal components of 6, the correlation coeffcient (R) and the root mean square error (RMS) are 0.9245 and 0.1682 in modeling stage, and 0.8417 and 0.2389 in leave-one-out prediction step, respectively.

  2. Systemic QSAR and phenotypic virtual screening: chasing butterflies in drug discovery.

    Science.gov (United States)

    Cruz-Monteagudo, Maykel; Schürer, Stephan; Tejera, Eduardo; Pérez-Castillo, Yunierkis; Medina-Franco, José L; Sánchez-Rodríguez, Aminael; Borges, Fernanda

    2017-03-06

    Current advances in systems biology suggest a new change of paradigm reinforcing the holistic nature of the drug discovery process. According to the principles of systems biology, a simple drug perturbing a network of targets can trigger complex reactions. Therefore, it is possible to connect initial events with final outcomes and consequently prioritize those events, leading to a desired effect. Here, we introduce a new concept, 'Systemic Chemogenomics/Quantitative Structure-Activity Relationship (QSAR)'. To elaborate on the concept, relevant information surrounding it is addressed. The concept is challenged by implementing a systemic QSAR approach for phenotypic virtual screening (VS) of candidate ligands acting as neuroprotective agents in Parkinson's disease (PD). The results support the suitability of the approach for the phenotypic prioritization of drug candidates.

  3. Prediction of activity of carbonic anhydrase inhibitor drugs based on QSAR studies

    Directory of Open Access Journals (Sweden)

    N. Darzi

    2015-06-01

    Full Text Available A quantitative structure-activity relationship (QSAR model, based on three quantum chemical descriptors obtained from the benzene sulphonamide derivatives using the density functional theory (DFT method. Then this developed model was used to predict the benzene sulphonamide binding constant. The QSAR model has correlation coefficient R of 0.901 and the standard error of 0.646. Also, the predictive power of this model was further examined by leave-7-out cross validation procedure which the obtained statistical parameters were: Q2= 0.991 and SPRESS= 0.4686 that giving a good enough predictive power. The selected descriptorsare: molecular weight (MW, absolute hardness (AH, HOMO energy (HOMO, respectively.

  4. The index of ideality of correlation: A criterion of predictive potential of QSPR/QSAR models?

    Science.gov (United States)

    Toropov, Andrey A; Toropova, Alla P

    2017-07-01

    The index of ideality of correlation (IIC) is a new criterion of the predictive potential of quantitative structure-property/activity relationships (QSPRs/QSARs). This IIC is calculated with using of the correlation coefficient between experimental and calculated values of endpoint for the calibration set, with taking into account the positive and negative dispersions between experimental and calculated values. The mutagenicity is well-known important characteristic of substances from ecological point of view. Consequently, the estimation of the IIC for mutagenicity is well motivated. It is confirmed that the utilization of this criterion significantly improves the predictive potential of QSAR models of mutagenicity. The new criterion can be used for other endpoints. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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.

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

    KAUST Repository

    Sudhakaran, Sairam

    2012-04-01

    Ozonation is an advanced water treatment process used to remove organic micropollutants (OMPs) such as pharmaceuticals and personal care products (PPCPs). In this study, Quantitative Structure Activity Relationship (QSAR) models, for ozonation and advanced oxidation process (AOP), were developed with percent-removal of OMPs by ozonation as the criterion variable. The models focused on PPCPs and pesticides elimination in bench-scale studies done within natural water matrices: Colorado River, Passaic River, Ohio River and Suwannee synthetic water. The OMPs removal for the different water matrices varied depending on the water quality conditions such as pH, DOC, alkalinity. The molecular descriptors used to define the OMPs physico-chemical properties range from one-dimensional (atom counts) to three-dimensional (quantum-chemical). Based on a statistical modeling approach using more than 40 molecular descriptors as predictors, descriptors influencing ozonation/AOP were chosen for inclusion in the QSAR models. The modeling approach was based on multiple linear regression (MLR). Also, a global model based on neural networks was created, compiling OMPs from all the four river water matrices. The chemically relevant molecular descriptors involved in the QSAR models were: energy difference between lowest unoccupied and highest occupied molecular orbital (E LUMO-E HOMO), electron-affinity (EA), number of halogen atoms (#X), number of ring atoms (#ring atoms), weakly polar component of the solvent accessible surface area (WPSA) and oxygen to carbon ratio (O/C). All the QSAR models resulted in a goodness-of-fit, R 2, greater than 0.8. Internal and external validations were performed on the models. © 2011 Elsevier Ltd.

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

    Science.gov (United States)

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

    2015-07-27

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

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

    Science.gov (United States)

    Moda, Tiago L; Andricopulo, Adriano D

    2012-04-15

    Consistent in silico models for ADME properties are useful tools in early drug discovery. Here, we report the hologram QSAR modeling of human intestinal absorption using a dataset of 638 compounds with experimental data associated. The final validated models are consistent and robust for the consensus prediction of this important pharmacokinetic property and are suitable for virtual screening applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Design, Fabrication, and Testing of Lumped Element Kinetic inductance Detectors for 3 mm CMB Observations

    Science.gov (United States)

    Lowitz, Amy E.; Brown, Ari David; Stevenson, Thomas R.; Timbie, Peter T.; Wollack, Edward J.

    2014-01-01

    Kinetic inductance detectors (KIDs) are a promising technology for low-noise, highly-multiplexible mm- and submm-wave detection. KIDs have a number of advantages over other detector technologies, which make them an appealing option in the cosmic microwave background B-mode anisotropy search, including passive frequency domain multiplexing and relatively simple fabrication, but have suffered from challenges associated with noise control. Here we describe design and fabrication of a 20-pixel prototype array of lumped element molybdenum KIDs. We show Q, frequency and temperature measurements from the array under dark conditions. We also present evidence for a double superconducting gap in molybdenum.

  10. New Procedure to Develop Lumped Kinetic Models for Heavy Fuel Oil Combustion

    KAUST Repository

    Han, Yunqing

    2016-09-20

    A new procedure to develop accurate lumped kinetic models for complex fuels is proposed, and applied to the experimental data of the heavy fuel oil measured by thermogravimetry. The new procedure is based on the pseudocomponents representing different reaction stages, which are determined by a systematic optimization process to ensure that the separation of different reaction stages with highest accuracy. The procedure is implemented and the model prediction was compared against that from a conventional method, yielding a significantly improved agreement with the experimental data. © 2016 American Chemical Society.

  11. Fluid dynamics of heart valves during atrial fibrillation: a lumped parameter-based approach

    CERN Document Server

    Scarsoglio, Stefania; Guala, Andrea; Ridolfi, Luca

    2015-01-01

    Atrial fibrillation (AF) consequences on the heart valve dynamics are usually studied along with a valvular disfunction or disease, since in medical monitoring the two pathologies are often concomitant. Aim of the present work is to study, through a stochastic lumped-parameter approach, the basic fluid dynamics variations of heart valves, when only paroxysmal AF is present with respect to the normal sinus rhythm (NSR) in absence of any valvular pathology. Among the most common parameters interpreting the valvular function, the most useful turns out to be the regurgitant volume. During AF both atrial valves do not seem to worsen their performance, while the ventricular efficiency is remarkably reduced.

  12. [A five-element lumped-parameter model for cerebral blood flow autoregulation].

    Science.gov (United States)

    Wang, Shengzhang; Yao, Wei; Ding, Guanghong

    2009-10-01

    Utilizing the third-order polynomial curve fitted to the experimental data, which represents the relationship between cerebral blood flow (CBF) and mean artery blood pressure (MABP), we constructed a lumped-parameter dynamic model with 5 elements. In this model; the resistance is not constants it is determined by the fitted curve. We simulated the process of CBF autoregulation numerically by solving the govern equation of this model and got quite accurate results. Furthermore, we studied the influence of hemodynamic parameters on the CBF autoregulation by this model and proved that the characteristic resistance is the most important factor.

  13. Parametric nonlinear lumped element model for circular CMUTs in collapsed mode.

    Science.gov (United States)

    Aydoğdu, Elif; Ozgurluk, Alper; Atalar, Abdullah; Köymen, Hayrettin

    2014-01-01

    We present a parametric equivalent circuit model for a circular CMUT in collapsed mode. First, we calculate the collapsed membrane deflection, utilizing the exact electrical force distribution in the analytical formulation of membrane deflection. Then we develop a lumped element model of collapsed membrane operation. The radiation impedance for collapsed mode is also included in the model. The model is merged with the uncollapsed mode model to obtain a simulation tool that handles all CMUT behavior, in transmit or receive. Large- and small-signal operation of a single CMUT can be fully simulated for any excitation regime. The results are in good agreement with FEM simulations.

  14. An Algorithm to Develop Lumped Model for Gunn-Diode Dynamics

    OpenAIRE

    Umesh Kumar

    1998-01-01

    A nonlinear lumped model can be developed for Gunn-Diodes to describe the diffusion effects as the domain travels from cathode to anode of a Gunn-Diode. The model describes the domain extinction and nucleation phenomena. It allows the user to specify arbitrary nonlinear drift velocity V(E) and nonlinear diffusion D(E).The model simulates arbitrary Gunn-Diode circuits operating in any matured high field domain or in the LSA mode.Here we have constructed an algorithm to lead to development of t...

  15. Fluid dynamics of heart valves during atrial fibrillation: a lumped parameter-based approach.

    Science.gov (United States)

    Scarsoglio, S; Camporeale, C; Guala, A; Ridolfi, L

    2016-01-01

    Atrial fibrillation (AF) consequences on the heart valve dynamics are usually studied along with a valvular disfunction or disease, since in medical monitoring, the two pathologies are often concomitant. Aim of the present work is to study, through a stochastic lumped-parameter approach, the basic fluid dynamics variations of heart valves, when only paroxysmal AF is present with respect to the normal sinus rhythm in absence of any valvular pathology. Among the most common parameters interpreting the valvular function, the most useful turns out to be the regurgitant volume. During AF, both atrial valves do not seem to worsen their performance, while the ventricular efficiency is remarkably reduced.

  16. Case report of an anal adenocarcinoma arising from a perineal lump

    Directory of Open Access Journals (Sweden)

    Dedrick Kok-Hong Chan

    2016-03-01

    Full Text Available Anal adenocarcinoma is a rare condition and can arise in chronic inflammatory states such as in Crohn's disease, or in a chronic fistula-in-ano. We report our diagnosis and management of a patient who presented with a large perineal lump with a long-standing history of perianal fistulous disease. This was initially evaluated with a Magnetic Resonance Imaging, and the diagnosis was confirmed with biopsy. Multimodality treatment with chemoradiotherapy and surgery should be offered to achieve the best outcomes.

  17. QSAR, docking, ADMET, and system pharmacology studies on tormentic acid derivatives for anticancer activity.

    Science.gov (United States)

    Alam, Sarfaraz; Khan, Feroz

    2017-08-02

    To explore the anticancer compounds from tormentic acid derivatives, a quantitative structure-activity relationship (QSAR) model was developed by the multiple linear regression methods. The developed QSAR model yielded a high activity-descriptors relationship accuracy of 94% referred by regression coefficient (r(2) = .94) and a high activity prediction accuracy of 91%. The QSAR study indicates that chemical descriptors, chiV5, T_T_Cl_7, T_2_T_4, SsCH3count, and Epsilon3 are significantly correlated with anticancer activity. This validated model was further been used for virtual screening and thus identification of new potential breast cancer inhibitors. Lipinski's rule of five, ADMET risk and synthetic accessibility are used to filter false positive hits. Filtered compounds were then docked to identify the possible target binding pocket, to obtain a set of aligned ligand poses and to prioritize the predicted active compounds. The scrutinized compounds, as well as their metabolites, were predicted and analyzed for different pharmacokinetics parameters such as absorption, distribution, metabolism, excretion, and toxicity. Finally, the top-ranked compound NB-12 was evaluated by system pharmacology approach. Later studied the metabolic networks, disease biomarker networks, pathway maps, drug-target networks and generate significant gene networks. The strategy applied in this research work may act as a framework for rational design of potential anticancer drugs.

  18. Comparative QSAR studies on toxicity of phenol derivatives using quantum topological molecular similarity indices.

    Science.gov (United States)

    Hemmateenejad, Bahram; Mehdipour, Ahmad R; Miri, Ramin; Shamsipur, Mojtaba

    2010-05-01

    Quantitative structure activity relationship (QSAR) analyses using a novel type of electronic descriptors called quantum topological molecular similarity (QTMS) indices were operated to describe and compare the mechanisms of toxicity of phenols toward five different strains (i.e., Tetrahymena pyriformis, L1210 Leukemia, Pseudomonas putida, Raja japonica and Cucumis sativus). The appropriate QSAR models for the toxicity data were obtained separately employing partial least squares (PLS) regression combined with genetic algorithms (GA), as a variable selection method. The resulting QSAR models were used to identify molecular fragments of phenol derivatives whose electronic properties contribute significantly to the observed toxicities. Using this information, it was feasible to discriminate between the mechanisms of action of phenol toxicity to the studied strains. It was found that toxicities of phenols to all strains, except with L1210 Leukemia, are significantly affected by electronic features of the phenolic hydroxyl group (C-O-H). Meanwhile, the resulting models can describe the inductive and resonance effects of substituents on various toxicities.

  19. A QSAR Study of Environmental Estrogens Based on a Novel Variable Selection Method

    Directory of Open Access Journals (Sweden)

    Aiqian Zhang

    2012-05-01

    Full Text Available A large number of descriptors were employed to characterize the molecular structure of 53 natural, synthetic, and environmental chemicals which are suspected of disrupting endocrine functions by mimicking or antagonizing natural hormones and may thus pose a serious threat to the health of humans and wildlife. In this work, a robust quantitative structure-activity relationship (QSAR model with a novel variable selection method has been proposed for the effective estrogens. The variable selection method is based on variable interaction (VSMVI with leave-multiple-out cross validation (LMOCV to select the best subset. During variable selection, model construction and assessment, the Organization for Economic Co-operation and Development (OECD principles for regulation of QSAR acceptability were fully considered, such as using an unambiguous multiple-linear regression (MLR algorithm to build the model, using several validation methods to assessment the performance of the model, giving the define of applicability domain and analyzing the outliers with the results of molecular docking. The performance of the QSAR model indicates that the VSMVI is an effective, feasible and practical tool for rapid screening of the best subset from large molecular descriptors.

  20. BCL::EMAS — Enantioselective Molecular Asymmetry Descriptor for 3D-QSAR

    Directory of Open Access Journals (Sweden)

    Mariusz Butkiewicz

    2012-08-01

    Full Text Available Stereochemistry is an important determinant of a molecule’s biological activity. Stereoisomers can have different degrees of efficacy or even opposing effects when interacting with a target protein. Stereochemistry is a molecular property difficult to represent in 2D-QSAR as it is an inherently three-dimensional phenomenon. A major drawback of most proposed descriptors for 3D-QSAR that encode stereochemistry is that they require a heuristic for defining all stereocenters and rank-ordering its substituents. Here we propose a novel 3D-QSAR descriptor termed Enantioselective Molecular ASymmetry (EMAS that is capable of distinguishing between enantiomers in the absence of such heuristics. The descriptor aims to measure the deviation from an overall symmetric shape of the molecule. A radial-distribution function (RDF determines a signed volume of tetrahedrons of all triplets of atoms and the molecule center. The descriptor can be enriched with atom-centric properties such as partial charge. This descriptor showed good predictability when tested with a dataset of thirty-one steroids commonly used to benchmark stereochemistry descriptors (r2 = 0.89, q2 = 0.78. Additionally, EMAS improved enrichment of 4.38 versus 3.94 without EMAS in a simulated virtual high-throughput screening (vHTS for inhibitors and substrates of cytochrome P450 (PUBCHEM AID891.