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Model Building (model + building)
Selected AbstractsThe Amber biomolecular simulation programsJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 16 2005David A. Case Abstract We describe the development, current features, and some directions for future development of the Amber package of computer programs. This package evolved from a program that was constructed in the late 1970s to do Assisted Model Building with Energy Refinement, and now contains a group of programs embodying a number of powerful tools of modern computational chemistry, focused on molecular dynamics and free energy calculations of proteins, nucleic acids, and carbohydrates. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 1668,1688, 2005 [source] Interpreting Experimental Data by Using Molecular Simulation Instead of Model BuildingCHEMISTRY - A EUROPEAN JOURNAL, Issue 26 2009Zrinka Gattin Abstract A proper description of the conformational equilibrium of polypeptides or proteins is essential for a correct description of their function. The conformational ensembles from 16 molecular dynamic simulations of two ,- heptapeptides were used to interpret the primary NMR data, which were also compared to a set of NMR model structures (see graphic). One of the most used spectroscopic techniques for resolving the structure of a biomolecule, such as a protein or peptide, is NMR spectroscopy. Because only NMR signal intensities and frequencies are measured in the experiment, a conformational interpretation of the primary data, that is, measured data, is not straightforward, especially for flexible molecules. It is hampered by the occurrence of conformational and/or time-averaging, by insufficient number of experimental data and by insufficient accuracy of experimental data. All three problematic aspects of structure refinement based on NMR nuclear Overhauser effect (NOE) intensities and 3J coupling data are illustrated by using two ,-heptapeptides in methanol as an example. We have performed 16 molecular dynamics (MD) simulations between 20 to 100,ns in length of unrestrained and NOE distance-restrained cases (instantaneous and time-averaged) of two ,-heptapeptides with a central ,-HAla(,-OH) amino acid in methanol at two different temperatures using two different GROMOS force-field parameter sets, 45,A3 and 53,A6. The created conformational ensembles were used to interpret the primary NMR data on these molecules. They also were compared to a set of NMR model structures derived by single-structure refinement in vacuo by using standard techniques. It is shown that the conformational interpretation of measured experimental data can be significantly improved by using unrestrained, instantaneous and time-averaged restrained MD simulations of the peptides by using a thermodynamically calibrated force field and by explicitly including solvent degrees of freedom. [source] D-branes in Standard Model building, gravity and cosmologyFORTSCHRITTE DER PHYSIK/PROGRESS OF PHYSICS, Issue 2-3 2004E. Kiritsis This is a review of aspects of D-brane applications to particle physics and cosmology. D-branes provide interesting alternatives to standard unification of interactions. Moreover they entail new mechanisms in cosmology that have the potential to explain recent observational data. [source] Techniques and tactics used in determining the structure of the trimeric ebolavirus glycoproteinACTA CRYSTALLOGRAPHICA SECTION D, Issue 11 2009Jeffrey E. Lee The trimeric membrane-anchored ebolavirus envelope glycoprotein (GP) is responsible for viral attachment, fusion and entry. Knowledge of its structure is important both for understanding ebolavirus entry and for the development of medical interventions. Crystal structures of viral glycoproteins, especially those in their metastable prefusion oligomeric states, can be difficult to achieve given the challenges in production, purification, crystallization and diffraction that are inherent in the heavily glycosylated flexible nature of these types of proteins. The crystal structure of ebolavirus GP in its trimeric prefusion conformation in complex with a human antibody derived from a survivor of the 1995 Kikwit outbreak has now been determined [Lee et al. (2008), Nature (London), 454, 177,182]. Here, the techniques, tactics and strategies used to overcome a series of technical roadblocks in crystallization and phasing are described. Glycoproteins were produced in human embryonic kidney 293T cells, which allowed rapid screening of constructs and expression of protein in milligram quantities. Complexes of GP with an antibody fragment (Fab) promoted crystallization and a series of deglycosylation strategies, including sugar mutants, enzymatic deglycosylation, insect-cell expression and glycan anabolic pathway inhibitors, were attempted to improve the weakly diffracting glycoprotein crystals. The signal-to-noise ratio of the search model for molecular replacement was improved by determining the structure of the uncomplexed Fab. Phase combination with Fab model phases and a selenium anomalous signal, followed by NCS-averaged density modification, resulted in a clear interpretable electron-density map. Model building was assisted by the use of B -value-sharpened electron-density maps and the proper sequence register was confirmed by building alternate sequences using N-linked glycan sites as anchors and secondary-structural predictions. [source] Model building and refinementACTA CRYSTALLOGRAPHICA SECTION D, Issue 12-1 2004Martin Noble First page of article [source] Expression, purification, crystallization and preliminary X-ray crystallographic analysis of a resuscitation-promoting factor from Mycobacterium tuberculosisACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 10 2007Alessia Ruggiero The resuscitation-promoting factor RpfB, the most complex of the five resuscitation-promoting factors produced by M. tuberculosis, is devoted to bacterial reactivation from the dormant state. RpfB consists of 362 residues predicted to form five domains. An RpfB fragment containing the protein catalytic domain and a G5 domain has been successfully crystallized using vapour-diffusion methods. This is the first crystallographic study of a resuscitation-promoting factor. Crystals of this protein belong to space group I422, with unit-cell parameters a = 97.63, b = 97.63, c = 114.87,Å. Diffraction data have also been collected from a selenomethionine derivative at 2.9,Å resolution. Model building using the phases derived from the multiwavelength anomalous dispersion experiment is in progress. [source] Cloning, expression, purification, crystallization and preliminary structure determination of glucose-1-phosphate uridylyltransferase (UgpG) from Sphingomonas elodea ATCC 31461 bound to glucose-1-phosphateACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 9 2006D. Aragão The cloning, expression, purification, crystallization and preliminary crystallographic analysis of glucose-1-phosphate uridylyltransferase (UgpG) from Sphingomonas elodea ATCC 31461 bound to glucose-1-phosphate are reported. Diffraction data sets were obtained from seven crystal forms in five different space groups, with highest resolutions ranging from 4.20 to 2.65,Å. The phase problem was solved for a P21 crystal form using multiple isomorphous replacement with anomalous scattering from an osmium derivative and a SeMet derivative. The best native crystal in space group P21 has unit-cell parameters a = 105.5, b = 85.7, c = 151.8,Å, , = 105.2°. Model building and refinement are currently under way. [source] Crystallization and preliminary X-ray crystallographic analysis of the Sulfolobus solfataricus nucleotide-exchange factor 1,ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 11 2005Paolo Arcari The nucleotide-exchange factor isolated from the hyperthermophilic archaeon Sulfolobus solfataricus (SsEF-1,) consists of 90 residues and differs from eukaryal EF-1,s. The protein has been successfully crystallized using either microbatch-under-oil or vapour-diffusion methods. Crystals of native SsEF-1, diffract to 1.97,Å resolution and belong to space group P21212, with unit-cell parameters a = 106.46, b = 54.87, c = 44.03,Å. Diffraction data have also been collected from a selenomethionine derivative of SsEF-1, at 1.83,Å resolution. Model building using the phases derived from the MAD experiment is in progress. [source] Population pharmacokinetic modelling of gentamicin and vancomycin in patients with unstable renal function following cardiothoracic surgeryBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2006Christine E. Staatz Aims To describe the population pharmacokinetics of gentamicin and vancomycin in cardiothoracic surgery patients with unstable renal function. Methods Data collected during routine care were analyzed using NONMEM. Linear relationships between creatinine clearance (CLCr) and drug clearance (CL) were identified, and two approaches to modelling changing CLCr were examined. The first included baseline (BCOV) and difference from baseline (DCOV) effects and the second allowed the influence of CLCr to vary between individuals. Final model predictive performance was evaluated using independent data. The data sets were then combined and parameters re-estimated. Results Model building was performed using data from 96 (gentamicin) and 102 (vancomycin) patients, aged 17,87 years. CLCr ranged from 9 to 172 ml min,1 and changes varied from ,76 to 58 ml min,1 (gentamicin) and ,86 to 93 ml min,1 (vancomycin). Inclusion of BCOV and DCOV improved the fit of the gentamicin data but had little effect on that for vancomycin. Inclusion of interindividual variability (IIV) in the influence of CLcr resulted in a poorly characterized model for gentamicin and had no effect on vancomycin modelling. No bias was seen in population compared with individual CL estimates in independent data from 39 (gentamicin) and 37 (vancomycin) patients. Mean (95% CI) differences were 4% (,3, 11%) and 2% (,2, 6%), respectively. Final estimates were: CLGent (l h,1) = 2.81 × (1 + 0.015 × (BCOVCLCr -BCOVCLCr,Median) + 0.0174 × DCOVCLCr); CLVanc (l h,1) = 2.97 × (1 + 0.0205 ×, (CLCr -CLCr,Median)). IIV in CL was 27% for both drugs. Conclusions A parameter describing individual changes in CLcr with time improves population pharmacokinetic modelling of gentamicin but not vancomycin in clinically unstable patients. [source] Self-Regulated Learning in Technology-Enhanced Learning Environments: lessons of a European peer reviewEUROPEAN JOURNAL OF EDUCATION, Issue 3-4 2006KARL STEFFENS This article first describes the state-of-the-art of model building and empirical research in the field of self-regulated learning (SRL) and then focuses on self-regulated learning in Technology-Enhanced Learning Environments (TELEs). We present recent research results obtained in a European project (TELEPEERS) in the context of which we evaluated TELEs in a peer review manner with respect to their potential for supporting self-regulated learning. In addition, data were obtained on a sample of TELEPEERS students working in these environments and comparative analyses were made across the European project partners. [source] Conformational studies on a unique bis-sulfated glycolipid using NMR spectroscopy and molecular dynamics simulationsFEBS JOURNAL, Issue 23 2000Naoko Iida-Tanaka The time-averaged solution conformation of a unique bis-sulfated glycolipid (HSO3)2 -2,6Man,-2Glc,-1- sn -2,3- O -alkylglycerol, was studied in terms of the torsional angles of two glycosidic linkages, , (H1-C1-O-Cx) and , (C1-O-Cx-Hx), derived from heteronuclear three-bond coupling constants (3JC,H), and inter-residual proton,proton distances from J-HMBC 2D and ROESY experiments, respectively. The dihedral angles of Glc,1Gro in glycolipids were determined for the first time. The C1-C4 diagonal line of the ,-glucose ring makes an angle of ,,120 ° with the glycerol backbone, suggesting that the ,-glucose ring is almost parallel to the membrane surface in contrast with the perpendicular orientation of the ,-isomer. Furthermore, minimum-energy states around the conformation were estimated by Monte Carlo/stochastic dynamics (MCSD) mixed-mode simulations and the energy minimization with assisted model building and energy refinement (AMBER) force field. The Glc,1Gro linkage has a single minimum-energy structure. On the other hand, three conformers were observed for the Man,2Glc linkage. The flexibility of Man,2Glc was further confirmed by the absence of inter-residual hydrogen bonds which were judged from the temperature coefficients of the chemical shifts, d,/dT (,10,3 p.p.m.·°C,1), of hydroxy protons. The conformational flexibility may facilitate interaction of extracellular substances with both sulfate groups. [source] The landscape of string theory (orientifolds and their statistics, D-brane instantons, AdS4 domain walls and black holes)FORTSCHRITTE DER PHYSIK/PROGRESS OF PHYSICS, Issue 7-9 2008D. Lüst Abstract In this talk we discuss various aspects of the string landscape: D-brane model building and their statistics, the generation of non-perturbative superpotentials from D-brane instantons, moduli stabilization by fluxes and non-perturbative effects, the relation between flux vacua and BPS black holes, the construction of AdS4 vacua and related domain wall solutions, transitions between flux vacua and also some constraints on the string landscape from black hole considerations. [source] Brane tilings and their applicationsFORTSCHRITTE DER PHYSIK/PROGRESS OF PHYSICS, Issue 6 2008M. Yamazaki Abstract We review recent developments in the theory of brane tilings and four-dimensional ,, = 1 supersymmetric quiver gauge theories. This review consists of two parts. In part I, we describe foundations of brane tilings, emphasizing the physical interpretation of brane tilings as fivebrane systems. In part II, we discuss application of brane tilings to AdS/CFT correspondence and homological mirror symmetry. More topics, such as orientifold of brane tilings, phenomenological model building, similarities with BPS solitons in supersymmetric gauge theories, are also briefly discussed. This paper is a revised version of the author's master's thesis submitted to Department of Physics, Faculty of Science, the University of Tokyo on January 2008, and is based on his several papers and some works in progress [1,7]. [source] Aspects of stability and phenomenology in type IIA orientifolds with intersecting D6-branesFORTSCHRITTE DER PHYSIK/PROGRESS OF PHYSICS, Issue 1 2004T. OttArticle first published online: 14 JAN 200 Abstract Intersecting branes have been the subject of an elaborate string model building for several years. After a general introduction into string theory, this work introduces in detail the toroidal and -orientifolds. The picture involving D9-branes with B-fluxes is shortly reviewed, but the main discussion employs the T-dual picture of intersecting D6-branes. The derivation of the R-R and NS-NS tadpole cancellation conditions in the conformal field theory is shown in great detail. Various aspects of the open and closed chiral and non-chiral massless spectrum are discussed, involving spacetime anomalies and the generalized Green-Schwarz mechanism. An introduction into possible gauge breaking mechanisms is given, too. Afterwards, both ,, = 1 supersymmetric and non-supersymmetric approaches to low energy model building are treated. Firstly, the problem of complex structure instabilities in toroidal ,R -orientifolds is approached by a -orbifolded model. In particular, a stable non-supersymmetric standard-like model with three fermion generations is discussed. This model features the standard model gauge groups at the same time as having a massless hypercharge, but possessing an additional global B - L symmetry. The electroweak Higgs mechanism and the Yukawa couplings are not realized in the usual way. It is shown that this model descends naturally from a flipped SU(5) GUT model, where the string scale has to be at least of the order of the GUT scale. Secondly, supersymmetric models on the -orbifold are discussed, involving exceptional 3-cycles and the explicit construction of fractional D-branes. A three generation Pati-Salam model is constructed as a particular example, where several brane recombination mechanisms are used, yielding non-flat and non-factorizable branes. This model even can be broken down to a MSSM-like model with a massless hypercharge. Finally, the possibility that unstable closed and open string moduli could have played the role of the inflaton in the evolution of the universe is being explored. In the closed string sector, the important slow-rolling requirement can only be fulfilled for very specific cases, where some moduli are frozen and a special choice of coordinates is taken. In the open string sector, inflation does not seem to be possible at all. [source] Landscape influences on aluminium and dissolved organic carbon in streams draining the Hubbard Brook valley, New Hampshire, USAHYDROLOGICAL PROCESSES, Issue 9 2005Sheila M. Palmer Abstract Concentrations of both aluminium (Al) and dissolved organic carbon (DOC) in stream waters are likely to be regulated by factors that influence water flowpaths and residence times, and by the nature of the soil horizons through which waters flow. In order to investigate landscape-scale spatial patterns in streamwater Al and DOC, we sampled seven streams draining the Hubbard Brook valley in central New Hampshire. We observed considerable variation in stream chemistry both within and between headwater watersheds. Across the valley, concentrations of total monomeric aluminium (Alm) ranged from below detection limits (<0·7 µmol l,1) to 22·3 µmol l,1. In general, concentrations of Alm decreased as pH increased downslope. There was a strong relationship between organic monomeric aluminium (Alo) and DOC concentrations (R2 = 0·92). We observed the highest Alm concentrations in: (i) a watershed characterized by a steep narrow drainage basin and shallow soils and (ii) a watershed characterized by exceptionally deep forest floor soils and high concentrations of DOC. Forest floor depth and drainage area together explained much of the variation in ln Alm (R2 = 0·79; N = 45) and ln DOC (R2 = 0·87; N = 45). Linear regression models were moderately successful in predicting ln Alm and ln DOC in streams that were not included in model building. However, when back-transformed, predicted DOC concentrations were as much as 72% adrift from observed DOC concentrations and Alm concentrations were up to 51% off. This geographic approach to modelling Al and DOC is useful for general prediction, but for more detailed predictions, process-level biogeochemical models are required. Copyright © 2005 John Wiley & Sons, Ltd. [source] Bankruptcy prediction: the influence of the year prior to failure selected for model building and the effects in a period of economic declineINTELLIGENT SYSTEMS IN ACCOUNTING, FINANCE & MANAGEMENT, Issue 2 2005Paul P. M. Pompe Using large amounts of data from small and medium-sized industrial firms, this study examines two aspects of bankruptcy prediction: the influence of the year prior to failure selected for model building and the effects in a period of economic decline. The results show that especially models generated from the final annual report published prior to bankruptcy were less successful in the timely prediction of failure. Furthermore, it was found that economic decline coincided with the deterioration of a model's performance. With respect to the methods used, we found that neural networks had a somewhat better overall performance than multiple discriminant analysis. Copyright © 2005 John Wiley & Sons, Ltd. [source] Twelve-year course and outcome predictors of anorexia nervosaINTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 2 2006Dipl-Psych, Manfred M. Fichter MD Abstract Objective The current study presents the long-term course of anorexia nervosa (AN) over 12 years in a large sample of 103 patients diagnosed according to criteria in the 4th ed. of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Method Assessments were made at the beginning of therapy, at the end of therapy, at the 2-year follow-up, at the 6-year follow-up, and at the 12-year follow-up. Self-rating and an expert-rating interview data were obtained. Results The participation rate at the 12-year follow-up was 88% of those alive. There was substantial improvement during therapy, a moderate (in many instances nonsignificant) decline during the first 2 years posttreatment, and further improvement from 3 to 12 years posttreatment. Based on a global 12-year outcome score, 27.5% had a good outcome, 25.3% an intermediate outcome, 39.6% had a poor outcome, and 7 (7.7%) were deceased. At the 12-year follow-up 19.0% had AN, 9.5% had bulimia nervosa-purging type (BN-P), 19.0% were classified as eating disorder not otherwise specified (EDNOS). A total of 52.4% showed no major DSM-IV eating disorder and 0% had binge eating disorder (BED). Systematic,strictly empirically based,model building resulted in a parsimonious model including four predictors of unfavorable 12-year outcome explaining 45% of the variance, that is, sexual problems, impulsivity, long duration of inpatient treatment, and long duration of an eating disorder. Conclusion Mortality was high and symptomatic recovery protracted. Impulsivity, symptom severity, and chronicity were the important factors for predicting the 12-year outcome. © 2005 by Wiley Periodicals, Inc. [source] Autolabo: an automated system for ligand-soaking experiments with protein crystalsJOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 4 2010Michihiro Sugahara Ligand soaking of protein crystals is important for the preparation of heavy-atom derivative crystals for experimental phasing as well as for large-scale ligand screening in pharmaceutical developments. To facilitate laborious large-scale ligand screening, to reduce the risk of human contact with hazardous ligand reagents and to increase the success rate of the soaking experiments, a protein crystallization robot `Autolabo' has been developed and implemented in the high-throughput crystallization-to-structure pipeline at RIKEN SPring-8 Center. The main functions of this robotic system are the production of protein crystals for experiments, the ligand soaking of these crystals and the observation of soaked crystals. The separate eight-channel dispensers of Autolabo eliminate the cross-contamination of reagents which should be strictly avoided in the ligand-soaking experiment. Furthermore, the automated approach reduces physical damage to crystals during experiments when compared with the conventional manual approach, and thereby has the potential to yield better quality diffraction data. Autolabo's performance as a ligand-soaking system was evaluated with a crystallization experiment on ten proteins from different sources and a heavy-atom derivatization experiment on three proteins using a versatile cryoprotectant containing heavy-atom reagents as ligands. The crystallization test confirmed reliable crystal reproduction in a single condition and the capability for crystallization with nucleants to improve crystal quality. Finally, Autolabo reproducibly derivatized the test protein crystals with sufficient diffraction quality for experimental phasing and model building, indicating a high potentiality of this automated approach in ligand-soaking experiments. [source] Cognitive perturbation through dynamic modelling: a pedagogical approach to conceptual change in scienceJOURNAL OF COMPUTER ASSISTED LEARNING, Issue 6 2006S. C. Li Abstract While simulations have widely been used to facilitate conceptual change in learning science, results indicate that significant disparity or gap between students' prior conceptions and scientific conceptions still exists. To bridge the gap, we argue that the applications of computer simulation in science education should be broadened to enable students to model their thoughts and to improve and advance their theories progressively. While computer simulations are often used to offer opportunities for students to explore scientific models, they do not give them the space to explore their own conceptions, and thus cannot effectively address the challenge of changing students' alternative conceptions. Findings from our recent empirical study reveal that, firstly, dynamic modelling using the environment WorldMaker 2000 in conjunction with the use of a cognitive perturbation strategy by the teacher was effective in helping students to migrate from their alternative conceptions towards a more scientifically inclined one; secondly, the pathways of conceptual change across groups were idiosyncratic and diverse. Respecting students' ideas seriously and providing cognitive perturbation at appropriate junctures of the inquiry process are found to be conducive to fostering conceptual change. In this paper, we will report on the details of the pedagogical approach adopted by the teacher and portray how students' conceptions change during the entire process of model building. [source] Monitoring of batch processes through state-space modelsAICHE JOURNAL, Issue 6 2004Jay H. Lee Abstract The development of a state-space framework for monitoring batch processes that can complement the existing multivariate monitoring methods is presented. A subspace identification method will be used to extract the dynamic and batch-to-batch trends of the process and quality variables from historical operation data in the form of a "lifted" state-space stochastic model. A simple monitoring procedure can be formed around the state and residuals of the model using appropriate scalar statistical metrics. The proposed state-space monitoring framework complements the existing multivariate methods like the multi-way PCA method, in that it allows us to build a more complete statistical representation of batch operations and use it with incoming measurements for early detection of not only large, abrupt changes but also subtle changes. In particular, it is shown to be effective for detecting changes in the batch-to-batch correlation structure, slow drifts, and mean shifts. Such information can be useful in adapting the prediction model for batch-to-batch control. The framework allows for the use of on-line process measurements and/or off-line quality measurements. When both types of measurements are used in model building, one can also use the model to predict the quality variables based on incoming on-line measurements and quality measurements of previous batches. © 2004 American Institute of Chemical Engineers AIChE J, 50: 1198,1210, 2004 [source] Developing a learning progression for scientific modeling: Making scientific modeling accessible and meaningful for learnersJOURNAL OF RESEARCH IN SCIENCE TEACHING, Issue 6 2009Christina V. Schwarz Abstract Modeling is a core practice in science and a central part of scientific literacy. We present theoretical and empirical motivation for a learning progression for scientific modeling that aims to make the practice accessible and meaningful for learners. We define scientific modeling as including the elements of the practice (constructing, using, evaluating, and revising scientific models) and the metaknowledge that guides and motivates the practice (e.g., understanding the nature and purpose of models). Our learning progression for scientific modeling includes two dimensions that combine metaknowledge and elements of practice,scientific models as tools for predicting and explaining, and models change as understanding improves. We describe levels of progress along these two dimensions of our progression and illustrate them with classroom examples from 5th and 6th graders engaged in modeling. Our illustrations indicate that both groups of learners productively engaged in constructing and revising increasingly accurate models that included powerful explanatory mechanisms, and applied these models to make predictions for closely related phenomena. Furthermore, we show how students engaged in modeling practices move along levels of this progression. In particular, students moved from illustrative to explanatory models, and developed increasingly sophisticated views of the explanatory nature of models, shifting from models as correct or incorrect to models as encompassing explanations for multiple aspects of a target phenomenon. They also developed more nuanced reasons to revise models. Finally, we present challenges for learners in modeling practices,such as understanding how constructing a model can aid their own sensemaking, and seeing model building as a way to generate new knowledge rather than represent what they have already learned. © 2009 Wiley Periodicals, Inc. J Res Sci Teach 46: 632,654, 2009 [source] Identification of individual tigers (Panthera tigris) from their pugmarksJOURNAL OF ZOOLOGY, Issue 1 2005Sandeep Sharma Abstract An objective multivariate technique is described for identification of individual tigers Panthera tigris from their pugmarks. Tracings and photographs of hind pugmarks were obtained from 23 pugmark-sets of 19 individually known tigers (17 wild and two captive tigers). These 23 pugmark-sets were then divided into two groups, one of 15 pugmark-sets for model building and another of eight pugmark-sets for model testing and validation. A total of 93 measurements were taken from each pugmark along with three gait measurements. We used CV ratio, F -ratio and removed highly correlated variables to finally select 11 variables from these 93 variables. These 11 variables did not differ between left and right pugmarks. Stepwise discriminant function analysis (DFA) based on these 11 variables correctly classified pugmark-sets to individual tigers. A realistic population estimation exercise was simulated using the validation dataset. The algorithms developed here correctly allocated each pugmark-set to the correct individual tiger. The effect of extraneous factors, i.e. soil depth and multiple tracers, was also tested and pugmark tracings compared with pugmark photographs. We recommend collecting pugmarks from soil depths ranging between 0.5 and 1.0 cm, and advocate the use of pugmark photographs rather than pugmark tracings to eliminate the chance of obtaining substandard data from untrained tracers. Our study suggests that tigers can be individually identified from their pugmarks with a high level of accuracy and pugmark-sets could be used for population estimation of tigers within a statistically designed mark,recapture framework. [source] PLS: A versatile tool for industrial process improvement and optimizationAPPLIED STOCHASTIC MODELS IN BUSINESS AND INDUSTRY, Issue 6 2008Alberto Ferrer Abstract Modern industrial processes are characterized by acquiring massive amounts of highly collinear data. In this context, partial least-squares (PLS) regression, if wisely used, can become a strategic tool for process improvement and optimization. In this paper we illustrate the versatility of this technique through several real case studies that basically differ in the structure of the X matrix (process variables) and Y matrix (response parameters). By using the PLS approach, the results show that it is possible to build predictive models (soft sensors) for monitoring the performance of a wastewater treatment plant, to help in the diagnosis of a complex batch polymerization process, to develop an automatic classifier based on image data, or to assist in the empirical model building of a continuous polymerization process. Copyright © 2008 John Wiley & Sons, Ltd. [source] Generation and Evaluation of a Homology Model of PfGSK-3ARCHIV DER PHARMAZIE, Issue 6 2009Sebastian Kruggel Abstract Plasmodial GSK-3 is a potential new target for malaria therapy. For a structure-based design project, the three-dimensional information of the designated target is needed. Unfortunately, experimental structure data for plasmodial GSK-3 is not yet available. Homology building can be used to generate such three-dimensional structure data using structure information of a homologous protein. GSK-3 possesses a very flexible ATP-binding site, a fact reflected in the variety of X-ray structures of the human GSK-3, which are deposited in the protein data base and are crystallized with different ligands. We used ten different HsGSK-3, templates for the model building of plasmodial GSK-3 and generated 200 models for each template with different modeling protocols. The quality of the models was evaluated with different tools. The results of these evaluations were used to calculate a rank-by-rank consensus score. The top models of this were used to compile an ensemble of PfGSK-3 models that reflect the flexibility of the ATP-binding site and that will be used for the structure-based design of potential ATP-binding site inhibitors of PfGSK-3. [source] Multivariate phase combination improves automated crystallographic model buildingACTA CRYSTALLOGRAPHICA SECTION D, Issue 7 2010Pavol Skubák Density modification is a standard technique in macromolecular crystallography that can significantly improve an initial electron-density map. To obtain optimal results, the initial and density-modified map are combined. Current methods assume that these two maps are independent and propagate the initial map information and its accuracy indirectly through previously determined coefficients. A multivariate equation has been derived that no longer assumes independence between the initial and density-modified map, considers the observed diffraction data directly and refines the errors that can occur in a single-wavelength anomalous diffraction experiment. The equation has been implemented and tested on over 100 real data sets. The results are dramatic: the method provides significantly improved maps over the current state of the art and leads to many more structures being built automatically. [source] Application of protein engineering to enhance crystallizability and improve crystal propertiesACTA CRYSTALLOGRAPHICA SECTION D, Issue 5 2010Zygmunt S. Derewenda Until recently, protein crystallization has mostly been regarded as a stochastic event over which the investigator has little or no control. With the dramatic technological advances in synchrotron-radiation sources and detectors and the equally impressive progress in crystallographic software, including automated model building and validation, crystallization has increasingly become the rate-limiting step in X-ray diffraction studies of macromolecules. However, with the advent of recombinant methods it has also become possible to engineer target proteins and their complexes for higher propensity to form crystals with desirable X-ray diffraction qualities. As most proteins that are under investigation today are obtained by heterologous overexpression, these techniques hold the promise of becoming routine tools with the potential to transform classical crystallization screening into a more rational high-success-rate approach. This article presents an overview of protein-engineering methods designed to enhance crystallizability and discusses a number of examples of their successful application. [source] Experimental phasing: best practice and pitfallsACTA CRYSTALLOGRAPHICA SECTION D, Issue 4 2010Airlie J. McCoy Developments in protein crystal structure determination by experimental phasing are reviewed, emphasizing the theoretical continuum between experimental phasing, density modification, model building and refinement. Traditional notions of the composition of the substructure and the best coefficients for map generation are discussed. Pitfalls such as determining the enantiomorph, identifying centrosymmetry (or pseudo-symmetry) in the substructure and crystal twinning are discussed in detail. An appendix introduces combined real,imaginary log-likelihood gradient map coefficients for SAD phasing and their use for substructure completion as implemented in the software Phaser. Supplementary material includes animated probabilistic Harker diagrams showing how maximum-likelihood-based phasing methods can be used to refine parameters in the case of SIR and MIR; it is hoped that these will be useful for those teaching best practice in experimental phasing methods. [source] Recent developments in classical density modificationACTA CRYSTALLOGRAPHICA SECTION D, Issue 4 2010Kevin Cowtan Classical density-modification techniques (as opposed to statistical approaches) offer a computationally cheap method for improving phase estimates in order to provide a good electron-density map for model building. The rise of statistical methods has lead to a shift in focus away from the classical approaches; as a result, some recent developments have not made their way into classical density-modification software. This paper describes the application of some recent techniques, including most importantly the use of prior phase information in the likelihood estimation of phase errors within a classical density-modification framework. The resulting software gives significantly better results than comparable classical methods, while remaining nearly two orders of magnitude faster than statistical methods. [source] Features and development of CootACTA CRYSTALLOGRAPHICA SECTION D, Issue 4 2010P. Emsley Coot is a molecular-graphics application for model building and validation of biological macromolecules. The program displays electron-density maps and atomic models and allows model manipulations such as idealization, real-space refinement, manual rotation/translation, rigid-body fitting, ligand search, solvation, mutations, rotamers and Ramachandran idealization. Furthermore, tools are provided for model validation as well as interfaces to external programs for refinement, validation and graphics. The software is designed to be easy to learn for novice users, which is achieved by ensuring that tools for common tasks are `discoverable' through familiar user-interface elements (menus and toolbars) or by intuitive behaviour (mouse controls). Recent developments have focused on providing tools for expert users, with customisable key bindings, extensions and an extensive scripting interface. The software is under rapid development, but has already achieved very widespread use within the crystallographic community. The current state of the software is presented, with a description of the facilities available and of some of the underlying methods employed. [source] Rapid model building of ,-helices in electron-density mapsACTA CRYSTALLOGRAPHICA SECTION D, Issue 3 2010Thomas C. Terwilliger A method for the identification of ,-helices in electron-density maps at low resolution followed by interpretation at moderate to high resolution is presented. Rapid identification is achieved at low resolution, where ,-helices appear as tubes of density. The positioning and direction of the ,-helices is obtained at moderate to high resolution, where the positions of side chains can be seen. The method was tested on a set of 42 experimental electron-density maps at resolutions ranging from 1.5 to 3.8,Å. An average of 63% of the ,-helical residues in these proteins were built and an average of 76% of the residues built matched helical residues in the refined models of the proteins. The overall average r.m.s.d. between main-chain atoms in the modeled ,-helices and the nearest atom with the same name in the refined models of the proteins was 1.3,Å. [source] | ||||||||||||||||