The dual role of fragments in fragment-assembly methods for de novo protein structure prediction

Science.gov (United States)

Handl, Julia; Knowles, Joshua; Vernon, Robert; Baker, David; Lovell, Simon C.

2013-01-01

In fragment-assembly techniques for protein structure prediction, models of protein structure are assembled from fragments of known protein structures. This process is typically guided by a knowledge-based energy function and uses a heuristic optimization method. The fragments play two important roles in this process: they define the set of structural parameters available, and they also assume the role of the main variation operators that are used by the optimiser. Previous analysis has typically focused on the first of these roles. In particular, the relationship between local amino acid sequence and local protein structure has been studied by a range of authors. The correlation between the two has been shown to vary with the window length considered, and the results of these analyses have informed directly the choice of fragment length in state-of-the-art prediction techniques. Here, we focus on the second role of fragments and aim to determine the effect of fragment length from an optimization perspective. We use theoretical analyses to reveal how the size and structure of the search space changes as a function of insertion length. Furthermore, empirical analyses are used to explore additional ways in which the size of the fragment insertion influences the search both in a simulation model and for the fragment-assembly technique, Rosetta. PMID:22095594

Quantum mechanical fragment methods based on partitioning atoms or partitioning coordinates.

Science.gov (United States)

Wang, Bo; Yang, Ke R; Xu, Xuefei; Isegawa, Miho; Leverentz, Hannah R; Truhlar, Donald G

2014-09-16

Conspectus The development of more efficient and more accurate ways to represent reactive potential energy surfaces is a requirement for extending the simulation of large systems to more complex systems, longer-time dynamical processes, and more complete statistical mechanical sampling. One way to treat large systems is by direct dynamics fragment methods. Another way is by fitting system-specific analytic potential energy functions with methods adapted to large systems. Here we consider both approaches. First we consider three fragment methods that allow a given monomer to appear in more than one fragment. The first two approaches are the electrostatically embedded many-body (EE-MB) expansion and the electrostatically embedded many-body expansion of the correlation energy (EE-MB-CE), which we have shown to yield quite accurate results even when one restricts the calculations to include only electrostatically embedded dimers. The third fragment method is the electrostatically embedded molecular tailoring approach (EE-MTA), which is more flexible than EE-MB and EE-MB-CE. We show that electrostatic embedding greatly improves the accuracy of these approaches compared with the original unembedded approaches. Quantum mechanical fragment methods share with combined quantum mechanical/molecular mechanical (QM/MM) methods the need to treat a quantum mechanical fragment in the presence of the rest of the system, which is especially challenging for those parts of the rest of the system that are close to the boundary of the quantum mechanical fragment. This is a delicate matter even for fragments that are not covalently bonded to the rest of the system, but it becomes even more difficult when the boundary of the quantum mechanical fragment cuts a bond. We have developed a suite of methods for more realistically treating interactions across such boundaries. These methods include redistributing and balancing the external partial atomic charges and the use of tuned fluorine

The linearly scaling 3D fragment method for large scale electronic structure calculations

Energy Technology Data Exchange (ETDEWEB)

Zhao Zhengji [National Energy Research Scientific Computing Center (NERSC) (United States); Meza, Juan; Shan Hongzhang; Strohmaier, Erich; Bailey, David; Wang Linwang [Computational Research Division, Lawrence Berkeley National Laboratory (United States); Lee, Byounghak, E-mail: ZZhao@lbl.go [Physics Department, Texas State University (United States)

2009-07-01

The linearly scaling three-dimensional fragment (LS3DF) method is an O(N) ab initio electronic structure method for large-scale nano material simulations. It is a divide-and-conquer approach with a novel patching scheme that effectively cancels out the artificial boundary effects, which exist in all divide-and-conquer schemes. This method has made ab initio simulations of thousand-atom nanosystems feasible in a couple of hours, while retaining essentially the same accuracy as the direct calculation methods. The LS3DF method won the 2008 ACM Gordon Bell Prize for algorithm innovation. Our code has reached 442 Tflop/s running on 147,456 processors on the Cray XT5 (Jaguar) at OLCF, and has been run on 163,840 processors on the Blue Gene/P (Intrepid) at ALCF, and has been applied to a system containing 36,000 atoms. In this paper, we will present the recent parallel performance results of this code, and will apply the method to asymmetric CdSe/CdS core/shell nanorods, which have potential applications in electronic devices and solar cells.

ALIS-FLP: Amplified ligation selected fragment-length polymorphism method for microbial genotyping

DEFF Research Database (Denmark)

Brillowska-Dabrowska, A.; Wianecka, M.; Dabrowski, Slawomir

2008-01-01

A DNA fingerprinting method known as ALIS-FLP (amplified ligation selected fragment-length polymorphism) has been developed for selective and specific amplification of restriction fragments from TspRI restriction endonuclease digested genomic DNA. The method is similar to AFLP, but differs...

Hot-stage microscopy for determination of API fragmentation: comparison with other methods.

Science.gov (United States)

Šimek, Michal; Grünwaldová, Veronika; Kratochvíl, Bohumil

2016-08-01

Although the fragmentation of the active pharmaceutical ingredient (API) is a phenomenon that is mentioned in many literature sources, no well-suited analytical tools for its investigation are currently known. We used the hot-stage microscopy method, already presented in our previous work, and studied the real fragmentation of the tadalafil particles in model tablets which were prepared under different compaction pressures. The morphology, spectral imaging and evaluation of plastic and elastic energies were also analyzed to support the hot-stage method. The prepared blend of tadalafil and excipients was compacted under a several forces from 5 to 35 kN to reveal the trend of fragmentation. The exact fragmentation of tadalafil with increased compaction pressure was revealed by the hot-stage microscopic method and it was in good agreement with plastic and elastic energies. Conversely, spectral imaging, which is being used for this analysis, was considered to be inaccurate methodology as mainly agglomerates, not individual particles, were measured. The availability of the hot-stage microscopic method equips pharmaceutical scientists with an in vitro assessment technique that will more reliably determine the fragmentation of the API in finished tablets and the behavior of the particles when compacted.

Research on Splicing Method of Digital Relic Fragment Model

Science.gov (United States)

Yan, X.; Hu, Y.; Hou, M.

2018-04-01

In the course of archaeological excavation, a large number of pieces of cultural relics were unearthed, and the restoration of these fragments was done manually by traditional arts and crafts experts. In this process, cultural relics experts often try to splice the existing cultural relics, and then use adhesive to stick together the fragments of correct location, which will cause irreversible secondary damage to cultural relics. In order to minimize such damage, the surveyors combine 3D laser scanning with computer technology, and use the method of establishing digital cultural relics fragments model to make virtual splicing of cultural relics. The 3D software on the common market can basically achieve the model translation and rotation, using this two functions can be achieved manually splicing between models, mosaic records after the completion of the specific location of each piece of fragments, so as to effectively reduce the damage to the relics had tried splicing process.

Fragmentation of rotating protostellar clouds

International Nuclear Information System (INIS)

Tohline, J.E.

1980-01-01

We examine, with a three-dimensional hydrodynamic computer code, the behavior of rotating, isothermal gas clouds as they collapse from Jeans unstable configurations, in order to determine whether they are susceptible to fragmentation during the initial dynamic collapse phase of their evolution. We find that a gas cloud will not fragment unless (a) it begins collapsing from a radius much smaller than the Jeans radius (i.e., the cloud initially encloses many Jeans masses) and (b) irregularities in the cloud's initial structure (specifically, density inhomogeneities) enclose more than one Jeans mass of material. Gas pressure smooths out features that are not initially Jeans unstable while rotation plays no direct role in damping inhomogeneities. Instead of fragmenting, most of our models collapse to a ring configuration (as has been observed by other investigators in two-dimensional, axisymmetric models). The rings appear to be less susceptible to gragmentation from arbitrary perturbations in their structure than has previously been indicated in other work. Because our models, which include the effects of gas pressure, do not readily fragment during a phase of dynamic collapse, we suggest that gas clouds in the galactic disk undergo fragmentation only during quasi-equilibrium phases of their evolution

Fragment-based drug discovery using rational design.

Science.gov (United States)

Jhoti, H

2007-01-01

Fragment-based drug discovery (FBDD) is established as an alternative approach to high-throughput screening for generating novel small molecule drug candidates. In FBDD, relatively small libraries of low molecular weight compounds (or fragments) are screened using sensitive biophysical techniques to detect their binding to the target protein. A lower absolute affinity of binding is expected from fragments, compared to much higher molecular weight hits detected by high-throughput screening, due to their reduced size and complexity. Through the use of iterative cycles of medicinal chemistry, ideally guided by three-dimensional structural data, it is often then relatively straightforward to optimize these weak binding fragment hits into potent and selective lead compounds. As with most other lead discovery methods there are two key components of FBDD; the detection technology and the compound library. In this review I outline the two main approaches used for detecting the binding of low affinity fragments and also some of the key principles that are used to generate a fragment library. In addition, I describe an example of how FBDD has led to the generation of a drug candidate that is now being tested in clinical trials for the treatment of cancer.

The identification method of the nuclear fragments in emulsions

International Nuclear Information System (INIS)

Jipa, Alexandru; Ocheseanu, Silvia; Caramarcu, Costin; Calin, Marius; Constantin, Florin; Stan, Emil

2003-01-01

The visualization detectors have been successfully used from the beginning of the study of the relativistic nuclear collisions. One of these detectors used in such experiments is the nuclear emulsion. To increase the speed of the passage from pictures to experimental data different methods and tools have been proposed during the time. For identifying the nuclear fragments obtained in the relativistic radioactive beams multiple layers of nuclear emulsions have been exposed in experiments performed at the Synchrophasotron from the JINR Dubna (BECQUEREL Collaboration). The nuclear fragments have been identified using PAVICOM scanning and measuring system. In the present work an identification method based on a real time image processing machine and a reconstruction algorithm based on special conformal transforms is proposed. The results obtained by this method are compared with those obtained using PAVICOM device. Because in this study only pictures have been used, not initial nuclear emulsions, some difficulties in the identification of the nuclear fragments with higher polar angles can appear. Generally, comparable results have been obtained. The authors thank Dr. Pavel Zarubin from JINR Dubna, Laboratory of High Energy Physics, and Dr. Maria Haiduc, Institute of Space Sciences Bucharest-Magurele, for the pictures of the nuclear emulsions exposed in these experiments. (authors)

Thermochemical Fragment Energy Method for Biomolecules: Application to a Collagen Model Peptide.

Science.gov (United States)

Suárez, Ernesto; Díaz, Natalia; Suárez, Dimas

2009-06-09

Herein, we first review different methodologies that have been proposed for computing the quantum mechanical (QM) energy and other molecular properties of large systems through a linear combination of subsystem (fragment) energies, which can be computed using conventional QM packages. Particularly, we emphasize the similarities among the different methods that can be considered as variants of the multibody expansion technique. Nevertheless, on the basis of thermochemical arguments, we propose yet another variant of the fragment energy methods, which could be useful for, and readily applicable to, biomolecules using either QM or hybrid quantum mechanical/molecular mechanics methods. The proposed computational scheme is applied to investigate the stability of a triple-helical collagen model peptide. To better address the actual applicability of the fragment QM method and to properly compare with experimental data, we compute average energies by carrying out single-point fragment QM calculations on structures generated by a classical molecular dynamics simulation. The QM calculations are done using a density functional level of theory combined with an implicit solvent model. Other free-energy terms such as attractive dispersion interactions or thermal contributions are included using molecular mechanics. The importance of correcting both the intermolecular and intramolecular basis set superposition error (BSSE) in the QM calculations is also discussed in detail. On the basis of the favorable comparison of our fragment-based energies with experimental data and former theoretical results, we conclude that the fragment QM energy strategy could be an interesting addition to the multimethod toolbox for biomolecular simulations in order to investigate those situations (e.g., interactions with metal clusters) that are beyond the range of applicability of common molecular mechanics methods.

Fragmentation of DNA affects the accuracy of the DNA quantitation by the commonly used methods

Directory of Open Access Journals (Sweden)

Sedlackova Tatiana

2013-02-01

Full Text Available Abstract Background Specific applications and modern technologies, like non-invasive prenatal testing, non-invasive cancer diagnostic and next generation sequencing, are currently in the focus of researchers worldwide. These have common characteristics in use of highly fragmented DNA molecules for analysis. Hence, for the performance of molecular methods, DNA concentration is a crucial parameter; we compared the influence of different levels of DNA fragmentation on the accuracy of DNA concentration measurements. Results In our comparison, the performance of the currently most commonly used methods for DNA concentration measurement (spectrophotometric, fluorometric and qPCR based were tested on artificially fragmented DNA samples. In our comparison, unfragmented and three specifically fragmented DNA samples were used. According to our results, the level of fragmentation did not influence the accuracy of spectrophotometric measurements of DNA concentration, while other methods, fluorometric as well as qPCR-based, were significantly influenced and a decrease in measured concentration was observed with more intensive DNA fragmentation. Conclusions Our study has confirmed that the level of fragmentation of DNA has significant impact on accuracy of DNA concentration measurement with two of three mostly used methods (PicoGreen and qPCR. Only spectrophotometric measurement was not influenced by the level of fragmentation, but sensitivity of this method was lowest among the three tested. Therefore if it is possible the DNA quantification should be performed with use of equally fragmented control DNA.

Self-gravitational Hydrodynamics with Three-dimensional Adaptive Mesh Refinement: Methodology and Applications to Molecular Cloud Collapse and Fragmentation

International Nuclear Information System (INIS)

Truelove, J.K.; Klein, R.I.; McKee, C.F.; Holliman, J.H. II; Truelove, J.K.; McKee, C.F.; Truelove, J.K.; Holliman, J.H. II; Klein, R.I.; Woods, D.T.; McKee, C.F.; Woods, D.T.; Howell, L.H.; Greenough, J.A.

1998-01-01

We describe a new code for numerical solution of three-dimensional self-gravitational hydrodynamics problems. This code utilizes the technique of local adaptive mesh refinement (AMR), employing multiple grids at multiple levels of resolution and automatically and dynamically adding and removing these grids as necessary to maintain adequate resolution. This technology allows solution of problems that would be prohibitively expensive with a code using fixed resolution, and it is more versatile and efficient than competing methods of achieving variable resolution. In particular, we apply this technique to simulate the collapse and fragmentation of a molecular cloud, a key step in star formation. The simulation involves many orders of magnitude of variation in length scale as fragments form at positions that are not a priori discernible from general initial conditions. In this paper, we describe the methodology behind this new code and present several illustrative applications. The criterion that guides the degree of adaptive mesh refinement is critical to the success of the scheme, and, for the isothermal problems considered here, we employ the Jeans condition for this purpose. By maintaining resolution finer than the local Jeans length, we set new benchmarks of accuracy by which to measure other codes on each problem we consider, including the uniform collapse of a finite pressured cloud. We find that the uniformly rotating, spherical clouds treated here first collapse to disks in the equatorial plane and then, in the presence of applied perturbations, form filamentary singularities that do not fragment while isothermal. Our results provide numerical confirmation of recent work by Inutsuka ampersand Miyama on this scenario of isothermal filament formation. copyright copyright 1998. The American Astronomical Society

Incorporation of charge transfer into the explicit polarization fragment method by grand canonical density functional theory.

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Isegawa, Miho; Gao, Jiali; Truhlar, Donald G

2011-08-28

Molecular fragmentation algorithms provide a powerful approach to extending electronic structure methods to very large systems. Here we present a method for including charge transfer between molecular fragments in the explicit polarization (X-Pol) fragment method for calculating potential energy surfaces. In the conventional X-Pol method, the total charge of each fragment is preserved, and charge transfer between fragments is not allowed. The description of charge transfer is made possible by treating each fragment as an open system with respect to the number of electrons. To achieve this, we applied Mermin's finite temperature method to the X-Pol wave function. In the application of this method to X-Pol, the fragments are open systems that partially equilibrate their number of electrons through a quasithermodynamics electron reservoir. The number of electrons in a given fragment can take a fractional value, and the electrons of each fragment obey the Fermi-Dirac distribution. The equilibrium state for the electrons is determined by electronegativity equalization with conservation of the total number of electrons. The amount of charge transfer is controlled by re-interpreting the temperature parameter in the Fermi-Dirac distribution function as a coupling strength parameter. We determined this coupling parameter so as to reproduce the charge transfer energy obtained by block localized energy decomposition analysis. We apply the new method to ten systems, and we show that it can yield reasonable approximations to potential energy profiles, to charge transfer stabilization energies, and to the direction and amount of charge transferred. © 2011 American Institute of Physics

Investigation of the Rock Fragmentation Process by a Single TBM Cutter Using a Voronoi Element-Based Numerical Manifold Method

Science.gov (United States)

Liu, Quansheng; Jiang, Yalong; Wu, Zhijun; Xu, Xiangyu; Liu, Qi

2018-04-01

In this study, a two-dimensional Voronoi element-based numerical manifold method (VE-NMM) is developed to analyze the granite fragmentation process by a single tunnel boring machine (TBM) cutter under different confining stresses. A Voronoi tessellation technique is adopted to generate the polygonal grain assemblage to approximate the microstructure of granite sample from the Gubei colliery of Huainan mining area in China. A modified interface contact model with cohesion and tensile strength is embedded into the numerical manifold method (NMM) to interpret the interactions between the rock grains. Numerical uniaxial compression and Brazilian splitting tests are first conducted to calibrate and validate the VE-NMM models based on the laboratory experiment results using a trial-and-error method. On this basis, numerical simulations of rock fragmentation by a single TBM cutter are conducted. The simulated crack initiation and propagation process as well as the indentation load-penetration depth behaviors in the numerical models accurately predict the laboratory indentation test results. The influence of confining stress on rock fragmentation is also investigated. Simulation results show that radial tensile cracks are more likely to be generated under a low confining stress, eventually coalescing into a major fracture along the loading axis. However, with the increase in confining stress, more side cracks initiate and coalesce, resulting in the formation of rock chips at the upper surface of the model. In addition, the peak indentation load also increases with the increasing confining stress, indicating that a higher thrust force is usually needed during the TBM boring process in deep tunnels.

Aspect Ratio Dependence of Impact Fragmentation

International Nuclear Information System (INIS)

Inaoka, H.; Toyosawa, E.; Takayasu, H.; Inaoka, H.

1997-01-01

A numerical model of three-dimensional impact fragmentation produces a power-law cumulative fragment mass distribution followed by a flat tail. The result is consistent with an experimental result in a recent paper by Meibom and Balslev [Phys. Rev. Lett. 76, 2492 (1996)]. Our numerical simulation also implies that the fragment mass distribution changes from a power law with a flat tail to a power law with a sudden cutoff, depending on the aspect ratio of the fractured object. copyright 1997 The American Physical Society

Prediction of inorganic superconductors with quasi-one-dimensional crystal structure

International Nuclear Information System (INIS)

Volkova, L M; Marinin, D V

2013-01-01

Models of superconductors having a quasi-one-dimensional crystal structure based on the convoluted into a tube Ginzburg sandwich, which comprises a layered dielectric–metal–dielectric structure, have been suggested. The critical crystal chemistry parameters of the Ginzburg sandwich determining the possibility of the emergence of superconductivity and the T c value in layered high-T c cuprates, which could have the same functions in quasi-one-dimensional fragments (sandwich-type tubes), have been examined. The crystal structures of known low-temperature superconductors, in which one can mark out similar quasi-one-dimensional fragments, have been analyzed. Five compounds with quasi-one-dimensional structures, which can be considered as potential parents of new superconductor families, possibly with high transition temperatures, have been suggested. The methods of doping and modification of these compounds are provided. (paper)

Current fragmentation in deep inelastic scattering

International Nuclear Information System (INIS)

Hamer, C.J.

1975-04-01

It is argued that the current fragmentation products in deep inelastic electron scattering will not be distributed in a 'one-dimensional' rapidity plateau as in the parton model picture of Feynman and Bjorken. A reaction mechanism with a multiperipheral topology, but which the above configuration might have been achieved, does not in fact populate the current fragmentation plateau; and unless partons are actually observed in the final state, it cannot lead to Bjorken scaling. The basic reason for this failure is shown to be the fact that when a particle is produced in the current fragmentation plateau, the adjacent momentum transfer in the multiperipheral chain becomes large and negative: such processes are inevitably suppressed. Instead, the current fragmentation products are likely to be generated by a fragmentation, or sequential decay process. (author)

The use of many-body expansions and geometry optimizations in fragment-based methods.

Science.gov (United States)

Fedorov, Dmitri G; Asada, Naoya; Nakanishi, Isao; Kitaura, Kazuo

2014-09-16

Conspectus Chemists routinely work with complex molecular systems: solutions, biochemical molecules, and amorphous and composite materials provide some typical examples. The questions one often asks are what are the driving forces for a chemical phenomenon? How reasonable are our views of chemical systems in terms of subunits, such as functional groups and individual molecules? How can one quantify the difference in physicochemical properties of functional units found in a different chemical environment? Are various effects on functional units in molecular systems additive? Can they be represented by pairwise potentials? Are there effects that cannot be represented in a simple picture of pairwise interactions? How can we obtain quantitative values for these effects? Many of these questions can be formulated in the language of many-body effects. They quantify the properties of subunits (fragments), referred to as one-body properties, pairwise interactions (two-body properties), couplings of two-body interactions described by three-body properties, and so on. By introducing the notion of fragments in the framework of quantum chemistry, one obtains two immense benefits: (a) chemists can finally relate to quantum chemistry, which now speaks their language, by discussing chemically interesting subunits and their interactions and (b) calculations become much faster due to a reduced computational scaling. For instance, the somewhat academic sounding question of the importance of three-body effects in water clusters is actually another way of asking how two hydrogen bonds affect each other, when they involve three water molecules. One aspect of this is the many-body charge transfer (CT), because the charge transfers in the two hydrogen bonds are coupled to each other (not independent). In this work, we provide a generalized view on the use of many-body expansions in fragment-based methods, focusing on the general aspects of the property expansion and a contraction of a

A new crystal structure fragment-based pharmacophore method for G protein-coupled receptors

DEFF Research Database (Denmark)

Fidom, Kimberley; Isberg, Vignir; Hauser, Alexander Sebastian

2015-01-01

and receptor residue pairs, from crystal structure complexes. We describe the procedure to collect a library with more than 250 fragments covering 29 residue positions within the generic transmembrane binding pocket. We describe how the library fragments are recombined and inferred to build pharmacophores...... for new targets. A validating retrospective virtual screening of histamine H1 and H3 receptor pharmacophores yielded area-under-the-curves of 0.88 and 0.82, respectively. The fragment-based method has the unique advantage that it can be applied to targets for which no (homologous) crystal structures...... or ligands are known. 47% of the class A G protein-coupled receptors can be targeted with at least four-element pharmacophores. The fragment libraries can also be used to grow known ligands or for rotamer refinement of homology models. Researchers can download the complete fragment library or a subset...

Analysis methods for Kevlar shield response to rotor fragments

Science.gov (United States)

Gerstle, J. H.

1977-01-01

Several empirical and analytical approaches to rotor burst shield sizing are compared and principal differences in metal and fabric dynamic behavior are discussed. The application of transient structural response computer programs to predict Kevlar containment limits is described. For preliminary shield sizing, present analytical methods are useful if insufficient test data for empirical modeling are available. To provide other information useful for engineering design, analytical methods require further developments in material characterization, failure criteria, loads definition, and post-impact fragment trajectory prediction.

Technique for Increasing the Selectivity of the Method of Laser Fragmentation/Laser-Induced Fluorescence

Science.gov (United States)

Bobrovnikov, S. M.; Gorlov, E. V.; Zharkov, V. I.

2018-05-01

A technique for increasing the selectivity of the method of detecting high-energy materials (HEMs) based on laser fragmentation of HEM molecules with subsequent laser excitation of fluorescence of the characteristic NO fragments from the first vibrational level of the ground state is suggested.

A method to calculate fission-fragment yields Y(Z,N) versus proton and neutron number in the Brownian shape-motion model. Application to calculations of U and Pu charge yields

Energy Technology Data Exchange (ETDEWEB)

Moeller, Peter [Los Alamos National Laboratory, Theoretical Division, Los Alamos, NM (United States); Ichikawa, Takatoshi [Kyoto University, Yukawa Institute for Theoretical Physics, Kyoto (Japan)

2015-12-15

We propose a method to calculate the two-dimensional (2D) fission-fragment yield Y(Z,N) versus both proton and neutron number, with inclusion of odd-even staggering effects in both variables. The approach is to use the Brownian shape-motion on a macroscopic-microscopic potential-energy surface which, for a particular compound system is calculated versus four shape variables: elongation (quadrupole moment Q{sub 2}), neck d, left nascent fragment spheroidal deformation ε{sub f1}, right nascent fragment deformation ε{sub f2} and two asymmetry variables, namely proton and neutron numbers in each of the two fragments. The extension of previous models 1) introduces a method to calculate this generalized potential-energy function and 2) allows the correlated transfer of nucleon pairs in one step, in addition to sequential transfer. In the previous version the potential energy was calculated as a function of Z and N of the compound system and its shape, including the asymmetry of the shape. We outline here how to generalize the model from the ''compound-system'' model to a model where the emerging fragment proton and neutron numbers also enter, over and above the compound system composition. (orig.)

Two-dimensional collapse calculations of cylindrical clouds

International Nuclear Information System (INIS)

Bastien, P.; Mitalas, R.

1979-01-01

A two-dimensional hydrodynamic computer code has been extensively modified and expanded to study the collapse of non-rotating interstellar clouds. The physics and the numerical methods involved are discussed. The results are presented and discussed in terms of the Jeans number. The critical Jeans number for collapse of non-rotating cylindrical clouds whose length is the same as their diameter is 1.00. No evidence for fragmentation has been found for these clouds, but fragmentation seems quite likely for more elongated cylindrical clouds. (author)

Calculations of three-dimensional collapse and fragmentation

International Nuclear Information System (INIS)

Larson, R.B.

1978-01-01

Calculations of the fragmentation of an isothermally collapsing cloud have been carried out using a method that follows the motion of individual fluid particles and includes pressure and viscosity forces between neighbouring particles. In a cloud or region whose mass is comparable to the Jeans mass, a highly condensed core forms, surrounded by a diffuse envelope that continues to accrete on to the core; in the presence of rotation, the inner part of the envelope becomes essentially an accretion disc. If the mass exceeds the Jeans mass, several such accreting cores are formed, the number being comparable to the initial number of jeans masses in the cloud. Binary systems and hierarchical multiple systems are frequently obtained. The mass of the largest object formed is independent of the Jeans mass but depends on the angular momentum and viscosity of the cloud, and is essentially the maximum mass accretable by a single object. The resulting mass spectrum may be determined by the development of a hierarchy of accreting objects of different sizes, such that each object has several smaller ones associated with it. The hypothesis of a self-similar accretion hierarchy predicts a power-law mass spectrum, which in the limit of inefficient accretion has an exponent x = 1, in reasonable agreement with observations. (author)

Fragment-Linking Approach Using (19)F NMR Spectroscopy To Obtain Highly Potent and Selective Inhibitors of β-Secretase.

Science.gov (United States)

Jordan, John B; Whittington, Douglas A; Bartberger, Michael D; Sickmier, E Allen; Chen, Kui; Cheng, Yuan; Judd, Ted

2016-04-28

Fragment-based drug discovery (FBDD) has become a widely used tool in small-molecule drug discovery efforts. One of the most commonly used biophysical methods in detecting weak binding of fragments is nuclear magnetic resonance (NMR) spectroscopy. In particular, FBDD performed with (19)F NMR-based methods has been shown to provide several advantages over (1)H NMR using traditional magnetization-transfer and/or two-dimensional methods. Here, we demonstrate the utility and power of (19)F-based fragment screening by detailing the identification of a second-site fragment through (19)F NMR screening that binds to a specific pocket of the aspartic acid protease, β-secretase (BACE-1). The identification of this second-site fragment allowed the undertaking of a fragment-linking approach, which ultimately yielded a molecule exhibiting a more than 360-fold increase in potency while maintaining reasonable ligand efficiency and gaining much improved selectivity over cathepsin-D (CatD). X-ray crystallographic studies of the molecules demonstrated that the linked fragments exhibited binding modes consistent with those predicted from the targeted screening approach, through-space NMR data, and molecular modeling.

Fragment based drug discovery: practical implementation based on ¹⁹F NMR spectroscopy.

Science.gov (United States)

Jordan, John B; Poppe, Leszek; Xia, Xiaoyang; Cheng, Alan C; Sun, Yax; Michelsen, Klaus; Eastwood, Heather; Schnier, Paul D; Nixey, Thomas; Zhong, Wenge

2012-01-26

Fragment based drug discovery (FBDD) is a widely used tool for discovering novel therapeutics. NMR is a powerful means for implementing FBDD, and several approaches have been proposed utilizing (1)H-(15)N heteronuclear single quantum coherence (HSQC) as well as one-dimensional (1)H and (19)F NMR to screen compound mixtures against a target of interest. While proton-based NMR methods of fragment screening (FBS) have been well documented and are widely used, the use of (19)F detection in FBS has been only recently introduced (Vulpetti et al. J. Am. Chem. Soc.2009, 131 (36), 12949-12959) with the aim of targeting "fluorophilic" sites in proteins. Here, we demonstrate a more general use of (19)F NMR-based fragment screening in several areas: as a key tool for rapid and sensitive detection of fragment hits, as a method for the rapid development of structure-activity relationship (SAR) on the hit-to-lead path using in-house libraries and/or commercially available compounds, and as a quick and efficient means of assessing target druggability.

Immobilization of Fab' fragments onto substrate surfaces: A survey of methods and applications.

Science.gov (United States)

Crivianu-Gaita, Victor; Thompson, Michael

2015-08-15

Antibody immobilization onto surfaces has widespread applications in many different fields. It is desirable to bind antibodies such that their fragment-antigen-binding (Fab) units are oriented away from the surface in order to maximize analyte binding. The immobilization of only Fab' fragments yields benefits over the more traditional whole antibody immobilization technique. Bound Fab' fragments display higher surface densities, yielding a higher binding capacity for the analyte. The nucleophilic sulfide of the Fab' fragments allows for specific orientations to be achieved. For biosensors, this indicates a higher sensitivity and lower detection limit for a target analyte. The last thirty years have shown tremendous progress in the immobilization of Fab' fragments onto gold, Si-based, polysaccharide-based, plastic-based, magnetic, and inorganic surfaces. This review will show the current scope of Fab' immobilization techniques available and illustrate methods employed to minimize non-specific adsorption of undesirables. Furthermore, a variety of examples will be given to show the versatility of immobilized Fab' fragments in different applications and future directions of the field will be addressed, especially regarding biosensors. Copyright © 2015 Elsevier B.V. All rights reserved.

Morphology of the posteromedial fragment in pertrochanteric fractures: A three-dimensional computed tomography analysis.

Science.gov (United States)

Sharma, Gaurav; Gn, Kiran Kumar; Khatri, Kavin; Singh, Ravijot; Gamanagatti, Shivanand; Sharma, Vijay

2017-02-01

In this study we describe the morphology of the posteromedial fragment in pertrochanteric fractures using 3D CT scans and answer two questions 1) Do differences exist between the 3D CT appearances of posteromedial fragments and the depictions made in the AO classification 2) Does the posteromedial fragment affect stability in pertrochanteric fractures, in terms of fracture collapse? Preoperative CT scans of eight 31-A1 and fifty 31-A2 fractures were analysed. The presence of PM fragment, its fragmentation, greater trochanter (GT) involvement, lesser trochanter (LT) fragment size (in terms of its posterior and medial extent as well as LT length), LT fragment displacement (in terms of medial displacement and rotation) were determined. All fractures were treated with a DHS. Fracture collapse was determined on postoperative radiographs. The relationship between fracture collapse and patient factors including age, gender, fracture type (A1 versus A2), characteristics of the posteromedial fragment, and the presence of a lateral wall fracture were determined. Three out of eight 31-A1 fractures demonstrated a separate GT fragment (three part fracture). Out of the 50 31-A2 fractures, 12 had a single PM fragment, which included the LT and GT in continuity. The more common four part fractures seem to form by further fragmentation of this basic form. In A2 fractures, the GT was almost always broken and the broken fragment comprised a mean 56% of normal GT. The LT fragment involved an average of 74% of the posterior wall, and an average of 36% of the medial wall of the proximal femur. Larger LT fragments were less displaced as compared to smaller fragments. Univariate regression analyses revealed that fracture collapse was significantly correlated with fracture type (A1 versus A2, p 0.036), GT size (p 0.002) and the presence of a lateral wall fracture (pfragmentation of the posteromedial fragment, nor the size of the lesser trochanter fragment was found to predict stability in

Iterative Two- and One-Dimensional Methods for Three-Dimensional Neutron Diffusion Calculations

International Nuclear Information System (INIS)

Lee, Hyun Chul; Lee, Deokjung; Downar, Thomas J.

2005-01-01

Two methods are proposed for solving the three-dimensional neutron diffusion equation by iterating between solutions of the two-dimensional (2-D) radial and one-dimensional (1-D) axial solutions. In the first method, the 2-D/1-D equations are coupled using a current correction factor (CCF) with the average fluxes of the lower and upper planes and the axial net currents at the plane interfaces. In the second method, an analytic expression for the axial net currents at the interface of the planes is used for planar coupling. A comparison of the new methods is made with two previously proposed methods, which use interface net currents and partial currents for planar coupling. A Fourier convergence analysis of the four methods was performed, and results indicate that the two new methods have at least three advantages over the previous methods. First, the new methods are unconditionally stable, whereas the net current method diverges for small axial mesh size. Second, the new methods provide better convergence performance than the other methods in the range of practical mesh sizes. Third, the spectral radii of the new methods asymptotically approach zero as the mesh size increases, while the spectral radius of the partial current method approaches a nonzero value as the mesh size increases. Of the two new methods proposed here, the analytic method provides a smaller spectral radius than the CCF method, but the CCF method has several advantages over the analytic method in practical applications

Toroidal and rotating bubble nuclei and the nuclear fragmentation

International Nuclear Information System (INIS)

Royer, G.; Fauchard, C.; Haddad, F.; Jouault, B.

1997-01-01

The energy of rotating bubble and toroidal nuclei predicted to be formed in central heavy ion collisions at intermediate energies is calculated within the generalized rotating liquid drop model. Previously, a one-parameter shape sequence has been defined to describe the path leading to pumpkin-like configurations and toroidal shapes. New analytical expressions for the shape dependent functions have been obtained. The potential barriers standing in these exotic deformation paths are compared with the three-dimensional and plane-fragmentation barriers. Metastable bubble-like minima only appear at very high angular momentum and above the three dimensional fragmentation barriers. In the toroidal deformation path of the heaviest systems exists a large potential pocket localized below the plane-fragmentation barriers. This might allow the temporary survival of heavy nuclear toroids before the final clusterization induced by the surface and proximity tension

Mass distribution of fission fragments within the Born-Oppenheimer approximation

Energy Technology Data Exchange (ETDEWEB)

Pomorski, K.; Nerlo-Pomorska, B. [M.C.S. University, Department of Theoretical Physics, Lublin (Poland); Ivanyuk, F.A. [Institute for Nuclear Research, Kiev (Ukraine)

2017-03-15

The fission fragments mass-yield of {sup 236} U is obtained by an approximate solution of the eigenvalue problem of the collective Hamiltonian that describes the dynamics of the fission process whose degrees of freedom are: the fission (elongation), the neck and mass-asymmetry modes. The macroscopic-microscopic method is used to evaluate the potential energy surface. The macroscopic energy part is calculated using the liquid drop model and the microscopic corrections are obtained using a Woods-Saxon single-particle levels. The four-dimensional modified Cassini ovals shape parametrization is used to describe the shape of the fissioning nucleus. The mass tensor is taken within a cranking-type approximation. The final fragment mass distribution is obtained by weighting the adiabatic density distribution in the collective space with the neck-dependent fission probability. The neck degree of freedom is found to play a significant role in determining the final fragment mass distribution. (orig.)

White blood cell fragments in platelet concentrates prepared by the platelet-rich plasma or buffy-coat methods

NARCIS (Netherlands)

Dijkstra-Tiekstra, M. J.; van der Schoot, C. E.; Pietersz, R. N. I.; Reesink, H. W.

2005-01-01

BACKGROUND AND OBJECTIVES: White blood cell (WBC) fragments in platelet concentrates (PCs) may induce allo-immunization in the recipient. MATERIALS AND METHODS: As the level of WBC fragments can differ between PCs produced using different methods, we compared PCs prepared by using the buffy-coat

Experimental and numerical studies of high-velocity impact fragmentation

Energy Technology Data Exchange (ETDEWEB)

Kipp, M.E.; Grady, D.E.; Swegle, J.W.

1993-08-01

Developments are reported in both experimental and numerical capabilities for characterizing the debris spray produced in penetration events. We have performed a series of high-velocity experiments specifically designed to examine the fragmentation of the projectile during impact. High-strength, well-characterized steel spheres (6.35 mm diameter) were launched with a two-stage light-gas gun to velocities in the range of 3 to 5 km/s. Normal impact with PMMA plates, thicknesses of 0.6 to 11 mm, applied impulsive loads of various amplitudes and durations to the steel sphere. Multiple flash radiography diagnostics and recovery techniques were used to assess size, velocity, trajectory and statistics of the impact-induced fragment debris. Damage modes to the primary target plate (plastic) and to a secondary target plate (aluminum) were also evaluated. Dynamic fragmentation theories, based on energy-balance principles, were used to evaluate local material deformation and fracture state information from CTH, a three-dimensional Eulerian solid dynamics shock wave propagation code. The local fragment characterization of the material defines a weighted fragment size distribution, and the sum of these distributions provides a composite particle size distribution for the steel sphere. The calculated axial and radial velocity changes agree well with experimental data, and the calculated fragment sizes are in qualitative agreement with the radiographic data. A secondary effort involved the experimental and computational analyses of normal and oblique copper ball impacts on steel target plates. High-resolution radiography and witness plate diagnostics provided impact motion and statistical fragment size data. CTH simulations were performed to test computational models and numerical methods.

Hyperion polarization and transverse momentum properties in proton fragmentation

International Nuclear Information System (INIS)

Andersson, B.; Gustafson, G.; Maansson, O.

1982-11-01

A dynamical mechanism for proton interaction in hadronic collisions is presented which provides a verification of the model with an essentially one-dimensional colour force field in the proton fragmentation region, proposed earlier. We include here a discussion of the transverse momentum properties of the final state particles and polarization properties for hyperions in proton fragmentation. (Author)

Three-dimensional display techniques: description and critique of methods

International Nuclear Information System (INIS)

Budinger, T.F.

1982-01-01

The recent advances in non invasive medical imaging of 3 dimensional spatial distribution of radionuclides, X-ray attenuation coefficients, and nuclear magnetic resonance parameters necessitate development of a general method for displaying these data. The objective of this paper is to give a systematic description and comparison of known methods for displaying three dimensional data. The discussion of display methods is divided into two major categories: 1) computer-graphics methods which use a two dimensional display screen; and 2) optical methods (such as holography, stereopsis and vari-focal systems)

Two-dimensional nuclear magnetic resonance spectroscopy

International Nuclear Information System (INIS)

Bax, A.; Lerner, L.

1986-01-01

Great spectral simplification can be obtained by spreading the conventional one-dimensional nuclear magnetic resonance (NMR) spectrum in two independent frequency dimensions. This so-called two-dimensional NMR spectroscopy removes spectral overlap, facilitates spectral assignment, and provides a wealth of additional information. For example, conformational information related to interproton distances is available from resonance intensities in certain types of two-dimensional experiments. Another method generates 1 H NMR spectra of a preselected fragment of the molecule, suppressing resonances from other regions and greatly simplifying spectral appearance. Two-dimensional NMR spectroscopy can also be applied to the study of 13 C and 15 N, not only providing valuable connectivity information but also improving sensitivity of 13 C and 15 N detection by up to two orders of magnitude. 45 references, 10 figures

Hypothesis-driven and field-validated method to prioritize fragmentation mitigation efforts in road projects.

Science.gov (United States)

Vanthomme, Hadrien; Kolowski, Joseph; Nzamba, Brave S; Alonso, Alfonso

2015-10-01

The active field of connectivity conservation has provided numerous methods to identify wildlife corridors with the aim of reducing the ecological effect of fragmentation. Nevertheless, these methods often rely on untested hypotheses of animal movements, usually fail to generate fine-scale predictions of road crossing sites, and do not allow managers to prioritize crossing sites for implementing road fragmentation mitigation measures. We propose a new method that addresses these limitations. We illustrate this method with data from southwestern Gabon (central Africa). We used stratified random transect surveys conducted in two seasons to model the distribution of African forest elephant (Loxodonta cyclotis), forest buffalo (Syncerus caffer nanus), and sitatunga (Tragelaphus spekii) in a mosaic landscape along a 38.5 km unpaved road scheduled for paving. Using a validation data set of recorded crossing locations, we evaluated the performance of three types of models (local suitability, local least-cost movement, and regional least-cost movement) in predicting actual road crossings for each species, and developed a unique and flexible scoring method for prioritizing road sections for the implementation of road fragmentation mitigation measures. With a data set collected in method was able to identify seasonal changes in animal movements for buffalo and sitatunga that shift from a local exploitation of the site in the wet season to movements through the study site in the dry season, whereas elephants use the entire study area in both seasons. These three species highlighted the need to use species- and season-specific modeling of movement. From these movement models, the method ranked road sections for their suitability for implementing fragmentation mitigation efforts, allowing managers to adjust priority thresholds based on budgets and management goals. The method relies on data that can be obtained in a period compatible with environmental impact assessment

Utility of three-dimensional method for diagnosing meniscal lesions

International Nuclear Information System (INIS)

Ohshima, Suguru; Nomura, Kazutoshi; Hirano, Mako; Hashimoto, Noburo; Fukumoto, Tetsuya; Katahira, Kazuhiro

1998-01-01

MRI of the knee is a useful method for diagnosing meniscal tears. Although the spin echo method is usually used for diagnosing meniscal tears, we examined the utility of thin slice scan with the three-dimensional method. We reviewed 70 menisci in which arthroscopic findings were confirmed. In this series, sensitivity was 90.9% for medial meniscal injuries and 68.8% for lateral meniscal injuries. There were 3 meniscal tears in which we could not detect tears on preoperative MRI. We could find tears in two of these cases when re-evaluated using the same MRI. In conclusion, we can get the same diagnostic rate with the three-dimensional method compared with the spin echo method. Scan time of the three-dimensional method is 3 minutes, on the other hand that of spin echo method in 17 minutes. This slice scan with three-dimensional method is useful for screening meniscal injuries before arthroscopy. (author)

A sparse grid based method for generative dimensionality reduction of high-dimensional data

Science.gov (United States)

Bohn, Bastian; Garcke, Jochen; Griebel, Michael

2016-03-01

Generative dimensionality reduction methods play an important role in machine learning applications because they construct an explicit mapping from a low-dimensional space to the high-dimensional data space. We discuss a general framework to describe generative dimensionality reduction methods, where the main focus lies on a regularized principal manifold learning variant. Since most generative dimensionality reduction algorithms exploit the representer theorem for reproducing kernel Hilbert spaces, their computational costs grow at least quadratically in the number n of data. Instead, we introduce a grid-based discretization approach which automatically scales just linearly in n. To circumvent the curse of dimensionality of full tensor product grids, we use the concept of sparse grids. Furthermore, in real-world applications, some embedding directions are usually more important than others and it is reasonable to refine the underlying discretization space only in these directions. To this end, we employ a dimension-adaptive algorithm which is based on the ANOVA (analysis of variance) decomposition of a function. In particular, the reconstruction error is used to measure the quality of an embedding. As an application, the study of large simulation data from an engineering application in the automotive industry (car crash simulation) is performed.

Nonlinear transient responses of beams and rings to impulse loading or fragment impact

International Nuclear Information System (INIS)

Witmer, E.A.; Stagliano, T.R.; Rodal, J.J.A.

1977-01-01

Nuclear power plant protective structures may be subjected to various external missiles such as aircraft and tornado-generated missiles: telephone poles, planks, pipes, rods, automobiles, and other blown vehicles. Also, 'internally-generated missiles' such as fragments from powerplant rotors and aircraft engine rotors may impact protective structures. The present paper is concerned with a very limited part of the cited fragment threat; namely, fragments from high speed rotating machinery such as (1) aircraft engine rotors and (2) stationary power plant turbine rotors. Further, it is assumed that the structures intended to contain or control these fragments consist of initially-isotopic elastic-plastic metals. Certain potential containment/control (C/C) structures behave in a planar (or two-dimensional) fashion while other fragment-attacked C/C structures will undergo general three-dimensional deformations. Predictions for only the former category of fragment-attacked structures are discussed in the present paper. Pertinent experimental data discussed on fragment-attacked structures include (a) steel-sphere impact data involving beam targets and (b) engine rotor fragment impact against a steel containment ring. In all of these cases large-deflection, elastic-plastic transient structural responses occur. (Auth.)

Method of dimensionality reduction in contact mechanics and friction

CERN Document Server

Popov, Valentin L

2015-01-01

This book describes for the first time a simulation method for the fast calculation of contact properties and friction between rough surfaces in a complete form. In contrast to existing simulation methods, the method of dimensionality reduction (MDR) is based on the exact mapping of various types of three-dimensional contact problems onto contacts of one-dimensional foundations. Within the confines of MDR, not only are three dimensional systems reduced to one-dimensional, but also the resulting degrees of freedom are independent from another. Therefore, MDR results in an enormous reduction of the development time for the numerical implementation of contact problems as well as the direct computation time and can ultimately assume a similar role in tribology as FEM has in structure mechanics or CFD methods, in hydrodynamics. Furthermore, it substantially simplifies analytical calculation and presents a sort of “pocket book edition” of the entirety contact mechanics. Measurements of the rheology of bodies in...

On the fragmentation of filaments in a molecular cloud simulation

Science.gov (United States)

Chira, R.-A.; Kainulainen, J.; Ibáñez-Mejía, J. C.; Henning, Th.; Mac Low, M.-M.

2018-03-01

Context. The fragmentation of filaments in molecular clouds has attracted a lot of attention recently as there seems to be a close relation between the evolution of filaments and star formation. The study of the fragmentation process has been motivated by simple analytical models. However, only a few comprehensive studies have analysed the evolution of filaments using numerical simulations where the filaments form self-consistently as part of large-scale molecular cloud evolution. Aim. We address the early evolution of parsec-scale filaments that form within individual clouds. In particular, we focus on three questions: How do the line masses of filaments evolve? How and when do the filaments fragment? How does the fragmentation relate to the line masses of the filaments? Methods: We examine three simulated molecular clouds formed in kiloparsec-scale numerical simulations performed with the FLASH adaptive mesh refinement magnetohydrodynamic code. The simulations model a self-gravitating, magnetised, stratified, supernova-driven interstellar medium, including photoelectric heating and radiative cooling. We follow the evolution of the clouds for 6 Myr from the time self-gravity starts to act. We identify filaments using the DisPerSe algorithm, and compare the results to other filament-finding algorithms. We determine the properties of the identified filaments and compare them with the predictions of analytic filament stability models. Results: The average line masses of the identified filaments, as well as the fraction of mass in filamentary structures, increases fairly continuously after the onset of self-gravity. The filaments show fragmentation starting relatively early: the first fragments appear when the line masses lie well below the critical line mass of Ostriker's isolated hydrostatic equilibrium solution ( 16 M⊙ pc-1), commonly used as a fragmentation criterion. The average line masses of filaments identified in three-dimensional volume density cubes

On the effect of grain burnback on STS-SRM fragment velocity

International Nuclear Information System (INIS)

Eck, M.B.; Mukunda, M.

1991-01-01

Concerns raised during the Ulysses Final Safety Analysis Review (FSAR) process called the solid rocket motor (SRM) fragment velocity prediction model into question. The specific area of concern was that there was a section of the SRM casing which was exposed to SRM chamber pressure as the grain (fuel) was consumed. These questions centered on the velocity of fragments which originated from the field joint region given that failure occurred between 37 and 72 seconds mission elapsed time (MET). Two dimensional coupled Eulerian-Lagrangian calculations were performed to assess the hot gas flow field which resulted from SRM casing fragmentation. The fragment to gas interface-pressure time-history obtained from these analyses was reduced to a boundary condition algorithm which was applied to an explicit-time-integration, finite element, three dimensional shell model of the SRM casing and unburned fuel. The results of these calculations showed that the velocity of fragments originating in the field joint was adequately described by the range of velocities given in the Shuttle Data Book (1988). Based on these results, no further analyses were required, and approval was obtained from the Launch Abort Subpanel of the Interagency Nuclear Safety Review Panel to use the SRM fragment velocity environments presented in the Ulysses FSAR (1990)

In search of new lead compounds for trypanosomiasis drug design: A protein structure-based linked-fragment approach

Science.gov (United States)

Verlinde, Christophe L. M. J.; Rudenko, Gabrielle; Hol, Wim G. J.

1992-04-01

A modular method for pursuing structure-based inhibitor design in the framework of a design cycle is presented. The approach entails four stages: (1) a design pathway is defined in the three-dimensional structure of a target protein; (2) this pathway is divided into subregions; (3) complementary building blocks, also called fragments, are designed in each subregion; complementarity is defined in terms of shape, hydrophobicity, hydrogen bond properties and electrostatics; and (4) fragments from different subregions are linked into potential lead compounds. Stages (3) and (4) are qualitatively guided by force-field calculations. In addition, the designed fragments serve as entries for retrieving existing compounds from chemical databases. This linked-fragment approach has been applied in the design of potentially selective inhibitors of triosephosphate isomerase from Trypanosoma brucei, the causative agent of sleeping sickness.

Dimensionality Reduction Methods: Comparative Analysis of methods PCA, PPCA and KPCA

Directory of Open Access Journals (Sweden)

Jorge Arroyo-Hernández

2016-01-01

Full Text Available The dimensionality reduction methods are algorithms mapping the set of data in subspaces derived from the original space, of fewer dimensions, that allow a description of the data at a lower cost. Due to their importance, they are widely used in processes associated with learning machine. This article presents a comparative analysis of PCA, PPCA and KPCA dimensionality reduction methods. A reconstruction experiment of worm-shape data was performed through structures of landmarks located in the body contour, with methods having different number of main components. The results showed that all methods can be seen as alternative processes. Nevertheless, thanks to the potential for analysis in the features space and the method for calculation of its preimage presented, KPCA offers a better method for recognition process and pattern extraction

Fragment-based drug discovery and protein–protein interactions

Directory of Open Access Journals (Sweden)

Turnbull AP

2014-09-01

Full Text Available Andrew P Turnbull,1 Susan M Boyd,2 Björn Walse31CRT Discovery Laboratories, Department of Biological Sciences, Birkbeck, University of London, London, UK; 2IOTA Pharmaceuticals Ltd, Cambridge, UK; 3SARomics Biostructures AB, Lund, SwedenAbstract: Protein–protein interactions (PPIs are involved in many biological processes, with an estimated 400,000 PPIs within the human proteome. There is significant interest in exploiting the relatively unexplored potential of these interactions in drug discovery, driven by the need to find new therapeutic targets. Compared with classical drug discovery against targets with well-defined binding sites, developing small-molecule inhibitors against PPIs where the contact surfaces are frequently more extensive and comparatively flat, with most of the binding energy localized in “hot spots”, has proven far more challenging. However, despite the difficulties associated with targeting PPIs, important progress has been made in recent years with fragment-based drug discovery playing a pivotal role in improving their tractability. Computational and empirical approaches can be used to identify hot-spot regions and assess the druggability and ligandability of new targets, whilst fragment screening campaigns can detect low-affinity fragments that either directly or indirectly perturb the PPI. Once fragment hits have been identified and confirmed using biochemical and biophysical approaches, three-dimensional structural data derived from nuclear magnetic resonance or X-ray crystallography can be used to drive medicinal chemistry efforts towards the development of more potent inhibitors. A small-scale comparison presented in this review of “standard” fragments with those targeting PPIs has revealed that the latter tend to be larger, be more lipophilic, and contain more polar (acid/base functionality, whereas three-dimensional descriptor data indicate that there is little difference in their three-dimensional

Rotating bubble and toroidal nuclei and fragmentation

International Nuclear Information System (INIS)

Royer, G.; Haddad, F.; Jouault, B.

1995-01-01

The energy of rotating bubble and toroidal nuclei predicted to be formed in central heavy-ion collisions at intermediate energies is calculated within the generalized rotating liquid drop model. The potential barriers standing in these exotic deformation paths are compared with the three dimensional and plane fragmentation barriers. In the toroidal deformation path of the heaviest systems exists a large potential pocket localised below the plane fragmentation barriers. This might allow the temporary survival of heavy nuclear toroids before the final clusterization induced by the surface and proximity tension. (author)

An efficient method for isolating antibody fragments against small peptides by antibody phage display

DEFF Research Database (Denmark)

Duan, Zhi; Siegumfeldt, Henrik

2010-01-01

We generated monoclonal scFv (single chain variable fragment) antibodies from an antibody phage display library towards three small synthetic peptides derived from the sequence of s1-casein. Key difficulties for selection of scFv-phages against small peptides were addressed. Small peptides do....... The scFvs were sequenced and characterized, and specificity was characterized by ELISA. The methods developed in this study are universally applicable for antibody phage display to efficiently produce antibody fragments against small peptides....

Computational methods for three-dimensional microscopy reconstruction

CERN Document Server

Frank, Joachim

2014-01-01

Approaches to the recovery of three-dimensional information on a biological object, which are often formulated or implemented initially in an intuitive way, are concisely described here based on physical models of the object and the image-formation process. Both three-dimensional electron microscopy and X-ray tomography can be captured in the same mathematical framework, leading to closely-related computational approaches, but the methodologies differ in detail and hence pose different challenges. The editors of this volume, Gabor T. Herman and Joachim Frank, are experts in the respective methodologies and present research at the forefront of biological imaging and structural biology.   Computational Methods for Three-Dimensional Microscopy Reconstruction will serve as a useful resource for scholars interested in the development of computational methods for structural biology and cell biology, particularly in the area of 3D imaging and modeling.

DIAGNOSTIC CHARACTERISTICS OF THE COMPUTER TESTS FORMED BY METHOD OF RESTORED FRAGMENTS

Directory of Open Access Journals (Sweden)

Oleksandr O. Petkov

2013-03-01

Full Text Available Definition of validity and reliability of tests which are formed by a method of restored fragments is considered in the article. The structure of the controlled theoretical material of limit field of knowledge, language expressions that describe the subject of control, and reliability of test, is analyzed. The technique of definition of the most important components of reliability of the considered tests is given: reliability of quantitative determination of coefficient of assimilation and technological reliability. Results of the lead pedagogical experiments have proved, that tests of the given class allow to make the control of mastering of a theoretical material over a level of reproduction in any field of knowledge with high reliability. It is shown, that validity tests with restored fragments basically caused by a degree of structurization and methodical study of a controllable material and can achieve beforehand set parameters, down to a level of absolute validity.

Nonlinear transient responses of beams and rings to impulse loading or fragment impact

International Nuclear Information System (INIS)

Witmer, E.A.; Stagliano, T.R.; Rodal, J.J.A.

1977-01-01

The present paper is concerned with a very limited part of the cited fragment threat; namely, fragments from high speed rotating machinery such as (1) aircraft engine rotors and (2) stationary power plant turbine rotors. Further, it is assumed that the structures intended to contain or control these fragments consist of initially-isotropic elastic-plastic metals. Certain potential containment/control (C/C) structures behave in a planar (or two-dimensional) fashion while other fragment-attacked C/C structures will undergo general three-dimensional deformations. Predictions for only the former category of fragment-attacked structures are discussed in the present paper. Pertinent experimental data discussed here on fragment-attacked structures include (a) steel-sphere impact data involving beam targets and (b) engine rotor fragment impact against a steel containment ring. In all of these cases large-deflection, elastic-plastic transient structural response occur. The governing equations employed are presented in the present analysis to predict the responses of protective (metal) structures to engine-rotor-fragment impact. The protective structure is intended either to contain or to deflect the attacking fragments away from important regions; large-deflection, elasic-plastic structural response is expected because these protective structures must have the least feasible weight. Concise geometric and assumed-displacement-field descriptions of the several types of finite elements to be utilized in subsequent examples are given, together with several categories of strain displacement relations. Both low- and higher-order elements are discussed

TSOM Method for Nanoelectronics Dimensional Metrology

International Nuclear Information System (INIS)

Attota, Ravikiran

2011-01-01

Through-focus scanning optical microscopy (TSOM) is a relatively new method that transforms conventional optical microscopes into truly three-dimensional metrology tools for nanoscale to microscale dimensional analysis. TSOM achieves this by acquiring and analyzing a set of optical images collected at various focus positions going through focus (from above-focus to under-focus). The measurement resolution is comparable to what is possible with typical light scatterometry, scanning electron microscopy (SEM) and atomic force microscopy (AFM). TSOM method is able to identify nanometer scale difference, type of the difference and magnitude of the difference between two nano/micro scale targets using a conventional optical microscope with visible wavelength illumination. Numerous industries could benefit from the TSOM method--such as the semiconductor industry, MEMS, NEMS, biotechnology, nanomanufacturing, data storage, and photonics. The method is relatively simple and inexpensive, has a high throughput, provides nanoscale sensitivity for 3D measurements and could enable significant savings and yield improvements in nanometrology and nanomanufacturing. Potential applications are demonstrated using experiments and simulations.

Dynameomics: Data-driven methods and models for utilizing large-scale protein structure repositories for improving fragment-based loop prediction

Science.gov (United States)

Rysavy, Steven J; Beck, David AC; Daggett, Valerie

2014-01-01

Protein function is intimately linked to protein structure and dynamics yet experimentally determined structures frequently omit regions within a protein due to indeterminate data, which is often due protein dynamics. We propose that atomistic molecular dynamics simulations provide a diverse sampling of biologically relevant structures for these missing segments (and beyond) to improve structural modeling and structure prediction. Here we make use of the Dynameomics data warehouse, which contains simulations of representatives of essentially all known protein folds. We developed novel computational methods to efficiently identify, rank and retrieve small peptide structures, or fragments, from this database. We also created a novel data model to analyze and compare large repositories of structural data, such as contained within the Protein Data Bank and the Dynameomics data warehouse. Our evaluation compares these structural repositories for improving loop predictions and analyzes the utility of our methods and models. Using a standard set of loop structures, containing 510 loops, 30 for each loop length from 4 to 20 residues, we find that the inclusion of Dynameomics structures in fragment-based methods improves the quality of the loop predictions without being dependent on sequence homology. Depending on loop length, ∼25–75% of the best predictions came from the Dynameomics set, resulting in lower main chain root-mean-square deviations for all fragment lengths using the combined fragment library. We also provide specific cases where Dynameomics fragments provide better predictions for NMR loop structures than fragments from crystal structures. Online access to these fragment libraries is available at http://www.dynameomics.org/fragments. PMID:25142412

Dynameomics: data-driven methods and models for utilizing large-scale protein structure repositories for improving fragment-based loop prediction.

Science.gov (United States)

Rysavy, Steven J; Beck, David A C; Daggett, Valerie

2014-11-01

Protein function is intimately linked to protein structure and dynamics yet experimentally determined structures frequently omit regions within a protein due to indeterminate data, which is often due protein dynamics. We propose that atomistic molecular dynamics simulations provide a diverse sampling of biologically relevant structures for these missing segments (and beyond) to improve structural modeling and structure prediction. Here we make use of the Dynameomics data warehouse, which contains simulations of representatives of essentially all known protein folds. We developed novel computational methods to efficiently identify, rank and retrieve small peptide structures, or fragments, from this database. We also created a novel data model to analyze and compare large repositories of structural data, such as contained within the Protein Data Bank and the Dynameomics data warehouse. Our evaluation compares these structural repositories for improving loop predictions and analyzes the utility of our methods and models. Using a standard set of loop structures, containing 510 loops, 30 for each loop length from 4 to 20 residues, we find that the inclusion of Dynameomics structures in fragment-based methods improves the quality of the loop predictions without being dependent on sequence homology. Depending on loop length, ∼ 25-75% of the best predictions came from the Dynameomics set, resulting in lower main chain root-mean-square deviations for all fragment lengths using the combined fragment library. We also provide specific cases where Dynameomics fragments provide better predictions for NMR loop structures than fragments from crystal structures. Online access to these fragment libraries is available at http://www.dynameomics.org/fragments. © 2014 The Protein Society.

[Analysis of Conformational Features of Watson-Crick Duplex Fragments by Molecular Mechanics and Quantum Mechanics Methods].

Science.gov (United States)

Poltev, V I; Anisimov, V M; Sanchez, C; Deriabina, A; Gonzalez, E; Garcia, D; Rivas, F; Polteva, N A

2016-01-01

It is generally accepted that the important characteristic features of the Watson-Crick duplex originate from the molecular structure of its subunits. However, it still remains to elucidate what properties of each subunit are responsible for the significant characteristic features of the DNA structure. The computations of desoxydinucleoside monophosphates complexes with Na-ions using density functional theory revealed a pivotal role of DNA conformational properties of single-chain minimal fragments in the development of unique features of the Watson-Crick duplex. We found that directionality of the sugar-phosphate backbone and the preferable ranges of its torsion angles, combined with the difference between purines and pyrimidines. in ring bases, define the dependence of three-dimensional structure of the Watson-Crick duplex on nucleotide base sequence. In this work, we extended these density functional theory computations to the minimal' fragments of DNA duplex, complementary desoxydinucleoside monophosphates complexes with Na-ions. Using several computational methods and various functionals, we performed a search for energy minima of BI-conformation for complementary desoxydinucleoside monophosphates complexes with different nucleoside sequences. Two sequences are optimized using ab initio method at the MP2/6-31++G** level of theory. The analysis of torsion angles, sugar ring puckering and mutual base positions of optimized structures demonstrates that the conformational characteristic features of complementary desoxydinucleoside monophosphates complexes with Na-ions remain within BI ranges and become closer to the corresponding characteristic features of the Watson-Crick duplex crystals. Qualitatively, the main characteristic features of each studied complementary desoxydinucleoside monophosphates complex remain invariant when different computational methods are used, although the quantitative values of some conformational parameters could vary lying within the

Controlled fragmentation

International Nuclear Information System (INIS)

Arnold, Werner

2002-01-01

Contrary to natural fragmentation, controlled fragmentation offers the possibility to adapt fragment parameters like size and mass to the performance requirements in a very flexible way. Known mechanisms like grooves inside the casing, weaken the structure. This is, however, excluded for applications with high accelerations during launch or piercing requirements for example on a semi armor piercing penetrator. Another method to achieve controlled fragmentation with an additional grid layer is presented with which the required grooves are produced 'just in time' inside the casing during detonation of the high explosive. The process of generating the grooves aided by the grid layer was studied using the hydrocode HULL with respect to varying grid designs and material combinations. Subsequent to this, a large range of these theoretically investigated combinations was contemplated in substantial experimental tests. With an optimised grid design and a suitable material selection, the controlled fragment admits a very flexible adaptation to the set requirements. Additional advantages like the increase of perforation performance or incendiary amplification can be realized with the grid layer

Exact Solutions of Fragmentation Equations with General Fragmentation Rates and Separable Particles Distribution Kernels

Directory of Open Access Journals (Sweden)

S. C. Oukouomi Noutchie

2014-01-01

Full Text Available We make use of Laplace transform techniques and the method of characteristics to solve fragmentation equations explicitly. Our result is a breakthrough in the analysis of pure fragmentation equations as this is the first instance where an exact solution is provided for the fragmentation evolution equation with general fragmentation rates. This paper is the key for resolving most of the open problems in fragmentation theory including “shattering” and the sudden appearance of infinitely many particles in some systems with initial finite particles number.

Scaling invariance of spherical projectile fragmentation upon high-velocity impact on a thin continuous shield

Energy Technology Data Exchange (ETDEWEB)

Myagkov, N. N., E-mail: nn-myagkov@mail.ru [Russian Academy of Sciences, Institute of Applied Mechanics (Russian Federation)

2017-01-15

The problem of aluminum projectile fragmentation upon high-velocity impact on a thin aluminum shield is considered. A distinctive feature of this description is that the fragmentation has been numerically simulated using the complete system of equations of deformed solid mechanics by a method of smoothed particle hydrodynamics in three-dimensional setting. The transition from damage to fragmentation is analyzed and scaling relations are derived in terms of the impact velocity (V), ratio of shield thickness to projectile diameter (h/D), and ultimate strength (σ{sub p}) in the criterion of projectile and shield fracture. Analysis shows that the critical impact velocity V{sub c} (separating the damage and fragmentation regions) is a power function of σ{sub p} and h/D. In the supercritical region (V > V{sub c}), the weight-average fragment mass asymptotically tends to a power function of the impact velocity with exponent independent of h/D and σ{sub p}. Mean cumulative fragment mass distributions at the critical point are scale-invariant with respect to parameters h/D and σ{sub p}. Average masses of the largest fragments are also scale-invariant at V > V{sub c}, but only with respect to variable parameter σ{sub p}.

Development of the Fragment Molecular Orbital Method for Calculating Nonlocal Excitations in Large Molecular Systems.

Science.gov (United States)

Fujita, Takatoshi; Mochizuki, Yuji

2018-04-19

We developed the fragment-based method for calculating nonlocal excitations in large molecular systems. This method is based on the multilayer fragment molecular orbital method and the configuration interaction single (CIS) wave function using localized molecular orbitals. The excited-state wave function for the whole system is described as a superposition of configuration state functions (CSFs) for intrafragment excitations and for interfragment charge-transfer excitations. The formulation and calculations of singlet excited-state Hamiltonian matrix elements in the fragment CSFs are presented in detail. The efficient approximation schemes for calculating the matrix elements are also presented. The computational efficiency and the accuracy were evaluated using the molecular dimers and molecular aggregates. We confirmed that absolute errors of 50 meV (relative to the conventional calculations) are achievable for the molecular systems in their equilibrium geometries. The perturbative electron correlation correction to the CIS excitation energies is also demonstrated. The present theory can compute a large number of excited states in large molecular systems; in addition, it allows for the systematic derivation of a model exciton Hamiltonian. These features are useful for studying excited-state dynamics in condensed molecular systems based on the ab initio electronic structure theory.

Impact failure and fragmentation properties of metals

Energy Technology Data Exchange (ETDEWEB)

Grady, D.E. [Applied Research Associates, Albuquerque, NM (United States); Kipp, M.E. [Sandia National Labs., Albuquerque, NM (United States)

1998-03-01

In the present study we describe the development of an experimental fracture material property test method specific to dynamic fragmentation. Spherical test samples of the metals of interest are subjected to controlled impulsive stress loads by acceleration to high velocities with a light-gas launcher facility and subsequent normal impact on thin plates. Motion, deformation and fragmentation of the test samples are diagnosed with multiple flash radiography methods. The impact plate materials are selected to be transparent to the x-ray method so that only test metal material is imaged. Through a systematic series of such tests both strain-to-failure and fragmentation resistance properties are determined through this experimental method. Fragmentation property data for several steels, copper, aluminum, tantalum and titanium have been obtained to date. Aspects of the dynamic data have been analyzed with computational methods to achieve a better understanding of the processes leading to failure and fragmentation, and to test an existing computational fragmentation model.

A feasibility study of the use of DNA fragmentation as a method for detecting irradiation of food

International Nuclear Information System (INIS)

Jones, J.L.; Bulford, B.B.

1990-07-01

The main conclusions of the study are: 1. Gamma-irradiation at doses of 1-10 kGy, as recommended for use in food irradiation, causes extensive fragmentation of DNA molecules. The degree of fragmentation increases with increasing doses of irradiation treatment. 2. Irradiation-induced DNA fragments can be rapidly separated from intact DNA using a simple ultra-filtration method. 3. The separated DNA fragments can be detected/quantified rapidly using the simple Invitrogen DNA DipStick procedure. Dot-blot assays based on probes to widely conserved genes (e.g. histone genes) may also prove of value, but will require further development. 4. As DNA is present in a wide range of foods, DNA fragmentation offers a potentially useful marker for the irradiation treatment of foods. The assay now requires assessment with DNA extracts of a variety of foods. (author)

Ternary-fragmentation-driving potential energies of 252Cf

Science.gov (United States)

Karthikraj, C.; Ren, Zhongzhou

2017-12-01

Within the framework of a simple macroscopic model, the ternary-fragmentation-driving potential energies of 252Cf are studied. In this work, all possible ternary-fragment combinations of 252Cf are generated by the use of atomic mass evaluation-2016 (AME2016) data and these combinations are minimized by using a two-dimensional minimization approach. This minimization process can be done in two ways: (i) with respect to proton numbers (Z1, Z2, Z3) and (ii) with respect to neutron numbers (N1, N2, N3) of the ternary fragments. In this paper, the driving potential energies for the ternary breakup of 252Cf are presented for both the spherical and deformed as well as the proton-minimized and neutron-minimized ternary fragments. From the proton-minimized spherical ternary fragments, we have obtained different possible ternary configurations with a minimum driving potential, in particular, the experimental expectation of Sn + Ni + Ca ternary fragmentation. However, the neutron-minimized ternary fragments exhibit a driving potential minimum in the true-ternary-fission (TTF) region as well. Further, the Q -value energy systematics of the neutron-minimized ternary fragments show larger values for the TTF fragments. From this, we have concluded that the TTF region fragments with the least driving potential and high Q values have a strong possibility in the ternary fragmentation of 252Cf. Further, the role of ground-state deformations (β2, β3, β4, and β6) in the ternary breakup of 252Cf is also studied. The deformed ternary fragmentation, which involves Z3=12 -19 fragments, possesses the driving potential minimum due to the larger oblate deformations. We also found that the ground-state deformations, particularly β2, strongly influence the driving potential energies and play a major role in determining the most probable fragment combinations in the ternary breakup of 252Cf.

Lessons from hot spot analysis for fragment-based drug discovery

Science.gov (United States)

Hall, David R.; Vajda, Sandor

2015-01-01

Analysis of binding energy hot spots at protein surfaces can provide crucial insights into the prospects for successful application of fragment-based drug discovery (FBDD), and whether a fragment hit can be advanced into a high affinity, druglike ligand. The key factor is the strength of the top ranking hot spot, and how well a given fragment complements it. We show that published data are sufficient to provide a sophisticated and quantitative understanding of how hot spots derive from protein three-dimensional structure, and how their strength, number and spatial arrangement govern the potential for a surface site to bind to fragment-sized and larger ligands. This improved understanding provides important guidance for the effective application of FBDD in drug discovery. PMID:26538314

Fission fragment charge and mass distributions in 239Pu(n ,f ) in the adiabatic nuclear energy density functional theory

Science.gov (United States)

Regnier, D.; Dubray, N.; Schunck, N.; Verrière, M.

2016-05-01

Background: Accurate knowledge of fission fragment yields is an essential ingredient of numerous applications ranging from the formation of elements in the r process to fuel cycle optimization for nuclear energy. The need for a predictive theory applicable where no data are available, together with the variety of potential applications, is an incentive to develop a fully microscopic approach to fission dynamics. Purpose: In this work, we calculate the pre-neutron emission charge and mass distributions of the fission fragments formed in the neutron-induced fission of 239Pu using a microscopic method based on nuclear density functional theory (DFT). Methods: Our theoretical framework is the nuclear energy density functional (EDF) method, where large-amplitude collective motion is treated adiabatically by using the time-dependent generator coordinate method (TDGCM) under the Gaussian overlap approximation (GOA). In practice, the TDGCM is implemented in two steps. First, a series of constrained EDF calculations map the configuration and potential-energy landscape of the fissioning system for a small set of collective variables (in this work, the axial quadrupole and octupole moments of the nucleus). Then, nuclear dynamics is modeled by propagating a collective wave packet on the potential-energy surface. Fission fragment distributions are extracted from the flux of the collective wave packet through the scission line. Results: We find that the main characteristics of the fission charge and mass distributions can be well reproduced by existing energy functionals even in two-dimensional collective spaces. Theory and experiment agree typically within two mass units for the position of the asymmetric peak. As expected, calculations are sensitive to the structure of the initial state and the prescription for the collective inertia. We emphasize that results are also sensitive to the continuity of the collective landscape near scission. Conclusions: Our analysis confirms

New method for solving three-dimensional Schroedinger equation

International Nuclear Information System (INIS)

Melezhik, V.S.

1990-01-01

The method derived recently for solving a multidimensional scattering problem is applied to a three-dimensional Schroedinger equation. As compared with direct three-dimensional calculations of finite elements and finite differences, this approach gives sufficiently accurate upper and lower approximations to the helium-atom binding energy, which demonstrates its efficiency. 15 refs.; 1 fig.; 2 tabs

Fragmentation of sperm DNA using the TUNEL method.

Science.gov (United States)

Chenlo, P H; Curi, S M; Pugliese, M N; Ariagno, J I; Sardi-Segovia, M; Furlan, M J; Repetto, H E; Zeitler, E; Cohen, M; Mendeluk, G R

2014-11-01

To establish the validity of the TUNEL assay in determining sperm DNA fragmentation, the relationship between the degree of fragmentation and the seminal parameters and the sample needed to conduct the test. We used semen samples from healthy fertile men (n=33), patients who consulted for infertility with a prescription for the TUNEL assay (n=77) and patients with intracytoplasmic sperm injection failure (n=20), analyzed according to the 2010 WHO. The TUNEL/propidium iodide test was performed by flow cytometry, on baseline and post-swim-up samples. The cutoff value for the TUNEL assay (ROC curves) was 26%, with a sensitivity and specificity of 85% and 89%, respectively. The pre-swim-up and post-swim-up medians of the results from the TUNEL assay showed no significant differences (17.0% vs. 12.9%, respectively). However, 39.1% of the samples showed a difference greater than 15 in absolute value between the results of the baseline and post-swim-up TUNEL assays. The linear correlation study of the morphology, mobility and vitality using the post-swim-up TUNEL assay showed a greater correlation than preselection, with significant results (r: -0.394, P<.0001; r: -0.461, P<.0001; r: -0.526, P<.0001). The TUNEL assay is a valid test for clinical use. DNA fragmentation is a factor independent from traditional semen tests. We found a greater susceptibility to damage generated in the laboratory procedures in the samples with lower quality. The sample of choice for evaluating DNA fragmentation will depend on whether the clinician is treating a natural or assisted fertilization. Copyright © 2014 AEU. Published by Elsevier Espana. All rights reserved.

Crystal structure of an Okazaki fragment at 2-A resolution

Science.gov (United States)

Egli, M.; Usman, N.; Zhang, S. G.; Rich, A.

1992-01-01

In DNA replication, Okazaki fragments are formed as double-stranded intermediates during synthesis of the lagging strand. They are composed of the growing DNA strand primed by RNA and the template strand. The DNA oligonucleotide d(GGGTATACGC) and the chimeric RNA-DNA oligonucleotide r(GCG)d(TATACCC) were combined to form a synthetic Okazaki fragment and its three-dimensional structure was determined by x-ray crystallography. The fragment adopts an overall A-type conformation with 11 residues per turn. Although the base-pair geometry, particularly in the central TATA part, is distorted, there is no evidence for a transition from the A- to the B-type conformation at the junction between RNA.DNA hybrid and DNA duplex. The RNA trimer may, therefore, lock the complete fragment in an A-type conformation.

A method of image improvement in three-dimensional imaging

International Nuclear Information System (INIS)

Suto, Yasuzo; Huang, Tewen; Furuhata, Kentaro; Uchino, Masafumi.

1988-01-01

In general, image interpolation is required when the surface configurations of such structures as bones and organs are three-dimensionally constructed from the multi-sliced images obtained by CT. Image interpolation is a processing method whereby an artificial image is inserted between two adjacent slices to make spatial resolution equal to slice resolution in appearance. Such image interpolation makes it possible to increase the image quality of the constructed three-dimensional image. In our newly-developed algorithm, we have converted the presently and subsequently sliced images to distance images, and generated the interpolation images from these two distance images. As a result, compared with the previous method, three-dimensional images with better image quality have been constructed. (author)

Automated building of organometallic complexes from 3D fragments.

Science.gov (United States)

Foscato, Marco; Venkatraman, Vishwesh; Occhipinti, Giovanni; Alsberg, Bjørn K; Jensen, Vidar R

2014-07-28

A method for the automated construction of three-dimensional (3D) molecular models of organometallic species in design studies is described. Molecular structure fragments derived from crystallographic structures and accurate molecular-level calculations are used as 3D building blocks in the construction of multiple molecular models of analogous compounds. The method allows for precise control of stereochemistry and geometrical features that may otherwise be very challenging, or even impossible, to achieve with commonly available generators of 3D chemical structures. The new method was tested in the construction of three sets of active or metastable organometallic species of catalytic reactions in the homogeneous phase. The performance of the method was compared with those of commonly available methods for automated generation of 3D models, demonstrating higher accuracy of the prepared 3D models in general, and, in particular, a much wider range with respect to the kind of chemical structures that can be built automatically, with capabilities far beyond standard organic and main-group chemistry.

Novel method for the production of spin-aligned RI beams in projectile fragmentation reaction with the dispersion matching technique

Energy Technology Data Exchange (ETDEWEB)

Ichikawa, Y., E-mail: yuichikawa@phys.titech.ac.jp [Tokyo Institute of Technology, Department of Physics (Japan); Ueno, H. [RIKEN Nishina Center (Japan); Ishii, Y. [Tokyo Institute of Technology, Department of Physics (Japan); Furukawa, T. [Tokyo Metropolitan University, Department of Physics (Japan); Yoshimi, A. [Okayama University, Research Core for Extreme Quantum World (Japan); Kameda, D.; Watanabe, H.; Aoi, N. [RIKEN Nishina Center (Japan); Asahi, K. [Tokyo Institute of Technology, Department of Physics (Japan); Balabanski, D. L. [Bulgarian Academy of Sciences, Institute for Nuclear Research and Nuclear Energy (Bulgaria); Chevrier, R.; Daugas, J. M. [CEA, DAM, DIF (France); Fukuda, N. [RIKEN Nishina Center (Japan); Georgiev, G. [CSNSM, IN2P3-CNRS, Universite Paris-sud (France); Hayashi, H.; Iijima, H. [Tokyo Institute of Technology, Department of Physics (Japan); Inabe, N. [RIKEN Nishina Center (Japan); Inoue, T. [Tokyo Institute of Technology, Department of Physics (Japan); Ishihara, M.; Kubo, T. [RIKEN Nishina Center (Japan); and others

2013-05-15

A novel method to produce spin-aligned rare-isotope (RI) beam has been developed, that is the two-step projectile fragmentation method with a technique of dispersion matching. The present method was verified in an experiment at the RIKEN RIBF, where an RI beam of {sup 32}Al with spin alignment of 8(1) % was successfully produced from a primary beam of {sup 48}Ca, with {sup 33}Al as an intermediate nucleus. Figure of merit of the present method was found to be improved by a factor larger than 50 compared with a conventional method employing single-step projectile fragmentation.

Predicting "Hot" and "Warm" Spots for Fragment Binding.

Science.gov (United States)

Rathi, Prakash Chandra; Ludlow, R Frederick; Hall, Richard J; Murray, Christopher W; Mortenson, Paul N; Verdonk, Marcel L

2017-05-11

Computational fragment mapping methods aim to predict hotspots on protein surfaces where small fragments will bind. Such methods are popular for druggability assessment as well as structure-based design. However, to date researchers developing or using such tools have had no clear way of assessing the performance of these methods. Here, we introduce the first diverse, high quality validation set for computational fragment mapping. The set contains 52 diverse examples of fragment binding "hot" and "warm" spots from the Protein Data Bank (PDB). Additionally, we describe PLImap, a novel protocol for fragment mapping based on the Protein-Ligand Informatics force field (PLIff). We evaluate PLImap against the new fragment mapping test set, and compare its performance to that of simple shape-based algorithms and fragment docking using GOLD. PLImap is made publicly available from https://bitbucket.org/AstexUK/pli .

MaRaCluster: A Fragment Rarity Metric for Clustering Fragment Spectra in Shotgun Proteomics.

Science.gov (United States)

The, Matthew; Käll, Lukas

2016-03-04

Shotgun proteomics experiments generate large amounts of fragment spectra as primary data, normally with high redundancy between and within experiments. Here, we have devised a clustering technique to identify fragment spectra stemming from the same species of peptide. This is a powerful alternative method to traditional search engines for analyzing spectra, specifically useful for larger scale mass spectrometry studies. As an aid in this process, we propose a distance calculation relying on the rarity of experimental fragment peaks, following the intuition that peaks shared by only a few spectra offer more evidence than peaks shared by a large number of spectra. We used this distance calculation and a complete-linkage scheme to cluster data from a recent large-scale mass spectrometry-based study. The clusterings produced by our method have up to 40% more identified peptides for their consensus spectra compared to those produced by the previous state-of-the-art method. We see that our method would advance the construction of spectral libraries as well as serve as a tool for mining large sets of fragment spectra. The source code and Ubuntu binary packages are available at https://github.com/statisticalbiotechnology/maracluster (under an Apache 2.0 license).

Assessment of fragment projection hazard: probability distributions for the initial direction of fragments.

Science.gov (United States)

Tugnoli, Alessandro; Gubinelli, Gianfilippo; Landucci, Gabriele; Cozzani, Valerio

2014-08-30

The evaluation of the initial direction and velocity of the fragments generated in the fragmentation of a vessel due to internal pressure is an important information in the assessment of damage caused by fragments, in particular within the quantitative risk assessment (QRA) of chemical and process plants. In the present study an approach is proposed to the identification and validation of probability density functions (pdfs) for the initial direction of the fragments. A detailed review of a large number of past accidents provided the background information for the validation procedure. A specific method was developed for the validation of the proposed pdfs. Validated pdfs were obtained for both the vertical and horizontal angles of projection and for the initial velocity of the fragments. Copyright © 2014 Elsevier B.V. All rights reserved.

Mapping enzymatic catalysis using the effective fragment molecular orbital method

DEFF Research Database (Denmark)

Svendsen, Casper Steinmann; Fedorov, Dmitri G.; Jensen, Jan Halborg

2013-01-01

We extend the Effective Fragment Molecular Orbital (EFMO) method to the frozen domain approach where only the geometry of an active part is optimized, while the many-body polarization effects are considered for the whole system. The new approach efficiently mapped out the entire reaction path...... of chorismate mutase in less than four days using 80 cores on 20 nodes, where the whole system containing 2398 atoms is treated in the ab initio fashion without using any force fields. The reaction path is constructed automatically with the only assumption of defining the reaction coordinate a priori. We...

A multi-dimensional sampling method for locating small scatterers

International Nuclear Information System (INIS)

Song, Rencheng; Zhong, Yu; Chen, Xudong

2012-01-01

A multiple signal classification (MUSIC)-like multi-dimensional sampling method (MDSM) is introduced to locate small three-dimensional scatterers using electromagnetic waves. The indicator is built with the most stable part of signal subspace of the multi-static response matrix on a set of combinatorial sampling nodes inside the domain of interest. It has two main advantages compared to the conventional MUSIC methods. First, the MDSM is more robust against noise. Second, it can work with a single incidence even for multi-scatterers. Numerical simulations are presented to show the good performance of the proposed method. (paper)

A DETERMINISTIC METHOD FOR TRANSIENT, THREE-DIMENSIONAL NUETRON TRANSPORT

International Nuclear Information System (INIS)

S. GOLUOGLU, C. BENTLEY, R. DEMEGLIO, M. DUNN, K. NORTON, R. PEVEY I.SUSLOV AND H.L. DODDS

1998-01-01

A deterministic method for solving the time-dependent, three-dimensional Boltzmam transport equation with explicit representation of delayed neutrons has been developed and evaluated. The methodology used in this study for the time variable of the neutron flux is known as the improved quasi-static (IQS) method. The position, energy, and angle-dependent neutron flux is computed deterministically by using the three-dimensional discrete ordinates code TORT. This paper briefly describes the methodology and selected results. The code developed at the University of Tennessee based on this methodology is called TDTORT. TDTORT can be used to model transients involving voided and/or strongly absorbing regions that require transport theory for accuracy. This code can also be used to model either small high-leakage systems, such as space reactors, or asymmetric control rod movements. TDTORT can model step, ramp, step followed by another step, and step followed by ramp type perturbations. It can also model columnwise rod movement can also be modeled. A special case of columnwise rod movement in a three-dimensional model of a boiling water reactor (BWR) with simple adiabatic feedback is also included. TDTORT is verified through several transient one-dimensional, two-dimensional, and three-dimensional benchmark problems. The results show that the transport methodology and corresponding code developed in this work have sufficient accuracy and speed for computing the dynamic behavior of complex multidimensional neutronic systems

Similarity measurement method of high-dimensional data based on normalized net lattice subspace

Institute of Scientific and Technical Information of China (English)

Li Wenfa; Wang Gongming; Li Ke; Huang Su

2017-01-01

The performance of conventional similarity measurement methods is affected seriously by the curse of dimensionality of high-dimensional data.The reason is that data difference between sparse and noisy dimensionalities occupies a large proportion of the similarity, leading to the dissimilarities between any results.A similarity measurement method of high-dimensional data based on normalized net lattice subspace is proposed.The data range of each dimension is divided into several intervals, and the components in different dimensions are mapped onto the corresponding interval.Only the component in the same or adjacent interval is used to calculate the similarity.To validate this meth-od, three data types are used, and seven common similarity measurement methods are compared. The experimental result indicates that the relative difference of the method is increasing with the di-mensionality and is approximately two or three orders of magnitude higher than the conventional method.In addition, the similarity range of this method in different dimensions is [0, 1], which is fit for similarity analysis after dimensionality reduction.

Composition and method for detecting cancer with technetium labeled antibody fragments

International Nuclear Information System (INIS)

Burchiel, S. W.; Crockford, D. R.; Rhodes, B. A.

1984-01-01

F(ab') 2 or Fab fragments of antibodies to: (a) human chorionic gonadotropin (hCG), hCG alpha subunit, hCG beta subunit, or an hCG-like material; or (b) other tumor specific or tumor associated molecules, to include carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), human melanoma associated antigens, human sarcoma associated antigens or other antigens, are radiolabeled with technetium-99m (Tc-99m). When the F(ab') 2 or Fab fragments of antibody to such tumor associated antigens are injected intravenously into a patient, the radiolabeled composition accumulates at tumor sites. The accumulation of the cancer seeking radiopharmaceutical at tumor sites permits detection by external gamma scintigraphy. Thus, the composition is useful in the monitoring, localization and detection of cancer in the body. In an alternative composition, a double antibody approach to tumor localization using radiolabeled F(ab') 2 or Fab fragments is utilized. In this approach, a tumor specific antibody in the form of IgG, F(ab') 2 or Fab is first administered to a patient intravenously. Following a sufficient period of time, a second antibody in the form of F(ab') 2 or Fab is administered. The second antibody is radiolabeled with Tc-99m and has the property that it is reactive with the first antibody. This double antibody method has the advantage over a single antibody approach in that smaller tumors can be localized and detected and that the total amount of radioactive trace localized at the cancer site is increased

Application of Tandem Two-Dimensional Mass Spectrometry for Top-Down Deep Sequencing of Calmodulin.

Science.gov (United States)

Floris, Federico; Chiron, Lionel; Lynch, Alice M; Barrow, Mark P; Delsuc, Marc-André; O'Connor, Peter B

2018-06-04

Two-dimensional mass spectrometry (2DMS) involves simultaneous acquisition of the fragmentation patterns of all the analytes in a mixture by correlating their precursor and fragment ions by modulating precursor ions systematically through a fragmentation zone. Tandem two-dimensional mass spectrometry (MS/2DMS) unites the ultra-high accuracy of Fourier transform ion cyclotron resonance (FT-ICR) MS/MS and the simultaneous data-independent fragmentation of 2DMS to achieve extensive inter-residue fragmentation of entire proteins. 2DMS was recently developed for top-down proteomics (TDP), and applied to the analysis of calmodulin (CaM), reporting a cleavage coverage of about ~23% using infrared multiphoton dissociation (IRMPD) as fragmentation technique. The goal of this work is to expand the utility of top-down protein analysis using MS/2DMS in order to extend the cleavage coverage in top-down proteomics further into the interior regions of the protein. In this case, using MS/2DMS, the cleavage coverage of CaM increased from ~23% to ~42%. Graphical Abstract Two-dimensional mass spectrometry, when applied to primary fragment ions from the source, allows deep-sequencing of the protein calmodulin.

The dimension split element-free Galerkin method for three-dimensional potential problems

Science.gov (United States)

Meng, Z. J.; Cheng, H.; Ma, L. D.; Cheng, Y. M.

2018-02-01

This paper presents the dimension split element-free Galerkin (DSEFG) method for three-dimensional potential problems, and the corresponding formulae are obtained. The main idea of the DSEFG method is that a three-dimensional potential problem can be transformed into a series of two-dimensional problems. For these two-dimensional problems, the improved moving least-squares (IMLS) approximation is applied to construct the shape function, which uses an orthogonal function system with a weight function as the basis functions. The Galerkin weak form is applied to obtain a discretized system equation, and the penalty method is employed to impose the essential boundary condition. The finite difference method is selected in the splitting direction. For the purposes of demonstration, some selected numerical examples are solved using the DSEFG method. The convergence study and error analysis of the DSEFG method are presented. The numerical examples show that the DSEFG method has greater computational precision and computational efficiency than the IEFG method.

A two-dimensional, semi-analytic expansion method for nodal calculations

International Nuclear Information System (INIS)

Palmtag, S.P.

1995-08-01

Most modern nodal methods used today are based upon the transverse integration procedure in which the multi-dimensional flux shape is integrated over the transverse directions in order to produce a set of coupled one-dimensional flux shapes. The one-dimensional flux shapes are then solved either analytically or by representing the flux shape by a finite polynomial expansion. While these methods have been verified for most light-water reactor applications, they have been found to have difficulty predicting the large thermal flux gradients near the interfaces of highly-enriched MOX fuel assemblies. A new method is presented here in which the neutron flux is represented by a non-seperable, two-dimensional, semi-analytic flux expansion. The main features of this method are (1) the leakage terms from the node are modeled explicitly and therefore, the transverse integration procedure is not used, (2) the corner point flux values for each node are directly edited from the solution method, and a corner-point interpolation is not needed in the flux reconstruction, (3) the thermal flux expansion contains hyperbolic terms representing analytic solutions to the thermal flux diffusion equation, and (4) the thermal flux expansion contains a thermal to fast flux ratio term which reduces the number of polynomial expansion functions needed to represent the thermal flux. This new nodal method has been incorporated into the computer code COLOR2G and has been used to solve a two-dimensional, two-group colorset problem containing uranium and highly-enriched MOX fuel assemblies. The results from this calculation are compared to the results found using a code based on the traditional transverse integration procedure

Fragment library design: using cheminformatics and expert chemists to fill gaps in existing fragment libraries.

Science.gov (United States)

Kutchukian, Peter S; So, Sung-Sau; Fischer, Christian; Waller, Chris L

2015-01-01

Fragment based screening (FBS) has emerged as a mainstream lead discovery strategy in academia, biotechnology start-ups, and large pharma. As a prerequisite of FBS, a structurally diverse library of fragments is desirable in order to identify chemical matter that will interact with the range of diverse target classes that are prosecuted in contemporary screening campaigns. In addition, it is also desirable to offer synthetically amenable starting points to increase the probability of a successful fragment evolution through medicinal chemistry. Herein we describe a method to identify biologically relevant chemical substructures that are missing from an existing fragment library (chemical gaps), and organize these chemical gaps hierarchically so that medicinal chemists can efficiently navigate the prioritized chemical space and subsequently select purchasable fragments for inclusion in an enhanced fragment library.

Three-dimensional compound comparison methods and their application in drug discovery.

Science.gov (United States)

Shin, Woong-Hee; Zhu, Xiaolei; Bures, Mark Gregory; Kihara, Daisuke

2015-07-16

Virtual screening has been widely used in the drug discovery process. Ligand-based virtual screening (LBVS) methods compare a library of compounds with a known active ligand. Two notable advantages of LBVS methods are that they do not require structural information of a target receptor and that they are faster than structure-based methods. LBVS methods can be classified based on the complexity of ligand structure information utilized: one-dimensional (1D), two-dimensional (2D), and three-dimensional (3D). Unlike 1D and 2D methods, 3D methods can have enhanced performance since they treat the conformational flexibility of compounds. In this paper, a number of 3D methods will be reviewed. In addition, four representative 3D methods were benchmarked to understand their performance in virtual screening. Specifically, we tested overall performance in key aspects including the ability to find dissimilar active compounds, and computational speed.

Three-dimensional image signals: processing methods

Science.gov (United States)

Schiopu, Paul; Manea, Adrian; Craciun, Anca-Ileana; Craciun, Alexandru

2010-11-01

Over the years extensive studies have been carried out to apply coherent optics methods in real-time processing, communications and transmission image. This is especially true when a large amount of information needs to be processed, e.g., in high-resolution imaging. The recent progress in data-processing networks and communication systems has considerably increased the capacity of information exchange. We describe the results of literature investigation research of processing methods for the signals of the three-dimensional images. All commercially available 3D technologies today are based on stereoscopic viewing. 3D technology was once the exclusive domain of skilled computer-graphics developers with high-end machines and software. The images capture from the advanced 3D digital camera can be displayed onto screen of the 3D digital viewer with/ without special glasses. For this is needed considerable processing power and memory to create and render the complex mix of colors, textures, and virtual lighting and perspective necessary to make figures appear three-dimensional. Also, using a standard digital camera and a technique called phase-shift interferometry we can capture "digital holograms." These are holograms that can be stored on computer and transmitted over conventional networks. We present some research methods to process "digital holograms" for the Internet transmission and results.

A NEW METHOD FOR ESTIMATING THE 3D SIZE-DISTRIBUTIONCURVE OF FRAGMENTED ROCKS OUT OF 2D IMAGES

Directory of Open Access Journals (Sweden)

Souhaïl Outal

2011-05-01

Full Text Available Image analysis of rock fragmentation is used in mines and quarries to control the quality of blasting. Obtained information is the particle-size-distribution curve relating volume-proportions to the sizes of fragments. Calculation by image analysis of this particle-size-distribution is carried out in several steps, and each step has its inherent limitations. We will focus in this paper on one of themost crucial steps: reconstructing the volumes (3D. For the 3D-step, we have noticed that, due to the current acquisition method, there is no correlation between the average grey level of surfaces of the fragments and their third dimension. Consequently volumes (3D as well as the sizes (1D has to be calculated indirectly from the extracted projected areas of the visible fragments of images. For this purpose, we have built in laboratory a set of images of fragmented rocks resulting from blasting. Moreover, several tests based on comparisons between image analysis and screening measurements were carried out. A new stereological method, based on the comparison of the densities of probability (histograms of the samemeasurements (with very weak covering and overlappingwas elaborated. It allows us to estimate correctly, for a given type of rock, two intrinsic laws weighing the projected areas distribution in order to predict the volumic distribution.

Detection of ligand binding hot spots on protein surfaces via fragment-based methods: application to DJ-1 and glucocerebrosidase

Energy Technology Data Exchange (ETDEWEB)

Landon, Melissa R.; Lieberman, Raquel L.; Hoang, Quyen Q.; Ju, Shulin; Caaveiro, Jose M.M.; Orwig, Susan D.; Kozakov, Dima; Brenke, Ryan; Chuang, Gwo-Yu; Beglov, Dmitry; Vajda, Sandor; Petsko, Gregory A.; Ringe, Dagmar; (BU-M); (Brandeis); (GIT)

2010-08-04

The identification of hot spots, i.e., binding regions that contribute substantially to the free energy of ligand binding, is a critical step for structure-based drug design. Here we present the application of two fragment-based methods to the detection of hot spots for DJ-1 and glucocerebrosidase (GCase), targets for the development of therapeutics for Parkinson's and Gaucher's diseases, respectively. While the structures of these two proteins are known, binding information is lacking. In this study we employ the experimental multiple solvent crystal structures (MSCS) method and computational fragment mapping (FTMap) to identify regions suitable for the development of pharmacological chaperones for DJ-1 and GCase. Comparison of data derived via MSCS and FTMap also shows that FTMap, a computational method for the identification of fragment binding hot spots, is an accurate and robust alternative to the performance of expensive and difficult crystallographic experiments.

DIAGNOSTIC CHARACTERISTICS OF THE COMPUTER TESTS FORMED BY METHOD OF RESTORED FRAGMENTS

OpenAIRE

Oleksandr O. Petkov

2013-01-01

Definition of validity and reliability of tests which are formed by a method of restored fragments is considered in the article. The structure of the controlled theoretical material of limit field of knowledge, language expressions that describe the subject of control, and reliability of test, is analyzed. The technique of definition of the most important components of reliability of the considered tests is given: reliability of quantitative determination of coefficient of assimilation and te...

Three-Dimensional Compound Comparison Methods and Their Application in Drug Discovery

Directory of Open Access Journals (Sweden)

Woong-Hee Shin

2015-07-01

Full Text Available Virtual screening has been widely used in the drug discovery process. Ligand-based virtual screening (LBVS methods compare a library of compounds with a known active ligand. Two notable advantages of LBVS methods are that they do not require structural information of a target receptor and that they are faster than structure-based methods. LBVS methods can be classified based on the complexity of ligand structure information utilized: one-dimensional (1D, two-dimensional (2D, and three-dimensional (3D. Unlike 1D and 2D methods, 3D methods can have enhanced performance since they treat the conformational flexibility of compounds. In this paper, a number of 3D methods will be reviewed. In addition, four representative 3D methods were benchmarked to understand their performance in virtual screening. Specifically, we tested overall performance in key aspects including the ability to find dissimilar active compounds, and computational speed.

Fragment approaches in structure-based drug discovery

International Nuclear Information System (INIS)

Hubbard, Roderick E.

2008-01-01

Fragment-based methods are successfully generating novel and selective drug-like inhibitors of protein targets, with a number of groups reporting compounds entering clinical trials. This paper summarizes the key features of the approach as one of the tools in structure-guided drug discovery. There has been considerable interest recently in what is known as 'fragment-based lead discovery'. The novel feature of the approach is to begin with small low-affinity compounds. The main advantage is that a larger potential chemical diversity can be sampled with fewer compounds, which is particularly important for new target classes. The approach relies on careful design of the fragment library, a method that can detect binding of the fragment to the protein target, determination of the structure of the fragment bound to the target, and the conventional use of structural information to guide compound optimization. In this article the methods are reviewed, and experiences in fragment-based discovery of lead series of compounds against kinases such as PDK1 and ATPases such as Hsp90 are discussed. The examples illustrate some of the key benefits and issues of the approach and also provide anecdotal examples of the patterns seen in selectivity and the binding mode of fragments across different protein targets

Comparison and combination of "direct" and fragment based local correlation methods: Cluster in molecules and domain based local pair natural orbital perturbation and coupled cluster theories

Science.gov (United States)

Guo, Yang; Becker, Ute; Neese, Frank

2018-03-01

Local correlation theories have been developed in two main flavors: (1) "direct" local correlation methods apply local approximation to the canonical equations and (2) fragment based methods reconstruct the correlation energy from a series of smaller calculations on subsystems. The present work serves two purposes. First, we investigate the relative efficiencies of the two approaches using the domain-based local pair natural orbital (DLPNO) approach as the "direct" method and the cluster in molecule (CIM) approach as the fragment based approach. Both approaches are applied in conjunction with second-order many-body perturbation theory (MP2) as well as coupled-cluster theory with single-, double- and perturbative triple excitations [CCSD(T)]. Second, we have investigated the possible merits of combining the two approaches by performing CIM calculations with DLPNO methods serving as the method of choice for performing the subsystem calculations. Our cluster-in-molecule approach is closely related to but slightly deviates from approaches in the literature since we have avoided real space cutoffs. Moreover, the neglected distant pair correlations in the previous CIM approach are considered approximately. Six very large molecules (503-2380 atoms) were studied. At both MP2 and CCSD(T) levels of theory, the CIM and DLPNO methods show similar efficiency. However, DLPNO methods are more accurate for 3-dimensional systems. While we have found only little incentive for the combination of CIM with DLPNO-MP2, the situation is different for CIM-DLPNO-CCSD(T). This combination is attractive because (1) the better parallelization opportunities offered by CIM; (2) the methodology is less memory intensive than the genuine DLPNO-CCSD(T) method and, hence, allows for large calculations on more modest hardware; and (3) the methodology is applicable and efficient in the frequently met cases, where the largest subsystem calculation is too large for the canonical CCSD(T) method.

Fragmentation of suddenly heated liquids in ICF reactors. Revision 1

International Nuclear Information System (INIS)

Blink, J.A.; Hoover, W.G.

1985-01-01

Fragmentation of free liquids in Inertial Confinement Fusion reactors could determine the upper bound on reactor pulse rate because increased surface area will enhance the cooling and condensation of coolant ablated by the fusion x rays. Relaxation from the suddenly (neutron) heated state will move a liquid into the negative pressure region under the liquid-vapor P-V dome. The resulting expansion in a diverging geometry will hydrodynamically force the liquid to fragment, with vapor then forming from the new surfaces to fill the cavities. An energy minimization model is used to determine the fragment size that produces the least amount of non-fragment-center-of-mass energy; i.e., the sum of the surface and dilational kinetic energies. This model predicts fragmentation dependence on original system size and amount of isochoric heating as well as liquid density, Grueneisen parameter, surface tension, and sound speed. A two dimensional molecular dynamics code was developed to test the model at a microscopic scale for the Lennard-Jones fluid with its two adjustable constants chosen to represent lithium

Variational iteration method for one dimensional nonlinear thermoelasticity

International Nuclear Information System (INIS)

Sweilam, N.H.; Khader, M.M.

2007-01-01

This paper applies the variational iteration method to solve the Cauchy problem arising in one dimensional nonlinear thermoelasticity. The advantage of this method is to overcome the difficulty of calculation of Adomian's polynomials in the Adomian's decomposition method. The numerical results of this method are compared with the exact solution of an artificial model to show the efficiency of the method. The approximate solutions show that the variational iteration method is a powerful mathematical tool for solving nonlinear problems

Robust Object Tracking Using Valid Fragments Selection.

Science.gov (United States)

Zheng, Jin; Li, Bo; Tian, Peng; Luo, Gang

Local features are widely used in visual tracking to improve robustness in cases of partial occlusion, deformation and rotation. This paper proposes a local fragment-based object tracking algorithm. Unlike many existing fragment-based algorithms that allocate the weights to each fragment, this method firstly defines discrimination and uniqueness for local fragment, and builds an automatic pre-selection of useful fragments for tracking. Then, a Harris-SIFT filter is used to choose the current valid fragments, excluding occluded or highly deformed fragments. Based on those valid fragments, fragment-based color histogram provides a structured and effective description for the object. Finally, the object is tracked using a valid fragment template combining the displacement constraint and similarity of each valid fragment. The object template is updated by fusing feature similarity and valid fragments, which is scale-adaptive and robust to partial occlusion. The experimental results show that the proposed algorithm is accurate and robust in challenging scenarios.

Direct Linear Transformation Method for Three-Dimensional Cinematography

Science.gov (United States)

Shapiro, Robert

1978-01-01

The ability of Direct Linear Transformation Method for three-dimensional cinematography to locate points in space was shown to meet the accuracy requirements associated with research on human movement. (JD)

Equilibrium and non equilibrium in fragmentation

International Nuclear Information System (INIS)

Dorso, C.O.; Chernomoretz, A.; Lopez, J.A.

2001-01-01

Full text: In this communication we present recent results regarding the interplay of equilibrium and non equilibrium in the process of fragmentation of excited finite Lennard Jones drops. Because the general features of such a potential resemble the ones of the nuclear interaction (fact that is reinforced by the similarity between the EOS of both systems) these studies are not only relevant from a fundamental point of view but also shed light on the problem of nuclear multifragmentation. We focus on the microscopic analysis of the state of the fragmenting system at fragmentation time. We show that the Caloric Curve (i e. the functional relationship between the temperature of the system and the excitation energy) is of the type rise plateau with no vapor branch. The usual rise plateau rise pattern is only recovered when equilibrium is artificially imposed. This result puts a serious question on the validity of the freeze out hypothesis. This feature is independent of the dimensionality or excitation mechanism. Moreover we explore the behavior of magnitudes which can help us determine the degree of the assumed phase transition. It is found that no clear cut criteria is presently available. (Author)

RNA FRABASE 2.0: an advanced web-accessible database with the capacity to search the three-dimensional fragments within RNA structures

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Wasik Szymon

2010-05-01

Full Text Available Abstract Background Recent discoveries concerning novel functions of RNA, such as RNA interference, have contributed towards the growing importance of the field. In this respect, a deeper knowledge of complex three-dimensional RNA structures is essential to understand their new biological functions. A number of bioinformatic tools have been proposed to explore two major structural databases (PDB, NDB in order to analyze various aspects of RNA tertiary structures. One of these tools is RNA FRABASE 1.0, the first web-accessible database with an engine for automatic search of 3D fragments within PDB-derived RNA structures. This search is based upon the user-defined RNA secondary structure pattern. In this paper, we present and discuss RNA FRABASE 2.0. This second version of the system represents a major extension of this tool in terms of providing new data and a wide spectrum of novel functionalities. An intuitionally operated web server platform enables very fast user-tailored search of three-dimensional RNA fragments, their multi-parameter conformational analysis and visualization. Description RNA FRABASE 2.0 has stored information on 1565 PDB-deposited RNA structures, including all NMR models. The RNA FRABASE 2.0 search engine algorithms operate on the database of the RNA sequences and the new library of RNA secondary structures, coded in the dot-bracket format extended to hold multi-stranded structures and to cover residues whose coordinates are missing in the PDB files. The library of RNA secondary structures (and their graphics is made available. A high level of efficiency of the 3D search has been achieved by introducing novel tools to formulate advanced searching patterns and to screen highly populated tertiary structure elements. RNA FRABASE 2.0 also stores data and conformational parameters in order to provide "on the spot" structural filters to explore the three-dimensional RNA structures. An instant visualization of the 3D RNA

Method and system for manipulating a digital representation of a three-dimensional object

DEFF Research Database (Denmark)

2010-01-01

A method of manipulating a three-dimensional virtual building block model by means of two-dimensional cursor movements, the virtual building block model including a plurality of virtual building blocks each including a number of connection elements for connecting the virtual building block...... with another virtual building block according to a set of connection rules, the method comprising positioning by means of cursor movements in a computer display area representing a two-dimensional projection of said model, a two-dimensional projection of a first virtual building block to be connected...... to the structure, resulting in a two-dimensional position; determining, from the two-dimensional position, a number of three-dimensional candidate positions of the first virtual building block in the three-dimensional coordinate system; selecting one of said candidate positions based on the connection rules...

Solution of the two-dimensional space-time reactor kinetics equation by a locally one-dimensional method

International Nuclear Information System (INIS)

Chen, G.S.; Christenson, J.M.

1985-01-01

In this paper, the authors present some initial results from an investigation of the application of a locally one-dimensional (LOD) finite difference method to the solution of the two-dimensional, two-group reactor kinetics equations. Although the LOD method is relatively well known, it apparently has not been previously applied to the space-time kinetics equations. In this investigation, the LOD results were benchmarked against similar computational results (using the same computing environment, the same programming structure, and the same sample problems) obtained by the TWIGL program. For all of the problems considered, the LOD method provided accurate results in one-half to one-eight of the time required by the TWIGL program

The rise of fragment-based drug discovery.

Science.gov (United States)

Murray, Christopher W; Rees, David C

2009-06-01

The search for new drugs is plagued by high attrition rates at all stages in research and development. Chemists have an opportunity to tackle this problem because attrition can be traced back, in part, to the quality of the chemical leads. Fragment-based drug discovery (FBDD) is a new approach, increasingly used in the pharmaceutical industry, for reducing attrition and providing leads for previously intractable biological targets. FBDD identifies low-molecular-weight ligands (∼150 Da) that bind to biologically important macromolecules. The three-dimensional experimental binding mode of these fragments is determined using X-ray crystallography or NMR spectroscopy, and is used to facilitate their optimization into potent molecules with drug-like properties. Compared with high-throughput-screening, the fragment approach requires fewer compounds to be screened, and, despite the lower initial potency of the screening hits, offers more efficient and fruitful optimization campaigns. Here, we review the rise of FBDD, including its application to discovering clinical candidates against targets for which other chemistry approaches have struggled.

Mechanics of fragmentation of crocodile skin and other thin films

Science.gov (United States)

Qin, Zhao; Pugno, Nicola M.; Buehler, Markus J.

2014-01-01

Fragmentation of thin layers of materials is mediated by a network of cracks on its surface. It is commonly seen in dehydrated paintings or asphalt pavements and even in graphene or other two-dimensional materials, but is also observed in the characteristic polygonal pattern on a crocodile's head. Here, we build a simple mechanical model of a thin film and investigate the generation and development of fragmentation patterns as the material is exposed to various modes of deformation. We find that the characteristic size of fragmentation, defined by the mean diameter of polygons, is strictly governed by mechanical properties of the film material. Our result demonstrates that skin fragmentation on the head of crocodiles is dominated by that it features a small ratio between the fracture energy and Young's modulus, and the patterns agree well with experimental observations. Understanding this mechanics-driven process could be applied to improve the lifetime and reliability of thin film coatings by mimicking crocodile skin. PMID:24862190

Mechanics of fragmentation of crocodile skin and other thin films

Science.gov (United States)

Qin, Zhao; Pugno, Nicola M.; Buehler, Markus J.

2014-05-01

Fragmentation of thin layers of materials is mediated by a network of cracks on its surface. It is commonly seen in dehydrated paintings or asphalt pavements and even in graphene or other two-dimensional materials, but is also observed in the characteristic polygonal pattern on a crocodile's head. Here, we build a simple mechanical model of a thin film and investigate the generation and development of fragmentation patterns as the material is exposed to various modes of deformation. We find that the characteristic size of fragmentation, defined by the mean diameter of polygons, is strictly governed by mechanical properties of the film material. Our result demonstrates that skin fragmentation on the head of crocodiles is dominated by that it features a small ratio between the fracture energy and Young's modulus, and the patterns agree well with experimental observations. Understanding this mechanics-driven process could be applied to improve the lifetime and reliability of thin film coatings by mimicking crocodile skin.

Improved non-dimensional dynamic influence function method based on tow-domain method for vibration analysis of membranes

Directory of Open Access Journals (Sweden)

SW Kang

2015-02-01

Full Text Available This article introduces an improved non-dimensional dynamic influence function method using a sub-domain method for efficiently extracting the eigenvalues and mode shapes of concave membranes with arbitrary shapes. The non-dimensional dynamic influence function method (non-dimensional dynamic influence function method, which was developed by the authors in 1999, gives highly accurate eigenvalues for membranes, plates, and acoustic cavities, compared with the finite element method. However, it needs the inefficient procedure of calculating the singularity of a system matrix in the frequency range of interest for extracting eigenvalues and mode shapes. To overcome the inefficient procedure, this article proposes a practical approach to make the system matrix equation of the concave membrane of interest into a form of algebraic eigenvalue problem. It is shown by several case studies that the proposed method has a good convergence characteristics and yields very accurate eigenvalues, compared with an exact method and finite element method (ANSYS.

Fragment informatics and computational fragment-based drug design: an overview and update.

Science.gov (United States)

Sheng, Chunquan; Zhang, Wannian

2013-05-01

Fragment-based drug design (FBDD) is a promising approach for the discovery and optimization of lead compounds. Despite its successes, FBDD also faces some internal limitations and challenges. FBDD requires a high quality of target protein and good solubility of fragments. Biophysical techniques for fragment screening necessitate expensive detection equipment and the strategies for evolving fragment hits to leads remain to be improved. Regardless, FBDD is necessary for investigating larger chemical space and can be applied to challenging biological targets. In this scenario, cheminformatics and computational chemistry can be used as alternative approaches that can significantly improve the efficiency and success rate of lead discovery and optimization. Cheminformatics and computational tools assist FBDD in a very flexible manner. Computational FBDD can be used independently or in parallel with experimental FBDD for efficiently generating and optimizing leads. Computational FBDD can also be integrated into each step of experimental FBDD and help to play a synergistic role by maximizing its performance. This review will provide critical analysis of the complementarity between computational and experimental FBDD and highlight recent advances in new algorithms and successful examples of their applications. In particular, fragment-based cheminformatics tools, high-throughput fragment docking, and fragment-based de novo drug design will provide the focus of this review. We will also discuss the advantages and limitations of different methods and the trends in new developments that should inspire future research. © 2012 Wiley Periodicals, Inc.

A three-dimensional correlation method for registration of medical images in radiology

Energy Technology Data Exchange (ETDEWEB)

Georgiou, Michalakis; Sfakianakis, George N [Department of Radiology, University of Miami, Jackson Memorial Hospital, Miami, FL 33136 (United States); Nagel, Joachim H [Institute of Biomedical Engineering, University of Stuttgart, Stuttgart 70174 (Germany)

1999-12-31

The availability of methods to register multi-modality images in order to `fuse` them to correlate their information is increasingly becoming an important requirement for various diagnostic and therapeutic procedures. A variety of image registration methods have been developed but they remain limited to specific clinical applications. Assuming rigid body transformation, two images can be registered if their differences are calculated in terms of translation, rotation and scaling. This paper describes the development and testing of a new correlation based approach for three-dimensional image registration. First, the scaling factors introduced by the imaging devices are calculated and compensated for. Then, the two images become translation invariant by computing their three-dimensional Fourier magnitude spectra. Subsequently, spherical coordinate transformation is performed and then the three-dimensional rotation is computed using a novice approach referred to as {sup p}olar Shells{sup .} The method of polar shells maps the three angles of rotation into one rotation and two translations of a two-dimensional function and then proceeds to calculate them using appropriate transformations based on the Fourier invariance properties. A basic assumption in the method is that the three-dimensional rotation is constrained to one large and two relatively small angles. This assumption is generally satisfied in normal clinical settings. The new three-dimensional image registration method was tested with simulations using computer generated phantom data as well as actual clinical data. Performance analysis and accuracy evaluation of the method using computer simulations yielded errors in the sub-pixel range. (authors) 6 refs., 3 figs.

A three-dimensional correlation method for registration of medical images in radiology

International Nuclear Information System (INIS)

Georgiou, Michalakis; Sfakianakis, George N.; Nagel, Joachim H.

1998-01-01

The availability of methods to register multi-modality images in order to 'fuse' them to correlate their information is increasingly becoming an important requirement for various diagnostic and therapeutic procedures. A variety of image registration methods have been developed but they remain limited to specific clinical applications. Assuming rigid body transformation, two images can be registered if their differences are calculated in terms of translation, rotation and scaling. This paper describes the development and testing of a new correlation based approach for three-dimensional image registration. First, the scaling factors introduced by the imaging devices are calculated and compensated for. Then, the two images become translation invariant by computing their three-dimensional Fourier magnitude spectra. Subsequently, spherical coordinate transformation is performed and then the three-dimensional rotation is computed using a novice approach referred to as p olar Shells . The method of polar shells maps the three angles of rotation into one rotation and two translations of a two-dimensional function and then proceeds to calculate them using appropriate transformations based on the Fourier invariance properties. A basic assumption in the method is that the three-dimensional rotation is constrained to one large and two relatively small angles. This assumption is generally satisfied in normal clinical settings. The new three-dimensional image registration method was tested with simulations using computer generated phantom data as well as actual clinical data. Performance analysis and accuracy evaluation of the method using computer simulations yielded errors in the sub-pixel range. (authors)

The stress analysis method for three-dimensional composite materials

Science.gov (United States)

Nagai, Kanehiro; Yokoyama, Atsushi; Maekawa, Zen'ichiro; Hamada, Hiroyuki

1994-05-01

This study proposes a stress analysis method for three-dimensionally fiber reinforced composite materials. In this method, the rule-of mixture for composites is successfully applied to 3-D space in which material properties would change 3-dimensionally. The fundamental formulas for Young's modulus, shear modulus, and Poisson's ratio are derived. Also, we discuss a strength estimation and an optimum material design technique for 3-D composite materials. The analysis is executed for a triaxial orthogonally woven fabric, and their results are compared to the experimental data in order to verify the accuracy of this method. The present methodology can be easily understood with basic material mechanics and elementary mathematics, so it enables us to write a computer program of this theory without difficulty. Furthermore, this method can be applied to various types of 3-D composites because of its general-purpose characteristics.

Fragmentation measurement using image processing

Directory of Open Access Journals (Sweden)

Farhang Sereshki

2016-12-01

Full Text Available In this research, first of all, the existing problems in fragmentation measurement are reviewed for the sake of its fast and reliable evaluation. Then, the available methods used for evaluation of blast results are mentioned. The produced errors especially in recognizing the rock fragments in computer-aided methods, and also, the importance of determination of their sizes in the image analysis methods are described. After reviewing the previous work done, an algorithm is proposed for the automated determination of rock particles’ boundary in the Matlab software. This method can determinate automatically the particles boundary in the minimum time. The results of proposed method are compared with those of Split Desktop and GoldSize software in two automated and manual states. Comparing the curves extracted from different methods reveals that the proposed approach is accurately applicable in measuring the size distribution of laboratory samples, while the manual determination of boundaries in the conventional software is very time-consuming, and the results of automated netting of fragments are very different with the real value due to the error in separation of the objects.

Biomedical applications of two- and three-dimensional deterministic radiation transport methods

International Nuclear Information System (INIS)

Nigg, D.W.

1992-01-01

Multidimensional deterministic radiation transport methods are routinely used in support of the Boron Neutron Capture Therapy (BNCT) Program at the Idaho National Engineering Laboratory (INEL). Typical applications of two-dimensional discrete-ordinates methods include neutron filter design, as well as phantom dosimetry. The epithermal-neutron filter for BNCT that is currently available at the Brookhaven Medical Research Reactor (BMRR) was designed using such methods. Good agreement between calculated and measured neutron fluxes was observed for this filter. Three-dimensional discrete-ordinates calculations are used routinely for dose-distribution calculations in three-dimensional phantoms placed in the BMRR beam, as well as for treatment planning verification for live canine subjects. Again, good agreement between calculated and measured neutron fluxes and dose levels is obtained

Mapping Enzymatic Catalysis Using the Effective Fragment Molecular Orbital Method: Towards all ab initio Biochemistry

DEFF Research Database (Denmark)

Svendsen, Casper Steinmann; Jensen, Jan; Fedorov, Dmitri

2013-01-01

We extend the Effective Fragment Molecular Orbital (EFMO) method to the frozen domain approach where only the geometry of an active part is optimized, while the many-body polarization effects are considered for the whole system. The new approach efficiently mapped out the entire reaction path of ...

New method for solving three-dimensional Schroedinger equation

International Nuclear Information System (INIS)

Melezhik, V.S.

1992-01-01

A new method is developed for solving the multidimensional Schroedinger equation without the variable separation. To solve the Schroedinger equation in a multidimensional coordinate space X, a difference grid Ω i (i=1,2,...,N) for some of variables, Ω, from X={R,Ω} is introduced and the initial partial-differential equation is reduced to a system of N differential-difference equations in terms of one of the variables R. The arising multi-channel scattering (or eigenvalue) problem is solved by the algorithm based on a continuous analog of the Newton method. The approach has been successfully tested for several two-dimensional problems (scattering on a nonspherical potential well and 'dipole' scatterer, a hydrogen atom in a homogenous magnetic field) and for a three-dimensional problem of the helium-atom bound states. (author)

Knowledge-based Fragment Binding Prediction

Science.gov (United States)

Tang, Grace W.; Altman, Russ B.

2014-01-01

Target-based drug discovery must assess many drug-like compounds for potential activity. Focusing on low-molecular-weight compounds (fragments) can dramatically reduce the chemical search space. However, approaches for determining protein-fragment interactions have limitations. Experimental assays are time-consuming, expensive, and not always applicable. At the same time, computational approaches using physics-based methods have limited accuracy. With increasing high-resolution structural data for protein-ligand complexes, there is now an opportunity for data-driven approaches to fragment binding prediction. We present FragFEATURE, a machine learning approach to predict small molecule fragments preferred by a target protein structure. We first create a knowledge base of protein structural environments annotated with the small molecule substructures they bind. These substructures have low-molecular weight and serve as a proxy for fragments. FragFEATURE then compares the structural environments within a target protein to those in the knowledge base to retrieve statistically preferred fragments. It merges information across diverse ligands with shared substructures to generate predictions. Our results demonstrate FragFEATURE's ability to rediscover fragments corresponding to the ligand bound with 74% precision and 82% recall on average. For many protein targets, it identifies high scoring fragments that are substructures of known inhibitors. FragFEATURE thus predicts fragments that can serve as inputs to fragment-based drug design or serve as refinement criteria for creating target-specific compound libraries for experimental or computational screening. PMID:24762971

Fragmentation, Cost and Environmental Effects of Plaster Stemming Method for Blasting at A Basalt Quarry

Science.gov (United States)

Cevizci, Halim

2014-10-01

In this study, the plaster stemming application for blasting at a basalt quarry is studied. Drill cuttings are generally used in open pits and quarries as the most common stemming material since these are most readily available at blast sites. However, dry drill cuttings eject very easily from blastholes without offering much resistance to blast energy. The plaster stemming method has been found to be better than the drill cuttings stemming method due to increased confinement inside the hole and better utilization of blast explosive energy in the rock. The main advantage of the new stemming method is the reduction in the cost of blasting. At a basalt quarry, blasting costs per unit volume of rock were reduced to 15% by increasing burden and spacing distances. In addition, better fragmentation was obtained by using the plaster stemming method. Blast trials showed that plaster stemming produced finer material. In the same blast tests, +30 cm size fragments were reduced to 47.3% of the total, compared to 32.6% in the conventional method of drill cuttings stemming. With this method of stemming, vibration and air shock values increased slightly due to more blast energy being available for rock breakage but generally these increased values were small and stayed under the permitted limit for blast damage criteria unless measuring distance is too close.

Determination of fragment orbitals and LCFO MO's in semiempirical methods with overlap matrices

International Nuclear Information System (INIS)

Konstantinavicius, K.V.; Lazauskas, V.M.

1988-01-01

We propose a technique for a fragment stage solution of the Roothaan equations, allowing us to obtain fragment orbitals (FO's) and to form molecular orbitals (LCFO MO'S) for the molecule from them. As an example, in the Mulliken-Wolfsberg-Helmholtz (MWH) approximation we obtain the orbitals for fragments of the simplest hydrocarbon molecules and we compare them with the FO's found in the CNDO/2 approximation. We discuss the possibilities in perturbation theory for joining the fragments and for study of the properties of the molecules in the FO basis

Synthesis of the proteinase inhibitor LEKTI domain 6 by the fragment condensation method and regioselective disulfide bond formation.

Science.gov (United States)

Vasileiou, Zoe; Barlos, Kostas K; Gatos, Dimitrios; Adermann, Knut; Deraison, Celine; Barlos, Kleomenis

2010-01-01

Proteinase inhibitors are of high pharmaceutical interest and are drug candidates for a variety of indications. Specific kallikrein inhibitors are important for their antitumor activity and their potential application to the treatment of skin diseases. In this study we describe the synthesis of domain 6 of the kallikrein inhibitor Lympho-Epithilial Kazal-Type Inhibitor (LEKTI) by the fragment condensation method and site-directed cystine bridge formation. To obtain the linear LEKTI precursor, the condensation was best performed in solution, coupling the protected fragment 1-22 to 23-68. This method yielded LEKTI domain 6 of high purity and equipotent to the recombinantly produced peptide. (c) 2010 Wiley Periodicals, Inc.

Application of Exp-function method for (2 + 1)-dimensional nonlinear evolution equations

International Nuclear Information System (INIS)

Bekir, Ahmet; Boz, Ahmet

2009-01-01

In this paper, the Exp-function method is used to construct solitary and soliton solutions of (2 + 1)-dimensional nonlinear evolution equations. (2 + 1)-dimensional breaking soliton (Calogero) equation, modified Zakharov-Kuznetsov and Konopelchenko-Dubrovsky equations are chosen to illustrate the effectiveness of the method. The method is straightforward and concise, and its applications are promising. The Exp-function method presents a wider applicability for handling nonlinear wave equations.

A Comparison of Machine Learning Methods in a High-Dimensional Classification Problem

OpenAIRE

Zekić-Sušac, Marijana; Pfeifer, Sanja; Šarlija, Nataša

2014-01-01

Background: Large-dimensional data modelling often relies on variable reduction methods in the pre-processing and in the post-processing stage. However, such a reduction usually provides less information and yields a lower accuracy of the model. Objectives: The aim of this paper is to assess the high-dimensional classification problem of recognizing entrepreneurial intentions of students by machine learning methods. Methods/Approach: Four methods were tested: artificial neural networks, CART ...

Inverse method for determining radon diffusion coefficient and free radon production rate of fragmented uranium ore

International Nuclear Information System (INIS)

Ye, Yong-jun; Wang, Li-heng; Ding, De-xin; Zhao, Ya-li; Fan, Nan-bin

2014-01-01

The radon diffusion coefficient and the free radon production rate are important parameters for describing radon migration in the fragmented uranium ore. In order to determine the two parameters, the pure diffusion migration equation for radon was firstly established and its analytic solution with the two parameters to be determined was derived. Then, a self manufactured experimental column was used to simulate the pure diffusion of the radon, the improved scintillation cell method was used to measure the pore radon concentrations at different depths of the column loaded with the fragmented uranium ore, and the nonlinear least square algorithm was used to inversely determine the radon diffusion coefficient and the free radon production rate. Finally, the solution with the two inversely determined parameters was used to predict the pore radon concentrations at some depths of the column, and the predicted results were compared with the measured results. The results show that the predicted results are in good agreement with the measured results and the numerical inverse method is applicable to the determination of the radon diffusion coefficient and the free radon production rate for the fragmented uranium ore. - Highlights: • Inverse method for determining two transport parameters of radon is proposed. • A self-made experimental apparatus is used to simulate radon diffusion process. • Sampling volume and position for measuring radon concentration are optimized. • The inverse results of an experimental sample are verified

An Alternative to Conventional Rock Fragmentation Methods Using SCDA: A Review

Directory of Open Access Journals (Sweden)

Radhika Vidanage De Silva

2016-11-01

Full Text Available Global energy and material consumption are expected to rise in exponential proportions during the next few decades, generating huge demands for deep earth energy (oil/gas recovery and mineral processing. Under such circumstances, the continuation of existing methods in rock fragmentation in such applications is questionable due to the proven adverse environmental impacts associated with them. In this regard; the possibility of using more environmentally friendly options as Soundless Chemical Demolition Agents (SCDAs play a vital role in replacing harmful conventional rock fragmentation techniques for gas; oil and mineral recovery. This study reviews up to date research on soundless cracking demolition agent (SCDA application on rock fracturing including its limitations and strengths, possible applications in the petroleum industry and the possibility of using existing rock fragmentation models for SCDA-based rock fragmentation; also known as fracking. Though the expansive properties of SCDAs are currently used in some demolition works, the poor usage guidelines available reflect the insufficient research carried out on its material’s behavior. SCDA is a cementitious powdery substance with quicklime (CaO as its primary ingredient that expands upon contact with water; which results in a huge expansive pressure if this CaO hydration reaction occurs in a confined condition. So, the mechanism can be used for rock fragmentation by injecting the SCDA into boreholes of a rock mass; where the resulting expansive pressure is sufficient to create an effective fracture network in the confined rock mass around the borehole. This expansive pressure development, however, dependent on many factors, where formation water content creates a negative influence on this due to required greater degree of hydration under greater water contents and temperature creates a positive influence by accelerating the reaction. Having a precise understanding of the fracture

Method translation and full metadata transfer from thermal to differential flow modulated comprehensive two dimensional gas chromatography: Profiling of suspected fragrance allergens.

Science.gov (United States)

Cordero, Chiara; Rubiolo, Patrizia; Reichenbach, Stephen E; Carretta, Andrea; Cobelli, Luigi; Giardina, Matthew; Bicchi, Carlo

2017-01-13

The possibility to transfer methods from thermal to differential-flow modulated comprehensive two-dimensional gas chromatographic (GC×GC) platforms is of high interest to improve GC×GC flexibility and increase the compatibility of results from different platforms. The principles of method translation are here applied to an original method, developed for a loop-type thermal modulated GC×GC-MS/FID system, suitable for quali-quantitative screening of suspected fragrance allergens. The analysis conditions were translated to a reverse-injection differential flow modulated platform (GC×2GC-MS/FID) with a dual-parallel secondary column and dual detection. The experimental results, for a model mixture of suspected volatile allergens and for raw fragrance mixtures of different composition, confirmed the feasibility of translating methods by preserving 1 D elution order, as well as the relative alignment of resulting 2D peak patterns. A correct translation produced several benefits including an effective transfer of metadata (compound names, MS fragmentation pattern, response factors) by automatic template transformation and matching from the original/reference method to its translated counterpart. The correct translation provided: (a) 2D pattern repeatability, (b) MS fragmentation pattern reliability for identity confirmation, and (c) comparable response factors and quantitation accuracy within a concentration range of three orders of magnitude. The adoption of a narrow bore (i.e. 0.1mm d c ) first-dimension column to operate under close-to-optimal conditions with the differential-flow modulation GC×GC platform was also advantageous in halving the total analysis under the translated conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Fragment-based lead generation: identification of seed fragments by a highly efficient fragment screening technology

Science.gov (United States)

Neumann, Lars; Ritscher, Allegra; Müller, Gerhard; Hafenbradl, Doris

2009-08-01

For the detection of the precise and unambiguous binding of fragments to a specific binding site on the target protein, we have developed a novel reporter displacement binding assay technology. The application of this technology for the fragment screening as well as the fragment evolution process with a specific modelling based design strategy is demonstrated for inhibitors of the protein kinase p38alpha. In a fragment screening approach seed fragments were identified which were then used to build compounds from the deep-pocket towards the hinge binding area of the protein kinase p38alpha based on a modelling approach. BIRB796 was used as a blueprint for the alignment of the fragments. The fragment evolution of these deep-pocket binding fragments towards the fully optimized inhibitor BIRB796 included the modulation of the residence time as well as the affinity. The goal of our study was to evaluate the robustness and efficiency of our novel fragment screening technology at high fragment concentrations, compare the screening data with biochemical activity data and to demonstrate the evolution of the hit fragments with fast kinetics, into slow kinetic inhibitors in an in silico approach.

A novel method to discover fluoroquinolone antibiotic resistance (qnr genes in fragmented nucleotide sequences

Directory of Open Access Journals (Sweden)

Boulund Fredrik

2012-12-01

Full Text Available Abstract Background Broad-spectrum fluoroquinolone antibiotics are central in modern health care and are used to treat and prevent a wide range of bacterial infections. The recently discovered qnr genes provide a mechanism of resistance with the potential to rapidly spread between bacteria using horizontal gene transfer. As for many antibiotic resistance genes present in pathogens today, qnr genes are hypothesized to originate from environmental bacteria. The vast amount of data generated by shotgun metagenomics can therefore be used to explore the diversity of qnr genes in more detail. Results In this paper we describe a new method to identify qnr genes in nucleotide sequence data. We show, using cross-validation, that the method has a high statistical power of correctly classifying sequences from novel classes of qnr genes, even for fragments as short as 100 nucleotides. Based on sequences from public repositories, the method was able to identify all previously reported plasmid-mediated qnr genes. In addition, several fragments from novel putative qnr genes were identified in metagenomes. The method was also able to annotate 39 chromosomal variants of which 11 have previously not been reported in literature. Conclusions The method described in this paper significantly improves the sensitivity and specificity of identification and annotation of qnr genes in nucleotide sequence data. The predicted novel putative qnr genes in the metagenomic data support the hypothesis of a large and uncharacterized diversity within this family of resistance genes in environmental bacterial communities. An implementation of the method is freely available at http://bioinformatics.math.chalmers.se/qnr/.

Nonlinear dimensionality reduction methods for synthetic biology biobricks' visualization.

Science.gov (United States)

Yang, Jiaoyun; Wang, Haipeng; Ding, Huitong; An, Ning; Alterovitz, Gil

2017-01-19

Visualizing data by dimensionality reduction is an important strategy in Bioinformatics, which could help to discover hidden data properties and detect data quality issues, e.g. data noise, inappropriately labeled data, etc. As crowdsourcing-based synthetic biology databases face similar data quality issues, we propose to visualize biobricks to tackle them. However, existing dimensionality reduction methods could not be directly applied on biobricks datasets. Hereby, we use normalized edit distance to enhance dimensionality reduction methods, including Isomap and Laplacian Eigenmaps. By extracting biobricks from synthetic biology database Registry of Standard Biological Parts, six combinations of various types of biobricks are tested. The visualization graphs illustrate discriminated biobricks and inappropriately labeled biobricks. Clustering algorithm K-means is adopted to quantify the reduction results. The average clustering accuracy for Isomap and Laplacian Eigenmaps are 0.857 and 0.844, respectively. Besides, Laplacian Eigenmaps is 5 times faster than Isomap, and its visualization graph is more concentrated to discriminate biobricks. By combining normalized edit distance with Isomap and Laplacian Eigenmaps, synthetic biology biobircks are successfully visualized in two dimensional space. Various types of biobricks could be discriminated and inappropriately labeled biobricks could be determined, which could help to assess crowdsourcing-based synthetic biology databases' quality, and make biobricks selection.

Dimensional analysis and self-similarity methods for engineers and scientists

CERN Document Server

Zohuri, Bahman

2015-01-01

This ground-breaking reference provides an overview of key concepts in dimensional analysis, and then pushes well beyond traditional applications in fluid mechanics to demonstrate how powerful this tool can be in solving complex problems across many diverse fields. Of particular interest is the book's coverage of  dimensional analysis and self-similarity methods in nuclear and energy engineering. Numerous practical examples of dimensional problems are presented throughout, allowing readers to link the book's theoretical explanations and step-by-step mathematical solutions to practical impleme

A finite-dimensional reduction method for slightly supercritical elliptic problems

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Riccardo Molle

2004-01-01

Full Text Available We describe a finite-dimensional reduction method to find solutions for a class of slightly supercritical elliptic problems. A suitable truncation argument allows us to work in the usual Sobolev space even in the presence of supercritical nonlinearities: we modify the supercritical term in such a way to have subcritical approximating problems; for these problems, the finite-dimensional reduction can be obtained applying the methods already developed in the subcritical case; finally, we show that, if the truncation is realized at a sufficiently large level, then the solutions of the approximating problems, given by these methods, also solve the supercritical problems when the parameter is small enough.

Effective method for construction of low-dimensional models for heat transfer process

Energy Technology Data Exchange (ETDEWEB)

Blinov, D.G.; Prokopov, V.G.; Sherenkovskii, Y.V.; Fialko, N.M.; Yurchuk, V.L. [National Academy of Sciences of Ukraine, Kiev (Ukraine). Inst. of Engineering Thermophysics

2004-12-01

A low-dimensional model based on the method of proper orthogonal decomposition (POD) and the method of polyargumental systems (MPS) for thermal conductivity problems with strongly localized source of heat has been presented. The key aspect of these methods is that they enable to avoid weak points of other projection methods, which consists in a priori choice of basis functions. It enables us to use the MPS method and the POD method as convenient means to construct low-dimensional models of heat and mass transfer problems. (Author)

Critical Features of Fragment Libraries for Protein Structure Prediction.

Science.gov (United States)

Trevizani, Raphael; Custódio, Fábio Lima; Dos Santos, Karina Baptista; Dardenne, Laurent Emmanuel

2017-01-01

The use of fragment libraries is a popular approach among protein structure prediction methods and has proven to substantially improve the quality of predicted structures. However, some vital aspects of a fragment library that influence the accuracy of modeling a native structure remain to be determined. This study investigates some of these features. Particularly, we analyze the effect of using secondary structure prediction guiding fragments selection, different fragments sizes and the effect of structural clustering of fragments within libraries. To have a clearer view of how these factors affect protein structure prediction, we isolated the process of model building by fragment assembly from some common limitations associated with prediction methods, e.g., imprecise energy functions and optimization algorithms, by employing an exact structure-based objective function under a greedy algorithm. Our results indicate that shorter fragments reproduce the native structure more accurately than the longer. Libraries composed of multiple fragment lengths generate even better structures, where longer fragments show to be more useful at the beginning of the simulations. The use of many different fragment sizes shows little improvement when compared to predictions carried out with libraries that comprise only three different fragment sizes. Models obtained from libraries built using only sequence similarity are, on average, better than those built with a secondary structure prediction bias. However, we found that the use of secondary structure prediction allows greater reduction of the search space, which is invaluable for prediction methods. The results of this study can be critical guidelines for the use of fragment libraries in protein structure prediction.

Fragment-based approaches to TB drugs.

Science.gov (United States)

Marchetti, Chiara; Chan, Daniel S H; Coyne, Anthony G; Abell, Chris

2018-02-01

Tuberculosis is an infectious disease associated with significant mortality and morbidity worldwide, particularly in developing countries. The rise of antibiotic resistance in Mycobacterium tuberculosis (Mtb) urgently demands the development of new drug leads to tackle resistant strains. Fragment-based methods have recently emerged at the forefront of pharmaceutical development as a means to generate more effective lead structures, via the identification of fragment molecules that form weak but high quality interactions with the target biomolecule and subsequent fragment optimization. This review highlights a number of novel inhibitors of Mtb targets that have been developed through fragment-based approaches in recent years.

Renormalization of the fragmentation equation: Exact self-similar solutions and turbulent cascades

Science.gov (United States)

Saveliev, V. L.; Gorokhovski, M. A.

2012-12-01

Using an approach developed earlier for renormalization of the Boltzmann collision integral [Saveliev and Nanbu, Phys. Rev. E1539-375510.1103/PhysRevE.65.051205 65, 051205 (2002)], we derive an exact divergence form for the fragmentation operator. Then we reduce the fragmentation equation to the continuity equation in size space, with the flux given explicitly. This allows us to obtain self-similar solutions and to find the integral of motion for these solutions (we call it the bare flux). We show how these solutions can be applied as a description of cascade processes in three- and two-dimensional turbulence. We also suggested an empirical cascade model of impact fragmentation of brittle materials.

Three-dimensional measurement of a tightly focused laser beam

Directory of Open Access Journals (Sweden)

Xiangsheng Xie

2013-02-01

Full Text Available The spatial structure of a tightly focused light field is measured with a double knife-edge scanning method. The measurement method is based on the use of a high-quality double knife-edge fabricated from a right-angled silicon fragment mounted on a photodetector. The reconstruction of the three-dimensional structures of tightly focused spots is carried out with both uniform and partially obstructed linearly polarized incident light beams. The optical field distribution is found to deviate substantially from the input beam profile in the tightly focused region, which is in good agreement with the results of numerical simulations.

Two-Dimensional Impact Reconstruction Method for Rail Defect Inspection

Directory of Open Access Journals (Sweden)

Jie Zhao

2014-01-01

Full Text Available The safety of train operating is seriously menaced by the rail defects, so it is of great significance to inspect rail defects dynamically while the train is operating. This paper presents a two-dimensional impact reconstruction method to realize the on-line inspection of rail defects. The proposed method utilizes preprocessing technology to convert time domain vertical vibration signals acquired by wireless sensor network to space signals. The modern time-frequency analysis method is improved to reconstruct the obtained multisensor information. Then, the image fusion processing technology based on spectrum threshold processing and node color labeling is proposed to reduce the noise, and blank the periodic impact signal caused by rail joints and locomotive running gear. This method can convert the aperiodic impact signals caused by rail defects to partial periodic impact signals, and locate the rail defects. An application indicates that the two-dimensional impact reconstruction method could display the impact caused by rail defects obviously, and is an effective on-line rail defects inspection method.

Irregular grid methods for pricing high-dimensional American options

NARCIS (Netherlands)

Berridge, S.J.

2004-01-01

This thesis proposes and studies numerical methods for pricing high-dimensional American options; important examples being basket options, Bermudan swaptions and real options. Four new methods are presented and analysed, both in terms of their application to various test problems, and in terms of

Application of the fragment molecular orbital method analysis to fragment-based drug discovery of BET (bromodomain and extra-terminal proteins) inhibitors.

Science.gov (United States)

Ozawa, Motoyasu; Ozawa, Tomonaga; Ueda, Kazuyoshi

2017-06-01

The molecular interactions of inhibitors of bromodomains (BRDs) were investigated. BRDs are protein interaction modules that recognizing ε-N-acetyl-lysine (εAc-Lys) motifs found in histone tails and are promising protein-protein interaction (PPI) targets. First, we analyzed a peptide ligand containing εAc-Lys to evaluate native PPIs. We then analyzed tetrahydroquinazoline-6-yl-benzensulfonamide derivatives found by fragment-based drug design (FBDD) and examined their interactions with the protein compared with the peptide ligand in terms of the inter-fragment interaction energy. In addition, we analyzed benzodiazepine derivatives that are high-affinity ligands for BRDs and examined differences in the CH/π interactions of the amino acid residues. We further surveyed changes in the charges of the amino acid residues among individual ligands, performed pair interaction energy decomposition analysis and estimated the water profile within the ligand binding site. Thus, useful insights for drug design were provided. Through these analyses and considerations, we show that the FMO method is a useful drug design tool to evaluate the process of FBDD and to explore PPI inhibitors. Copyright © 2017 Elsevier Inc. All rights reserved.

Structural Refinement of Proteins by Restrained Molecular Dynamics Simulations with Non-interacting Molecular Fragments.

Directory of Open Access Journals (Sweden)

Rong Shen

2015-10-01

Full Text Available The knowledge of multiple conformational states is a prerequisite to understand the function of membrane transport proteins. Unfortunately, the determination of detailed atomic structures for all these functionally important conformational states with conventional high-resolution approaches is often difficult and unsuccessful. In some cases, biophysical and biochemical approaches can provide important complementary structural information that can be exploited with the help of advanced computational methods to derive structural models of specific conformational states. In particular, functional and spectroscopic measurements in combination with site-directed mutations constitute one important source of information to obtain these mixed-resolution structural models. A very common problem with this strategy, however, is the difficulty to simultaneously integrate all the information from multiple independent experiments involving different mutations or chemical labels to derive a unique structural model consistent with the data. To resolve this issue, a novel restrained molecular dynamics structural refinement method is developed to simultaneously incorporate multiple experimentally determined constraints (e.g., engineered metal bridges or spin-labels, each treated as an individual molecular fragment with all atomic details. The internal structure of each of the molecular fragments is treated realistically, while there is no interaction between different molecular fragments to avoid unphysical steric clashes. The information from all the molecular fragments is exploited simultaneously to constrain the backbone to refine a three-dimensional model of the conformational state of the protein. The method is illustrated by refining the structure of the voltage-sensing domain (VSD of the Kv1.2 potassium channel in the resting state and by exploring the distance histograms between spin-labels attached to T4 lysozyme. The resulting VSD structures are in good

Fragment emission in relativistic heavy-ion reactions

International Nuclear Information System (INIS)

Csernai, L.P.; Subramanian, P.R.; Buchwald, G.; Graebner, G.; Rosenhauer, A.; Maruhn, J.A.; Greiner, W.

1982-05-01

The authors present a theoretical description of nuclear collisions which consists of a three-dimensional fluid-dynamical model, a chemical equilibrium break-up calculation for local light fragment (i.e. p, n, d, t, 3 He, 4 He) production and a final thermal evaporation of these particles. The light fragment cross section and some properties of the heavy target residues are calculated for the asymmetric systems Ne+U at 400 MeV/N, Ne+Pb at 800 MeV/N and C+Sn at 86 MeV/N. The results of the model calculations are compared with recent experimental data. Several observable signs of the collective hydrodynamical processes are consistent with the present data. An event-by-event analysis of the flow patterns of the various clusters is proposed which can yield deeper insight into collision dynamics. (author)

SCEDS: protein fragments for molecular replacement in Phaser

Energy Technology Data Exchange (ETDEWEB)

McCoy, Airlie J., E-mail: ajm201@cam.ac.uk [University of Cambridge, Hills Road, Cambridge CB2 0XY (United Kingdom); Nicholls, Robert A. [MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH (United Kingdom); Schneider, Thomas R. [Hamburg Unit c/o DESY, Notkestrasse 85, 22603 Hamburg (Germany); University of Cambridge, Hills Road, Cambridge CB2 0XY (United Kingdom)

2013-11-01

Protein fragments suitable for use in molecular replacement can be generated by normal-mode perturbation, analysis of the difference distance matrix of the original versus normal-mode perturbed structures, and SCEDS, a score that measures the sphericity, continuity, equality and density of the resulting fragments. A method is described for generating protein fragments suitable for use as molecular-replacement (MR) template models. The template model for a protein suspected to undergo a conformational change is perturbed along combinations of low-frequency normal modes of the elastic network model. The unperturbed structure is then compared with each perturbed structure in turn and the structurally invariant regions are identified by analysing the difference distance matrix. These fragments are scored with SCEDS, which is a combined measure of the sphericity of the fragments, the continuity of the fragments with respect to the polypeptide chain, the equality in number of atoms in the fragments and the density of C{sup α} atoms in the triaxial ellipsoid of the fragment extents. The fragment divisions with the highest SCEDS are then used as separate template models for MR. Test cases show that where the protein contains fragments that undergo a change in juxtaposition between template model and target, SCEDS can identify fragments that lead to a lower R factor after ten cycles of all-atom refinement with REFMAC5 than the original template structure. The method has been implemented in the software Phaser.

SCEDS: protein fragments for molecular replacement in Phaser

International Nuclear Information System (INIS)

McCoy, Airlie J.; Nicholls, Robert A.; Schneider, Thomas R.

2013-01-01

Protein fragments suitable for use in molecular replacement can be generated by normal-mode perturbation, analysis of the difference distance matrix of the original versus normal-mode perturbed structures, and SCEDS, a score that measures the sphericity, continuity, equality and density of the resulting fragments. A method is described for generating protein fragments suitable for use as molecular-replacement (MR) template models. The template model for a protein suspected to undergo a conformational change is perturbed along combinations of low-frequency normal modes of the elastic network model. The unperturbed structure is then compared with each perturbed structure in turn and the structurally invariant regions are identified by analysing the difference distance matrix. These fragments are scored with SCEDS, which is a combined measure of the sphericity of the fragments, the continuity of the fragments with respect to the polypeptide chain, the equality in number of atoms in the fragments and the density of C α atoms in the triaxial ellipsoid of the fragment extents. The fragment divisions with the highest SCEDS are then used as separate template models for MR. Test cases show that where the protein contains fragments that undergo a change in juxtaposition between template model and target, SCEDS can identify fragments that lead to a lower R factor after ten cycles of all-atom refinement with REFMAC5 than the original template structure. The method has been implemented in the software Phaser

A numerical method for two-dimensional anisotropic transport problem in cylindrical geometry

International Nuclear Information System (INIS)

Du Mingsheng; Feng Tiekai; Fu Lianxiang; Cao Changshu; Liu Yulan

1988-01-01

The authors deal with the triangular mesh-discontinuous finite element method for solving the time-dependent anisotropic neutron transport problem in two-dimensional cylindrical geometry. A prior estimate of the numerical solution is given. Stability is proved. The authors have computed a two dimensional anisotropic neutron transport problem and a Tungsten-Carbide critical assembly problem by using the numerical method. In comparision with DSN method and the experimental results obtained by others both at home and abroad, the method is satisfactory

One-dimensional calculation of flow branching using the method of characteristics

International Nuclear Information System (INIS)

Meier, R.W.; Gido, R.G.

1978-05-01

In one-dimensional flow systems, the flow often branches, such as at a tee or manifold. The study develops a formulation for calculating the flow through branch points with one-dimensional method of characteristics equations. The resultant equations were verified by comparison with experimental measurements

Theories to support method development in comprehensive two-dimensional liquid chromatography - A review

NARCIS (Netherlands)

Bedani, F.; Schoenmakers, P.J.; Janssen, H.-G.

2012-01-01

On-line comprehensive two-dimensional liquid chromatography techniques promise to resolve samples that current one-dimensional liquid chromatography methods cannot adequately deal with. To make full use of the potential of two-dimensional liquid chromatography, optimization is required. Optimization

Fragment screening by SPR and advanced application to GPCRs.

Science.gov (United States)

Shepherd, Claire A; Hopkins, Andrew L; Navratilova, Iva

2014-01-01

Surface plasmon resonance (SPR) is one of the primary biophysical methods for the screening of low molecular weight 'fragment' libraries, due to its low protein consumption and 'label-free' methodology. SPR biosensor interaction analysis is employed to both screen and confirm the binding of compounds in fragment screening experiments, as it provides accurate information on the affinity and kinetics of molecular interactions. The most advanced application of the use of SPR for fragment screening is against membrane protein drug targets, such G-protein coupled receptors (GPCRs). Biophysical GPCR assays using SPR have been validated with pharmacological measurements approximate to cell-based methods, yet provide the advantage of biophysical methods in their ability to measure the weak affinities of low molecular weight fragments. A number of SPR fragment screens against GPCRs have now been disclosed in the literature. SPR fragment screening is proving versatile to screen both thermostabilised GPCRs and solubilised wild type receptors. In this chapter, we discuss the state-of-the-art in GPCR fragment screening by SPR and the technical considerations in performing such experiments. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Fragmentation Energy-Saving Theory of Full Face Rock Tunnel Boring Machine Disc Cutters

Science.gov (United States)

Zhang, Zhao-Huang; Gong, Guo-Fang; Gao, Qing-Feng; Sun, Fei

2017-07-01

Attempts to minimize energy consumption of a tunnel boring machine disc cutter during the process of fragmentation have largely focused on optimizing disc-cutter spacing, as determined by the minimum specific energy required for fragmentation; however, indentation tests showed that rock deforms plastically beneath the cutters. Equations for thrust were developed for both the traditional, popularly employed disc cutter and anew design based on three-dimensional theory. The respective energy consumption for penetration, rolling, and side-slip fragmentations were obtained. A change in disc-cutter fragmentation angles resulted in a change in the nature of the interaction between the cutter and rock, which lowered the specific energy of fragmentation. During actual field excavations to the same penetration length, the combined energy consumption for fragmentation using the newly designed cutters was 15% lower than that when using the traditional design. This paper presents a theory for energy saving in tunnel boring machines. Investigation results showed that the disc cutters designed using this theory were more durable than traditional designs, and effectively lowered the energy consumption.

Development of methods to measure hemoglobin adducts by gel electrophoresis - Preliminary results

International Nuclear Information System (INIS)

Sun, J.D.; McBride, S.M.

1988-01-01

Chemical adducts formed on blood hemoglobin may be a useful biomarker for assessing human exposures to these compounds. This paper reports preliminary results in the development of methods to measure such adducts that may be generally applicable for a wide variety of chemicals. Male F344/N rats were intraperitoneally injected with 14 C-BaP dissolved in corn oil. Twenty-four hours later, the rats were sacrificed. Blood samples were collected and globin was isolated. Globin protein was then cleaved into peptide fragments using cyanogen bromide and the fragments separated using 2-dimensional gel electrophoresis. The results showed that the adducted 14 C-globin fragments migrated to different areas of the gel than did unadducted fragments. Further research is being conducted to develop methods that will allow quantitation of separated adducted globin fragments from human blood samples without the use of a radiolabel. (author)

Research on a Rotating Machinery Fault Prognosis Method Using Three-Dimensional Spatial Representations

Directory of Open Access Journals (Sweden)

Xiaoni Dong

2016-01-01

Full Text Available Process models and parameters are two critical steps for fault prognosis in the operation of rotating machinery. Due to the requirement for a short and rapid response, it is important to study robust sensor data representation schemes. However, the conventional holospectrum defined by one-dimensional or two-dimensional methods does not sufficiently present this information in both the frequency and time domains. To supply a complete holospectrum model, a new three-dimensional spatial representation method is proposed. This method integrates improved three-dimensional (3D holospectra and 3D filtered orbits, leading to the integration of radial and axial vibration features in one bearing section. The results from simulation and experimental analysis on a complex compressor show that the proposed method can present the real operational status and clearly reveal early faults, thus demonstrating great potential for condition-based maintenance prediction in industrial machinery.

Heart Rate Fragmentation: A Symbolic Dynamical Approach

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Madalena D. Costa

2017-11-01

Full Text Available Background: We recently introduced the concept of heart rate fragmentation along with a set of metrics for its quantification. The term was coined to refer to an increase in the percentage of changes in heart rate acceleration sign, a dynamical marker of a type of anomalous variability. The effort was motivated by the observation that fragmentation, which is consistent with the breakdown of the neuroautonomic-electrophysiologic control system of the sino-atrial node, could confound traditional short-term analysis of heart rate variability.Objective: The objectives of this study were to: (1 introduce a symbolic dynamical approach to the problem of quantifying heart rate fragmentation; (2 evaluate how the distribution of the different dynamical patterns (“words” varied with the participants' age in a group of healthy subjects and patients with coronary artery disease (CAD; and (3 quantify the differences in the fragmentation patterns between the two sample populations.Methods: The symbolic dynamical method employed here was based on a ternary map of the increment NN interval time series and on the analysis of the relative frequency of symbolic sequences (words with a pre-defined set of features. We analyzed annotated, open-access Holter databases of healthy subjects and patients with CAD, provided by the University of Rochester Telemetric and Holter ECG Warehouse (THEW.Results: The degree of fragmentation was significantly higher in older individuals than in their younger counterparts. However, the fragmentation patterns were different in the two sample populations. In healthy subjects, older age was significantly associated with a higher percentage of transitions from acceleration/deceleration to zero acceleration and vice versa (termed “soft” inflection points. In patients with CAD, older age was also significantly associated with higher percentages of frank reversals in heart rate acceleration (transitions from acceleration to

The Fragmentation Criteria in Local Vertically Stratified Self-gravitating Disk Simulations

Energy Technology Data Exchange (ETDEWEB)

Baehr, Hans; Klahr, Hubert [Max Planck Institute for Astronomy, Königstuhl 17, D-69117 Heidelberg (Germany); Kratter, Kaitlin M., E-mail: baehr@mpia.de [Steward Observatory, University of Arizona, Tucson, AZ 85721 (United States)

2017-10-10

Massive circumstellar disks are prone to gravitational instabilities, which trigger the formation of spiral arms that can fragment into bound clumps under the right conditions. Two-dimensional simulations of self-gravitating disks are useful starting points for studying fragmentation because they allow high-resolution simulations of thin disks. However, convergence issues can arise in 2D from various sources. One of these sources is the 2D approximation of self-gravity, which exaggerates the effect of self-gravity on small scales when the potential is not smoothed to account for the assumed vertical extent of the disk. This effect is enhanced by increased resolution, resulting in fragmentation at longer cooling timescales β . If true, it suggests that the 3D simulations of disk fragmentation may not have the same convergence problem and could be used to examine the nature of fragmentation without smoothing self-gravity on scales similar to the disk scale height. To that end, we have carried out local 3D self-gravitating disk simulations with simple β cooling with fixed background irradiation to determine if 3D is necessary to properly describe disk fragmentation. Above a resolution of ∼40 grid cells per scale height, we find that our simulations converge with respect to the cooling timescale. This result converges in agreement with analytic expectations which place a fragmentation boundary at β {sub crit} = 3.

Multiple and sequential data acquisition method: an improved method for fragmentation and detection of cross-linked peptides on a hybrid linear trap quadrupole Orbitrap Velos mass spectrometer.

Science.gov (United States)

Rudashevskaya, Elena L; Breitwieser, Florian P; Huber, Marie L; Colinge, Jacques; Müller, André C; Bennett, Keiryn L

2013-02-05

The identification and validation of cross-linked peptides by mass spectrometry remains a daunting challenge for protein-protein cross-linking approaches when investigating protein interactions. This includes the fragmentation of cross-linked peptides in the mass spectrometer per se and following database searching, the matching of the molecular masses of the fragment ions to the correct cross-linked peptides. The hybrid linear trap quadrupole (LTQ) Orbitrap Velos combines the speed of the tandem mass spectrometry (MS/MS) duty circle with high mass accuracy, and these features were utilized in the current study to substantially improve the confidence in the identification of cross-linked peptides. An MS/MS method termed multiple and sequential data acquisition method (MSDAM) was developed. Preliminary optimization of the MS/MS settings was performed with a synthetic peptide (TP1) cross-linked with bis[sulfosuccinimidyl] suberate (BS(3)). On the basis of these results, MSDAM was created and assessed on the BS(3)-cross-linked bovine serum albumin (BSA) homodimer. MSDAM applies a series of multiple sequential fragmentation events with a range of different normalized collision energies (NCE) to the same precursor ion. The combination of a series of NCE enabled a considerable improvement in the quality of the fragmentation spectra for cross-linked peptides, and ultimately aided in the identification of the sequences of the cross-linked peptides. Concurrently, MSDAM provides confirmatory evidence from the formation of reporter ions fragments, which reduces the false positive rate of incorrectly assigned cross-linked peptides.

Reduced basis ANOVA methods for partial differential equations with high-dimensional random inputs

Energy Technology Data Exchange (ETDEWEB)

Liao, Qifeng, E-mail: liaoqf@shanghaitech.edu.cn [School of Information Science and Technology, ShanghaiTech University, Shanghai 200031 (China); Lin, Guang, E-mail: guanglin@purdue.edu [Department of Mathematics & School of Mechanical Engineering, Purdue University, West Lafayette, IN 47907 (United States)

2016-07-15

In this paper we present a reduced basis ANOVA approach for partial deferential equations (PDEs) with random inputs. The ANOVA method combined with stochastic collocation methods provides model reduction in high-dimensional parameter space through decomposing high-dimensional inputs into unions of low-dimensional inputs. In this work, to further reduce the computational cost, we investigate spatial low-rank structures in the ANOVA-collocation method, and develop efficient spatial model reduction techniques using hierarchically generated reduced bases. We present a general mathematical framework of the methodology, validate its accuracy and demonstrate its efficiency with numerical experiments.

Identifying Interactions that Determine Fragment Binding at Protein Hotspots.

Science.gov (United States)

Radoux, Chris J; Olsson, Tjelvar S G; Pitt, Will R; Groom, Colin R; Blundell, Tom L

2016-05-12

Locating a ligand-binding site is an important first step in structure-guided drug discovery, but current methods do little to suggest which interactions within a pocket are the most important for binding. Here we illustrate a method that samples atomic hotspots with simple molecular probes to produce fragment hotspot maps. These maps specifically highlight fragment-binding sites and their corresponding pharmacophores. For ligand-bound structures, they provide an intuitive visual guide within the binding site, directing medicinal chemists where to grow the molecule and alerting them to suboptimal interactions within the original hit. The fragment hotspot map calculation is validated using experimental binding positions of 21 fragments and subsequent lead molecules. The ligands are found in high scoring areas of the fragment hotspot maps, with fragment atoms having a median percentage rank of 97%. Protein kinase B and pantothenate synthetase are examined in detail. In each case, the fragment hotspot maps are able to rationalize a Free-Wilson analysis of SAR data from a fragment-based drug design project.

High-throughput fragment screening by affinity LC-MS.

Science.gov (United States)

Duong-Thi, Minh-Dao; Bergström, Maria; Fex, Tomas; Isaksson, Roland; Ohlson, Sten

2013-02-01

Fragment screening, an emerging approach for hit finding in drug discovery, has recently been proven effective by its first approved drug, vemurafenib, for cancer treatment. Techniques such as nuclear magnetic resonance, surface plasmon resonance, and isothemal titration calorimetry, with their own pros and cons, have been employed for screening fragment libraries. As an alternative approach, screening based on high-performance liquid chromatography separation has been developed. In this work, we present weak affinity LC/MS as a method to screen fragments under high-throughput conditions. Affinity-based capillary columns with immobilized thrombin were used to screen a collection of 590 compounds from a fragment library. The collection was divided into 11 mixtures (each containing 35 to 65 fragments) and screened by MS detection. The primary screening was performed in 3500 fragments per day). Thirty hits were defined, which subsequently entered a secondary screening using an active site-blocked thrombin column for confirmation of specificity. One hit showed selective binding to thrombin with an estimated dissociation constant (K (D)) in the 0.1 mM range. This study shows that affinity LC/MS is characterized by high throughput, ease of operation, and low consumption of target and fragments, and therefore it promises to be a valuable method for fragment screening.

Fragmented one dimensional man / El hombre unidimensional fragmentado

Directory of Open Access Journals (Sweden)

Juan Antonio Rodríguez del Pino

2013-10-01

Full Text Available Paraphrase the title of the famous essay by Herbert Marcuse, since the image has traditionally been generated of man, masculinity, has been one-dimensional. I mean, the man was characterized by traits and behaviors established and entrenched since ancient time, considering all other distinguishing signs as mere deviations from the normative improper. But observe that this undeniable reality, as analyzed various researchers through what has come to be called Men's studies, has proven to be a fallacy difficult to maintain throughout history and today turns into fallacious and ineffective against changes in our current existing corporate models.

Binding-site assessment by virtual fragment screening.

Directory of Open Access Journals (Sweden)

Niu Huang

2010-04-01

Full Text Available The accurate prediction of protein druggability (propensity to bind high-affinity drug-like small molecules would greatly benefit the fields of chemical genomics and drug discovery. We have developed a novel approach to quantitatively assess protein druggability by computationally screening a fragment-like compound library. In analogy to NMR-based fragment screening, we dock approximately 11,000 fragments against a given binding site and compute a computational hit rate based on the fraction of molecules that exceed an empirically chosen score cutoff. We perform a large-scale evaluation of the approach on four datasets, totaling 152 binding sites. We demonstrate that computed hit rates correlate with hit rates measured experimentally in a previously published NMR-based screening method. Secondly, we show that the in silico fragment screening method can be used to distinguish known druggable and non-druggable targets, including both enzymes and protein-protein interaction sites. Finally, we explore the sensitivity of the results to different receptor conformations, including flexible protein-protein interaction sites. Besides its original aim to assess druggability of different protein targets, this method could be used to identifying druggable conformations of flexible binding site for lead discovery, and suggesting strategies for growing or joining initial fragment hits to obtain more potent inhibitors.

The power to detect recent fragmentation events using genetic differentiation methods.

Directory of Open Access Journals (Sweden)

Michael W Lloyd

Full Text Available Habitat loss and fragmentation are imminent threats to biological diversity worldwide and thus are fundamental issues in conservation biology. Increased isolation alone has been implicated as a driver of negative impacts in populations associated with fragmented landscapes. Genetic monitoring and the use of measures of genetic divergence have been proposed as means to detect changes in landscape connectivity. Our goal was to evaluate the sensitivity of Wright's F st, Hedrick' G'st , Sherwin's MI, and Jost's D to recent fragmentation events across a range of population sizes and sampling regimes. We constructed an individual-based model, which used a factorial design to compare effects of varying population size, presence or absence of overlapping generations, and presence or absence of population sub-structuring. Increases in population size, overlapping generations, and population sub-structuring each reduced F st, G'st , MI, and D. The signal of fragmentation was detected within two generations for all metrics. However, the magnitude of the change in each was small in all cases, and when N e was >100 individuals it was extremely small. Multi-generational sampling and population estimates are required to differentiate the signal of background divergence from changes in Fst , G'st , MI, and D associated with fragmentation. Finally, the window during which rapid change in Fst , G'st , MI, and D between generations occurs can be small, and if missed would lead to inconclusive results. For these reasons, use of F st, G'st , MI, or D for detecting and monitoring changes in connectivity is likely to prove difficult in real-world scenarios. We advocate use of genetic monitoring only in conjunction with estimates of actual movement among patches such that one could compare current movement with the genetic signature of past movement to determine there has been a change.

An improved algorithm for MFR fragment assembly

International Nuclear Information System (INIS)

Kontaxis, Georg

2012-01-01

A method for generating protein backbone models from backbone only NMR data is presented, which is based on molecular fragment replacement (MFR). In a first step, the PDB database is mined for homologous peptide fragments using experimental backbone-only data i.e. backbone chemical shifts (CS) and residual dipolar couplings (RDC). Second, this fragment library is refined against the experimental restraints. Finally, the fragments are assembled into a protein backbone fold using a rigid body docking algorithm using the RDCs as restraints. For improved performance, backbone nuclear Overhauser effects (NOEs) may be included at that stage. Compared to previous implementations of MFR-derived structure determination protocols this model-building algorithm offers improved stability and reliability. Furthermore, relative to CS-ROSETTA based methods, it provides faster performance and straightforward implementation with the option to easily include further types of restraints and additional energy terms.

Advanced numerical methods for three dimensional two-phase flow calculations

Energy Technology Data Exchange (ETDEWEB)

Toumi, I. [Laboratoire d`Etudes Thermiques des Reacteurs, Gif sur Yvette (France); Caruge, D. [Institut de Protection et de Surete Nucleaire, Fontenay aux Roses (France)

1997-07-01

This paper is devoted to new numerical methods developed for both one and three dimensional two-phase flow calculations. These methods are finite volume numerical methods and are based on the use of Approximate Riemann Solvers concepts to define convective fluxes versus mean cell quantities. The first part of the paper presents the numerical method for a one dimensional hyperbolic two-fluid model including differential terms as added mass and interface pressure. This numerical solution scheme makes use of the Riemann problem solution to define backward and forward differencing to approximate spatial derivatives. The construction of this approximate Riemann solver uses an extension of Roe`s method that has been successfully used to solve gas dynamic equations. As far as the two-fluid model is hyperbolic, this numerical method seems very efficient for the numerical solution of two-phase flow problems. The scheme was applied both to shock tube problems and to standard tests for two-fluid computer codes. The second part describes the numerical method in the three dimensional case. The authors discuss also some improvements performed to obtain a fully implicit solution method that provides fast running steady state calculations. Such a scheme is not implemented in a thermal-hydraulic computer code devoted to 3-D steady-state and transient computations. Some results obtained for Pressurised Water Reactors concerning upper plenum calculations and a steady state flow in the core with rod bow effect evaluation are presented. In practice these new numerical methods have proved to be stable on non staggered grids and capable of generating accurate non oscillating solutions for two-phase flow calculations.

Advanced numerical methods for three dimensional two-phase flow calculations

International Nuclear Information System (INIS)

Toumi, I.; Caruge, D.

1997-01-01

This paper is devoted to new numerical methods developed for both one and three dimensional two-phase flow calculations. These methods are finite volume numerical methods and are based on the use of Approximate Riemann Solvers concepts to define convective fluxes versus mean cell quantities. The first part of the paper presents the numerical method for a one dimensional hyperbolic two-fluid model including differential terms as added mass and interface pressure. This numerical solution scheme makes use of the Riemann problem solution to define backward and forward differencing to approximate spatial derivatives. The construction of this approximate Riemann solver uses an extension of Roe's method that has been successfully used to solve gas dynamic equations. As far as the two-fluid model is hyperbolic, this numerical method seems very efficient for the numerical solution of two-phase flow problems. The scheme was applied both to shock tube problems and to standard tests for two-fluid computer codes. The second part describes the numerical method in the three dimensional case. The authors discuss also some improvements performed to obtain a fully implicit solution method that provides fast running steady state calculations. Such a scheme is not implemented in a thermal-hydraulic computer code devoted to 3-D steady-state and transient computations. Some results obtained for Pressurised Water Reactors concerning upper plenum calculations and a steady state flow in the core with rod bow effect evaluation are presented. In practice these new numerical methods have proved to be stable on non staggered grids and capable of generating accurate non oscillating solutions for two-phase flow calculations

De novo analysis of electron impact mass spectra using fragmentation trees

International Nuclear Information System (INIS)

Hufsky, Franziska; Rempt, Martin; Rasche, Florian; Pohnert, Georg; Böcker, Sebastian

2012-01-01

Highlights: ► We present a method for de novo analysis of accurate mass EI mass spectra of small molecules. ► This method identifies the molecular ion and thus the molecular formula where the molecular ion is present in the spectrum. ► Fragmentation trees are constructed by automated signal extraction and evaluation. ► These trees explain relevant fragmentation reactions. ► This method will be very helpful in the automated analysis of unknown metabolites. - Abstract: The automated fragmentation analysis of high resolution EI mass spectra based on a fragmentation tree algorithm is introduced. Fragmentation trees are constructed from EI spectra by automated signal extraction and evaluation. These trees explain relevant fragmentation reactions and assign molecular formulas to fragments. The method enables the identification of the molecular ion and the molecular formula of a metabolite if the molecular ion is present in the spectrum. These identifications are independent of existing library knowledge and, thus, support assignment and structural elucidation of unknown compounds. The method works even if the molecular ion is of very low abundance or hidden under contaminants with higher masses. We apply the algorithm to a selection of 50 derivatized and underivatized metabolites and demonstrate that in 78% of cases the molecular ion can be correctly assigned. The automatically constructed fragmentation trees correspond very well to published mechanisms and allow the assignment of specific relevant fragments and fragmentation pathways even in the most complex EI-spectra in our dataset. This method will be very helpful in the automated analysis of metabolites that are not included in common libraries and it thus has the potential to support the explorative character of metabolomics studies.

A Fragment-Based Method of Creating Small-Molecule Libraries to Target the Aggregation of Intrinsically Disordered Proteins.

Science.gov (United States)

Joshi, Priyanka; Chia, Sean; Habchi, Johnny; Knowles, Tuomas P J; Dobson, Christopher M; Vendruscolo, Michele

2016-03-14

The aggregation process of intrinsically disordered proteins (IDPs) has been associated with a wide range of neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Currently, however, no drug in clinical use targets IDP aggregation. To facilitate drug discovery programs in this important and challenging area, we describe a fragment-based approach of generating small-molecule libraries that target specific IDPs. The method is based on the use of molecular fragments extracted from compounds reported in the literature to inhibit of the aggregation of IDPs. These fragments are used to screen existing large generic libraries of small molecules to form smaller libraries specific for given IDPs. We illustrate this approach by describing three distinct small-molecule libraries to target, Aβ, tau, and α-synuclein, which are three IDPs implicated in Alzheimer's and Parkinson's diseases. The strategy described here offers novel opportunities for the identification of effective molecular scaffolds for drug discovery for neurodegenerative disorders and to provide insights into the mechanism of small-molecule binding to IDPs.

Brooks–Corey Modeling by One-Dimensional Vertical Infiltration Method

Directory of Open Access Journals (Sweden)

Xuguang Xing

2018-05-01

Full Text Available The laboratory methods used for the soil water retention curve (SWRC construction and parameter estimation is time-consuming. A vertical infiltration method was proposed to estimate parameters α and n and to further construct the SWRC. In the present study, the relationships describing the cumulative infiltration and infiltration rate with the depth of the wetting front were established, and simplified expressions for estimating α and n parameters were proposed. The one-dimensional vertical infiltration experiments of four soils were conducted to verify if the proposed method would accurately estimate α and n. The fitted values of α and n, obtained from the RETC software, were consistent with the calculated values obtained from the infiltration method. The comparison between the measured SWRCs obtained from the centrifuge method and the calculated SWRCs that were based on the infiltration method displayed small values of root mean square error (RMSE, mean absolute percentage error (MAPE, and mean absolute error. SWMS_2D-based simulations of cumulative infiltration, based on the calculated α and n, remained consistent with the measured values due to small RMSE and MAPE values. The experiments verified the proposed one-dimensional vertical infiltration method, which has applications in field hydraulic parameter estimation.

Metabolite identification through multiple kernel learning on fragmentation trees.

Science.gov (United States)

Shen, Huibin; Dührkop, Kai; Böcker, Sebastian; Rousu, Juho

2014-06-15

Metabolite identification from tandem mass spectrometric data is a key task in metabolomics. Various computational methods have been proposed for the identification of metabolites from tandem mass spectra. Fragmentation tree methods explore the space of possible ways in which the metabolite can fragment, and base the metabolite identification on scoring of these fragmentation trees. Machine learning methods have been used to map mass spectra to molecular fingerprints; predicted fingerprints, in turn, can be used to score candidate molecular structures. Here, we combine fragmentation tree computations with kernel-based machine learning to predict molecular fingerprints and identify molecular structures. We introduce a family of kernels capturing the similarity of fragmentation trees, and combine these kernels using recently proposed multiple kernel learning approaches. Experiments on two large reference datasets show that the new methods significantly improve molecular fingerprint prediction accuracy. These improvements result in better metabolite identification, doubling the number of metabolites ranked at the top position of the candidates list. © The Author 2014. Published by Oxford University Press.

Calculation of two-dimensional thermal transients by the method of finite elements

International Nuclear Information System (INIS)

Fontoura Rodrigues, J.L.A. da.

1980-08-01

The unsteady linear heat conduction analysis throught anisotropic and/or heterogeneous matter, in either two-dimensional fields with any kind of geometry or three-dimensional fields with axial symmetry is presented. The boundary conditions and the internal heat generation are supposed time - independent. The solution is obtained by modal analysis employing the finite element method under Galerkin formulation. Optionally, it can be used with a reduced resolution method called Stoker Economizing Method wich allows a decrease on the program processing costs. (Author) [pt

A New Ensemble Method with Feature Space Partitioning for High-Dimensional Data Classification

Directory of Open Access Journals (Sweden)

Yongjun Piao

2015-01-01

Full Text Available Ensemble data mining methods, also known as classifier combination, are often used to improve the performance of classification. Various classifier combination methods such as bagging, boosting, and random forest have been devised and have received considerable attention in the past. However, data dimensionality increases rapidly day by day. Such a trend poses various challenges as these methods are not suitable to directly apply to high-dimensional datasets. In this paper, we propose an ensemble method for classification of high-dimensional data, with each classifier constructed from a different set of features determined by partitioning of redundant features. In our method, the redundancy of features is considered to divide the original feature space. Then, each generated feature subset is trained by a support vector machine, and the results of each classifier are combined by majority voting. The efficiency and effectiveness of our method are demonstrated through comparisons with other ensemble techniques, and the results show that our method outperforms other methods.

High efficiency hydrodynamic DNA fragmentation in a bubbling system

NARCIS (Netherlands)

Li, Lanhui; Jin, Mingliang; Sun, Chenglong; Wang, Xiaoxue; Xie, Shuting; Zhou, Guofu; Van Den Berg, Albert; Eijkel, Jan C.T.; Shui, Lingling

2017-01-01

DNA fragmentation down to a precise fragment size is important for biomedical applications, disease determination, gene therapy and shotgun sequencing. In this work, a cheap, easy to operate and high efficiency DNA fragmentation method is demonstrated based on hydrodynamic shearing in a bubbling

[Fragment-based drug discovery: concept and aim].

Science.gov (United States)

Tanaka, Daisuke

2010-03-01

Fragment-Based Drug Discovery (FBDD) has been recognized as a newly emerging lead discovery methodology that involves biophysical fragment screening and chemistry-driven fragment-to-lead stages. Although fragments, defined as structurally simple and small compounds (typically FBDD primarily turns our attention to weakly but specifically binding fragments (hit fragments) as the starting point of medicinal chemistry. Hit fragments are then promoted to more potent lead compounds through linking or merging with another hit fragment and/or attaching functional groups. Another positive aspect of FBDD is ligand efficiency. Ligand efficiency is a useful guide in screening hit selection and hit-to-lead phases to achieve lead-likeness. Owing to these features, a number of successful applications of FBDD to "undruggable targets" (where HTS and other lead identification methods failed to identify useful lead compounds) have been reported. As a result, FBDD is now expected to complement more conventional methodologies. This review, as an introduction of the following articles, will summarize the fundamental concepts of FBDD and will discuss its advantages over other conventional drug discovery approaches.

One-dimensional treatment of polyatomic crystals by the Laplace transform method

International Nuclear Information System (INIS)

Rosato, A.; Santana, P.H.A.

1976-01-01

The one dimensional periodic potential problem is solved using the Laplace transform method and a condensed expression for the relation E x k and effective mass for one electron in a polyatomic structure is determined. Applications related to the effect of the asymmetry of the potential upon the one dimensional band structure are discussed [pt

The Topology Optimization of Three-dimensional Cooling Fins by the Internal Element Connectivity Parameterization Method

International Nuclear Information System (INIS)

Yoo, Sung Min; Kim, Yoon Young

2007-01-01

This work is concerned with the topology optimization of three-dimensional cooling fins or heat sinks. Motivated by earlier success of the Internal Element Connectivity Method (I-ECP) method in two dimensional problems, the extension of I-ECP to three-dimensional problems is carried out. The main efforts were made to maintain the numerical trouble-free characteristics of I-ECP for full three-dimensional problems; a serious numerical problem appearing in thermal topology optimization is erroneous temperature undershooting. The effectiveness of the present implementation was checked through the design optimization of three-dimensional fins

A two-dimensional adaptive numerical grids generation method and its realization

International Nuclear Information System (INIS)

Xu Tao; Shui Hongshou

1998-12-01

A two-dimensional adaptive numerical grids generation method and its particular realization is discussed. This method is effective and easy to realize if the control functions are given continuously, and the grids for some regions is showed in this case. For Computational Fluid Dynamics, because the control values of adaptive grids-numerical solution is given in dispersed form, it is needed to interpolate these values to get the continuous control functions. These interpolation techniques are discussed, and some efficient adaptive grids are given. A two-dimensional fluid dynamics example was also given

Development of three-dimensional individual bubble-velocity measurement method by bubble tracking

International Nuclear Information System (INIS)

Kanai, Taizo; Furuya, Masahiro; Arai, Takahiro; Shirakawa, Kenetsu; Nishi, Yoshihisa

2012-01-01

A gas-liquid two-phase flow in a large diameter pipe exhibits a three-dimensional flow structure. Wire-Mesh Sensor (WMS) consists of a pair of parallel wire layers located at the cross section of a pipe. Both the parallel wires cross at 90o with a small gap and each intersection acts as an electrode. The WMS allows the measurement of the instantaneous two-dimensional void-fraction distribution over the cross-section of a pipe, based on the difference between the local instantaneous conductivity of the two-phase flow. Furthermore, the WMS can acquire a phasic-velocity on the basis of the time lag of void signals between two sets of WMS. Previously, the acquired phasic velocity was one-dimensional with time-averaged distributions. The authors propose a method to estimate the three-dimensional bubble-velocity individually WMS data. The bubble velocity is determined by the tracing method. In this tracing method, each bubble is separated from WMS signal, volume and center coordinates of the bubble is acquired. Two bubbles with near volume at two WMS are considered as the same bubble and bubble velocity is estimated from the displacement of the center coordinates of the two bubbles. The validity of this method is verified by a swirl flow. The proposed method can successfully visualize a swirl flow structure and the results of this method agree with the results of cross-correlation analysis. (author)

Development of two dimensional electrophoresis method using single chain DNA

International Nuclear Information System (INIS)

Ikeda, Junichi; Hidaka, So

1998-01-01

By combining a separation method due to molecular weight and a method to distinguish difference of mono-bases, it was aimed to develop a two dimensional single chain DNA labeled with Radioisotope (RI). From electrophoretic pattern difference of parent and variant strands, it was investigated to isolate the root module implantation control gene. At first, a Single Strand Conformation Polymorphism (SSCP) method using concentration gradient gel was investigated. As a result, it was formed that intervals between double chain and single chain DNAs expanded, but intervals of both single chain DNAs did not expand. On next, combination of non-modified acrylic amide electrophoresis method and Denaturing Gradient-Gel Electrophoresis (DGGE) method was examined. As a result, hybrid DNA developed by two dimensional electrophoresis arranged on two lines. But, among them a band of DNA modified by high concentration of urea could not be found. Therefore, in this fiscal year's experiments, no preferable result could be obtained. By the used method, it was thought to be impossible to detect the differences. (G.K.)

Semi-implicit method for three-dimensional compressible MHD simulation

International Nuclear Information System (INIS)

Harned, D.S.; Kerner, W.

1984-03-01

A semi-implicit method for solving the full compressible MHD equations in three dimensions is presented. The method is unconditionally stable with respect to the fast compressional modes. The time step is instead limited by the slower shear Alfven motion. The computing time required for one time step is essentially the same as for explicit methods. Linear stability limits are derived and verified by three-dimensional tests on linear waves in slab geometry. (orig.)

Three-dimensional dynamics of protostellar evolution

International Nuclear Information System (INIS)

Cook, T.L.

1977-06-01

A three-dimensional finite difference numerical methodology was developed for self-gravitating, rotating gaseous systems. The fully nonlinear equations for time-varying fluid dynamics are solved by high speed computer in a cylindrical coordinate system rotating with an instantaneous angular velocity, selected such that the net angular momentum relative to the rotating frame is zero. The time-dependent adiabatic collapse of gravitationally bound, rotating, protostellar clouds is studied for specified uniform and nonuniform initial conditions. Uniform clouds can form axisymmetric, rotating toroidal configurations. If the thermal pressure is high, nonuniform clouds can also collapse to axisymmetric toroids. For low thermal pressures, however, the collapsing cloud is unstable to initial perturbations. The fragmentation of protostellar clouds is investigated by studying the response of rotating, self-gravitating, equilibrium toroids to non-axisymmetric perturbations. The detailed evolution of the fragmenting toroid depends upon a non-dimensional function of the initial entropy, the total mass in the toroid, the angular velocity of rotation, and the number of perturbation wavelengths around the circumference of the toroid. For low and intermediate entropies, the configuration develops into co-rotating components with spiral streamers. In the spiral regions retrograde vortices are observed in some examples. For high levels of entropy, barred spirals can exist as intermediate states of the fragmentation

High dimensional model representation method for fuzzy structural dynamics

Science.gov (United States)

Adhikari, S.; Chowdhury, R.; Friswell, M. I.

2011-03-01

Uncertainty propagation in multi-parameter complex structures possess significant computational challenges. This paper investigates the possibility of using the High Dimensional Model Representation (HDMR) approach when uncertain system parameters are modeled using fuzzy variables. In particular, the application of HDMR is proposed for fuzzy finite element analysis of linear dynamical systems. The HDMR expansion is an efficient formulation for high-dimensional mapping in complex systems if the higher order variable correlations are weak, thereby permitting the input-output relationship behavior to be captured by the terms of low-order. The computational effort to determine the expansion functions using the α-cut method scales polynomically with the number of variables rather than exponentially. This logic is based on the fundamental assumption underlying the HDMR representation that only low-order correlations among the input variables are likely to have significant impacts upon the outputs for most high-dimensional complex systems. The proposed method is first illustrated for multi-parameter nonlinear mathematical test functions with fuzzy variables. The method is then integrated with a commercial finite element software (ADINA). Modal analysis of a simplified aircraft wing with fuzzy parameters has been used to illustrate the generality of the proposed approach. In the numerical examples, triangular membership functions have been used and the results have been validated against direct Monte Carlo simulations. It is shown that using the proposed HDMR approach, the number of finite element function calls can be reduced without significantly compromising the accuracy.

An Enumerative Combinatorics Model for Fragmentation Patterns in RNA Sequencing Provides Insights into Nonuniformity of the Expected Fragment Starting-Point and Coverage Profile.

Science.gov (United States)

Prakash, Celine; Haeseler, Arndt Von

2017-03-01

RNA sequencing (RNA-seq) has emerged as the method of choice for measuring the expression of RNAs in a given cell population. In most RNA-seq technologies, sequencing the full length of RNA molecules requires fragmentation into smaller pieces. Unfortunately, the issue of nonuniform sequencing coverage across a genomic feature has been a concern in RNA-seq and is attributed to biases for certain fragments in RNA-seq library preparation and sequencing. To investigate the expected coverage obtained from fragmentation, we develop a simple fragmentation model that is independent of bias from the experimental method and is not specific to the transcript sequence. Essentially, we enumerate all configurations for maximal placement of a given fragment length, F, on transcript length, T, to represent every possible fragmentation pattern, from which we compute the expected coverage profile across a transcript. We extend this model to incorporate general empirical attributes such as read length, fragment length distribution, and number of molecules of the transcript. We further introduce the fragment starting-point, fragment coverage, and read coverage profiles. We find that the expected profiles are not uniform and that factors such as fragment length to transcript length ratio, read length to fragment length ratio, fragment length distribution, and number of molecules influence the variability of coverage across a transcript. Finally, we explore a potential application of the model where, with simulations, we show that it is possible to correctly estimate the transcript copy number for any transcript in the RNA-seq experiment.

Multi-GPU accelerated three-dimensional FDTD method for electromagnetic simulation.

Science.gov (United States)

Nagaoka, Tomoaki; Watanabe, Soichi

2011-01-01

Numerical simulation with a numerical human model using the finite-difference time domain (FDTD) method has recently been performed in a number of fields in biomedical engineering. To improve the method's calculation speed and realize large-scale computing with the numerical human model, we adapt three-dimensional FDTD code to a multi-GPU environment using Compute Unified Device Architecture (CUDA). In this study, we used NVIDIA Tesla C2070 as GPGPU boards. The performance of multi-GPU is evaluated in comparison with that of a single GPU and vector supercomputer. The calculation speed with four GPUs was approximately 3.5 times faster than with a single GPU, and was slightly (approx. 1.3 times) slower than with the supercomputer. Calculation speed of the three-dimensional FDTD method using GPUs can significantly improve with an expanding number of GPUs.

Application of TensorFlow to recognition of visualized results of fragment molecular orbital (FMO) calculations

OpenAIRE

Saitou, Sona; Iijima, Jun; Fujimoto, Mayu; Mochizuki, Yuji; Okuwaki, Koji; Doi, Hideo; Komeiji, Yuto

2018-01-01

We have applied Google's TensorFlow deep learning toolkit to recognize the visualized results of the fragment molecular orbital (FMO) calculations. Typical protein structures of alpha-helix and beta-sheet provide some characteristic patterns in the two-dimensional map of inter-fragment interaction energy termed as IFIE-map (Kurisaki et al., Biophys. Chem. 130 (2007) 1). A thousand of IFIE-map images with labels depending on the existences of alpha-helix and beta-sheet were prepared by employi...

Fragmentation in DNA double-strand breaks

International Nuclear Information System (INIS)

Wei Zhiyong; Suzhou Univ., Suzhou; Zhang Lihui; Li Ming; Fan Wo; Xu Yujie

2005-01-01

DNA double strand breaks are important lesions induced by irradiations. Random breakage model or quantification supported by this concept is suitable to analyze DNA double strand break data induced by low LET radiation, but deviation from random breakage model is more evident in high LET radiation data analysis. In this work we develop a new method, statistical fragmentation model, to analyze the fragmentation process of DNA double strand breaks. After charged particles enter the biological cell, they produce ionizations along their tracks, and transfer their energies to the cells and break the cellular DNA strands into fragments. The probable distribution of the fragments is obtained under the condition in which the entropy is maximum. Under the approximation E≅E 0 + E 1 l + E 2 l 2 , the distribution functions are obtained as exp(αl + βl 2 ). There are two components, the one proportional to exp(βl 2 ), mainly contributes to the low mass fragment yields, the other component, proportional to exp(αl), decreases slowly as the mass of the fragments increases. Numerical solution of the constraint equations provides parameters α and β. Experimental data, especially when the energy deposition is higher, support the statistical fragmentation model. (authors)

A simple three dimensional wide-angle beam propagation method

Science.gov (United States)

Ma, Changbao; van Keuren, Edward

2006-05-01

The development of three dimensional (3-D) waveguide structures for chip scale planar lightwave circuits (PLCs) is hampered by the lack of effective 3-D wide-angle (WA) beam propagation methods (BPMs). We present a simple 3-D wide-angle beam propagation method (WA-BPM) using Hoekstra’s scheme along with a new 3-D wave equation splitting method. The applicability, accuracy and effectiveness of our method are demonstrated by applying it to simulations of wide-angle beam propagation and comparing them with analytical solutions.

FRAGSION: ultra-fast protein fragment library generation by IOHMM sampling.

Science.gov (United States)

Bhattacharya, Debswapna; Adhikari, Badri; Li, Jilong; Cheng, Jianlin

2016-07-01

Speed, accuracy and robustness of building protein fragment library have important implications in de novo protein structure prediction since fragment-based methods are one of the most successful approaches in template-free modeling (FM). Majority of the existing fragment detection methods rely on database-driven search strategies to identify candidate fragments, which are inherently time-consuming and often hinder the possibility to locate longer fragments due to the limited sizes of databases. Also, it is difficult to alleviate the effect of noisy sequence-based predicted features such as secondary structures on the quality of fragment. Here, we present FRAGSION, a database-free method to efficiently generate protein fragment library by sampling from an Input-Output Hidden Markov Model. FRAGSION offers some unique features compared to existing approaches in that it (i) is lightning-fast, consuming only few seconds of CPU time to generate fragment library for a protein of typical length (300 residues); (ii) can generate dynamic-size fragments of any length (even for the whole protein sequence) and (iii) offers ways to handle noise in predicted secondary structure during fragment sampling. On a FM dataset from the most recent Critical Assessment of Structure Prediction, we demonstrate that FGRAGSION provides advantages over the state-of-the-art fragment picking protocol of ROSETTA suite by speeding up computation by several orders of magnitude while achieving comparable performance in fragment quality. Source code and executable versions of FRAGSION for Linux and MacOS is freely available to non-commercial users at http://sysbio.rnet.missouri.edu/FRAGSION/ It is bundled with a manual and example data. chengji@missouri.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Calculation of two-dimensional thermal transients by the finite element method

International Nuclear Information System (INIS)

Fontoura Rodrigues, J.L.A. da; Barcellos, C.S. de

1981-01-01

The linear heat conduction through anisotropic and/or heterogeneous matter, in either two-dimensional fields with any kind of geometry or three-dimensional fields with axial symmetry is analysed. It only accepts time-independent boundary conditions and it is possible to have internal heat generation. The solution is obtained by modal analysis employing the finite element method under Galerkin formulation. (Author) [pt

Measurement of cardiac ventricular volumes using multidetector row computed tomography: comparison of two- and three-dimensional methods

International Nuclear Information System (INIS)

Montaudon, M.; Laffon, E.; Berger, P.; Corneloup, O.; Latrabe, V.; Laurent, F.

2006-01-01

This study compared a three-dimensional volumetric threshold-based method to a two-dimensional Simpson's rule based short-axis multiplanar method for measuring right (RV) and left ventricular (LV) volumes, stroke volumes, and ejection fraction using electrocardiography-gated multidetector computed tomography (MDCT) data sets. End-diastolic volume (EDV) and end-systolic volume (ESV) of RV and LV were measured independently and blindly by two observers from contrast-enhanced MDCT images using commercial software in 18 patients. For RV and LV the three-dimensionally calculated EDV and ESV values were smaller than those provided by two-dimensional short axis (10%, 5%, 15% and 26% differences respectively). Agreement between the two methods was found for LV (EDV/ESV: r=0.974/0.910, ICC=0.905/0.890) but not for RV (r=0.882/0.930, ICC=0.663/0.544). Measurement errors were significant only for EDV of LV using the two-dimensional method. Similar reproducibility was found for LV measurements, but the three-dimensional method provided greater reproducibility for RV measurements than the two-dimensional. The threshold value supported three-dimensional method provides reproducible cardiac ventricular volume measurements, comparable to those obtained using the short-axis Simpson based method. (orig.)

Transplantation of storm-generated coral fragments to enhance Caribbean coral reefs: A successful method but not a solution

Directory of Open Access Journals (Sweden)

Virginia H. Garrison

2012-03-01

Full Text Available In response to dramatic losses of reef-building corals and ongoing lack of recovery, a small-scale coral transplant project was initiated in the Caribbean (U.S. Virgin Islands in 1999 and was followed for 12 years. The primary objectives were to (1 identify a source of coral colonies for transplantation that would not result in damage to reefs, (2 test the feasibility of transplanting storm-generated coral fragments, and (3 develop a simple, inexpensive method for transplanting fragments that could be conducted by the local community. The ultimate goal was to enhance abundance of threatened reef-building species on local reefs. Storm-produced coral fragments of two threatened reef-building species [Acropora palmata and A. cervicornis (Acroporidae] and another fast-growing species [Porites porites (Poritidae] were collected from environments hostile to coral fragment survival and transplanted to degraded reefs. Inert nylon cable ties were used to attach transplanted coral fragments to dead coral substrate. Survival of 75 reference colonies and 60 transplants was assessed over 12 years. Only 9% of colonies were alive after 12 years: no A. cervicornis; 3% of A. palmata transplants and 18% of reference colonies; and 13% of P. porites transplants and 7% of reference colonies. Mortality rates for all species were high and were similar for transplant and reference colonies. Physical dislodgement resulted in the loss of 56% of colonies, whereas 35% died in place. Only A. palmata showed a difference between transplant and reference colony survival and that was in the first year only. Location was a factor in survival only for A. palmata reference colonies and after year 10. Even though the tested methods and concepts were proven effective in the field over the 12-year study, they do not present a solution. No coral conservation strategy will be effective until underlying intrinsic and/or extrinsic factors driving high mortality rates are understood and

A Comparison of Methods for Estimating the Determinant of High-Dimensional Covariance Matrix

KAUST Repository

Hu, Zongliang; Dong, Kai; Dai, Wenlin; Tong, Tiejun

2017-01-01

The determinant of the covariance matrix for high-dimensional data plays an important role in statistical inference and decision. It has many real applications including statistical tests and information theory. Due to the statistical and computational challenges with high dimensionality, little work has been proposed in the literature for estimating the determinant of high-dimensional covariance matrix. In this paper, we estimate the determinant of the covariance matrix using some recent proposals for estimating high-dimensional covariance matrix. Specifically, we consider a total of eight covariance matrix estimation methods for comparison. Through extensive simulation studies, we explore and summarize some interesting comparison results among all compared methods. We also provide practical guidelines based on the sample size, the dimension, and the correlation of the data set for estimating the determinant of high-dimensional covariance matrix. Finally, from a perspective of the loss function, the comparison study in this paper may also serve as a proxy to assess the performance of the covariance matrix estimation.

A Comparison of Methods for Estimating the Determinant of High-Dimensional Covariance Matrix

KAUST Repository

Hu, Zongliang

2017-09-27

The determinant of the covariance matrix for high-dimensional data plays an important role in statistical inference and decision. It has many real applications including statistical tests and information theory. Due to the statistical and computational challenges with high dimensionality, little work has been proposed in the literature for estimating the determinant of high-dimensional covariance matrix. In this paper, we estimate the determinant of the covariance matrix using some recent proposals for estimating high-dimensional covariance matrix. Specifically, we consider a total of eight covariance matrix estimation methods for comparison. Through extensive simulation studies, we explore and summarize some interesting comparison results among all compared methods. We also provide practical guidelines based on the sample size, the dimension, and the correlation of the data set for estimating the determinant of high-dimensional covariance matrix. Finally, from a perspective of the loss function, the comparison study in this paper may also serve as a proxy to assess the performance of the covariance matrix estimation.

A Comparison of Methods for Estimating the Determinant of High-Dimensional Covariance Matrix.

Science.gov (United States)

Hu, Zongliang; Dong, Kai; Dai, Wenlin; Tong, Tiejun

2017-09-21

The determinant of the covariance matrix for high-dimensional data plays an important role in statistical inference and decision. It has many real applications including statistical tests and information theory. Due to the statistical and computational challenges with high dimensionality, little work has been proposed in the literature for estimating the determinant of high-dimensional covariance matrix. In this paper, we estimate the determinant of the covariance matrix using some recent proposals for estimating high-dimensional covariance matrix. Specifically, we consider a total of eight covariance matrix estimation methods for comparison. Through extensive simulation studies, we explore and summarize some interesting comparison results among all compared methods. We also provide practical guidelines based on the sample size, the dimension, and the correlation of the data set for estimating the determinant of high-dimensional covariance matrix. Finally, from a perspective of the loss function, the comparison study in this paper may also serve as a proxy to assess the performance of the covariance matrix estimation.

Searching Fragment Spaces with feature trees.

Science.gov (United States)

Lessel, Uta; Wellenzohn, Bernd; Lilienthal, Markus; Claussen, Holger

2009-02-01

Virtual combinatorial chemistry easily produces billions of compounds, for which conventional virtual screening cannot be performed even with the fastest methods available. An efficient solution for such a scenario is the generation of Fragment Spaces, which encode huge numbers of virtual compounds by their fragments/reagents and rules of how to combine them. Similarity-based searches can be performed in such spaces without ever fully enumerating all virtual products. Here we describe the generation of a huge Fragment Space encoding about 5 * 10(11) compounds based on established in-house synthesis protocols for combinatorial libraries, i.e., we encode practically evaluated combinatorial chemistry protocols in a machine readable form, rendering them accessible to in silico search methods. We show how such searches in this Fragment Space can be integrated as a first step in an overall workflow. It reduces the extremely huge number of virtual products by several orders of magnitude so that the resulting list of molecules becomes more manageable for further more elaborated and time-consuming analysis steps. Results of a case study are presented and discussed, which lead to some general conclusions for an efficient expansion of the chemical space to be screened in pharmaceutical companies.

A novel three-dimensional mesh deformation method based on sphere relaxation

International Nuclear Information System (INIS)

Zhou, Xuan; Li, Shuixiang

2015-01-01

In our previous work (2013) [19], we developed a disk relaxation based mesh deformation method for two-dimensional mesh deformation. In this paper, the idea of the disk relaxation is extended to the sphere relaxation for three-dimensional meshes with large deformations. We develop a node based pre-displacement procedure to apply initial movements on nodes according to their layer indices. Afterwards, the nodes are moved locally by the improved sphere relaxation algorithm to transfer boundary deformations and increase the mesh quality. A three-dimensional mesh smoothing method is also adopted to prevent the occurrence of the negative volume of elements, and further improve the mesh quality. Numerical applications in three-dimension including the wing rotation, bending beam and morphing aircraft are carried out. The results demonstrate that the sphere relaxation based approach generates the deformed mesh with high quality, especially regarding complex boundaries and large deformations

A novel three-dimensional mesh deformation method based on sphere relaxation

Energy Technology Data Exchange (ETDEWEB)

Zhou, Xuan [Department of Mechanics & Engineering Science, College of Engineering, Peking University, Beijing, 100871 (China); Institute of Applied Physics and Computational Mathematics, Beijing, 100094 (China); Li, Shuixiang, E-mail: lsx@pku.edu.cn [Department of Mechanics & Engineering Science, College of Engineering, Peking University, Beijing, 100871 (China)

2015-10-01

In our previous work (2013) [19], we developed a disk relaxation based mesh deformation method for two-dimensional mesh deformation. In this paper, the idea of the disk relaxation is extended to the sphere relaxation for three-dimensional meshes with large deformations. We develop a node based pre-displacement procedure to apply initial movements on nodes according to their layer indices. Afterwards, the nodes are moved locally by the improved sphere relaxation algorithm to transfer boundary deformations and increase the mesh quality. A three-dimensional mesh smoothing method is also adopted to prevent the occurrence of the negative volume of elements, and further improve the mesh quality. Numerical applications in three-dimension including the wing rotation, bending beam and morphing aircraft are carried out. The results demonstrate that the sphere relaxation based approach generates the deformed mesh with high quality, especially regarding complex boundaries and large deformations.

LINKAGE ANALYSIS BY 2-DIMENSIONAL DNA TYPING

NARCIS (Netherlands)

MEERMAN, GJT; MULLAART, E; VANDERMEULEN, MA; DENDAAS, JHG; MOROLLI, B; UITTERLINDEN, AG; VIJG, J

1993-01-01

In two-dimensional (2-D) DNA typing, genomic DNA fragments are separated, first according to size by electrophoresis in a neutral polyacrylamide gel and second according to sequence by denaturing gradient gel electrophoresis, followed by hybridization analysis using micro- and minisatellite core

Linkage analysis by two-dimensional DNA typing

NARCIS (Netherlands)

te Meerman, G J; Mullaart, E; Meulen ,van der Martin; den Daas, J H; Morolli, B; Uitterlinden, A G; Vijg, J

1993-01-01

In two-dimensional (2-D) DNA typing, genomic DNA fragments are separated, first according to size by electrophoresis in a neutral polyacrylamide gel and second according to sequence by denaturing gradient gel electrophoresis, followed by hybridization analysis using micro- and minisatellite core

Revisiting the Lund Fragmentation Model

International Nuclear Information System (INIS)

Andersson, B.; Nilsson, A.

1992-10-01

We present a new method to implement the Lund Model fragmentation distributions for multi-gluon situations. The method of Sjoestrand, implemented in the well-known Monte Carlo simulation program JETSET, is robust and direct and according to his findings there are no observable differences between different ways to implement his scheme. His method can be described as a space-time method because the breakup proper time plays a major role. The method described in this paper is built on energy-momentum space methods. We make use of the χ-curve, which is defined directly from the energy momentum vectors of the partons. We have shown that the χ-curve describes the breakup properties and the final state energy momentum distributions in the mean. We present a method to find the variations around the χ-curve, which also implements the basic Lund Model fragmentation distributions (the area-law and the corresponding iterative cascade). We find differences when comparing the corresponding Monte Carlo implementation REVJET to the JETSET distributions inside the gluon jets. (au)

Assessing the composition of fragmented agglutinated foraminiferal assemblages in ancient sediments: comparison of counting and area-based methods in Famennian samples (Late Devonian)

Science.gov (United States)

Girard, Catherine; Dufour, Anne-Béatrice; Charruault, Anne-Lise; Renaud, Sabrina

2018-01-01

Benthic foraminifera have been used as proxies for various paleoenvironmental variables such as food availability, carbon flux from surface waters, microhabitats, and indirectly water depth. Estimating assemblage composition based on morphotypes, as opposed to genus- or species-level identification, potentially loses important ecological information but opens the way to the study of ancient time periods. However, the ability to accurately constrain benthic foraminiferal assemblages has been questioned when the most abundant foraminifera are fragile agglutinated forms, particularly prone to fragmentation. Here we test an alternate method for accurately estimating the composition of fragmented assemblages. The cumulated area per morphotype method is assessed, i.e., the sum of the area of all tests or fragments of a given morphotype in a sample. The percentage of each morphotype is calculated as a portion of the total cumulated area. Percentages of different morphotypes based on counting and cumulated area methods are compared one by one and analyzed using principal component analyses, a co-inertia analysis, and Shannon diversity indices. Morphotype percentages are further compared to an estimate of water depth based on microfacies description. Percentages of the morphotypes are not related to water depth. In all cases, counting and cumulated area methods deliver highly similar results, suggesting that the less time-consuming traditional counting method may provide robust estimates of assemblages. The size of each morphotype may deliver paleobiological information, for instance regarding biomass, but should be considered carefully due to the pervasive issue of fragmentation.

Jet fragmentation

International Nuclear Information System (INIS)

Saxon, D.H.

1985-10-01

The paper reviews studies on jet fragmentation. The subject is discussed under the topic headings: fragmentation models, charged particle multiplicity, bose-einstein correlations, identified hadrons in jets, heavy quark fragmentation, baryon production, gluon and quark jets compared, the string effect, and two successful models. (U.K.)

Flow cytometric method for measuring chromatin fragmentation in fixed sperm from yellow perch (Perca flavescens).

Science.gov (United States)

Jenkins, J A; Draugelis-Dale, R O; Pinkney, A E; Iwanowicz, L R; Blazer, V S

2015-03-15

Declining harvests of yellow perch, Perca flavescens, in urbanized watersheds of Chesapeake Bay have prompted investigations of their reproductive fitness. The purpose of this study was to establish a flow cytometric technique for DNA analysis of fixed samples sent from the field to provide reliable gamete quality measurements. Similar to the sperm chromatin structure assay, measures were made on the susceptibility of nuclear DNA to acid-induced denaturation, but used fixed rather than live or thawed cells. Nuclei were best exposed to the acid treatment for 1 minute at 37 °C followed by the addition of cold (4 °C) propidium iodide staining solution before flow cytometry. The rationale for protocol development is presented graphically through cytograms. Field results collected in 2008 and 2009 revealed DNA fragmentation up to 14.5%. In 2008, DNA fragmentation from the more urbanized watersheds was significantly greater than from reference sites (P = 0.026) and in 2009, higher percentages of haploid testicular cells were noted from the less urbanized watersheds (P = 0.032) indicating better reproductive condition at sites with less urbanization. For both years, total and progressive live sperm motilities by computer-assisted sperm motion analysis ranged from 19.1% to 76.5%, being significantly higher at the less urbanized sites (P < 0.05). This flow cytometric method takes advantage of the propensity of fragmented DNA to be denatured under standard conditions, or 1 minute at 37 °C with 10% buffered formalin-fixed cells. The study of fixed sperm makes possible the restrospective investigation of germplasm fragmentation, spermatogenic ploidy patterns, and chromatin compaction levels from samples translocated over distance and time. The protocol provides an approach that can be modified for other species across taxa. Published by Elsevier Inc.

Missing Fragments: Detecting Cooperative Binding in Fragment-Based Drug Design

Science.gov (United States)

2012-01-01

The aim of fragment-based drug design (FBDD) is to identify molecular fragments that bind to alternate subsites within a given binding pocket leading to cooperative binding when linked. In this study, the binding of fragments to human phenylethanolamine N-methyltransferase is used to illustrate how (a) current protocols may fail to detect fragments that bind cooperatively, (b) theoretical approaches can be used to validate potential hits, and (c) apparent false positives obtained when screening against cocktails of fragments may in fact indicate promising leads. PMID:24900472

Moderator feedback effects in two-dimensional nodal methods for pressurized water reactor analysis

International Nuclear Information System (INIS)

Downar, T.J.

1987-01-01

A method was developed for incorporating moderator feedback effects in two-dimensional nodal codes used for pressurized water reactor (PWR) neutronic analysis. Equations for the assembly average quality and density are developed in terms of the assembly power calculated in two dimensions. The method is validated with a Westinghouse PWR using the Electric Power Research Institute code SIMULATE-E. Results show a several percent improvement is achieved in the two-dimensional power distribution prediction compared to methods without moderator feedback

The Validity of Dimensional Regularization Method on Fractal Spacetime

Directory of Open Access Journals (Sweden)

Yong Tao

2013-01-01

Full Text Available Svozil developed a regularization method for quantum field theory on fractal spacetime (1987. Such a method can be applied to the low-order perturbative renormalization of quantum electrodynamics but will depend on a conjectural integral formula on non-integer-dimensional topological spaces. The main purpose of this paper is to construct a fractal measure so as to guarantee the validity of the conjectural integral formula.

DNA fragments assembly based on nicking enzyme system.

Directory of Open Access Journals (Sweden)

Rui-Yan Wang

Full Text Available A couple of DNA ligation-independent cloning (LIC methods have been reported to meet various requirements in metabolic engineering and synthetic biology. The principle of LIC is the assembly of multiple overlapping DNA fragments by single-stranded (ss DNA overlaps annealing. Here we present a method to generate single-stranded DNA overlaps based on Nicking Endonucleases (NEases for LIC, the method was termed NE-LIC. Factors related to cloning efficiency were optimized in this study. This NE-LIC allows generating 3'-end or 5'-end ss DNA overlaps of various lengths for fragments assembly. We demonstrated that the 10 bp/15 bp overlaps had the highest DNA fragments assembling efficiency, while 5 bp/10 bp overlaps showed the highest efficiency when T4 DNA ligase was added. Its advantage over Sequence and Ligation Independent Cloning (SLIC and Uracil-Specific Excision Reagent (USER was obvious. The mechanism can be applied to many other LIC strategies. Finally, the NEases based LIC (NE-LIC was successfully applied to assemble a pathway of six gene fragments responsible for synthesizing microbial poly-3-hydroxybutyrate (PHB.

Evaluation and analysis of geological condition of in-situ fragmentation leaching uranium

International Nuclear Information System (INIS)

Yang Jianming; Tan Kaixuan; Huang Xiaonai

2003-01-01

The ore geological condition, hydrogeological condition, engineering geological condition and technological mineralogical character of in-situ fragmentation leaching uranium are analyzed, and it is considered that the implementation of in-situ fragmentation leaching uranium technology is decided by different geological factor. Previously prospecting and geological condition evaluation of uranium ore is based on traditional mining method. If in-situ fragmentation leaching uranium method is adopted, one must re-evaluate previously prospected deposits before they are mined, or one must evaluate new prospecting deposits according to geological conditions of in-situ fragmentation leaching uranium method. The feasibility evaluation method of uranium deposit by in-situ fragmentation leaching uranium put forward by B. N. Mociniets is introducd, and it is considered that B. N. Mociniets method has guidable significance for geological condition evaluation before uranium deposits are mined. A feasibility study is done by applying B. N. Mociniets method to a uranium deposit. (authors)

Diffusion mediated coagulation and fragmentation based study of domain formation in lipid bilayer membrane

Energy Technology Data Exchange (ETDEWEB)

Rao, Laxminarsimha V., E-mail: laxman@iitk.ac.in [Mechanics and Applied Mathematics Group, Department of Mechanical Engineering, Indian Institute of Technology Kanpur, Kanpur 208016 (India); Roy, Subhradeep [Department of Biomedical Engineering and Mechanics (MC 0219), Virginia Tech, 495 Old Turner Street, Blacksburg, VA 24061 (United States); Das, Sovan Lal [Mechanics and Applied Mathematics Group, Department of Mechanical Engineering, Indian Institute of Technology Kanpur, Kanpur 208016 (India)

2017-01-15

We estimate the equilibrium size distribution of cholesterol rich micro-domains on a lipid bilayer by solving Smoluchowski equation for coagulation and fragmentation. Towards this aim, we first derive the coagulation kernels based on the diffusion behaviour of domains moving in a two dimensional membrane sheet, as this represents the reality better. We incorporate three different diffusion scenarios of domain diffusion into our coagulation kernel. Subsequently, we investigate the influence of the parameters in our model on the coagulation and fragmentation behaviour. The observed behaviours of the coagulation and fragmentation kernels are also manifested in the equilibrium domain size distribution and its first moment. Finally, considering the liquid domains diffusing in a supported lipid bilayer, we fit the equilibrium domain size distribution to a benchmark solution.

Simulations of High Speed Fragment Trajectories

Science.gov (United States)

Yeh, Peter; Attaway, Stephen; Arunajatesan, Srinivasan; Fisher, Travis

2017-11-01

Flying shrapnel from an explosion are capable of traveling at supersonic speeds and distances much farther than expected due to aerodynamic interactions. Predicting the trajectories and stable tumbling modes of arbitrary shaped fragments is a fundamental problem applicable to range safety calculations, damage assessment, and military technology. Traditional approaches rely on characterizing fragment flight using a single drag coefficient, which may be inaccurate for fragments with large aspect ratios. In our work we develop a procedure to simulate trajectories of arbitrary shaped fragments with higher fidelity using high performance computing. We employ a two-step approach in which the force and moment coefficients are first computed as a function of orientation using compressible computational fluid dynamics. The force and moment data are then input into a six-degree-of-freedom rigid body dynamics solver to integrate trajectories in time. Results of these high fidelity simulations allow us to further understand the flight dynamics and tumbling modes of a single fragment. Furthermore, we use these results to determine the validity and uncertainty of inexpensive methods such as the single drag coefficient model.

Pseudo three-dimensional modeling of particle-fuel packing using distinct element method

International Nuclear Information System (INIS)

Yuki, Daisuke; Takata, Takashi; Yamaguchi, Akira

2007-01-01

Vibration-based packing of sphere-pac fuel is a key technology in a nuclear fuel manufacturing. In the production process of sphere-pac fuel, a Mixed Oxide (MOX) fuel is formed to spherical form and is packed in a cladding tube by adding a vibration force. In the present study, we have developed a numerical simulation method to investigate the behavior of the particles in a vibrated tube using the Distinct Element Method (DEM). In general, the DEM requires a significant computational cost. Therefore we propose a new approach in which a small particle can move through the space between three larger particles even in the two-dimensional simulation. We take into account an equivalent three-dimensional effect in the equations of motion. Thus it is named pseudo three-dimensional modeling. (author)

Fragment-assisted hit investigation involving integrated HTS and fragment screening: Application to the identification of phosphodiesterase 10A (PDE10A) inhibitors.

Science.gov (United States)

Varnes, Jeffrey G; Geschwindner, Stefan; Holmquist, Christopher R; Forst, Janet; Wang, Xia; Dekker, Niek; Scott, Clay W; Tian, Gaochao; Wood, Michael W; Albert, Jeffrey S

2016-01-01

Fragment-based drug design (FBDD) relies on direct elaboration of fragment hits and typically requires high resolution structural information to guide optimization. In fragment-assisted drug discovery (FADD), fragments provide information to guide selection and design but do not serve as starting points for elaboration. We describe FADD and high-throughput screening (HTS) campaign strategies conducted in parallel against PDE10A where fragment hit co-crystallography was not available. The fragment screen led to prioritized fragment hits (IC50's ∼500μM), which were used to generate a hypothetical core scaffold. Application of this scaffold as a filter to HTS output afforded a 4μM hit, which, after preparation of a small number of analogs, was elaborated into a 16nM lead. This approach highlights the strength of FADD, as fragment methods were applied despite the absence of co-crystallographical information to efficiently identify a lead compound for further optimization. Copyright © 2015 Elsevier Ltd. All rights reserved.

NMR screening in fragment-based drug design: a practical guide.

Science.gov (United States)

Kim, Hai-Young; Wyss, Daniel F

2015-01-01

Fragment-based drug design (FBDD) comprises both fragment-based screening (FBS) to find hits and elaboration of these hits to lead compounds. Typical fragment hits have lower molecular weight (FBDD since it identifies and localizes the binding site of weakly interacting hits on the target protein. Here we describe ligand-based NMR methods for hit identification from fragment libraries and for functional cross-validation of primary hits.

Labeling and stability of radiolabeled antibody fragments by a direct 99mTc-labeling method

International Nuclear Information System (INIS)

Pak, K.Y.; Nedelman, M.A.; Tam, S.H.; Wilson, E.; Daddona, P.E.

1992-01-01

The in vitro labeling and stability of 99m Tc-labeled antibody Fab' fragments prepared by a direct labeling technique were evaluated. Eight antibody fragments derived from murine IgG1 (N = 5), IgG2a (N = 2) and IgG3 (N = 1) isotypes were labeled with a preformed 99m Tc-D-glucarate complex. No loss of radioactivity incorporation was observed for all the 99m Tc-labeled antibody fragments after 24 h incubation at 37 o C. 99m Tc-labeled antibody fragments (IgG1, N = 2; IgG2a, n = 2; IgG3, N = 1) were stable upon challenge with DTPA, EDTA or acidic pH. Using the affinity chromatography technique, two of the 99m Tc-labeled antibody fragments displayed no loss of immunoreactivity after prolonged incubation in phosphate buffer up to 24 h at 37 o C. Bonding between 99m Tc and antibody fragments was elucidated by challenging with a diamide ditholate (N 2 S 2 ) compound. The Fab' with IgG2a isotype displayed tighter binding to 99m Tc in comparison to Fab' from IgG1 and IgG3 isotype in N 2 S 2 challenge and incubation with human plasma. The in vivo biodistribution of five 99m Tc-labeled fragments were evaluated in normal mice. (Author)

A Simple yet Accurate Method for Students to Determine Asteroid Rotation Periods from Fragmented Light Curve Data

Science.gov (United States)

Beare, R. A.

2008-01-01

Professional astronomers use specialized software not normally available to students to determine the rotation periods of asteroids from fragmented light curve data. This paper describes a simple yet accurate method based on Microsoft Excel[R] that enables students to find periods in asteroid light curve and other discontinuous time series data of…

Solution of (3+1-Dimensional Nonlinear Cubic Schrodinger Equation by Differential Transform Method

Directory of Open Access Journals (Sweden)

Hassan A. Zedan

2012-01-01

Full Text Available Four-dimensional differential transform method has been introduced and fundamental theorems have been defined for the first time. Moreover, as an application of four-dimensional differential transform, exact solutions of nonlinear system of partial differential equations have been investigated. The results of the present method are compared very well with analytical solution of the system. Differential transform method can easily be applied to linear or nonlinear problems and reduces the size of computational work. With this method, exact solutions may be obtained without any need of cumbersome work, and it is a useful tool for analytical and numerical solutions.

Dynamic fragmentation of laser shock-melted tin: experiment and modelling

Energy Technology Data Exchange (ETDEWEB)

De Resseguier, T. [CNRS ENSMA, Lab Combust and Deton, F-86961 Futuroscope (France); Signor, L.; Dragon, A. [CNRS ENSMA, Mecan and Phys Mat Lab, F-86961 Futuroscope (France); Signor, L.; Roy, G. [CEA Valduc, 21 - Is-sur-Tille (France)

2010-07-01

Dynamic fragmentation of shock-loaded metals is an issue of considerable importance for both basic science and a variety of technological applications, such as pyrotechnics or inertial confinement fusion, the latter involving high energy laser irradiation of thin metallic shells. Whereas spall fracture in solid materials has been extensively studied for many years, little data can be found yet about the evolution of this phenomenon after partial or full melting on compression or on release. Here, we present an investigation of dynamic fragmentation in laser shock-melted tin, from the 'micro-spall' process (ejection of a cloud of fine droplets) occurring upon reflection of the compressive pulse from the target free surface, to the late rupture observed in the un-spalled melted layer (leading to the formation of larger spherical fragments). Experimental results consist of time-resolved velocity measurements and post-shock observations of recovered targets and fragments. They provide original information regarding the loss of tensile strength associated with melting, the cavitation mechanism likely to occur in the melted metal, the sizes of the subsequent fragments and their ejection velocities. A theoretical description based on an energetic approach adapted to the case of a liquid metal is implemented as a failure criterion in a one-dimensional hydro-code including a multi-phase equation of state for tin. The resulting predictions of the micro-spall process are compared with experimental data. In particular, the use of a new experimental technique to quantify the fragment size distributions leads to a much better agreement with theory than previously reported. Finally, a complementary approach focused on cavitation is proposed to evaluate the role of this phenomenon in the fragmentation of the melted metal. (authors)

A probabilistic fragment-based protein structure prediction algorithm.

Directory of Open Access Journals (Sweden)

David Simoncini

Full Text Available Conformational sampling is one of the bottlenecks in fragment-based protein structure prediction approaches. They generally start with a coarse-grained optimization where mainchain atoms and centroids of side chains are considered, followed by a fine-grained optimization with an all-atom representation of proteins. It is during this coarse-grained phase that fragment-based methods sample intensely the conformational space. If the native-like region is sampled more, the accuracy of the final all-atom predictions may be improved accordingly. In this work we present EdaFold, a new method for fragment-based protein structure prediction based on an Estimation of Distribution Algorithm. Fragment-based approaches build protein models by assembling short fragments from known protein structures. Whereas the probability mass functions over the fragment libraries are uniform in the usual case, we propose an algorithm that learns from previously generated decoys and steers the search toward native-like regions. A comparison with Rosetta AbInitio protocol shows that EdaFold is able to generate models with lower energies and to enhance the percentage of near-native coarse-grained decoys on a benchmark of [Formula: see text] proteins. The best coarse-grained models produced by both methods were refined into all-atom models and used in molecular replacement. All atom decoys produced out of EdaFold's decoy set reach high enough accuracy to solve the crystallographic phase problem by molecular replacement for some test proteins. EdaFold showed a higher success rate in molecular replacement when compared to Rosetta. Our study suggests that improving low resolution coarse-grained decoys allows computational methods to avoid subsequent sampling issues during all-atom refinement and to produce better all-atom models. EdaFold can be downloaded from http://www.riken.jp/zhangiru/software.html [corrected].

Structures of endothiapepsin-fragment complexes from crystallographic fragment screening using a novel, diverse and affordable 96-compound fragment library.

Science.gov (United States)

Huschmann, Franziska U; Linnik, Janina; Sparta, Karine; Ühlein, Monika; Wang, Xiaojie; Metz, Alexander; Schiebel, Johannes; Heine, Andreas; Klebe, Gerhard; Weiss, Manfred S; Mueller, Uwe

2016-05-01

Crystallographic screening of the binding of small organic compounds (termed fragments) to proteins is increasingly important for medicinal chemistry-oriented drug discovery. To enable such experiments in a widespread manner, an affordable 96-compound library has been assembled for fragment screening in both academia and industry. The library is selected from already existing protein-ligand structures and is characterized by a broad ligand diversity, including buffer ingredients, carbohydrates, nucleotides, amino acids, peptide-like fragments and various drug-like organic compounds. When applied to the model protease endothiapepsin in a crystallographic screening experiment, a hit rate of nearly 10% was obtained. In comparison to other fragment libraries and considering that no pre-screening was performed, this hit rate is remarkably high. This demonstrates the general suitability of the selected compounds for an initial fragment-screening campaign. The library composition, experimental considerations and time requirements for a complete crystallographic fragment-screening campaign are discussed as well as the nine fully refined obtained endothiapepsin-fragment structures. While most of the fragments bind close to the catalytic centre of endothiapepsin in poses that have been observed previously, two fragments address new sites on the protein surface. ITC measurements show that the fragments bind to endothiapepsin with millimolar affinity.

Structures of endothiapepsin–fragment complexes from crystallographic fragment screening using a novel, diverse and affordable 96-compound fragment library

Science.gov (United States)

Huschmann, Franziska U.; Linnik, Janina; Sparta, Karine; Ühlein, Monika; Wang, Xiaojie; Metz, Alexander; Schiebel, Johannes; Heine, Andreas; Klebe, Gerhard; Weiss, Manfred S.; Mueller, Uwe

2016-01-01

Crystallographic screening of the binding of small organic compounds (termed fragments) to proteins is increasingly important for medicinal chemistry-oriented drug discovery. To enable such experiments in a widespread manner, an affordable 96-compound library has been assembled for fragment screening in both academia and industry. The library is selected from already existing protein–ligand structures and is characterized by a broad ligand diversity, including buffer ingredients, carbohydrates, nucleotides, amino acids, peptide-like fragments and various drug-like organic compounds. When applied to the model protease endothiapepsin in a crystallographic screening experiment, a hit rate of nearly 10% was obtained. In comparison to other fragment libraries and considering that no pre-screening was performed, this hit rate is remarkably high. This demonstrates the general suitability of the selected compounds for an initial fragment-screening campaign. The library composition, experimental considerations and time requirements for a complete crystallographic fragment-screening campaign are discussed as well as the nine fully refined obtained endothiapepsin–fragment structures. While most of the fragments bind close to the catalytic centre of endothiapepsin in poses that have been observed previously, two fragments address new sites on the protein surface. ITC measurements show that the fragments bind to endothiapepsin with millimolar affinity. PMID:27139825

Towards novel therapeutics for HIV through fragment-based screening and drug design.

Science.gov (United States)

Tiefendbrunn, Theresa; Stout, C David

2014-01-01

Fragment-based drug discovery has been applied with varying levels of success to a number of proteins involved in the HIV (Human Immunodeficiency Virus) life cycle. Fragment-based approaches have led to the discovery of novel binding sites within protease, reverse transcriptase, integrase, and gp41. Novel compounds that bind to known pockets within CCR5 have also been identified via fragment screening, and a fragment-based approach to target the TAR-Tat interaction was explored. In the context of HIV-1 reverse transcriptase (RT), fragment-based approaches have yielded fragment hits with mid-μM activity in an in vitro activity assay, as well as fragment hits that are active against drug-resistant variants of RT. Fragment-based drug discovery is a powerful method to elucidate novel binding sites within proteins, and the method has had significant success in the context of HIV proteins.

Towards a population synthesis model of self-gravitating disc fragmentation and tidal downsizing II: the effect of fragment-fragment interactions

Science.gov (United States)

Forgan, D. H.; Hall, C.; Meru, F.; Rice, W. K. M.

2018-03-01

It is likely that most protostellar systems undergo a brief phase where the protostellar disc is self-gravitating. If these discs are prone to fragmentation, then they are able to rapidly form objects that are initially of several Jupiter masses and larger. The fate of these disc fragments (and the fate of planetary bodies formed afterwards via core accretion) depends sensitively not only on the fragment's interaction with the disc, but also with its neighbouring fragments. We return to and revise our population synthesis model of self-gravitating disc fragmentation and tidal downsizing. Amongst other improvements, the model now directly incorporates fragment-fragment interactions while the disc is still present. We find that fragment-fragment scattering dominates the orbital evolution, even when we enforce rapid migration and inefficient gap formation. Compared to our previous model, we see a small increase in the number of terrestrial-type objects being formed, although their survival under tidal evolution is at best unclear. We also see evidence for disrupted fragments with evolved grain populations - this is circumstantial evidence for the formation of planetesimal belts, a phenomenon not seen in runs where fragment-fragment interactions are ignored. In spite of intense dynamical evolution, our population is dominated by massive giant planets and brown dwarfs at large semimajor axis, which direct imaging surveys should, but only rarely, detect. Finally, disc fragmentation is shown to be an efficient manufacturer of free-floating planetary mass objects, and the typical multiplicity of systems formed via gravitational instability will be low.

Three-dimensional display by computer graphics method of hepatocellular carcinoma using seen with the hepatic arteriogram

International Nuclear Information System (INIS)

Itsubo, Mariko; Kameda, Haruo; Suzuki, Naoki; Okamura, Tetsuo

1989-01-01

The method of three-dimensional display of hepatocellular carcinoma using conventional hepatic arteriogram by computer graphics method was newly exploited and applied in clinical use. Three-dimensional models were reconstructed from contour lines of tumors demonstrated as hypervascular lesions by hepatic arteriography. Although objects were limited by angiographic images in which tumors need to be demonstrated as nodules with hypervascularity, this method of three-dimensional display was not worse on accuracy than that using computed tomographic images. According to this method property of the tumor expressed by vascularity was demonstrated clear and in addition volume of the tumor was calculated easily. When the tumor arose in necrotic changes in which demonstrated as a vascular lesion by hepatic arteriography with reduction of size in usual by conservative treatment such as transcathter arterial embolization therapy, this three-dimensional display was able to demonstrate such changes clear. This preliminary study demonstrates the feasibility and clinical usefulness of three-dimensional display of hepatocellular carcinoma using hepatic arteriogram by computer graphics method. (author)

One-Dimensional Finite Elements An Introduction to the FE Method

CERN Document Server

Öchsner, Andreas

2013-01-01

 This textbook presents finite element methods using exclusively  one-dimensional elements. The aim is to present the complex methodology in  an easily understandable but mathematically correct fashion. The approach of  one-dimensional elements enables the reader to focus on the understanding of  the principles of basic and advanced mechanical problems. The reader easily  understands the assumptions and limitations of mechanical modeling as well  as the underlying physics without struggling with complex mathematics. But  although the description is easy it remains scientifically correct.   The approach using only one-dimensional elements covers not only standard  problems but allows also for advanced topics like plasticity or the  mechanics of composite materials. Many examples illustrate the concepts and  problems at the end of every chapter help to familiarize with the topics.

Transplantation of storm-generated coral fragments to enhance Caribbean coral reefs: A successful method but not a solution

Science.gov (United States)

Garrison, Virginia H.; Ward, Greg A.

2012-01-01

In response to dramatic losses of reef-building corals and ongoing lack of recovery, a small-scale coral transplant project was initiated in the Caribbean (U.S. Virgin Islands) in 1999 and was followed for 12 years. The primary objectives were to (1) identify a source of coral colonies for transplantation that would not result in damage to reefs, (2) test the feasibility of transplanting storm-generated coral fragments, and (3) develop a simple, inexpensive method for transplanting fragments that could be conducted by the local community.  The ultimate goal was to enhance abundance of threatened reef-building species on local reefs.  Storm-produced coral fragments of two threatened reef-building species [Acropora palmata and A. cervicornis (Acroporidae)] and another fast-growing species [Porites porites (Poritidae)] were collected from environments hostile to coral fragment survival and transplanted to degraded reefs.  Inert nylon cable ties were used to attach transplanted coral fragments to dead coral substrate.  Survival of 75 reference colonies and 60 transplants was assessed over 12 years. Only 9% of colonies were alive after 12 years: no A. cervicornis; 3% of A. palmata transplants and 18% of reference colonies; and 13% of P. porites transplants and 7% of reference colonies. Mortality rates for all species were high and were similar for transplant and reference colonies. Physical dislodgement resulted in the loss of 56% of colonies, whereas 35% died in place.  Only A. palmata showed a difference between transplant and reference colony survival and that was in the first year only.  Location was a factor in survival only for A. palmata reference colonies and after year 10.  Even though the tested methods and concepts were proven effective in the field over the 12-year study, they do not present a solution. No coral conservation strategy will be effective until underlying intrinsic and/or extrinsic factors driving high mortality rates are

Three dimensional wavefield modeling using the pseudospectral method; Pseudospectral ho ni yoru sanjigen hadoba modeling

Energy Technology Data Exchange (ETDEWEB)

Sato, T; Matsuoka, T [Japan Petroleum Exploration Corp., Tokyo (Japan); Saeki, T [Japan National Oil Corp., Tokyo (Japan). Technology Research Center

1997-05-27

Discussed in this report is a wavefield simulation in the 3-dimensional seismic survey. With the level of the object of exploration growing deeper and the object more complicated in structure, the survey method is now turning 3-dimensional. There are several modelling methods for numerical calculation of 3-dimensional wavefields, such as the difference method, pseudospectral method, and the like, all of which demand an exorbitantly large memory and long calculation time, and are costly. Such methods have of late become feasible, however, thanks to the advent of the parallel computer. As compared with the difference method, the pseudospectral method requires a smaller computer memory and shorter computation time, and is more flexible in accepting models. It outputs the result in fullwave just like the difference method, and does not cause wavefield numerical variance. As the computation platform, the parallel computer nCUBE-2S is used. The object domain is divided into the number of the processors, and each of the processors takes care only of its share so that parallel computation as a whole may realize a very high-speed computation. By the use of the pseudospectral method, a 3-dimensional simulation is completed within a tolerable computation time length. 7 refs., 3 figs., 1 tab.

Graph Theory. 1. Fragmentation of Structural Graphs

Directory of Open Access Journals (Sweden)

Lorentz JÄNTSCHI

2002-12-01

Full Text Available The investigation of structural graphs has many fields of applications in engineering, especially in applied sciences like as applied chemistry and physics, computer sciences and automation, electronics and telecommunication. The main subject of the paper is to express fragmentation criteria in graph using a new method of investigation: terminal paths. Using terminal paths are defined most of the fragmentation criteria that are in use in molecular topology, but the fields of applications are more generally than that, as I mentioned before. Graphical examples of fragmentation are given for every fragmentation criteria. Note that all fragmentation is made with a computer program that implements a routine for every criterion.[1] A web routine for tracing all terminal paths in graph can be found at the address: http://vl.academicdirect.ro/molecular_topology/tpaths/ [1] M. V. Diudea, I. Gutman, L. Jäntschi, Molecular Topology, Nova Science, Commack, New York, 2001, 2002.

Development of a three dimensional circulation model based on fractional step method

Directory of Open Access Journals (Sweden)

Mazen Abualtayef

2010-03-01

Full Text Available A numerical model was developed for simulating a three-dimensional multilayer hydrodynamic and thermodynamic model in domains with irregular bottom topography. The model was designed for examining the interactions between flow and topography. The model was based on the three-dimensional Navier-Stokes equations and was solved using the fractional step method, which combines the finite difference method in the horizontal plane and the finite element method in the vertical plane. The numerical techniques were described and the model test and application were presented. For the model application to the northern part of Ariake Sea, the hydrodynamic and thermodynamic results were predicted. The numerically predicted amplitudes and phase angles were well consistent with the field observations.

Improved description of the fragmentation of nuclear collective states

International Nuclear Information System (INIS)

Soloviev, V.G.

1984-01-01

A mathematical method is deveioped for a more accurate description of the fragmentation of one-phonon states forming giant resonances. The method consists in that the one-phonon states already fragmented are used in the two-phonon terms of wave functions. Strength functions are obtained for the exci excitation of collective charge-exchange states ano giant resonances in spherical nuclei

An Efficient Method to Evaluate Intermolecular Interaction Energies in Large Systems Using Overlapping Multicenter ONIOM and the Fragment Molecular Orbital Method

Science.gov (United States)

Asada, Naoya; Fedorov, Dmitri G.; Kitaura, Kazuo; Nakanishi, Isao; Merz, Kenneth M.

2012-01-01

We propose an approach based on the overlapping multicenter ONIOM to evaluate intermolecular interaction energies in large systems and demonstrate its accuracy on several representative systems in the complete basis set limit at the MP2 and CCSD(T) level of theory. In the application to the intermolecular interaction energy between insulin dimer and 4′-hydroxyacetanilide at the MP2/CBS level, we use the fragment molecular orbital method for the calculation of the entire complex assigned to the lowest layer in three-layer ONIOM. The developed method is shown to be efficient and accurate in the evaluation of the protein-ligand interaction energies. PMID:23050059

Universal elements of fragmentation

International Nuclear Information System (INIS)

Yanovsky, V. V.; Tur, A. V.; Kuklina, O. V.

2010-01-01

A fragmentation theory is proposed that explains the universal asymptotic behavior of the fragment-size distribution in the large-size range, based on simple physical principles. The basic principles of the theory are the total mass conservation in a fragmentation process and a balance condition for the energy expended in increasing the surface of fragments during their breakup. A flux-based approach is used that makes it possible to supplement the basic principles and develop a minimal theory of fragmentation. Such a supplementary principle is that of decreasing fragment-volume flux with increasing energy expended in fragmentation. It is shown that the behavior of the decreasing flux is directly related to the form of a power-law fragment-size distribution. The minimal theory is used to find universal asymptotic fragment-size distributions and to develop a natural physical classification of fragmentation models. A more general, nonlinear theory of strong fragmentation is also developed. It is demonstrated that solutions to a nonlinear kinetic equation consistent with both basic principles approach a universal asymptotic size distribution. Agreement between the predicted asymptotic fragment-size distributions and experimental observations is discussed.

Four-Dimensional Data Assimilation Using the Adjoint Method

Science.gov (United States)

Bao, Jian-Wen

The calculus of variations is used to confirm that variational four-dimensional data assimilation (FDDA) using the adjoint method can be implemented when the numerical model equations have a finite number of first-order discontinuous points. These points represent the on/off switches associated with physical processes, for which the Jacobian matrix of the model equation does not exist. Numerical evidence suggests that, in some situations when the adjoint method is used for FDDA, the temperature field retrieved using horizontal wind data is numerically not unique. A physical interpretation of this type of non-uniqueness of the retrieval is proposed in terms of energetics. The adjoint equations of a numerical model can also be used for model-parameter estimation. A general computational procedure is developed to determine the size and distribution of any internal model parameter. The procedure is then applied to a one-dimensional shallow -fluid model in the context of analysis-nudging FDDA: the weighting coefficients used by the Newtonian nudging technique are determined. The sensitivity of these nudging coefficients to the optimal objectives and constraints is investigated. Experiments of FDDA using the adjoint method are conducted using the dry version of the hydrostatic Penn State/NCAR mesoscale model (MM4) and its adjoint. The minimization procedure converges and the initialization experiment is successful. Temperature-retrieval experiments involving an assimilation of the horizontal wind are also carried out using the adjoint of MM4.

Geotechnical applications of a two-dimensional elastodynamic displacement discontinuity method

CSIR Research Space (South Africa)

Siebrits, E

1993-12-01

Full Text Available A general two-dimensional elastodynamic displacement discontinuity method is used to model a variety of application problems. The plane strain problems are: the elastodynamic motions induced on a cavity by shear slip on a nearby crack; the dynamic...

Method for the manufacture of a thin-layer battery stack on a three-dimensional substrate

NARCIS (Netherlands)

2008-01-01

The invention relates to a method for the manufacture of a thin-layer battery stack on a three-dimensional substrate. The invention further relates to a thin-layer battery stack on a three-dimensional substrate obtainable by such a method. Moreover, the invention relates to a device comprising such

Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry

Science.gov (United States)

2018-01-01

Natural products are well known for their biological relevance, high degree of three-dimensionality, and access to areas of largely unexplored chemical space. To shape our understanding of the interaction between natural products and protein targets in the postgenomic era, we have used native mass spectrometry to investigate 62 potential protein targets for malaria using a natural-product-based fragment library. We reveal here 96 low-molecular-weight natural products identified as binding partners of 32 of the putative malarial targets. Seventy-nine (79) fragments have direct growth inhibition on Plasmodium falciparum at concentrations that are promising for the development of fragment hits against these protein targets. This adds a fragment library to the published HTS active libraries in the public domain. PMID:29436819

Completion of autobuilt protein models using a database of protein fragments

International Nuclear Information System (INIS)

Cowtan, Kevin

2012-01-01

Two developments in the process of automated protein model building in the Buccaneer software are described: the use of a database of protein fragments in improving the model completeness and the assembly of disconnected chain fragments into complete molecules. Two developments in the process of automated protein model building in the Buccaneer software are presented. A general-purpose library for protein fragments of arbitrary size is described, with a highly optimized search method allowing the use of a larger database than in previous work. The problem of assembling an autobuilt model into complete chains is discussed. This involves the assembly of disconnected chain fragments into complete molecules and the use of the database of protein fragments in improving the model completeness. Assembly of fragments into molecules is a standard step in existing model-building software, but the methods have not received detailed discussion in the literature

Wave field restoration using three-dimensional Fourier filtering method.

Science.gov (United States)

Kawasaki, T; Takai, Y; Ikuta, T; Shimizu, R

2001-11-01

A wave field restoration method in transmission electron microscopy (TEM) was mathematically derived based on a three-dimensional (3D) image formation theory. Wave field restoration using this method together with spherical aberration correction was experimentally confirmed in through-focus images of amorphous tungsten thin film, and the resolution of the reconstructed phase image was successfully improved from the Scherzer resolution limit to the information limit. In an application of this method to a crystalline sample, the surface structure of Au(110) was observed in a profile-imaging mode. The processed phase image showed quantitatively the atomic relaxation of the topmost layer.

The Chimera Method of Simulation for Unsteady Three-Dimensional Viscous Flow

Science.gov (United States)

Meakin, Robert L.

1996-01-01

The Chimera overset grid method is reviewed and discussed in the context of a method of solution and analysis of unsteady three-dimensional viscous flows. The state of maturity of the various pieces of support software required to use the approach is discussed. A variety of recent applications of the method is presented. Current limitations of the approach are defined.

Identification of Histamine H3 Receptor Ligands Using a New Crystal Structure Fragment-based Method

DEFF Research Database (Denmark)

Frandsen, Ida Osborn; Boesgaard, Michael W; Fidom, Kimberley

2017-01-01

Virtual screening offers an efficient alternative to high-throughput screening in the identification of pharmacological tools and lead compounds. Virtual screening is typically based on the matching of target structures or ligand pharmacophores to commercial or in-house compound catalogues....... The complete pharmacophore fragment library is freely available through the GPCR database, GPCRdb, allowing the successful application herein to be repeated for most of the 285 class A GPCR targets. The method could also easily be adapted to other protein families....

Elaboration of a model of the nuclear fragmentation and application to the method of isotopic separation of projectile fragments

International Nuclear Information System (INIS)

Gaimard, J.J.

1990-10-01

In this thesis the experimental results on the cross sections for the production of 36 P in the fragmentation of 403 MeV/u 40 Ar on a carbon target are presented. Furthermore some models of the nuclear fragmentation are elaborated and compared by means of experimental data for the production of gold and cerium isotopes in the reaction 12 C+ 209 Bi at 400 MeV/u, of chlorine, sulfur, aluminium, magnesium, and oxygen isotopes in the reactions 40 Ar+ 12 C at 600 MeV/u and 48 Ca+ 9 Be at 212 MeV/u, and of cobalt, manganese, vanadium, and scandium isotopes together with the charge distributions for A=43 and A=44 in the reactions 40 Ar+ 64 Cu at 2 GeV/u and 56 Fe+ 12 C at 600 MeV/u. (HSI)

An axial calculation method for accurate two-dimensional PWR core simulation

International Nuclear Information System (INIS)

Grimm, P.

1985-02-01

An axial calculation method, which improves the agreement of the multiplication factors determined by two- and three-dimensional PWR neutronic calculations, is presented. The axial buckling is determined at each time point so as to reproduce the increase of the leakage due to the flattening of the axial power distribution and the effect of the axial variation of the group constants of the fuel on the reactivity is taken into account. The results of a test example show that the differences of k-eff and cycle length between two- and three-dimensional calculations, which are unsatisfactorily large if a constant buckling is used, become negligible if the results of the axial calculation are used in the two-dimensional core simulation. (Auth.)

Native State Mass Spectrometry, Surface Plasmon Resonance, and X-ray Crystallography Correlate Strongly as a Fragment Screening Combination.

Science.gov (United States)

Woods, Lucy A; Dolezal, Olan; Ren, Bin; Ryan, John H; Peat, Thomas S; Poulsen, Sally-Ann

2016-03-10

Fragment-based drug discovery (FBDD) is contingent on the development of analytical methods to identify weak protein-fragment noncovalent interactions. Herein we have combined an underutilized fragment screening method, native state mass spectrometry, together with two proven and popular fragment screening methods, surface plasmon resonance and X-ray crystallography, in a fragment screening campaign against human carbonic anhydrase II (CA II). In an initial fragment screen against a 720-member fragment library (the "CSIRO Fragment Library") seven CA II binding fragments, including a selection of nonclassical CA II binding chemotypes, were identified. A further 70 compounds that comprised the initial hit chemotypes were subsequently sourced from the full CSIRO compound collection and screened. The fragment results were extremely well correlated across the three methods. Our findings demonstrate that there is a tremendous opportunity to apply native state mass spectrometry as a complementary fragment screening method to accelerate drug discovery.

Numerical analysis of fragmentation mechanisms in vapor explosions

Energy Technology Data Exchange (ETDEWEB)

Koshizuka, Seiichi; Ikeda, Hirokazu; Oka, Yoshiaki [Tokyo Univ., Tokai, Ibaraki (Japan). Nuclear Engineering Research Lab.

1998-01-01

Fragmentation of molten metal is the key process in vapor explosions. However this process is so rapid that the mechanisms have not been clarified yet in the experimental studies. Besides, numerical simulation is difficult because we have to analyze water, steam and molten metal simultaneously with evaporation and fragmentation. The authors have been developing a new numerical method, the Moving Particle Semi-implicit (MPS) method, based on moving particles and their interactions. Grids are not necessary. Incompressible flows with fragmentation on free surfaces have been calculated successfully using the MPS method. In the present study numerical simulation of the fragmentation processes using the MPS method is carried out to investigate the mechanisms. A numerical model to calculate evaporation from water to steam is developed. In this model, new particles are generated on water-steam interfaces. Effect of evaporation is also investigated. Growth of the filament is not accelerated when the normal evaporation is considered. This is because the normal evaporation needs a longer time than the moment of the jet impingement, though the filament growth is decided in this moment. Next, rapid evaporation based on spontaneous nucleation is considered. The filament growth is markedly accelerated. This result is consistent with the experimental fact that the spontaneous nucleation temperature is a necessary condition of small-scale vapor explosions. (J.P.N.)

The analysis of carbohydrates in milk powder by a new "heart-cutting" two-dimensional liquid chromatography method.

Science.gov (United States)

Ma, Jing; Hou, Xiaofang; Zhang, Bing; Wang, Yunan; He, Langchong

2014-03-01

In this study, a new"heart-cutting" two-dimensional liquid chromatography method for the simultaneous determination of carbohydrate contents in milk powder was presented. In this two dimensional liquid chromatography system, a Venusil XBP-C4 analysis column was used in the first dimension ((1)D) as a pre-separation column, a ZORBAX carbohydrates analysis column was used in the second dimension ((2)D) as a final-analysis column. The whole process was completed in less than 35min without a particular sample preparation procedure. The capability of the new two dimensional HPLC method was demonstrated in the determination of carbohydrates in various brands of milk powder samples. A conventional one dimensional chromatography method was also proposed. The two proposed methods were both validated in terms of linearity, limits of detection, accuracy and precision. The comparison between the results obtained with the two methods showed that the new and completely automated two dimensional liquid chromatography method is more suitable for milk powder sample because of its online cleanup effect involved. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Adaptive frozen orbital treatment for the fragment molecular orbital method combined with density-functional tight-binding

Science.gov (United States)

Nishimoto, Yoshio; Fedorov, Dmitri G.

2018-02-01

The exactly analytic gradient is derived and implemented for the fragment molecular orbital (FMO) method combined with density-functional tight-binding (DFTB) using adaptive frozen orbitals. The response contributions which arise from freezing detached molecular orbitals on the border between fragments are computed by solving Z-vector equations. The accuracy of the energy, its gradient, and optimized structures is verified on a set of representative inorganic materials and polypeptides. FMO-DFTB is applied to optimize the structure of a silicon nano-wire, and the results are compared to those of density functional theory and experiment. FMO accelerates the DFTB calculation of a boron nitride nano-ring with 7872 atoms by a factor of 406. Molecular dynamics simulations using FMO-DFTB applied to a 10.7 μm chain of boron nitride nano-rings, consisting of about 1.2 × 106 atoms, reveal the rippling and twisting of nano-rings at room temperature.

Casimir effect in a d-dimensional flat spacetime and the cut-off method

International Nuclear Information System (INIS)

Svaiter, N.F.; Svaiter, B.F.

1989-01-01

The CasiMir efeect in a D-dimensional spacetime produced by a Hermitian massless scalar field in the presence of a pair of perfectly reflecting parallel flat plates is discussed. The exponential cut-off regularization method is employed. The regularized vacuum energy and the Casimir energy of this field are evaluated and a detailed analysis of the divergent terms in the regularized vacuum energy is carried out. The two-dimensional version of the Casimir effect is discussed by means of the same cut-off method. A comparison between the above method and the zeta function regularization procedure is presented in a way which gives the unification between these two methods in the present case. (author) [pt

RAY TRACING RENDER MENGGUNAKAN FRAGMENT ANTI ALIASING

Directory of Open Access Journals (Sweden)

Febriliyan Samopa

2008-07-01

Full Text Available Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin-top:0cm; mso-para-margin-right:0cm; mso-para-margin-bottom:10.0pt; mso-para-margin-left:0cm; line-height:115%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} Rendering is generating surface and three-dimensional effects on an object displayed on a monitor screen. Ray tracing as a rendering method that traces ray for each image pixel has a drawback, that is, aliasing (jaggies effect. There are some methods for executing anti aliasing. One of those methods is OGSS (Ordered Grid Super Sampling. OGSS is able to perform aliasing well. However, this method requires more computation time since sampling of all pixels in the image will be increased. Fragment Anti Aliasing (FAA is a new alternative method that can cope with the drawback. FAA will check the image when performing rendering to a scene. Jaggies effect is only happened at curve and gradient object. Therefore, only this part of object that will experience sampling magnification. After this sampling magnification and the pixel values are computed, then downsample is performed to retrieve the original pixel values. Experimental results show that the software can implement ray tracing well in order to form images, and it can implement FAA and OGSS technique to perform anti aliasing. In general, rendering using FAA is faster than using OGSS

Crystallization of SHARPIN using an automated two-dimensional grid screen for optimization

International Nuclear Information System (INIS)

Stieglitz, Benjamin; Rittinger, Katrin; Haire, Lesley F.

2012-01-01

The expression, purification and crystallization of an N-terminal fragment of SHARPIN are reported. Diffraction-quality crystals were obtained using a two-dimensional grid-screen seeding technique. An N-terminal fragment of human SHARPIN was recombinantly expressed in Escherichia coli, purified and crystallized. Crystals suitable for X-ray diffraction were obtained by a one-step optimization of seed dilution and protein concentration using a two-dimensional grid screen. The crystals belonged to the primitive tetragonal space group P4 3 2 1 2, with unit-cell parameters a = b = 61.55, c = 222.81 Å. Complete data sets were collected from native and selenomethionine-substituted protein crystals at 100 K to 2.6 and 2.0 Å resolution, respectively

Many Drops Interactions I: Simulation of Coalescence, Flocculation and Fragmentation of Multiple Colliding Drops with Smoothed Particle Hydrodynamics

Directory of Open Access Journals (Sweden)

Alejandro Acevedo-Malavé

2012-06-01

Full Text Available Smoothed Particle Hydrodynamics (SPH is a Lagrangian mesh-free formalism and has been useful to model continuous fluid. This formalism is employed to solve the Navier-Stokes equations by replacing the fluid with a set of particles. These particles are interpolation points from which properties of the fluid can be determined. In this study, the SPH method is applied to simulate the hydrodynamics interaction of many drops, showing some settings for the coalescence, fragmentation and flocculation problem of equally sized liquid drops in three-dimensional spaces. For small velocities the drops interact only through their deformed surfaces and the flocculation of the droplets arises. This result is very different if the collision velocity is large enough for the fragmentation of droplets takes place. We observe that for velocities around 15 mm/ms the coalescence of droplets occurs. The velocity vector fields formed inside the drops during the collision process are shown.

Prompt neutrons from {sup 236}U fission fragments

Energy Technology Data Exchange (ETDEWEB)

Boldeman, J W; Musgrove, A.R. de L.; Walsch, R L

1971-03-01

Measurements were made of prompt neutron emission in the thermal neutron fission of {sup 235}U. The mean neutron emission per fragment was obtained for particular values of the fragment mass and total kinetic energy. A direct neutron counting method was employed and a comparison made with data from previous experiments of this type. (author)

New method of three-dimensional reconstruction from two-dimensional MR data sets

International Nuclear Information System (INIS)

Wrazidlo, W.; Schneider, S.; Brambs, H.J.; Richter, G.M.; Kauffmann, G.W.; Geiger, B.; Fischer, C.

1989-01-01

In medical diagnosis and therapy, cross-sectional images are obtained by means of US, CT, or MR imaging. The authors propose a new solution to the problem of constructing a shape over a set of cross-sectional contours from two-dimensional (2D) MR data sets. The authors' method reduces the problem of constructing a shape over the cross sections to one of constructing a sequence of partial shapes, each of them connecting two cross sections lying on adjacent planes. The solution makes use of the Delaunay triangulation, which is isomorphic in that specific situation. The authors compute this Delaunay triangulation. Shape reconstruction is then achieved section by pruning Delaunay triangulations

Fragmentation cross sections outside the limiting-fragmentation regime

CERN Document Server

Sümmerer, K

2003-01-01

The empirical parametrization of fragmentation cross sections, EPAX, has been successfully applied to estimate fragment production cross sections in reactions of heavy ions at high incident energies. It is checked whether a similar parametrization can be found for proton-induced spallation around 1 GeV, the range of interest for ISOL-type RIB facilities. The validity of EPAX for medium-energy heavy-ion induced reactions is also checked. Only a few datasets are available, but in general EPAX predicts the cross sections rather well, except for fragments close to the projectile, where the experimental cross sections are found to be larger.

Two- and three-dimensional CT analysis of ankle fractures

International Nuclear Information System (INIS)

Magid, D.; Fishman, E.K.; Ney, D.R.; Kuhlman, J.E.

1988-01-01

CT with coronal and sagittal reformatting (two-dimensional CT) and animated volumetric image rendering (three-dimensional CT) was used to assess ankle fractures. Partial volume limits transaxial CT in assessments of horizontally oriented structures. Two-dimensional CT, being orthogonal to the plafond, superior mortise, talar dome, and tibial epiphysis, often provides the most clinically useful images. Two-dimensional CT is most useful in characterizing potentially confusing fractures, such as Tillaux (anterior tubercle), triplane, osteochondral talar dome, or nondisplaced talar neck fractures, and it is the best study to confirm intraarticular fragments. Two-and three-dimensional CT best indicate the percentage of articular surface involvement and best demonstrate postoperative results or complications (hardware migration, residual step-off, delayed union, DJD, AVN, etc). Animated three-dimensional images are the preferred means of integrating the two-dimensional findings for surgical planning, as these images more closely simulate the clinical problem

Finite element method for radiation heat transfer in multi-dimensional graded index medium

International Nuclear Information System (INIS)

Liu, L.H.; Zhang, L.; Tan, H.P.

2006-01-01

In graded index medium, ray goes along a curved path determined by Fermat principle, and curved ray-tracing is very difficult and complex. To avoid the complicated and time-consuming computation of curved ray trajectories, a finite element method based on discrete ordinate equation is developed to solve the radiative transfer problem in a multi-dimensional semitransparent graded index medium. Two particular test problems of radiative transfer are taken as examples to verify this finite element method. The predicted dimensionless net radiative heat fluxes are determined by the proposed method and compared with the results obtained by finite volume method. The results show that the finite element method presented in this paper has a good accuracy in solving the multi-dimensional radiative transfer problem in semitransparent graded index medium

Universality of fragment shapes.

Science.gov (United States)

Domokos, Gábor; Kun, Ferenc; Sipos, András Árpád; Szabó, Tímea

2015-03-16

The shape of fragments generated by the breakup of solids is central to a wide variety of problems ranging from the geomorphic evolution of boulders to the accumulation of space debris orbiting Earth. Although the statistics of the mass of fragments has been found to show a universal scaling behavior, the comprehensive characterization of fragment shapes still remained a fundamental challenge. We performed a thorough experimental study of the problem fragmenting various types of materials by slowly proceeding weathering and by rapid breakup due to explosion and hammering. We demonstrate that the shape of fragments obeys an astonishing universality having the same generic evolution with the fragment size irrespective of materials details and loading conditions. There exists a cutoff size below which fragments have an isotropic shape, however, as the size increases an exponential convergence is obtained to a unique elongated form. We show that a discrete stochastic model of fragmentation reproduces both the size and shape of fragments tuning only a single parameter which strengthens the general validity of the scaling laws. The dependence of the probability of the crack plan orientation on the linear extension of fragments proved to be essential for the shape selection mechanism.

A simple method for in vivo measurement of implant rod three-dimensional geometry during scoliosis surgery.

Science.gov (United States)

Salmingo, Remel A; Tadano, Shigeru; Fujisaki, Kazuhiro; Abe, Yuichiro; Ito, Manabu

2012-05-01

Scoliosis is defined as a spinal pathology characterized as a three-dimensional deformity of the spine combined with vertebral rotation. Treatment for severe scoliosis is achieved when the scoliotic spine is surgically corrected and fixed using implanted rods and screws. Several studies performed biomechanical modeling and corrective forces measurements of scoliosis correction. These studies were able to predict the clinical outcome and measured the corrective forces acting on screws, however, they were not able to measure the intraoperative three-dimensional geometry of the spinal rod. In effect, the results of biomechanical modeling might not be so realistic and the corrective forces during the surgical correction procedure were intra-operatively difficult to measure. Projective geometry has been shown to be successful in the reconstruction of a three-dimensional structure using a series of images obtained from different views. In this study, we propose a new method to measure the three-dimensional geometry of an implant rod using two cameras. The reconstruction method requires only a few parameters, the included angle θ between the two cameras, the actual length of the rod in mm, and the location of points for curve fitting. The implant rod utilized in spine surgery was used to evaluate the accuracy of the current method. The three-dimensional geometry of the rod was measured from the image obtained by a scanner and compared to the proposed method using two cameras. The mean error in the reconstruction measurements ranged from 0.32 to 0.45 mm. The method presented here demonstrated the possibility of intra-operatively measuring the three-dimensional geometry of spinal rod. The proposed method could be used in surgical procedures to better understand the biomechanics of scoliosis correction through real-time measurement of three-dimensional implant rod geometry in vivo.

Two-dimensional semi-analytic nodal method for multigroup pin power reconstruction

International Nuclear Information System (INIS)

Seung Gyou, Baek; Han Gyu, Joo; Un Chul, Lee

2007-01-01

A pin power reconstruction method applicable to multigroup problems involving square fuel assemblies is presented. The method is based on a two-dimensional semi-analytic nodal solution which consists of eight exponential terms and 13 polynomial terms. The 13 polynomial terms represent the particular solution obtained under the condition of a 2-dimensional 13 term source expansion. In order to achieve better approximation of the source distribution, the least square fitting method is employed. The 8 exponential terms represent a part of the analytically obtained homogeneous solution and the 8 coefficients are determined by imposing constraints on the 4 surface average currents and 4 corner point fluxes. The surface average currents determined from a transverse-integrated nodal solution are used directly whereas the corner point fluxes are determined during the course of the reconstruction by employing an iterative scheme that would realize the corner point balance condition. The outgoing current based corner point flux determination scheme is newly introduced. The accuracy of the proposed method is demonstrated with the L336C5 benchmark problem. (authors)

Improving the accuracy of CT dimensional metrology by a novel beam hardening correction method

International Nuclear Information System (INIS)

Zhang, Xiang; Li, Lei; Zhang, Feng; Xi, Xiaoqi; Deng, Lin; Yan, Bin

2015-01-01

Its powerful nondestructive characteristics are attracting more and more research into the study of computed tomography (CT) for dimensional metrology, which offers a practical alternative to the common measurement methods. However, the inaccuracy and uncertainty severely limit the further utilization of CT for dimensional metrology due to many factors, among which the beam hardening (BH) effect plays a vital role. This paper mainly focuses on eliminating the influence of the BH effect in the accuracy of CT dimensional metrology. To correct the BH effect, a novel exponential correction model is proposed. The parameters of the model are determined by minimizing the gray entropy of the reconstructed volume. In order to maintain the consistency and contrast of the corrected volume, a punishment term is added to the cost function, enabling more accurate measurement results to be obtained by the simple global threshold method. The proposed method is efficient, and especially suited to the case where there is a large difference in gray value between material and background. Different spheres with known diameters are used to verify the accuracy of dimensional measurement. Both simulation and real experimental results demonstrate the improvement in measurement precision. Moreover, a more complex workpiece is also tested to show that the proposed method is of general feasibility. (paper)

Inclusive breakup of three-fragment weakly bound nuclei

International Nuclear Information System (INIS)

Carlson, B.V.; Frederico, T.; Hussein, M.S.

2017-01-01

The inclusive breakup of three-fragment projectiles is discussed within a four-body spectator model. Both the elastic breakup and the non-elastic breakup are obtained in a unified framework. Originally developed in the 80's for two-fragment projectiles such as the deuteron, in this paper the theory is successfully generalized to three-fragment projectiles. The expression obtained for the inclusive cross section allows the extraction of the incomplete fusion cross section, and accordingly generalizes the surrogate method to cases such as (t, p) and (t, n) reactions. It is found that two-fragment correlations inside the projectile affect in a conspicuous way the elastic breakup cross section. The inclusive non-elastic breakup cross section is calculated and is found to contain the contribution of a three-body absorption term that is also strongly influenced by the two-fragment correlations. This latter cross section contains the so-called incomplete fusion where more than one compound nuclei are formed. Our theory describes both stable weakly bound three-fragment projectiles and unstable ones such as the Borromean nuclei.

Inclusive breakup of three-fragment weakly bound nuclei

Energy Technology Data Exchange (ETDEWEB)

Carlson, B.V.; Frederico, T. [Instituto Tecnológico de Aeronáutica, DCTA, 12.228-900 São José dos Campos, SP (Brazil); Hussein, M.S., E-mail: hussein@if.usp.br [Instituto Tecnológico de Aeronáutica, DCTA, 12.228-900 São José dos Campos, SP (Brazil); Instituto de Estudos Avançados, Universidade de São Paulo, C.P. 72012, 05508-970 São Paulo, SP (Brazil); Instituto de Física, Universidade de São Paulo, C.P. 66318, 05314-970 São Paulo, SP (Brazil)

2017-04-10

The inclusive breakup of three-fragment projectiles is discussed within a four-body spectator model. Both the elastic breakup and the non-elastic breakup are obtained in a unified framework. Originally developed in the 80's for two-fragment projectiles such as the deuteron, in this paper the theory is successfully generalized to three-fragment projectiles. The expression obtained for the inclusive cross section allows the extraction of the incomplete fusion cross section, and accordingly generalizes the surrogate method to cases such as (t, p) and (t, n) reactions. It is found that two-fragment correlations inside the projectile affect in a conspicuous way the elastic breakup cross section. The inclusive non-elastic breakup cross section is calculated and is found to contain the contribution of a three-body absorption term that is also strongly influenced by the two-fragment correlations. This latter cross section contains the so-called incomplete fusion where more than one compound nuclei are formed. Our theory describes both stable weakly bound three-fragment projectiles and unstable ones such as the Borromean nuclei.

[Detection of UGT1A1*28 Polymorphism Using Fragment Analysis].

Science.gov (United States)

Huang, Ying; Su, Jian; Huang, Xiaosui; Lu, Danxia; Xie, Zhi; Yang, Suqing; Guo, Weibang; Lv, Zhiyi; Wu, Hongsui; Zhang, Xuchao

2017-12-20

Uridine-diphosphoglucuronosyl transferase 1A1 (UGT1A1), UGT1A1*28 polymorphism can reduce UGT1A1 enzymatic activity, which may lead to severe toxicities in patients who receive irinotecan. This study tries to build a fragment analysis method to detect UGT1A1*28 polymorphism. A total of 286 blood specimens from the lung cancer patients who were hospitalized in Guangdong General Hospital between April 2014 to May 2015 were detected UGT1A1*28 polymorphism by fragment analysis method. Comparing with Sanger sequencing, precision and accuracy of the fragment analysis method were 100%. Of the 286 patients, 236 (82.5% harbored TA6/6 genotype, 48 (16.8%) TA 6/7 genotype and 2 (0.7%) TA7/7 genotype. Our data suggest hat the fragment analysis method is robust for detecting UGT1A1*28 polymorphism in clinical practice. It's simple, time-saving, and easy-to-carry.

On two flexible methods of 2-dimensional regression analysis

Czech Academy of Sciences Publication Activity Database

Volf, Petr

2012-01-01

Roč. 18, č. 4 (2012), s. 154-164 ISSN 1803-9782 Grant - others:GA ČR(CZ) GAP209/10/2045 Institutional support: RVO:67985556 Keywords : regression analysis * Gordon surface * prediction error * projection pursuit Subject RIV: BB - Applied Statistics, Operational Research http://library.utia.cas.cz/separaty/2013/SI/volf-on two flexible methods of 2-dimensional regression analysis.pdf

Direct-coupled-ray method for design-oriented three-dimensional transport analysis

International Nuclear Information System (INIS)

Bucholz, J.A.; Poncelet, C.G.

1977-01-01

A fast three-dimensional design-oriented transport method has been developed for the solution of both neutron and gamma transport problems. It combines a nodal approach with analytic integral transport to achieve relative speed and accuracy. An analytic solution is obtained for the angular flux in each of the 14 directions defined by the six faces and eight corners of a cubic mesh block. The scheme used to accommodate high-order anisotropic scattering is based on the formulation of ray-to-ray scattering probabilities in an integral sense. A variable mesh approximation has also been introduced to provide greater flexibility. The details of a direct-coupled-ray (DCR) → P 1 conversion technique have been developed but not yet implemented. The DCR method, as implemented in the TRANS3 code, has been used in a number of liquid-metal fast breeder reactor shielding applications. These included a one-dimensional deep penetration configuration and one-, two-, and three dimensional representations of the lower axial shield of the Clinch River Breeder Reactor. Comparisons with ANISN and DOT-III solutions indicated good to excellent agreement in most situations

Fragment screening of cyclin G-associated kinase by weak affinity chromatography.

Science.gov (United States)

Meiby, Elinor; Knapp, Stefan; Elkins, Jonathan M; Ohlson, Sten

2012-11-01

Fragment-based drug discovery (FBDD) has become a new strategy for drug discovery where lead compounds are evolved from small molecules. These fragments form low affinity interactions (dissociation constant (K(D)) = mM - μM) with protein targets, which require fragment screening methods of sufficient sensitivity. Weak affinity chromatography (WAC) is a promising new technology for fragment screening based on selective retention of fragments by a drug target. Kinases are a major pharmaceutical target, and FBDD has been successfully applied to several of these targets. In this work, we have demonstrated the potential to use WAC in combination with mass spectrometry (MS) detection for fragment screening of a kinase target-cyclin G-associated kinase (GAK). One hundred seventy fragments were selected for WAC screening by virtual screening of a commercial fragment library against the ATP-binding site of five different proteins. GAK protein was immobilized on a capillary HPLC column, and compound binding was characterized by frontal affinity chromatography. Compounds were screened in sets of 13 or 14, in combination with MS detection for enhanced throughput. Seventy-eight fragments (46 %) with K(D) < 200 μM were detected, including a few highly efficient GAK binders (K(D) of 2 μM; ligand efficiency = 0.51). Of special interest is that chiral screening by WAC may be possible, as two stereoisomeric fragments, which both contained one chiral center, demonstrated twin peaks. This ability, in combination with the robustness, sensitivity, and simplicity of WAC makes it a new method for fragment screening of considerable potential.

Gene prediction in metagenomic fragments: A large scale machine learning approach

Directory of Open Access Journals (Sweden)

Morgenstern Burkhard

2008-04-01

Full Text Available Abstract Background Metagenomics is an approach to the characterization of microbial genomes via the direct isolation of genomic sequences from the environment without prior cultivation. The amount of metagenomic sequence data is growing fast while computational methods for metagenome analysis are still in their infancy. In contrast to genomic sequences of single species, which can usually be assembled and analyzed by many available methods, a large proportion of metagenome data remains as unassembled anonymous sequencing reads. One of the aims of all metagenomic sequencing projects is the identification of novel genes. Short length, for example, Sanger sequencing yields on average 700 bp fragments, and unknown phylogenetic origin of most fragments require approaches to gene prediction that are different from the currently available methods for genomes of single species. In particular, the large size of metagenomic samples requires fast and accurate methods with small numbers of false positive predictions. Results We introduce a novel gene prediction algorithm for metagenomic fragments based on a two-stage machine learning approach. In the first stage, we use linear discriminants for monocodon usage, dicodon usage and translation initiation sites to extract features from DNA sequences. In the second stage, an artificial neural network combines these features with open reading frame length and fragment GC-content to compute the probability that this open reading frame encodes a protein. This probability is used for the classification and scoring of gene candidates. With large scale training, our method provides fast single fragment predictions with good sensitivity and specificity on artificially fragmented genomic DNA. Additionally, this method is able to predict translation initiation sites accurately and distinguishes complete from incomplete genes with high reliability. Conclusion Large scale machine learning methods are well-suited for gene

One New Method to Generate 3-Dimensional Virtual Mannequin

Science.gov (United States)

Xiu-jin, Shi; Zhi-jun, Wang; Jia-jin, Le

The personal virtual mannequin is very important in electronic made to measure (eMTM) system. There is one new easy method to generate personal virtual mannequin. First, the characteristic information of customer's body is got from two photos. Secondly, some human body part templates corresponding with the customer are selected from the templates library. Thirdly, these templates are modified and assembled according to certain rules to generate a personalized 3-dimensional human, and then the virtual mannequin is realized. Experimental result shows that the method is easy and feasible.

Anomalous nuclear fragments

International Nuclear Information System (INIS)

Karmanov, V.A.

1983-01-01

Experimental data are given, the status of anomalon problem is discussed, theoretical approaches to this problem are outlined. Anomalons are exotic objects formed following fragmentation of nuclei-targets under the effect of nuclei - a beam at the energy of several GeV/nucleon. These nuclear fragments have an anomalously large cross section of interaction and respectively, small free path, considerably shorter than primary nuclei have. The experimental daa are obtained in accelerators following irradiation of nuclear emulsions by 16 O, 56 Fe, 40 Ar beams, as well as propane by 12 C beams. The experimental data testify to dependence of fragment free path on the distance L from the point of the fragment formation. A decrease in the fragment free path is established more reliably than its dependence on L. The problem of the anomalon existence cannot be yet considered resolved. Theoretical models suggested for explanation of anomalously large cross sections of nuclear fragment interaction are variable and rather speculative

A novel method for in Situ detection of hydrolyzable casein fragments in a cheese matrix by antibody phage display technique and CLSM

DEFF Research Database (Denmark)

Duan, Zhi; Brüggemann, Dagmar Adeline; Siegumfeldt, Henrik

2009-01-01

three small synthetic peptides of the alpha(s1)-casein sequence. These peptides traverse enzymatic cleavage sites of casein during cheese ripening. The specificity of the generated anti-peptide antibodies was determined by ELISA and Western blot. Finally, an immunofluorescent labeling protocol......A novel method to monitor in situ hydrolyzable casein fragments during cheese ripening by using immunofluorescent labeling and confocal laser scanning microscopy (CLSM) was developed. Monoclonal single chain variable fragments of antibody (scFvs) were generated by antibody phage display toward...

Modelling of the PELE fragmentation dynamics

Science.gov (United States)

Verreault, J.

2014-05-01

The Penetrator with Enhanced Lateral Effect (PELE) is a type of explosive-free projectile that undergoes radial fragmentation upon an impact with a target plate. This type of projectile is composed of a brittle cylindrical shell (the jacket) filled in its core with a material characterized with a large Poisson's ratio. Upon an impact with a target, the axial compression causes the filling to expand in the radial direction. However, due to the brittleness of the jacket material, very little radial deformation can occur which creates a radial stress between the two materials and a hoop stress in the jacket. Fragmentation of the jacket occurs if the hoop stress exceeds the material's ultimate stress. The PELE fragmentation dynamics is explored via Finite-Element Method (FEM) simulations using the Autodyn explicit dynamics hydrocode. The numerical results are compared with an analytical model based on wave interactions, as well as with the experimental investigation of Paulus and Schirm (1996). The comparison is based on the mechanical stress in the filling and the qualitative fragmentation of the jacket.

Modelling of the PELE fragmentation dynamics

International Nuclear Information System (INIS)

Verreault, J

2014-01-01

The Penetrator with Enhanced Lateral Effect (PELE) is a type of explosive-free projectile that undergoes radial fragmentation upon an impact with a target plate. This type of projectile is composed of a brittle cylindrical shell (the jacket) filled in its core with a material characterized with a large Poisson's ratio. Upon an impact with a target, the axial compression causes the filling to expand in the radial direction. However, due to the brittleness of the jacket material, very little radial deformation can occur which creates a radial stress between the two materials and a hoop stress in the jacket. Fragmentation of the jacket occurs if the hoop stress exceeds the material's ultimate stress. The PELE fragmentation dynamics is explored via Finite-Element Method (FEM) simulations using the Autodyn explicit dynamics hydrocode. The numerical results are compared with an analytical model based on wave interactions, as well as with the experimental investigation of Paulus and Schirm (1996). The comparison is based on the mechanical stress in the filling and the qualitative fragmentation of the jacket.

The fragmentation of proto-globular clusters. I. Thermal instabilities

International Nuclear Information System (INIS)

Murray, S.D.; Lin, D.N.C.

1989-01-01

The metal abundances among the stars within a typical globular cluster are remarkably homogeneous. This indicates that star formation in these systems was a globally coordinated event which occurred over a time span less than or comparable to the collapse time scale of the cluster. This issue is addressed by assuming that the fragmentation of a proto-globular cluster cloud proceeded in two steps. In the first step, thermal instability led to the rapid growth of initial fluctuations. This led to a large contrast in the dynamical time scales between the perturbations and the parent cloud, and the perturbations then underwent gravitational instabilities on short time scales. This process is modeled using one-dimensional hydrodynamic simulations of clouds both with and without external heat sources and self-gravity. The models include the effects of a non-equilibrium H2 abundance. The results indicate that fragmentation can occur on time scales significantly less than the dynamical time scale of the parent cloud. 21 refs

A SPH Method-based Numerical Simulation of the Space Debris Fragments Interaction with Spacecraft Structure Components

Directory of Open Access Journals (Sweden)

V. V. Zelentsov

2017-01-01

Full Text Available Significant amount of space debris available in the near-Earth space is a reason to protect space vehicles from the fragments of space debris. Existing empirical calculation methods do not allow us to estimate quality of developed protection. Experimental verification of protection requires complex and expensive installations that do not allow having a desirable impact velocity. The article proposes to use the ANSYS AUTODYN software environment – a software complex of the nonlinear dynamic analysis to evaluate quality of developed protection. The ANSYS AUTODYN environment is based on the integration methods of a system of equations of continuum mechanics. The SPH (smoothed particle method method is used as a solver. The SPH method is based on the area of sampling by a finite set of the Lagrangian particles that can be represented as the elementary volumes of the medium. In modeling the targets were under attack of 2 and 3 mm spheres and cylinders with 2 mm in bottom diameter and with generator of 2 and 3 mm. The apheres and cylinders are solid and hollow, with a wall thickness of 0.5 mm. The impact velocity of the particles with a target was assumed to be 7.5 km / s. The number of integration cycles in all cases of calculation was assumed to be 1000. The rate of flying debris fragments of the target material as a function of the h / d ratio (h - the thickness of the target, / d - the diameter of a sphere or a cylinder end is obtained. In simulation the sample picture obtained coincides both with results of experimental study carried out at the Tomsk State Technical University and  with results described in the literature.

A method for measurements of neutral fragments kinetic energies released to a specific dissociation threshold: optical translational spectroscopy

International Nuclear Information System (INIS)

Roney, A.; Frigon, C.; Larzilliere, M.

1999-01-01

The optical translational spectroscopy technique, based on the principles of fast ion beam laser spectroscopy (FIBLAS) and translational spectroscopy, allows the kinetic energies study of neutral fragments released through free dissociation of a neutral molecule. This method presents interesting features such as near-threshold energy measurements and selection of a specific dissociation limit. The fragments resulting from free dissociation (not induced) of neutral molecules, produced by charge exchange processes with a fast ion beam, are probed by laser radiation. Monitoring of the laser-induced fluorescence allows high-resolution spectra due to the kinematic compression of the velocity spread. Measurements of kinetic energies released to the second limit of dissociation H(1s) + H(2l) of H 2 are put forth and compared with those obtained by means of off-axis translational spectroscopy

Metagenome Fragment Classification Using -Mer Frequency Profiles

Directory of Open Access Journals (Sweden)

Gail Rosen

2008-01-01

Full Text Available A vast amount of microbial sequencing data is being generated through large-scale projects in ecology, agriculture, and human health. Efficient high-throughput methods are needed to analyze the mass amounts of metagenomic data, all DNA present in an environmental sample. A major obstacle in metagenomics is the inability to obtain accuracy using technology that yields short reads. We construct the unique -mer frequency profiles of 635 microbial genomes publicly available as of February 2008. These profiles are used to train a naive Bayes classifier (NBC that can be used to identify the genome of any fragment. We show that our method is comparable to BLAST for small 25 bp fragments but does not have the ambiguity of BLAST's tied top scores. We demonstrate that this approach is scalable to identify any fragment from hundreds of genomes. It also performs quite well at the strain, species, and genera levels and achieves strain resolution despite classifying ubiquitous genomic fragments (gene and nongene regions. Cross-validation analysis demonstrates that species-accuracy achieves 90% for highly-represented species containing an average of 8 strains. We demonstrate that such a tool can be used on the Sargasso Sea dataset, and our analysis shows that NBC can be further enhanced.

Homotopy decomposition method for solving one-dimensional time-fractional diffusion equation

Science.gov (United States)

Abuasad, Salah; Hashim, Ishak

2018-04-01

In this paper, we present the homotopy decomposition method with a modified definition of beta fractional derivative for the first time to find exact solution of one-dimensional time-fractional diffusion equation. In this method, the solution takes the form of a convergent series with easily computable terms. The exact solution obtained by the proposed method is compared with the exact solution obtained by using fractional variational homotopy perturbation iteration method via a modified Riemann-Liouville derivative.

A multi-method analysis of forest fragmentation and loss: The case ...

African Journals Online (AJOL)

Lazie

2014-02-01

Feb 1, 2014 ... mented, where the fragmented landscape represents the endpoint of the ... For example, some plants can only be pollinated by a certain kind of bird or ... tropical forests, and of the remainder, temperate and boreal forests ...

The transmission probability method in one-dimensional cylindrical geometry

International Nuclear Information System (INIS)

Rubin, I.E.

1983-01-01

The collision probability method widely used in solving the problems of neutron transpopt in a reactor cell is reliable for simple cells with small number of zones. The increase of the number of zones and also taking into account the anisotropy of scattering greatly increase the scope of calculations. In order to reduce the time of calculation the transmission probability method is suggested to be used for flux calculation in one-dimensional cylindrical geometry taking into account the scattering anisotropy. The efficiency of the suggested method is verified using the one-group calculations for cylindrical cells. The use of the transmission probability method allows to present completely angular and spatial dependences is neutrons distributions without the increase in the scope of calculations. The method is especially effective in solving the multi-group problems

A new method for information retrieval in two-dimensional grating-based X-ray phase contrast imaging

International Nuclear Information System (INIS)

Wang Zhi-Li; Gao Kun; Chen Jian; Ge Xin; Tian Yang-Chao; Wu Zi-Yu; Zhu Pei-Ping

2012-01-01

Grating-based X-ray phase contrast imaging has been demonstrated to be an extremely powerful phase-sensitive imaging technique. By using two-dimensional (2D) gratings, the observable contrast is extended to two refraction directions. Recently, we have developed a novel reverse-projection (RP) method, which is capable of retrieving the object information efficiently with one-dimensional (1D) grating-based phase contrast imaging. In this contribution, we present its extension to the 2D grating-based X-ray phase contrast imaging, named the two-dimensional reverse-projection (2D-RP) method, for information retrieval. The method takes into account the nonlinear contributions of two refraction directions and allows the retrieval of the absorption, the horizontal and the vertical refraction images. The obtained information can be used for the reconstruction of the three-dimensional phase gradient field, and for an improved phase map retrieval and reconstruction. Numerical experiments are carried out, and the results confirm the validity of the 2D-RP method

Telomere Restriction Fragment (TRF) Analysis.

Science.gov (United States)

Mender, Ilgen; Shay, Jerry W

2015-11-20

While telomerase is expressed in ~90% of primary human tumors, most somatic tissue cells except transiently proliferating stem-like cells do not have detectable telomerase activity (Shay and Wright, 1996; Shay and Wright, 2001). Telomeres progressively shorten with each cell division in normal cells, including proliferating stem-like cells, due to the end replication (lagging strand synthesis) problem and other causes such as oxidative damage, therefore all somatic cells have limited cell proliferation capacity (Hayflick limit) (Hayflick and Moorhead, 1961; Olovnikov, 1973). The progressive telomere shortening eventually leads to growth arrest in normal cells, which is known as replicative senescence (Shay et al. , 1991). Once telomerase is activated in cancer cells, telomere length is stabilized by the addition of TTAGGG repeats to the end of chromosomes, thus enabling the limitless continuation of cell division (Shay and Wright, 1996; Shay and Wright, 2001). Therefore, the link between aging and cancer can be partially explained by telomere biology. There are many rapid and convenient methods to study telomere biology such as Telomere Restriction Fragment (TRF), Telomere Repeat Amplification Protocol (TRAP) (Mender and Shay, 2015b) and Telomere dysfunction Induced Foci (TIF) analysis (Mender and Shay, 2015a). In this protocol paper we describe Telomere Restriction Fragment (TRF) analysis to determine average telomeric length of cells. Telomeric length can be indirectly measured by a technique called Telomere Restriction Fragment analysis (TRF). This technique is a modified Southern blot, which measures the heterogeneous range of telomere lengths in a cell population using the length distribution of the terminal restriction fragments (Harley et al. , 1990; Ouellette et al. , 2000). This method can be used in eukaryotic cells. The description below focuses on the measurement of human cancer cells telomere length. The principle of this method relies on the lack of

A linear relationship between crystal size and fragment binding time observed crystallographically: implications for fragment library screening using acoustic droplet ejection.

Directory of Open Access Journals (Sweden)

Krystal Cole

Full Text Available High throughput screening technologies such as acoustic droplet ejection (ADE greatly increase the rate at which X-ray diffraction data can be acquired from crystals. One promising high throughput screening application of ADE is to rapidly combine protein crystals with fragment libraries. In this approach, each fragment soaks into a protein crystal either directly on data collection media or on a moving conveyor belt which then delivers the crystals to the X-ray beam. By simultaneously handling multiple crystals combined with fragment specimens, these techniques relax the automounter duty-cycle bottleneck that currently prevents optimal exploitation of third generation synchrotrons. Two factors limit the speed and scope of projects that are suitable for fragment screening using techniques such as ADE. Firstly, in applications where the high throughput screening apparatus is located inside the X-ray station (such as the conveyor belt system described above, the speed of data acquisition is limited by the time required for each fragment to soak into its protein crystal. Secondly, in applications where crystals are combined with fragments directly on data acquisition media (including both of the ADE methods described above, the maximum time that fragments have to soak into crystals is limited by evaporative dehydration of the protein crystals during the fragment soak. Here we demonstrate that both of these problems can be minimized by using small crystals, because the soak time required for a fragment hit to attain high occupancy depends approximately linearly on crystal size.

A new method for three-dimensional laparoscopic ultrasound model reconstruction

DEFF Research Database (Denmark)

Fristrup, C W; Pless, T; Durup, J

2004-01-01

BACKGROUND: Laparoscopic ultrasound is an important modality in the staging of gastrointestinal tumors. Correct staging depends on good spatial understanding of the regional tumor infiltration. Three-dimensional (3D) models may facilitate the evaluation of tumor infiltration. The aim of the study...... accuracy of the new method was tested ex vivo, and the clinical feasibility was tested on a small series of patients. RESULTS: Both electromagnetic tracked reconstructions and the new 3D method gave good volumetric information with no significant difference. Clinical use of the new 3D method showed...

Production of a phage-displayed single chain variable fragment ...

African Journals Online (AJOL)

Purpose: To develop specific single chain variable fragments (scFv) against infectious bursal disease virus (IBDV) via phage display technology. Methods: Purified viruses were initially applied for iterative panning rounds of scFv phage display libraries. The binding ability of the selected scFv antibody fragments against the ...

A Computational/Experimental Platform for Investigating Three-Dimensional Puzzle Solving of Comminuted Articular Fractures

Science.gov (United States)

Thomas, Thaddeus P.; Anderson, Donald D.; Willis, Andrew R.; Liu, Pengcheng; Frank, Matthew C.; Marsh, J. Lawrence; Brown, Thomas D.

2011-01-01

Reconstructing highly comminuted articular fractures poses a difficult surgical challenge, akin to solving a complicated three-dimensional (3D) puzzle. Pre-operative planning using CT is critically important, given the desirability of less invasive surgical approaches. The goal of this work is to advance 3D puzzle solving methods toward use as a pre-operative tool for reconstructing these complex fractures. Methodology for generating typical fragmentation/dispersal patterns was developed. Five identical replicas of human distal tibia anatomy, were machined from blocks of high-density polyetherurethane foam (bone fragmentation surrogate), and were fractured using an instrumented drop tower. Pre- and post-fracture geometries were obtained using laser scans and CT. A semi-automatic virtual reconstruction computer program aligned fragment native (non-fracture) surfaces to a pre-fracture template. The tibias were precisely reconstructed with alignment accuracies ranging from 0.03-0.4mm. This novel technology has potential to significantly enhance surgical techniques for reconstructing comminuted intra-articular fractures, as illustrated for a representative clinical case. PMID:20924863

Dynamics and instabilities in nuclear fragmentation

International Nuclear Information System (INIS)

Colonna, M.; Guarnera, A.; Di Toro, M.; Latora, V.; Smerzi, A.; Catania Univ.

1993-01-01

A general procedure to identify instability regions which lead to multifragmentation events is presented. The method covers all possible sources of dynamical instabilities. Informations on the instability point, like the time when the nuclear system enters the critical region, the most unstable modes and the time constant of the exponential growing of the relative variances, are deduced without any numerical bias. Important memory effects in the fragmentation pattern are revealed. Some hints towards a fully dynamical picture of fragmentation processes are finally suggested. (author) 7 refs., 3 figs

Gene Prediction in Metagenomic Fragments with Deep Learning

Directory of Open Access Journals (Sweden)

Shao-Wu Zhang

2017-01-01

Full Text Available Next generation sequencing technologies used in metagenomics yield numerous sequencing fragments which come from thousands of different species. Accurately identifying genes from metagenomics fragments is one of the most fundamental issues in metagenomics. In this article, by fusing multifeatures (i.e., monocodon usage, monoamino acid usage, ORF length coverage, and Z-curve features and using deep stacking networks learning model, we present a novel method (called Meta-MFDL to predict the metagenomic genes. The results with 10 CV and independent tests show that Meta-MFDL is a powerful tool for identifying genes from metagenomic fragments.

A GPU-based calculation using the three-dimensional FDTD method for electromagnetic field analysis.

Science.gov (United States)

Nagaoka, Tomoaki; Watanabe, Soichi

2010-01-01

Numerical simulations with the numerical human model using the finite-difference time domain (FDTD) method have recently been performed frequently in a number of fields in biomedical engineering. However, the FDTD calculation runs too slowly. We focus, therefore, on general purpose programming on the graphics processing unit (GPGPU). The three-dimensional FDTD method was implemented on the GPU using Compute Unified Device Architecture (CUDA). In this study, we used the NVIDIA Tesla C1060 as a GPGPU board. The performance of the GPU is evaluated in comparison with the performance of a conventional CPU and a vector supercomputer. The results indicate that three-dimensional FDTD calculations using a GPU can significantly reduce run time in comparison with that using a conventional CPU, even a native GPU implementation of the three-dimensional FDTD method, while the GPU/CPU speed ratio varies with the calculation domain and thread block size.

New method of 2-dimensional metrology using mask contouring

Science.gov (United States)

Matsuoka, Ryoichi; Yamagata, Yoshikazu; Sugiyama, Akiyuki; Toyoda, Yasutaka

2008-10-01

We have developed a new method of accurately profiling and measuring of a mask shape by utilizing a Mask CD-SEM. The method is intended to realize high accuracy, stability and reproducibility of the Mask CD-SEM adopting an edge detection algorithm as the key technology used in CD-SEM for high accuracy CD measurement. In comparison with a conventional image processing method for contour profiling, this edge detection method is possible to create the profiles with much higher accuracy which is comparable with CD-SEM for semiconductor device CD measurement. This method realizes two-dimensional metrology for refined pattern that had been difficult to measure conventionally by utilizing high precision contour profile. In this report, we will introduce the algorithm in general, the experimental results and the application in practice. As shrinkage of design rule for semiconductor device has further advanced, an aggressive OPC (Optical Proximity Correction) is indispensable in RET (Resolution Enhancement Technology). From the view point of DFM (Design for Manufacturability), a dramatic increase of data processing cost for advanced MDP (Mask Data Preparation) for instance and surge of mask making cost have become a big concern to the device manufacturers. This is to say, demands for quality is becoming strenuous because of enormous quantity of data growth with increasing of refined pattern on photo mask manufacture. In the result, massive amount of simulated error occurs on mask inspection that causes lengthening of mask production and inspection period, cost increasing, and long delivery time. In a sense, it is a trade-off between the high accuracy RET and the mask production cost, while it gives a significant impact on the semiconductor market centered around the mask business. To cope with the problem, we propose the best method of a DFM solution using two-dimensional metrology for refined pattern.

FragIt: a tool to prepare input files for fragment based quantum chemical calculations.

Directory of Open Access Journals (Sweden)

Casper Steinmann

Full Text Available Near linear scaling fragment based quantum chemical calculations are becoming increasingly popular for treating large systems with high accuracy and is an active field of research. However, it remains difficult to set up these calculations without expert knowledge. To facilitate the use of such methods, software tools need to be available to support these methods and help to set up reasonable input files which will lower the barrier of entry for usage by non-experts. Previous tools relies on specific annotations in structure files for automatic and successful fragmentation such as residues in PDB files. We present a general fragmentation methodology and accompanying tools called FragIt to help setup these calculations. FragIt uses the SMARTS language to locate chemically appropriate fragments in large structures and is applicable to fragmentation of any molecular system given suitable SMARTS patterns. We present SMARTS patterns of fragmentation for proteins, DNA and polysaccharides, specifically for D-galactopyranose for use in cyclodextrins. FragIt is used to prepare input files for the Fragment Molecular Orbital method in the GAMESS program package, but can be extended to other computational methods easily.

Computational Methods for Inviscid and Viscous Two-and-Three-Dimensional Flow Fields.

Science.gov (United States)

1975-01-01

Difference Equations Over a Network, Watson Sei. Comput. Lab. Report, 19U9. 173- Isaacson, E. and Keller, H. B., Analaysis of Numerical Methods...element method has given a new impulse to the old mathematical theory of multivariate interpolation. We first study the one-dimensional case, which

Newton-sor iterative method for solving the two-dimensional porous ...

African Journals Online (AJOL)

In this paper, we consider the application of the Newton-SOR iterative method in obtaining the approximate solution of the two-dimensional porous medium equation (2D PME). The nonlinear finite difference approximation equation to the 2D PME is derived by using the implicit finite difference scheme. The developed ...

Nuclear fragmentation

International Nuclear Information System (INIS)

Chung, K.C.

1989-01-01

An introduction to nuclear fragmentation, with emphasis in percolation ideas, is presented. The main theoretical models are discussed and as an application, the uniform expansion approximation is presented and the statistical multifragmentation model is used to calculate the fragment energy spectra. (L.C.)

Development of 2-D/1-D fusion method for three-dimensional whole-core heterogeneous neutron transport calculations

International Nuclear Information System (INIS)

Lee, Gil Soo

2006-02-01

To describe power distribution and multiplication factor of a reactor core accurately, it is necessary to perform calculations based on neutron transport equation considering heterogeneous geometry and scattering angles. These calculations require very heavy calculations and were nearly impossible with computers of old days. From the limitation of computing power, traditional approach of reactor core design consists of heterogeneous transport calculation in fuel assembly level and whole core diffusion nodal calculation with assembly homogenized properties, resulting from fuel assembly transport calculation. This approach may be effective in computation time, but it gives less accurate results for highly heterogeneous problems. As potential for whole core heterogeneous transport calculation became more feasible owing to rapid development of computing power during last several years, the interests in two and three dimensional whole core heterogeneous transport calculations by deterministic method are increased. For two dimensional calculation, there were several successful approaches using even parity transport equation with triangular meshes, S N method with refined rectangular meshes, the method of characteristics (MOC) with unstructured meshes, and so on. The work in this thesis originally started from the two dimensional whole core heterogeneous transport calculation by using MOC. After successful achievement in two dimensional calculation, there were efforts in three-dimensional whole-core heterogeneous transport calculation using MOC. Since direct extension to three dimensional calculation of MOC requires too much computing power, indirect approach to three dimensional calculation was considered.Thus, 2D/1D fusion method for three dimensional heterogeneous transport calculation was developed and successfully implemented in a computer code. The 2D/1D fusion method is synergistic combination of the MOC for radial 2-D calculation and S N -like methods for axial 1

Predicting Flavin and Nicotinamide Adenine Dinucleotide-Binding Sites in Proteins Using the Fragment Transformation Method

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Chih-Hao Lu

2015-01-01

Full Text Available We developed a computational method to identify NAD- and FAD-binding sites in proteins. First, we extracted from the Protein Data Bank structures of proteins that bind to at least one of these ligands. NAD-/FAD-binding residue templates were then constructed by identifying binding residues through the ligand-binding database BioLiP. The fragment transformation method was used to identify structures within query proteins that resembled the ligand-binding templates. By comparing residue types and their relative spatial positions, potential binding sites were identified and a ligand-binding potential for each residue was calculated. Setting the false positive rate at 5%, our method predicted NAD- and FAD-binding sites at true positive rates of 67.1% and 68.4%, respectively. Our method provides excellent results for identifying FAD- and NAD-binding sites in proteins, and the most important is that the requirement of conservation of residue types and local structures in the FAD- and NAD-binding sites can be verified.

Modeling of biologically motivated self-learning equivalent-convolutional recurrent-multilayer neural structures (BLM_SL_EC_RMNS) for image fragments clustering and recognition

Science.gov (United States)

Krasilenko, Vladimir G.; Lazarev, Alexander A.; Nikitovich, Diana V.

2018-03-01

The biologically-motivated self-learning equivalence-convolutional recurrent-multilayer neural structures (BLM_SL_EC_RMNS) for fragments images clustering and recognition will be discussed. We shall consider these neural structures and their spatial-invariant equivalental models (SIEMs) based on proposed equivalent two-dimensional functions of image similarity and the corresponding matrix-matrix (or tensor) procedures using as basic operations of continuous logic and nonlinear processing. These SIEMs can simply describe the signals processing during the all training and recognition stages and they are suitable for unipolar-coding multilevel signals. The clustering efficiency in such models and their implementation depends on the discriminant properties of neural elements of hidden layers. Therefore, the main models and architecture parameters and characteristics depends on the applied types of non-linear processing and function used for image comparison or for adaptive-equivalent weighing of input patterns. We show that these SL_EC_RMNSs have several advantages, such as the self-study and self-identification of features and signs of the similarity of fragments, ability to clustering and recognize of image fragments with best efficiency and strong mutual correlation. The proposed combined with learning-recognition clustering method of fragments with regard to their structural features is suitable not only for binary, but also color images and combines self-learning and the formation of weight clustered matrix-patterns. Its model is constructed and designed on the basis of recursively continuous logic and nonlinear processing algorithms and to k-average method or method the winner takes all (WTA). The experimental results confirmed that fragments with a large numbers of elements may be clustered. For the first time the possibility of generalization of these models for space invariant case is shown. The experiment for an images of different dimensions (a reference

Advanced numerical methods for three dimensional two-phase flow calculations in PWR

International Nuclear Information System (INIS)

Toumi, I.; Gallo, D.; Royer, E.

1997-01-01

This paper is devoted to new numerical methods developed for three dimensional two-phase flow calculations. These methods are finite volume numerical methods. They are based on an extension of Roe's approximate Riemann solver to define convective fluxes versus mean cell quantities. To go forward in time, a linearized conservative implicit integrating step is used, together with a Newton iterative method. We also present here some improvements performed to obtain a fully implicit solution method that provides fast running steady state calculations. This kind of numerical method, which is widely used for fluid dynamic calculations, is proved to be very efficient for the numerical solution to two-phase flow problems. This numerical method has been implemented for the three dimensional thermal-hydraulic code FLICA-4 which is mainly dedicated to core thermal-hydraulic transient and steady-state analysis. Hereafter, we will also find some results obtained for the EPR reactor running in a steady-state at 60% of nominal power with 3 pumps out of 4, and a thermal-hydraulic core analysis for a 1300 MW PWR at low flow steam-line-break conditions. (author)

Production and characterization of anti-human IgG F(ab')2 antibody fragment.

Science.gov (United States)

Valedkarimi, Zahra; Nasiri, Hadi; Aghebati-Maleki, Leili; Abdolalizadeh, Jalal; Esparvarinha, Mojghan; Majidi, Jafar

2018-04-10

In present study an optimized protocol for the separation of antibodies into antigen-binding fragments F(ab')2 using pepsin digestion was investigated. The production of these fragments is a consequential step in the development of medical research, treatment and diagnosis. For production of polyclonal antibody rabbit received antigen in four steps. The rabbit serum at 1/128000 dilution showed high absorbance in reaction with human IgG at the designed ELISA method. Rabbit IgG was purified by Ion-Exchange Chromatography (IEC) method. Purity was assessed by SDS-PAGE method. In non-reduced condition only one band was seen in about 150 kDa MW position and in reduced form, two bands were seen in 50 and 25 kDa MW positions. Rabbit IgG was digested by pepsin enzyme. The antibody fragments solution was applied to Gel filtration column to isolate the F(ab')2. Non-reduced SDS-PAGE for determining the purity of F(ab')2 fragment resulted in one band in 100 kDa corresponds to F(ab')2 fragment and a band in 150 kDa MW position corresponds to undigested IgG antibodies. The activities of FITC conjugated F(ab')2 fragment and commercial ones were compared using flowcytometry method. The activity results implied that the FITC conjugated- anti human F(ab')2 fragment worked as efficiently as the commercial one.

Advances in fragment-based drug discovery platforms.

Science.gov (United States)

Orita, Masaya; Warizaya, Masaichi; Amano, Yasushi; Ohno, Kazuki; Niimi, Tatsuya

2009-11-01

Fragment-based drug discovery (FBDD) has been established as a powerful alternative and complement to traditional high-throughput screening techniques for identifying drug leads. At present, this technique is widely used among academic groups as well as small biotech and large pharmaceutical companies. In recent years, > 10 new compounds developed with FBDD have entered clinical development, and more and more attention in the drug discovery field is being focused on this technique. Under the FBDD approach, a fragment library of relatively small compounds (molecular mass = 100 - 300 Da) is screened by various methods and the identified fragment hits which normally weakly bind to the target are used as starting points to generate more potent drug leads. Because FBDD is still a relatively new drug discovery technology, further developments and optimizations in screening platforms and fragment exploitation can be expected. This review summarizes recent advances in FBDD platforms and discusses the factors important for the successful application of this technique. Under the FBDD approach, both identifying the starting fragment hit to be developed and generating the drug lead from that starting fragment hit are important. Integration of various techniques, such as computational technology, X-ray crystallography, NMR, surface plasmon resonance, isothermal titration calorimetry, mass spectrometry and high-concentration screening, must be applied in a situation-appropriate manner.

Extraction of Phrase-Structure Fragments with a Linear Average Time Tree-Kernel

NARCIS (Netherlands)

van Cranenburgh, Andreas

2014-01-01

We present an algorithm and implementation for extracting recurring fragments from treebanks. Using a tree-kernel method the largest common fragments are extracted from each pair of trees. The algorithm presented achieves a thirty-fold speedup over the previously available method on the Wall Street

BcL-xL Conformational Changes upon Fragment Binding Revealed by NMR

Science.gov (United States)

Aguirre, Clémentine; ten Brink, Tim; Walker, Olivier; Guillière, Florence; Davesne, Dany; Krimm, Isabelle

2013-01-01

Protein-protein interactions represent difficult but increasingly important targets for the design of therapeutic compounds able to interfere with biological processes. Recently, fragment-based strategies have been proposed as attractive approaches for the elaboration of protein-protein surface inhibitors from fragment-like molecules. One major challenge in targeting protein-protein interactions is related to the structural adaptation of the protein surface upon molecular recognition. Methods capable of identifying subtle conformational changes of proteins upon fragment binding are therefore required at the early steps of the drug design process. In this report we present a fast NMR method able to probe subtle conformational changes upon fragment binding. The approach relies on the comparison of experimental fragment-induced Chemical Shift Perturbation (CSP) of amine protons to CSP simulated for a set of docked fragment poses, considering the ring-current effect from fragment binding. We illustrate the method by the retrospective analysis of the complex between the anti-apoptotic Bcl-xL protein and the fragment 4′-fluoro-[1,1′-biphenyl]-4-carboxylic acid that was previously shown to bind one of the Bcl-xL hot spots. The CSP-based approach shows that the protein undergoes a subtle conformational rearrangement upon interaction, for residues located in helices 2, 3 and the very beginning of 5. Our observations are corroborated by residual dipolar coupling measurements performed on the free and fragment-bound forms of the Bcl-xL protein. These NMR-based results are in total agreement with previous molecular dynamic calculations that evidenced a high flexibility of Bcl-xL around the binding site. Here we show that CSP of protein amine protons are useful and reliable structural probes. Therefore, we propose to use CSP simulation to assess protein conformational changes upon ligand binding in the fragment-based drug design approach. PMID:23717610

A Monte Carlo Green's function method for three-dimensional neutron transport

International Nuclear Information System (INIS)

Gamino, R.G.; Brown, F.B.; Mendelson, M.R.

1992-01-01

This paper describes a Monte Carlo transport kernel capability, which has recently been incorporated into the RACER continuous-energy Monte Carlo code. The kernels represent a Green's function method for neutron transport from a fixed-source volume out to a particular volume of interest. This method is very powerful transport technique. Also, since kernels are evaluated numerically by Monte Carlo, the problem geometry can be arbitrarily complex, yet exact. This method is intended for problems where an ex-core neutron response must be determined for a variety of reactor conditions. Two examples are ex-core neutron detector response and vessel critical weld fast flux. The response is expressed in terms of neutron transport kernels weighted by a core fission source distribution. In these types of calculations, the response must be computed for hundreds of source distributions, but the kernels only need to be calculated once. The advance described in this paper is that the kernels are generated with a highly accurate three-dimensional Monte Carlo transport calculation instead of an approximate method such as line-of-sight attenuation theory or a synthesized three-dimensional discrete ordinates solution

Some comments on jet fragmentation models and sup(α)s determinations

International Nuclear Information System (INIS)

Sjoestrand, T.

1984-03-01

A number of interrelated topics on jet properties in e + e - annihilation is discussed. The need for different αsub(s) values in different fragmentation models is explained, with particular emphasis on the sensitivity to the choice of momentum conservation scheme in independent fragmentation models. Also other factors leading to a broad range of experimental αsub(s) values are discussed. Old and new methods to distinguish different fragmentation models are presented, with particular emphasis on gluon jet fragmentation properties. (orig.)

Three-dimensional protein structure prediction: Methods and computational strategies.

Science.gov (United States)

Dorn, Márcio; E Silva, Mariel Barbachan; Buriol, Luciana S; Lamb, Luis C

2014-10-12

A long standing problem in structural bioinformatics is to determine the three-dimensional (3-D) structure of a protein when only a sequence of amino acid residues is given. Many computational methodologies and algorithms have been proposed as a solution to the 3-D Protein Structure Prediction (3-D-PSP) problem. These methods can be divided in four main classes: (a) first principle methods without database information; (b) first principle methods with database information; (c) fold recognition and threading methods; and (d) comparative modeling methods and sequence alignment strategies. Deterministic computational techniques, optimization techniques, data mining and machine learning approaches are typically used in the construction of computational solutions for the PSP problem. Our main goal with this work is to review the methods and computational strategies that are currently used in 3-D protein prediction. Copyright © 2014 Elsevier Ltd. All rights reserved.

A fast semi-discrete Kansa method to solve the two-dimensional spatiotemporal fractional diffusion equation

Science.gov (United States)

Sun, HongGuang; Liu, Xiaoting; Zhang, Yong; Pang, Guofei; Garrard, Rhiannon

2017-09-01

Fractional-order diffusion equations (FDEs) extend classical diffusion equations by quantifying anomalous diffusion frequently observed in heterogeneous media. Real-world diffusion can be multi-dimensional, requiring efficient numerical solvers that can handle long-term memory embedded in mass transport. To address this challenge, a semi-discrete Kansa method is developed to approximate the two-dimensional spatiotemporal FDE, where the Kansa approach first discretizes the FDE, then the Gauss-Jacobi quadrature rule solves the corresponding matrix, and finally the Mittag-Leffler function provides an analytical solution for the resultant time-fractional ordinary differential equation. Numerical experiments are then conducted to check how the accuracy and convergence rate of the numerical solution are affected by the distribution mode and number of spatial discretization nodes. Applications further show that the numerical method can efficiently solve two-dimensional spatiotemporal FDE models with either a continuous or discrete mixing measure. Hence this study provides an efficient and fast computational method for modeling super-diffusive, sub-diffusive, and mixed diffusive processes in large, two-dimensional domains with irregular shapes.

Development of three-dimensional transport code by the double finite element method

International Nuclear Information System (INIS)

Fujimura, Toichiro

1985-01-01

Development of a three-dimensional neutron transport code by the double finite element method is described. Both of the Galerkin and variational methods are adopted to solve the problem, and then the characteristics of them are compared. Computational results of the collocation method, developed as a technique for the vaviational one, are illustrated in comparison with those of an Ssub(n) code. (author)

A Comparison of Machine Learning Methods in a High-Dimensional Classification Problem

Directory of Open Access Journals (Sweden)

Zekić-Sušac Marijana

2014-09-01

Full Text Available Background: Large-dimensional data modelling often relies on variable reduction methods in the pre-processing and in the post-processing stage. However, such a reduction usually provides less information and yields a lower accuracy of the model. Objectives: The aim of this paper is to assess the high-dimensional classification problem of recognizing entrepreneurial intentions of students by machine learning methods. Methods/Approach: Four methods were tested: artificial neural networks, CART classification trees, support vector machines, and k-nearest neighbour on the same dataset in order to compare their efficiency in the sense of classification accuracy. The performance of each method was compared on ten subsamples in a 10-fold cross-validation procedure in order to assess computing sensitivity and specificity of each model. Results: The artificial neural network model based on multilayer perceptron yielded a higher classification rate than the models produced by other methods. The pairwise t-test showed a statistical significance between the artificial neural network and the k-nearest neighbour model, while the difference among other methods was not statistically significant. Conclusions: Tested machine learning methods are able to learn fast and achieve high classification accuracy. However, further advancement can be assured by testing a few additional methodological refinements in machine learning methods.

Gamma Radiation from Fission Fragments Experimental Apparatus-Mass Spectrum Resolution

Energy Technology Data Exchange (ETDEWEB)

Higbie, Jack

1969-08-15

The gamma-radiation from fission fragments was studied as a function of the fragment mass. The mass was determined from the fragment energies using solid state detectors. The mass resolution which can be achieved by this method is treated in detail. The average initial fragment mass and the initial mass resolution is calculated as a function of the measured (apparent) mass yield for three different thicknesses of the fissile material deposit. This treatment gives a clear indication of those factors most important for good mass resolution work. A detailed description of the experimental apparatus is given in the appendices.

A Generic multi-dimensional feature extraction method using multiobjective genetic programming.

Science.gov (United States)

Zhang, Yang; Rockett, Peter I

2009-01-01

In this paper, we present a generic feature extraction method for pattern classification using multiobjective genetic programming. This not only evolves the (near-)optimal set of mappings from a pattern space to a multi-dimensional decision space, but also simultaneously optimizes the dimensionality of that decision space. The presented framework evolves vector-to-vector feature extractors that maximize class separability. We demonstrate the efficacy of our approach by making statistically-founded comparisons with a wide variety of established classifier paradigms over a range of datasets and find that for most of the pairwise comparisons, our evolutionary method delivers statistically smaller misclassification errors. At very worst, our method displays no statistical difference in a few pairwise comparisons with established classifier/dataset combinations; crucially, none of the misclassification results produced by our method is worse than any comparator classifier. Although principally focused on feature extraction, feature selection is also performed as an implicit side effect; we show that both feature extraction and selection are important to the success of our technique. The presented method has the practical consequence of obviating the need to exhaustively evaluate a large family of conventional classifiers when faced with a new pattern recognition problem in order to attain a good classification accuracy.

String fragmentation; La fragmentation des cordes

Energy Technology Data Exchange (ETDEWEB)

Drescher, H.J.; Werner, K. [Laboratoire de Physique Subatomique et des Technologies Associees - SUBATECH, Centre National de la Recherche Scientifique, 44 - Nantes (France)

1997-10-01

The classical string model is used in VENUS as a fragmentation model. For the soft domain simple 2-parton strings were sufficient, whereas for higher energies up to LHC, the perturbative regime of the QCD gives additional soft gluons, which are mapped on the string as so called kinks, energy singularities between the leading partons. The kinky string model is chosen to handle fragmentation of these strings by application of the Lorentz invariant area law. The `kinky strings` model, corresponding to the perturbative gluons coming from pQCD, takes into consideration this effect by treating the partons and gluons on the same footing. The decay law is always the Artru-Menessier area law which is the most realistic since it is invariant to the Lorentz and gauge transformations. For low mass strings a manipulation of the rupture point is necessary if the string corresponds already to an elementary particle determined by the mass and the flavor content. By means of the fragmentation model it will be possible to simulate the data from future experiments at LHC and RHIC 3 refs.

Method for coupling two-dimensional to three-dimensional discrete ordinates calculations

International Nuclear Information System (INIS)

Thompson, J.L.; Emmett, M.B.; Rhoades, W.A.; Dodds, H.L. Jr.

1985-01-01

A three-dimensional (3-D) discrete ordinates transport code, TORT, has been developed at the Oak Ridge National Laboratory for radiation penetration studies. It is not feasible to solve some 3-D penetration problems with TORT, such as a building located a large distance from a point source, because (a) the discretized 3-D problem is simply too big to fit on the computer or (b) the computing time (and corresponding cost) is prohibitive. Fortunately, such problems can be solved with a hybrid approach by coupling a two-dimensional (2-D) description of the point source, which is assumed to be azimuthally symmetric, to a 3-D description of the building, the region of interest. The purpose of this paper is to describe this hybrid methodology along with its implementation and evaluation in the DOTTOR (Discrete Ordinates to Three-dimensional Oak Ridge Transport) code

Fragment separator momentum compression schemes

Energy Technology Data Exchange (ETDEWEB)

Bandura, Laura, E-mail: bandura@anl.gov [Facility for Rare Isotope Beams (FRIB), 1 Cyclotron, East Lansing, MI 48824-1321 (United States); National Superconducting Cyclotron Lab, Michigan State University, 1 Cyclotron, East Lansing, MI 48824-1321 (United States); Erdelyi, Bela [Argonne National Laboratory, Argonne, IL 60439 (United States); Northern Illinois University, DeKalb, IL 60115 (United States); Hausmann, Marc [Facility for Rare Isotope Beams (FRIB), 1 Cyclotron, East Lansing, MI 48824-1321 (United States); Kubo, Toshiyuki [RIKEN Nishina Center, RIKEN, Wako (Japan); Nolen, Jerry [Argonne National Laboratory, Argonne, IL 60439 (United States); Portillo, Mauricio [Facility for Rare Isotope Beams (FRIB), 1 Cyclotron, East Lansing, MI 48824-1321 (United States); Sherrill, Bradley M. [National Superconducting Cyclotron Lab, Michigan State University, 1 Cyclotron, East Lansing, MI 48824-1321 (United States)

2011-07-21

We present a scheme to use a fragment separator and profiled energy degraders to transfer longitudinal phase space into transverse phase space while maintaining achromatic beam transport. The first order beam optics theory of the method is presented and the consequent enlargement of the transverse phase space is discussed. An interesting consequence of the technique is that the first order mass resolving power of the system is determined by the first dispersive section up to the energy degrader, independent of whether or not momentum compression is used. The fragment separator at the Facility for Rare Isotope Beams is a specific application of this technique and is described along with simulations by the code COSY INFINITY.

Fragment separator momentum compression schemes

International Nuclear Information System (INIS)

Bandura, Laura; Erdelyi, Bela; Hausmann, Marc; Kubo, Toshiyuki; Nolen, Jerry; Portillo, Mauricio; Sherrill, Bradley M.

2011-01-01

We present a scheme to use a fragment separator and profiled energy degraders to transfer longitudinal phase space into transverse phase space while maintaining achromatic beam transport. The first order beam optics theory of the method is presented and the consequent enlargement of the transverse phase space is discussed. An interesting consequence of the technique is that the first order mass resolving power of the system is determined by the first dispersive section up to the energy degrader, independent of whether or not momentum compression is used. The fragment separator at the Facility for Rare Isotope Beams is a specific application of this technique and is described along with simulations by the code COSY INFINITY.

Moving Least Squares Method for a One-Dimensional Parabolic Inverse Problem

Directory of Open Access Journals (Sweden)

Baiyu Wang

2014-01-01

Full Text Available This paper investigates the numerical solution of a class of one-dimensional inverse parabolic problems using the moving least squares approximation; the inverse problem is the determination of an unknown source term depending on time. The collocation method is used for solving the equation; some numerical experiments are presented and discussed to illustrate the stability and high efficiency of the method.

Building a better fragment library for de novo protein structure prediction.

Directory of Open Access Journals (Sweden)

Saulo H P de Oliveira

Full Text Available Fragment-based approaches are the current standard for de novo protein structure prediction. These approaches rely on accurate and reliable fragment libraries to generate good structural models. In this work, we describe a novel method for structure fragment library generation and its application in fragment-based de novo protein structure prediction. The importance of correct testing procedures in assessing the quality of fragment libraries is demonstrated. In particular, the exclusion of homologs to the target from the libraries to correctly simulate a de novo protein structure prediction scenario, something which surprisingly is not always done. We demonstrate that fragments presenting different predominant predicted secondary structures should be treated differently during the fragment library generation step and that exhaustive and random search strategies should both be used. This information was used to develop a novel method, Flib. On a validation set of 41 structurally diverse proteins, Flib libraries presents both a higher precision and coverage than two of the state-of-the-art methods, NNMake and HHFrag. Flib also achieves better precision and coverage on the set of 275 protein domains used in the two previous experiments of the the Critical Assessment of Structure Prediction (CASP9 and CASP10. We compared Flib libraries against NNMake libraries in a structure prediction context. Of the 13 cases in which a correct answer was generated, Flib models were more accurate than NNMake models for 10. "Flib is available for download at: http://www.stats.ox.ac.uk/research/proteins/resources".

Building a Better Fragment Library for De Novo Protein Structure Prediction

Science.gov (United States)

de Oliveira, Saulo H. P.; Shi, Jiye; Deane, Charlotte M.

2015-01-01

Fragment-based approaches are the current standard for de novo protein structure prediction. These approaches rely on accurate and reliable fragment libraries to generate good structural models. In this work, we describe a novel method for structure fragment library generation and its application in fragment-based de novo protein structure prediction. The importance of correct testing procedures in assessing the quality of fragment libraries is demonstrated. In particular, the exclusion of homologs to the target from the libraries to correctly simulate a de novo protein structure prediction scenario, something which surprisingly is not always done. We demonstrate that fragments presenting different predominant predicted secondary structures should be treated differently during the fragment library generation step and that exhaustive and random search strategies should both be used. This information was used to develop a novel method, Flib. On a validation set of 41 structurally diverse proteins, Flib libraries presents both a higher precision and coverage than two of the state-of-the-art methods, NNMake and HHFrag. Flib also achieves better precision and coverage on the set of 275 protein domains used in the two previous experiments of the the Critical Assessment of Structure Prediction (CASP9 and CASP10). We compared Flib libraries against NNMake libraries in a structure prediction context. Of the 13 cases in which a correct answer was generated, Flib models were more accurate than NNMake models for 10. “Flib is available for download at: http://www.stats.ox.ac.uk/research/proteins/resources”. PMID:25901595

Quantum molecular dynamics: Numerical methods and physical study of the structure, thermodynamics, stability and fragmentation of sodium metallic clusters

International Nuclear Information System (INIS)

Blaise, Philippe

1998-01-01

The aim of this thesis is to study metallic sodium clusters by numerical simulation. We have developed two ab initio molecular dynamics programs within the formalism of density functional theory. The first is based on the semi-classical extended Thomas-Fermi approach. We use a real-space grid and a Car-Parrinello-like scheme. The computational cost is O(N), and we have built a pseudopotential that speeds up the calculations. By neglecting quantum shell effects, we are able to study a very large set of clusters. We show that sodium cluster energies fit well a liquid drop formula, by adjusting a few parameters. We have investigated breathing modes, surface oscillations and the net charge density. We have shown that the surface energy varies strongly with temperature, and that clusters have a lower melting point than bulk material. We have calculated fission barriers by a constraint method. The second program is based on the quantum Kohn-Sham approach. We use a real-space grid, and combine a generalized Broyden scheme for assuring self-consistency with an iterative Davidson-Lanczos algorithm for solving the Eigen-problem. The cost of the method is much higher. First of all, we have calculated some stable structures for small clusters and their energetics. We obtained very good agreement with previous works. Then, we have investigated highly charged cluster dynamics. We have identified a chaotic fission process. For high fissility systems, we observe a multi-fragmentation dynamics and we find preferential emission of monomers on a characteristic time scale less than a pico-second. This has been simulated for the first time, with the help of our adaptive grid method which follows each fragment as they move apart during the fragmentation. (author)

Experiences in fragment-based drug discovery.

Science.gov (United States)

Murray, Christopher W; Verdonk, Marcel L; Rees, David C

2012-05-01

Fragment-based drug discovery (FBDD) has become established in both industry and academia as an alternative approach to high-throughput screening for the generation of chemical leads for drug targets. In FBDD, specialised detection methods are used to identify small chemical compounds (fragments) that bind to the drug target, and structural biology is usually employed to establish their binding mode and to facilitate their optimisation. In this article, we present three recent and successful case histories in FBDD. We then re-examine the key concepts and challenges of FBDD with particular emphasis on recent literature and our own experience from a substantial number of FBDD applications. Our opinion is that careful application of FBDD is living up to its promise of delivering high quality leads with good physical properties and that in future many drug molecules will be derived from fragment-based approaches. Copyright © 2012 Elsevier Ltd. All rights reserved.

Fission fragment angular momentum

International Nuclear Information System (INIS)

Frenne, D. De

1991-01-01

Most of the energy released in fission is converted into translational kinetic energy of the fragments. The remaining excitation energy will be distributed among neutrons and gammas. An important parameter characterizing the scission configuration is the primary angular momentum of the nascent fragments. Neutron emission is not expected to decrease the spin of the fragments by more than one unit of angular momentum and is as such of less importance in the determination of the initial fragment spins. Gamma emission is a suitable tool in studying initial fragment spins because the emission time, number, energy, and multipolarity of the gammas strongly depend on the value of the primary angular momentum. The main conclusions of experiments on gamma emission were that the initial angular momentum of the fragments is large compared to the ground state spin and oriented perpendicular to the fission axis. Most of the recent information concerning initial fragment spin distributions comes from the measurement of isomeric ratios for isomeric pairs produced in fission. Although in nearly every mass chain isomers are known, only a small number are suitable for initial fission fragment spin studies. Yield and half-life considerations strongly limit the number of candidates. This has the advantage that the behavior of a specific isomeric pair can be investigated for a number of fissioning systems at different excitation energies of the fragments and fissioning nuclei. Because most of the recent information on primary angular momenta comes from measurements of isomeric ratios, the global deexcitation process of the fragments and the calculation of the initial fragment spin distribution from measured isomeric ratios are discussed here. The most important results on primary angular momentum determinations are reviewed and some theoretical approaches are given. 45 refs., 7 figs., 2 tabs

The discrete cones method for two-dimensional neutron transport calculations

International Nuclear Information System (INIS)

Watanabe, Y.; Maynard, C.W.

1986-01-01

A novel method, the discrete cones method (DC/sub N/), is proposed as an alternative to the discrete ordinates method (S/sub N/) for solutions of the two-dimensional neutron transport equation. The new method utilizes a new concept, discrete cones, which are made by partitioning a unit spherical surface that the direction vector of particles covers. In this method particles in a cone are simultaneously traced instead of those in discrete directions so that an anomaly of the S/sub N/ method, the ray effects, can be eliminated. The DC/sub N/ method has been formulated for X-Y geometry and a program has been creaed by modifying the standard S/sub N/ program TWOTRAN-II. Our sample calculations demonstrate a strong mitigation of the ray effects without a computing cost penalty

A finite element method for calculating the 3-dimensional magnetic fields of cyclotron

International Nuclear Information System (INIS)

Zhao Xiaofeng

1986-01-01

A series of formula of the finite element method (scalar potential) for calculating the three-dimensional magnetic field of the main magnet of a sector focused cyclotron, and the realization method of the periodic boundary conditions in the code are given

Protein-Templated Fragment Ligations-From Molecular Recognition to Drug Discovery.

Science.gov (United States)

Jaegle, Mike; Wong, Ee Lin; Tauber, Carolin; Nawrotzky, Eric; Arkona, Christoph; Rademann, Jörg

2017-06-19

Protein-templated fragment ligation is a novel concept to support drug discovery and can help to improve the efficacy of protein ligands. Protein-templated fragment ligations are chemical reactions between small molecules ("fragments") utilizing a protein's surface as a reaction vessel to catalyze the formation of a protein ligand with increased binding affinity. The approach exploits the molecular recognition of reactive small-molecule fragments by proteins both for ligand assembly and for the identification of bioactive fragment combinations. In this way, chemical synthesis and bioassay are integrated in one single step. This Review discusses the biophysical basis of reversible and irreversible fragment ligations and gives an overview of the available methods to detect protein-templated ligation products. The chemical scope and recent applications as well as future potential of the concept in drug discovery are reviewed. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

High Efficiency Hydrodynamic DNA Fragmentation in a Bubbling System.

Science.gov (United States)

Li, Lanhui; Jin, Mingliang; Sun, Chenglong; Wang, Xiaoxue; Xie, Shuting; Zhou, Guofu; van den Berg, Albert; Eijkel, Jan C T; Shui, Lingling

2017-01-18

DNA fragmentation down to a precise fragment size is important for biomedical applications, disease determination, gene therapy and shotgun sequencing. In this work, a cheap, easy to operate and high efficiency DNA fragmentation method is demonstrated based on hydrodynamic shearing in a bubbling system. We expect that hydrodynamic forces generated during the bubbling process shear the DNA molecules, extending and breaking them at the points where shearing forces are larger than the strength of the phosphate backbone. Factors of applied pressure, bubbling time and temperature have been investigated. Genomic DNA could be fragmented down to controllable 1-10 Kbp fragment lengths with a yield of 75.30-91.60%. We demonstrate that the ends of the genomic DNAs generated from hydrodynamic shearing can be ligated by T4 ligase and the fragmented DNAs can be used as templates for polymerase chain reaction. Therefore, in the bubbling system, DNAs could be hydrodynamically sheared to achieve smaller pieces in dsDNAs available for further processes. It could potentially serve as a DNA sample pretreatment technique in the future.

Azimuthal Anisotropies in Nuclear Fragmentation

International Nuclear Information System (INIS)

Dabrowska, A.; Szarska, M.; Trzupek, A.; Wolter, W.; Wosiek, B.

2002-01-01

The directed and elliptic flow of fragments emitted from the excited projectile nuclei has been observed for 158 AGeV Pb collisions with the lead and plastic targets. For comparison the flow analysis has been performed for 10.6 AGeV Au collisions with the emulsion target. The strong directed flow of heaviest fragments is found. Light fragments exhibit directed flow opposite to that of heavy fragments. The elliptic flow for all multiply charged fragments is positive and increases with the charge of the fragment. The observed flow patterns in the fragmentation of the projectile nucleus are practically independent of the mass of the target nucleus and the collision energy. Emission of fragments in nuclear multifragmentation shows similar, although weaker, flow effects. (author)

Analysis of fission-fragment mass distribution within the quantum-mechanical fragmentation theory

Energy Technology Data Exchange (ETDEWEB)

Singh, Pardeep; Kaur, Harjeet [Guru Nanak Dev University, Department of Physics, Amritsar (India)

2016-11-15

The fission-fragment mass distribution is analysed for the {sup 208}Pb({sup 18}O, f) reaction within the quantum-mechanical fragmentation theory (QMFT). The reaction potential has been calculated by taking the binding energies, Coulomb potential and proximity potential of all possible decay channels and a stationary Schroedinger equation has been solved numerically to calculate the fission-fragment yield. The overall results for mass distribution are compared with those obtained in experiment. Fine structure dips in yield, corresponding to fragment shell closures at Z = 50 and N=82, which are observed by Bogachev et al., are reproduced successfully in the present calculations. These calculations will help to estimate the formation probabilities of fission fragments and to understand many related phenomena occurring in the fission process. (orig.)

The interpolation method based on endpoint coordinate for CT three-dimensional image

International Nuclear Information System (INIS)

Suto, Yasuzo; Ueno, Shigeru.

1997-01-01

Image interpolation is frequently used to improve slice resolution to reach spatial resolution. Improved quality of reconstructed three-dimensional images can be attained with this technique as a result. Linear interpolation is a well-known and widely used method. The distance-image method, which is a non-linear interpolation technique, is also used to convert CT value images to distance images. This paper describes a newly developed method that makes use of end-point coordinates: CT-value images are initially converted to binary images by thresholding them and then sequences of pixels with 1-value are arranged in vertical or horizontal directions. A sequence of pixels with 1-value is defined as a line segment which has starting and end points. For each pair of adjacent line segments, another line segment was composed by spatial interpolation of the start and end points. Binary slice images are constructed from the composed line segments. Three-dimensional images were reconstructed from clinical X-ray CT images, using three different interpolation methods and their quality and processing speed were evaluated and compared. (author)

AFLP fragment isolation technique as a method to produce random sequences for single nucleotide polymorphism discovery in the green turtle, Chelonia mydas.

Science.gov (United States)

Roden, Suzanne E; Dutton, Peter H; Morin, Phillip A

2009-01-01

The green sea turtle, Chelonia mydas, was used as a case study for single nucleotide polymorphism (SNP) discovery in a species that has little genetic sequence information available. As green turtles have a complex population structure, additional nuclear markers other than microsatellites could add to our understanding of their complex life history. Amplified fragment length polymorphism technique was used to generate sets of random fragments of genomic DNA, which were then electrophoretically separated with precast gels, stained with SYBR green, excised, and directly sequenced. It was possible to perform this method without the use of polyacrylamide gels, radioactive or fluorescent labeled primers, or hybridization methods, reducing the time, expense, and safety hazards of SNP discovery. Within 13 loci, 2547 base pairs were screened, resulting in the discovery of 35 SNPs. Using this method, it was possible to yield a sufficient number of loci to screen for SNP markers without the availability of prior sequence information.

Quantification of habitat fragmentation reveals extinction risk in terrestrial mammals

Science.gov (United States)

Crooks, Kevin R.; Burdett, Christopher L.; Theobald, David M.; King, Sarah R. B.; Rondinini, Carlo; Boitani, Luigi

2017-01-01

Although habitat fragmentation is often assumed to be a primary driver of extinction, global patterns of fragmentation and its relationship to extinction risk have not been consistently quantified for any major animal taxon. We developed high-resolution habitat fragmentation models and used phylogenetic comparative methods to quantify the effects of habitat fragmentation on the world’s terrestrial mammals, including 4,018 species across 26 taxonomic Orders. Results demonstrate that species with more fragmentation are at greater risk of extinction, even after accounting for the effects of key macroecological predictors, such as body size and geographic range size. Species with higher fragmentation had smaller ranges and a lower proportion of high-suitability habitat within their range, and most high-suitability habitat occurred outside of protected areas, further elevating extinction risk. Our models provide a quantitative evaluation of extinction risk assessments for species, allow for identification of emerging threats in species not classified as threatened, and provide maps of global hotspots of fragmentation for the world’s terrestrial mammals. Quantification of habitat fragmentation will help guide threat assessment and strategic priorities for global mammal conservation. PMID:28673992

A hybrid method for quasi-three-dimensional slope stability analysis in a municipal solid waste landfill

International Nuclear Information System (INIS)

Yu, L.; Batlle, F.

2011-01-01

Highlights: → A quasi-three-dimensional slope stability analysis method was proposed. → The proposed method is a good engineering tool for 3D slope stability analysis. → Factor of safety from 3D analysis is higher than from 2D analysis. → 3D analysis results are more sensitive to cohesion than 2D analysis. - Abstract: Limited space for accommodating the ever increasing mounds of municipal solid waste (MSW) demands the capacity of MSW landfill be maximized by building landfills to greater heights with steeper slopes. This situation has raised concerns regarding the stability of high MSW landfills. A hybrid method for quasi-three-dimensional slope stability analysis based on the finite element stress analysis was applied in a case study at a MSW landfill in north-east Spain. Potential slides can be assumed to be located within the waste mass due to the lack of weak foundation soils and geosynthetic membranes at the landfill base. The only triggering factor of deep-seated slope failure is the higher leachate level and the relatively high and steep slope in the front. The valley-shaped geometry and layered construction procedure at the site make three-dimensional slope stability analyses necessary for this landfill. In the finite element stress analysis, variations of leachate level during construction and continuous settlement of the landfill were taken into account. The 'equivalent' three-dimensional factor of safety (FoS) was computed from the individual result of the two-dimensional analysis for a series of evenly spaced cross sections within the potential sliding body. Results indicate that the hybrid method for quasi-three-dimensional slope stability analysis adopted in this paper is capable of locating roughly the spatial position of the potential sliding mass. This easy to manipulate method can serve as an engineering tool in the preliminary estimate of the FoS as well as the approximate position and extent of the potential sliding mass. The result that

Morphologies of fission fragment impacts in diamond and silica

International Nuclear Information System (INIS)

Gammage, R.B.; Espinosa, G.; Vazquez, C.; Moreno, A.

2005-01-01

The morphologies of fission-fragment impact craters in diamond and silica were investigated by atomic force microscopy. The impacts produced micron-sized craters that were especially obvious in diamond; irradiations in air may have allowed the cratering in carbon to be oxidally enhanced. The eject deposit preferentially at ordered sites and have the appearance of hillocks of a few tenths microns in size. On quartz, the hillocks have a parallel-perpendicular, x-y pattern; on diamond, the hillocks form one dimensional, parallel rows. In contrast, the hillocks on amorphous silica fiber show a random pattern. (Author)

Observation of different isoscaling behavior between emitted fragments and residues

Energy Technology Data Exchange (ETDEWEB)

Youngs, M., E-mail: mdyoungs@comp.tamu.edu [Cyclotron Institute, Texas A& M University, College Station, TX 77843 (United States); McIntosh, A.B.; Hagel, K. [Cyclotron Institute, Texas A& M University, College Station, TX 77843 (United States); Heilborn, L. [Cyclotron Institute, Texas A& M University, College Station, TX 77843 (United States); Chemistry Department, Texas A& M University, College Station, TX 77843 (United States); Huang, M. [Cyclotron Institute, Texas A& M University, College Station, TX 77843 (United States); Jedele, A.; Kohley, Z.; May, L.W. [Cyclotron Institute, Texas A& M University, College Station, TX 77843 (United States); Chemistry Department, Texas A& M University, College Station, TX 77843 (United States); McCleskey, E. [Cyclotron Institute, Texas A& M University, College Station, TX 77843 (United States); Zarrella, A.; Yennello, S.J. [Cyclotron Institute, Texas A& M University, College Station, TX 77843 (United States); Chemistry Department, Texas A& M University, College Station, TX 77843 (United States)

2017-06-15

The traditional isoscaling technique has been used to analyze all isotopically identified particles from {sup 70}Zn+{sup 70}Zn and {sup 64}Zn+{sup 64}Zn collisions at 35 MeV/u. Two additional techniques, using an energy-averaged ratio and using the data present in the tail of energy spectra, are compared to the traditional method and show similar results. Isoscaling fit parameters α and β are found both globally and for each individual series of constant Z and N. The data are then split up between emitted fragments and projectile-like fragments. Isoscaling values for the two different types of fragments are shown to be different, emphasizing the importance of experimentally distinguishing between projectile-like fragments and emitted fragments in order to achieve accurate isoscaling parameters.

Development of three-dimensional ENRICHED FREE MESH METHOD and its application to crack analysis

International Nuclear Information System (INIS)

Suzuki, Hayato; Matsubara, Hitoshi; Ezawa, Yoshitaka; Yagawa, Genki

2010-01-01

In this paper, we describe a method for three-dimensional high accurate analysis of a crack included in a large-scale structure. The Enriched Free Mesh Method (EFMM) is a method for improving the accuracy of the Free Mesh Method (FMM), which is a kind of meshless method. First, we developed an algorithm of the three-dimensional EFMM. The elastic problem was analyzed using the EFMM and we find that its accuracy compares advantageously with the FMM, and the number of CG iterations is smaller. Next, we developed a method for calculating the stress intensity factor by employing the EFMM. The structure with a crack was analyzed using the EFMM, and the stress intensity factor was calculated by the developed method. The analysis results were very well in agreement with reference solution. It was shown that the proposed method is very effective in the analysis of the crack included in a large-scale structure. (author)

On the nuclear fragmentation mechanisms in nuclear collisions at intermediate and high energies

International Nuclear Information System (INIS)

Jipa, Al; Besliu, C.; Felea, D.

2004-01-01

The nuclear fragmentation mechanisms can be discussed by taking into account different scales related to the fragment sizes. Considering two fragmentation mechanisms of the nuclei at the same incident energy an analysis of the experimental results obtained was done. Goldhaber formula was improved by analyzing the discrepancies between data and theories concerning the projectile fragmentation. We implied that the projectile fragmentation process would be governed by the distribution of nucleon momenta in the projectile after the collision occurred. We used in our analysis protons from the 4 He + 7 Li at 4.5 GeV/c per nucleon incident momentum, as well as from 40 Ar + 12 C at 213 AMeV bombarding energy. We proved that in order to proceed in analyzing the projectile fragmentation process at intermediate and high energies one has to consider the dependence σ 0 on the apparent temperature of projectile nucleus after the collision took place. The generalized Bertsch correction for light projectile nuclei and fragments was used and the number of spatial correlations between identical nucleons having anticorrelated momenta was found. Thus we found apparent temperature values close to the separation energies of the considered fragments per number of fragments. The temperatures associated to kinetic energy spectra of the projectile fragments were calculated following two methods. The results from Bauer's method were compared with those obtained by fitting the kinetic energy distributions of the projectile fragments in the rest frame of the projectile with a Maxwellian curve. We also accomplished the comparison of the experimental results with similar events simulated with RQMD 2.4. All the results obtained suggested two nuclear fragmentation mechanisms: a sudden fragmentation by explosive mechanisms, like shock waves and a slow fragmentation by the 'fission' of the spectator regions, mainly because of the interactions with the particles or fragments emitted from the

Hypervelocity Impact Test Fragment Modeling: Modifications to the Fragment Rotation Analysis and Lightcurve Code

Science.gov (United States)

Gouge, Michael F.

2011-01-01

Hypervelocity impact tests on test satellites are performed by members of the orbital debris scientific community in order to understand and typify the on-orbit collision breakup process. By analysis of these test satellite fragments, the fragment size and mass distributions are derived and incorporated into various orbital debris models. These same fragments are currently being put to new use using emerging technologies. Digital models of these fragments are created using a laser scanner. A group of computer programs referred to as the Fragment Rotation Analysis and Lightcurve code uses these digital representations in a multitude of ways that describe, measure, and model on-orbit fragments and fragment behavior. The Dynamic Rotation subroutine generates all of the possible reflected intensities from a scanned fragment as if it were observed to rotate dynamically while in orbit about the Earth. This calls an additional subroutine that graphically displays the intensities and the resulting frequency of those intensities as a range of solar phase angles in a Probability Density Function plot. This document reports the additions and modifications to the subset of the Fragment Rotation Analysis and Lightcurve concerned with the Dynamic Rotation and Probability Density Function plotting subroutines.

Two-dimensional simulation of broad-band ferrite electromagnetic wave absorbers by using the FDTD method

Energy Technology Data Exchange (ETDEWEB)

Yoon, Hyun Jin; Kim, Dong Il [Korea Maritime University, Busan (Korea, Republic of)

2004-10-15

The purpose of this simulation study is to design and fabricate an electromagnetic (EM) wave absorber in order to develop a wide-band absorber. We have proposed and modeled a bird-eye-type and cutting-cone-type EM wave absorber by using the equivalent material constants method (EMCM), and we simulated them by using a finite-difference time-domain (FDTD) method. A two or a three-dimensional simulation would be desirable to analyze the EM wave absorber characteristics and to develop new structures. The two-dimensional FDTD simulation requires less computer resources than a three-dimensional simulation to consider the structural effects of the EM wave absorbers. The numerical simulation by using the FDTD method shows propagating EM waves in various types of periodic structure EM wave absorbers. Simultaneously, a Fourier analysis is used to characterize the input pulse and the reflected EM waves for ferrite absorbers with various structures. The results have a wide-band reflection-reducing characteristic. The validity of the proposed model was confirmed by comparing the two-dimensional simulation with the experimental results. The simulations were carried out in the frequency band from 30 MHz to 10 GHz.

Two-dimensional simulation of broad-band ferrite electromagnetic wave absorbers by using the FDTD method

International Nuclear Information System (INIS)

Yoon, Hyun Jin; Kim, Dong Il

2004-01-01

The purpose of this simulation study is to design and fabricate an electromagnetic (EM) wave absorber in order to develop a wide-band absorber. We have proposed and modeled a bird-eye-type and cutting-cone-type EM wave absorber by using the equivalent material constants method (EMCM), and we simulated them by using a finite-difference time-domain (FDTD) method. A two or a three-dimensional simulation would be desirable to analyze the EM wave absorber characteristics and to develop new structures. The two-dimensional FDTD simulation requires less computer resources than a three-dimensional simulation to consider the structural effects of the EM wave absorbers. The numerical simulation by using the FDTD method shows propagating EM waves in various types of periodic structure EM wave absorbers. Simultaneously, a Fourier analysis is used to characterize the input pulse and the reflected EM waves for ferrite absorbers with various structures. The results have a wide-band reflection-reducing characteristic. The validity of the proposed model was confirmed by comparing the two-dimensional simulation with the experimental results. The simulations were carried out in the frequency band from 30 MHz to 10 GHz.

Computational fragment-based screening using RosettaLigand: the SAMPL3 challenge

Science.gov (United States)

Kumar, Ashutosh; Zhang, Kam Y. J.

2012-05-01

SAMPL3 fragment based virtual screening challenge provides a valuable opportunity for researchers to test their programs, methods and screening protocols in a blind testing environment. We participated in SAMPL3 challenge and evaluated our virtual fragment screening protocol, which involves RosettaLigand as the core component by screening a 500 fragments Maybridge library against bovine pancreatic trypsin. Our study reaffirmed that the real test for any virtual screening approach would be in a blind testing environment. The analyses presented in this paper also showed that virtual screening performance can be improved, if a set of known active compounds is available and parameters and methods that yield better enrichment are selected. Our study also highlighted that to achieve accurate orientation and conformation of ligands within a binding site, selecting an appropriate method to calculate partial charges is important. Another finding is that using multiple receptor ensembles in docking does not always yield better enrichment than individual receptors. On the basis of our results and retrospective analyses from SAMPL3 fragment screening challenge we anticipate that chances of success in a fragment screening process could be increased significantly with careful selection of receptor structures, protein flexibility, sufficient conformational sampling within binding pocket and accurate assignment of ligand and protein partial charges.

The equivalence of information-theoretic and likelihood-based methods for neural dimensionality reduction.

Directory of Open Access Journals (Sweden)

Ross S Williamson

2015-04-01

Full Text Available Stimulus dimensionality-reduction methods in neuroscience seek to identify a low-dimensional space of stimulus features that affect a neuron's probability of spiking. One popular method, known as maximally informative dimensions (MID, uses an information-theoretic quantity known as "single-spike information" to identify this space. Here we examine MID from a model-based perspective. We show that MID is a maximum-likelihood estimator for the parameters of a linear-nonlinear-Poisson (LNP model, and that the empirical single-spike information corresponds to the normalized log-likelihood under a Poisson model. This equivalence implies that MID does not necessarily find maximally informative stimulus dimensions when spiking is not well described as Poisson. We provide several examples to illustrate this shortcoming, and derive a lower bound on the information lost when spiking is Bernoulli in discrete time bins. To overcome this limitation, we introduce model-based dimensionality reduction methods for neurons with non-Poisson firing statistics, and show that they can be framed equivalently in likelihood-based or information-theoretic terms. Finally, we show how to overcome practical limitations on the number of stimulus dimensions that MID can estimate by constraining the form of the non-parametric nonlinearity in an LNP model. We illustrate these methods with simulations and data from primate visual cortex.

Correlation based method for comparing and reconstructing quasi-identical two-dimensional structures

International Nuclear Information System (INIS)

Mejia-Barbosa, Y.

2000-03-01

We show a method for comparing and reconstructing two similar amplitude-only structures, which are composed by the same number of identical apertures. The structures are two-dimensional and differ only in the location of one of the apertures. The method is based on a subtraction algorithm, which involves the auto-correlations and cross-correlation functions of the compared structures. Experimental results illustrate the feasibility of the method. (author)

A Feature Subset Selection Method Based On High-Dimensional Mutual Information

Directory of Open Access Journals (Sweden)

Chee Keong Kwoh

2011-04-01

Full Text Available Feature selection is an important step in building accurate classifiers and provides better understanding of the data sets. In this paper, we propose a feature subset selection method based on high-dimensional mutual information. We also propose to use the entropy of the class attribute as a criterion to determine the appropriate subset of features when building classifiers. We prove that if the mutual information between a feature set X and the class attribute Y equals to the entropy of Y , then X is a Markov Blanket of Y . We show that in some cases, it is infeasible to approximate the high-dimensional mutual information with algebraic combinations of pairwise mutual information in any forms. In addition, the exhaustive searches of all combinations of features are prerequisite for finding the optimal feature subsets for classifying these kinds of data sets. We show that our approach outperforms existing filter feature subset selection methods for most of the 24 selected benchmark data sets.

Fragment capture device

Science.gov (United States)

Payne, Lloyd R.; Cole, David L.

2010-03-30

A fragment capture device for use in explosive containment. The device comprises an assembly of at least two rows of bars positioned to eliminate line-of-sight trajectories between the generation point of fragments and a surrounding containment vessel or asset. The device comprises an array of at least two rows of bars, wherein each row is staggered with respect to the adjacent row, and wherein a lateral dimension of each bar and a relative position of each bar in combination provides blockage of a straight-line passage of a solid fragment through the adjacent rows of bars, wherein a generation point of the solid fragment is located within a cavity at least partially enclosed by the array of bars.

A new analytical method to solve the heat equation for a multi-dimensional composite slab

International Nuclear Information System (INIS)

Lu, X; Tervola, P; Viljanen, M

2005-01-01

A novel analytical approach has been developed for heat conduction in a multi-dimensional composite slab subject to time-dependent boundary changes of the first kind. Boundary temperatures are represented as Fourier series. Taking advantage of the periodic properties of boundary changes, the analytical solution is obtained and expressed explicitly. Nearly all the published works necessitate searching for associated eigenvalues in solving such a problem even for a one-dimensional composite slab. In this paper, the proposed method involves no iterative computation such as numerically searching for eigenvalues and no residue evaluation. The adopted method is simple which represents an extension of the novel analytical approach derived for the one-dimensional composite slab. Moreover, the method of 'separation of variables' employed in this paper is new. The mathematical formula for solutions is concise and straightforward. The physical parameters are clearly shown in the formula. Further comparison with numerical calculations is presented

Modified Splitting FDTD Methods for Two-Dimensional Maxwell’s Equations

Directory of Open Access Journals (Sweden)

Liping Gao

2017-01-01

Full Text Available In this paper, we develop a new method to reduce the error in the splitting finite-difference method of Maxwell’s equations. By this method two modified splitting FDTD methods (MS-FDTDI, MS-FDTDII for the two-dimensional Maxwell equations are proposed. It is shown that the two methods are second-order accurate in time and space and unconditionally stable by Fourier methods. By energy method, it is proved that MS-FDTDI is second-order convergent. By deriving the numerical dispersion (ND relations, we prove rigorously that MS-FDTDI has less ND errors than the ADI-FDTD method and the ND errors of ADI-FDTD are less than those of MS-FDTDII. Numerical experiments for computing ND errors and simulating a wave guide problem and a scattering problem are carried out and the efficiency of the MS-FDTDI and MS-FDTDII methods is confirmed.

Modeling of three-dimensional diffusible resistors with the one-dimensional tube multiplexing method

International Nuclear Information System (INIS)

Gillet, Jean-Numa; Degorce, Jean-Yves; Meunier, Michel

2009-01-01

Electronic-behavior modeling of three-dimensional (3D) p + -π-p + and n + -ν-n + semiconducting diffusible devices with highly accurate resistances for the design of analog resistors, which are compatible with the CMOS (complementary-metal-oxide-semiconductor) technologies, is performed in three dimensions with the fast tube multiplexing method (TMM). The current–voltage (I–V) curve of a silicon device is usually computed with traditional device simulators of technology computer-aided design (TCAD) based on the finite-element method (FEM). However, for the design of 3D p + -π-p + and n + -ν-n + diffusible resistors, they show a high computational cost and convergence that may fail with fully non-separable 3D dopant concentration profiles as observed in many diffusible resistors resulting from laser trimming. These problems are avoided with the proposed TMM, which divides the 3D resistor into one-dimensional (1D) thin tubes with longitudinal axes following the main orientation of the average electrical field in the tubes. The I–V curve is rapidly obtained for a device with a realistic 3D dopant profile, since a system of three first-order ordinary differential equations has to be solved for each 1D multiplexed tube with the TMM instead of three second-order partial differential equations in the traditional TCADs. Simulations with the TMM are successfully compared to experimental results from silicon-based 3D resistors fabricated by laser-induced dopant diffusion in the gaps of MOSFETs (metal-oxide-semiconductor field-effect transistors) without initial gate. Using thin tubes with other shapes than parallelepipeds as ring segments with toroidal lateral surfaces, the TMM can be generalized to electronic devices with other types of 3D diffusible microstructures

Quantum molecular dynamics: Numerical methods and physical study of the structure, thermodynamics, stability and fragmentation of sodium metallic clusters; Dynamique moleculaire quantique: Methodes numeriques et etude physique de la structure, de la thermodynamique, de la stabilite et de la fragmentation des agregats metalliques de sodium

Energy Technology Data Exchange (ETDEWEB)

Blaise, Philippe [Universite Joseph Fourier, Grenoble 1, 74 Annecy (France)

1998-09-29

The aim of this thesis is to study metallic sodium clusters by numerical simulation. We have developed two ab initio molecular dynamics programs within the formalism of density functional theory. The first is based on the semi-classical extended Thomas-Fermi approach. We use a real-space grid and a Car-Parrinello-like scheme. The computational cost is O(N), and we have built a pseudopotential that speeds up the calculations. By neglecting quantum shell effects, we are able to study a very large set of clusters. We show that sodium cluster energies fit well a liquid drop formula, by adjusting a few parameters. We have investigated breathing modes, surface oscillations and the net charge density. We have shown that the surface energy varies strongly with temperature, and that clusters have a lower melting point than bulk material. We have calculated fission barriers by a constraint method. The second program is based on the quantum Kohn-Sham approach. We use a real-space grid, and combine a generalized Broyden scheme for assuring self-consistency with an iterative Davidson-Lanczos algorithm for solving the Eigen-problem. The cost of the method is much higher. First of all, we have calculated some stable structures for small clusters and their energetics. We obtained very good agreement with previous works. Then, we have investigated highly charged cluster dynamics. We have identified a chaotic fission process. For high fissility systems, we observe a multi-fragmentation dynamics and we find preferential emission of monomers on a characteristic time scale less than a pico-second. This has been simulated for the first time, with the help of our adaptive grid method which follows each fragment as they move apart during the fragmentation. (author) 87 refs., 57 figs., 4 tabs.

Mutant DNA quantification by digital PCR can be confounded by heating during DNA fragmentation.

Science.gov (United States)

Kang, Qing; Parkin, Brian; Giraldez, Maria D; Tewari, Muneesh

2016-04-01

Digital PCR (dPCR) is gaining popularity as a DNA mutation quantification method for clinical specimens. Fragmentation prior to dPCR is required for non-fragmented genomic DNA samples; however, the effect of fragmentation on DNA analysis has not been well-studied. Here we evaluated three fragmentation methods for their effects on dPCR point mutation assay performance. Wild-type (WT) human genomic DNA was fragmented by heating, restriction digestion, or acoustic shearing using a Covaris focused-ultrasonicator. dPCR was then used to determine the limit of blank (LoB) by quantifying observed WT and mutant allele counts of the proto-oncogenes KRAS and BRAF in the WT DNA sample. DNA fragmentation by heating to 95°C, while the simplest and least expensive method, produced a high background mutation frequency for certain KRAS mutations relative to the other methods. This was due to heat-induced mutations, specifically affecting dPCR assays designed to interrogate guanine to adenine (G>A) mutations. Moreover, heat-induced fragmentation overestimated gene copy number, potentially due to denaturation and partition of single-stranded DNA into different droplets. Covaris acoustic shearing and restriction enzyme digestion showed similar LoBs and gene copy number estimates to one another. It should be noted that moderate heating, commonly used in genomic DNA extraction protocols, did not significantly increase observed KRAS mutation counts.

New Traveling Wave Solutions of the Higher Dimensional Nonlinear Partial Differential Equation by the Exp-Function Method

Directory of Open Access Journals (Sweden)

Hasibun Naher

2012-01-01

Full Text Available We construct new analytical solutions of the (3+1-dimensional modified KdV-Zakharov-Kuznetsev equation by the Exp-function method. Plentiful exact traveling wave solutions with arbitrary parameters are effectively obtained by the method. The obtained results show that the Exp-function method is effective and straightforward mathematical tool for searching analytical solutions with arbitrary parameters of higher-dimensional nonlinear partial differential equation.

Intravitreal Phacoemulsification Using Torsional Handpiece for Retained Lens Fragments

OpenAIRE

Kumar, Vinod; Takkar, Brijesh

2016-01-01

Purpose: To evaluate the results of intravitreal phacoemulsification with torsional hand piece in eyes with posteriorly dislocated lens fragments. Methods: In this prospective, interventional case series, 15 eyes with retained lens fragments following phacoemulsification were included. All patients underwent standard three-port pars plana vitrectomy and intravitreal phacoemulsification using sleeveless, torsional hand piece (OZiL™, Alcon's Infiniti Vision System). Patients were followed up...

The Y4-RNA fragment, a potential diagnostic marker, exists in saliva

Directory of Open Access Journals (Sweden)

Tatsuya Ishikawa

2017-06-01

Full Text Available The 94-nt full-length Y4-RNA is thought to have roles in the initiation of DNA replication and RNA quality control. Although its 31/32-nt fragment also exists abundantly in plasma, little is known about its physiological role. Since the 31/32-nt Y4-RNA fragment in sera is reported to be more abundant in patients with coronary artery disease than healthy persons, the fragment may have a potential for a diagnostic and/or prognostic biomarker for some diseases regardless of its functionality. As a step toward further investigation of its potential utility, we examined if the 31/32-nt Y4-RNA fragment also exists in saliva that can be obtained noninvasively, and showed that, in addition to the 31/32-nt fragment, 14- and 11-nt Y4-RNA fragments are present in all saliva RNA samples from four healthy persons. We established a PCR method to accurately quantitate the amount of the 31/32-nt Y4-RNA fragment, and estimated its amount in saliva of healthy persons to be 0.06 ± 0.04 fmol per nanogram of saliva RNA. We also tried to develop an easier quantitation method using a DNA molecular beacon. Keywords: Y4-RNA fragment, Saliva RNA, Diagnostic/prognostic marker, Next-generation sequencing, RT-PCR, Molecular beacon

Using DNase Hi-C techniques to map global and local three-dimensional genome architecture at high resolution.

Science.gov (United States)

Ma, Wenxiu; Ay, Ferhat; Lee, Choli; Gulsoy, Gunhan; Deng, Xinxian; Cook, Savannah; Hesson, Jennifer; Cavanaugh, Christopher; Ware, Carol B; Krumm, Anton; Shendure, Jay; Blau, C Anthony; Disteche, Christine M; Noble, William S; Duan, ZhiJun

2018-06-01

The folding and three-dimensional (3D) organization of chromatin in the nucleus critically impacts genome function. The past decade has witnessed rapid advances in genomic tools for delineating 3D genome architecture. Among them, chromosome conformation capture (3C)-based methods such as Hi-C are the most widely used techniques for mapping chromatin interactions. However, traditional Hi-C protocols rely on restriction enzymes (REs) to fragment chromatin and are therefore limited in resolution. We recently developed DNase Hi-C for mapping 3D genome organization, which uses DNase I for chromatin fragmentation. DNase Hi-C overcomes RE-related limitations associated with traditional Hi-C methods, leading to improved methodological resolution. Furthermore, combining this method with DNA capture technology provides a high-throughput approach (targeted DNase Hi-C) that allows for mapping fine-scale chromatin architecture at exceptionally high resolution. Hence, targeted DNase Hi-C will be valuable for delineating the physical landscapes of cis-regulatory networks that control gene expression and for characterizing phenotype-associated chromatin 3D signatures. Here, we provide a detailed description of method design and step-by-step working protocols for these two methods. Copyright © 2018 Elsevier Inc. All rights reserved.

NMR characterization of weak interactions between RhoGDI2 and fragment screening hits.

Science.gov (United States)

Liu, Jiuyang; Gao, Jia; Li, Fudong; Ma, Rongsheng; Wei, Qingtao; Wang, Aidong; Wu, Jihui; Ruan, Ke

2017-01-01

The delineation of intrinsically weak interactions between novel targets and fragment screening hits has long limited the pace of hit-to-lead evolution. Rho guanine-nucleotide dissociation inhibitor 2 (RhoGDI2) is a novel target that lacks any chemical probes for the treatment of tumor metastasis. Protein-observed and ligand-observed NMR spectroscopy was used to characterize the weak interactions between RhoGDI2 and fragment screening hits. We identified three hits of RhoGDI2 using streamlined NMR fragment-based screening. The binding site residues were assigned using non-uniformly sampled C α - and H α -based three dimensional NMR spectra. The molecular docking to the proposed geranylgeranyl binding pocket of RhoGDI2 was guided by NMR restraints of chemical shift perturbations and ligand-observed transferred paramagnetic relaxation enhancement. We further validated the weak RhoGDI2-hit interactions using mutagenesis and structure-affinity analysis. Weak interactions between RhoGDI2 and fragment screening hits were delineated using an integrated NMR approach. Binders to RhoGDI2 as a potential anti-cancer target have been first reported, and their weak interactions were depicted using NMR spectroscopy. Our work highlights the powerfulness and the versatility of the integrative NMR techniques to provide valuable structural insight into the intrinsically weak interactions between RhoGDI2 and the fragment screening hits, which could hardly be conceived using other biochemical techniques. Copyright © 2016 Elsevier B.V. All rights reserved.

Restriction site extension PCR: a novel method for high-throughput characterization of tagged DNA fragments and genome walking.

Directory of Open Access Journals (Sweden)

Jiabing Ji

Full Text Available BACKGROUND: Insertion mutant isolation and characterization are extremely valuable for linking genes to physiological function. Once an insertion mutant phenotype is identified, the challenge is to isolate the responsible gene. Multiple strategies have been employed to isolate unknown genomic DNA that flanks mutagenic insertions, however, all these methods suffer from limitations due to inefficient ligation steps, inclusion of restriction sites within the target DNA, and non-specific product generation. These limitations become close to insurmountable when the goal is to identify insertion sites in a high throughput manner. METHODOLOGY/PRINCIPAL FINDINGS: We designed a novel strategy called Restriction Site Extension PCR (RSE-PCR to efficiently conduct large-scale isolation of unknown genomic DNA fragments linked to DNA insertions. The strategy is a modified adaptor-mediated PCR without ligation. An adapter, with complementarity to the 3' overhang of the endonuclease (KpnI, NsiI, PstI, or SacI restricted DNA fragments, extends the 3' end of the DNA fragments in the first cycle of the primary RSE-PCR. During subsequent PCR cycles and a second semi-nested PCR (secondary RSE-PCR, touchdown and two-step PCR are combined to increase the amplification specificity of target fragments. The efficiency and specificity was demonstrated in our characterization of 37 tex mutants of Arabidopsis. All the steps of RSE-PCR can be executed in a 96 well PCR plate. Finally, RSE-PCR serves as a successful alternative to Genome Walker as demonstrated by gene isolation from maize, a plant with a more complex genome than Arabidopsis. CONCLUSIONS/SIGNIFICANCE: RSE-PCR has high potential application in identifying tagged (T-DNA or transposon sequence or walking from known DNA toward unknown regions in large-genome plants, with likely application in other organisms as well.

A simplified method for rapid quantification of intracellular nucleoside triphosphates by one-dimensional thin-layer chromatography

DEFF Research Database (Denmark)

Jendresen, Christian Bille; Kilstrup, Mogens; Martinussen, Jan

2011-01-01

-pyrophosphate (PRPP), and inorganic pyrophosphate (PPi) in cell extracts. The method uses one-dimensional thin-layer chromatography (TLC) and radiolabeled biological samples. Nucleotides are resolved at the level of ionic charge in an optimized acidic ammonium formate and chloride solvent, permitting...... quantification of NTPs. The method is significantly simpler and faster than both current two-dimensional methods and high-performance liquid chromatography (HPLC)-based procedures, allowing a higher throughput while common sources of inaccuracies and technical problems are avoided. For determination of PPi...

Land fragmentation and production diversification

NARCIS (Netherlands)

Ciaian, Pavel; Guri, Fatmir; Rajcaniova, Miroslava; Drabik, Dusan; Paloma, Sergio Gomez Y.

2018-01-01

We analyze the impact of land fragmentation on production diversification in rural Albania. Albania represents a particularly interesting case for studying land fragmentation as the fragmentation is a direct outcome of land reforms. The results indicate that land fragmentation is an important driver

A Two-Dimensional Solar Tracking Stationary Guidance Method Based on Feature-Based Time Series

Directory of Open Access Journals (Sweden)

Keke Zhang

2018-01-01

Full Text Available The amount of satellite energy acquired has a direct impact on operational capacities of the satellite. As for practical high functional density microsatellites, solar tracking guidance design of solar panels plays an extremely important role. Targeted at stationary tracking problems incurred in a new system that utilizes panels mounted in the two-dimensional turntable to acquire energies to the greatest extent, a two-dimensional solar tracking stationary guidance method based on feature-based time series was proposed under the constraint of limited satellite attitude coupling control capability. By analyzing solar vector variation characteristics within an orbit period and solar vector changes within the whole life cycle, such a method could be adopted to establish a two-dimensional solar tracking guidance model based on the feature-based time series to realize automatic switching of feature-based time series and stationary guidance under the circumstance of different β angles and the maximum angular velocity control, which was applicable to near-earth orbits of all orbital inclination. It was employed to design a two-dimensional solar tracking stationary guidance system, and a mathematical simulation for guidance performance was carried out in diverse conditions under the background of in-orbit application. The simulation results show that the solar tracking accuracy of two-dimensional stationary guidance reaches 10∘ and below under the integrated constraints, which meet engineering application requirements.

The analysis of RPV fast neutron flux calculation for PWR with three-dimensional SN method

International Nuclear Information System (INIS)

Yang Shouhai; Chen Yixue; Wang Weijin; Shi Shengchun; Lu Daogang

2011-01-01

Discrete ordinates (S N ) method is one of the most widely used method for reactor pressure vessel (RPV) design. As the fast development of computer CPU speed and memory capacity and consummation of three-dimensional discrete-ordinates method, it is mature for 3-D S N method to be used to engineering design for nuclear facilities. This work was done specifically for PWR model, with the results of 3-D core neutron transport calculation by 3-D core calculation, 3-D RPV fast neutron flux distribution obtain by 3-D S N method were compared with gained by 1-D and 2-D S N method and the 3-D Monte Carlo (MC) method. In this paper, the application of three-dimensional S N method in calculating RPV fast neutron flux distribution for pressurized water reactor (PWR) is presented and discussed. (authors)

A semiclassical model for quark jet fragmentation

International Nuclear Information System (INIS)

Andersson, B.; Gustafson, G.; Peterson, C.

1979-01-01

A semiclassical model is presented for the way the energy of a fast quark is transformed into observable hadrons. It reproduces the features of 1+1 dimensional QED (the Schwinger model) concerning a flat rapidity distribution in the central region. It also reproduces results from phenomenological considerations, which, based upon scaling, predict that meson formation in the fragmentation region can be described by an iterative scheme, implying a set of coupled integral equations. In particular the model predicts that the probability to find a meson containing the leading quark is independent of the Feynman scaling variable z. The iterative structure corresponds to a Brownian motion with relevance both to the cofinement problems and to the distribution of mass in the quark jet. (orig.) [de

Fragmentation processes in nuclear reactions

International Nuclear Information System (INIS)

Legrain, R.

1984-08-01

Projectile and nuclear fragmentation are defined and processes referred to are recalled. The two different aspects of fragmentation are considered but the emphasis is also put on heavy ion induced reactions. The preliminary results of an experiment performed at GANIL to study peripheral heavy ions induced reactions at intermediate energy are presented. The results of this experiment will illustrate the characteristics of projectile fragmentation and this will also give the opportunity to study projectile fragmentation in the transition region. Then nuclear fragmentation is considered which is associated with more central collisions in the case of heavy ion induced reactions. This aspect of fragmentation is also ilustrated with two heavy ion experiments in which fragments emitted at large angle have been observed

Fragment assignment in the cloud with eXpress-D

Science.gov (United States)

2013-01-01

Background Probabilistic assignment of ambiguously mapped fragments produced by high-throughput sequencing experiments has been demonstrated to greatly improve accuracy in the analysis of RNA-Seq and ChIP-Seq, and is an essential step in many other sequence census experiments. A maximum likelihood method using the expectation-maximization (EM) algorithm for optimization is commonly used to solve this problem. However, batch EM-based approaches do not scale well with the size of sequencing datasets, which have been increasing dramatically over the past few years. Thus, current approaches to fragment assignment rely on heuristics or approximations for tractability. Results We present an implementation of a distributed EM solution to the fragment assignment problem using Spark, a data analytics framework that can scale by leveraging compute clusters within datacenters–“the cloud”. We demonstrate that our implementation easily scales to billions of sequenced fragments, while providing the exact maximum likelihood assignment of ambiguous fragments. The accuracy of the method is shown to be an improvement over the most widely used tools available and can be run in a constant amount of time when cluster resources are scaled linearly with the amount of input data. Conclusions The cloud offers one solution for the difficulties faced in the analysis of massive high-thoughput sequencing data, which continue to grow rapidly. Researchers in bioinformatics must follow developments in distributed systems–such as new frameworks like Spark–for ways to port existing methods to the cloud and help them scale to the datasets of the future. Our software, eXpress-D, is freely available at: http://github.com/adarob/express-d. PMID:24314033

Three-dimensional static and dynamic reactor calculations by the nodal expansion method

International Nuclear Information System (INIS)

Christensen, B.

1985-05-01

This report reviews various method for the calculation of the neutron-flux- and power distribution in an nuclear reactor. The nodal expansion method (NEM) is especially described in much detail. The nodal expansion method solves the diffusion equation. In this method the reactor core is divided into nodes, typically 10 to 20 cm in each direction, and the average flux in each node is calculated. To obtain the coupling between the nodes the local flux inside each node is expressed by use of a polynomial expansion. The expansion is one-dimensional, so inside each node such three expansions occur. To calculate the expansion coefficients it is necessary that the polynomial expansion is a solution to the one-dimensional diffusion equation. When the one-dimensional diffusion equation is established a term with the transversal leakage occur, and this term is expanded after the same polynomials. The resulting equation system with the expansion coefficients as the unknowns is solved with weigthed residual technique. The nodal expansion method is built into a computer program (also called NEM), which is divided into two parts, one part for steady-state calculations and one part for dynamic calculations. It is possible to take advantage of symmetry properties of the reactor core. The program is very flexible with regard to the number of energy groups, the node size, the flux expansion order and the transverse leakage expansion order. The boundary of the core is described by albedos. The program and input to it are described. The program is tested on a number of examples extending from small theoretical one up to realistic reactor cores. Many calculations are done on the wellknown IAEA benchmark case. The calculations have tested the accuracy and the computing time for various node sizes and polynomial expansions. In the dynamic examples various strategies for variation of the time step-length have been tested. (author)

Amplification of deoxyribonucleic acid (DNA) fragment using two ...

African Journals Online (AJOL)

user

2011-04-11

Apr 11, 2011 ... polymerases on this method, whether different lengths of. DNA fragments could be amplified by two-step PCR and the difference of DNA product quality produced by the two methods. MATERIALS AND METHODS. PCR template and reagents. Enterobacteria phage lambda DNA (GenBank no: V00636) ...

Simulation of a relativistic heavy ions beam transport in the matter: contribution of the fragmentation process and biological implications; Simulation du transport d`un faisceau d`ions lourds relativistes dans la matiere: contribution du processus de fragmentation et implication sur le plan biologique

Energy Technology Data Exchange (ETDEWEB)

Ibnouzahir, M

1995-03-01

The study of relativistic heavy ion collisions permit an approach of the properties of dense and not hadronic matter, and an analysis of the reaction mechanisms. Such studies are also interesting on the biological point of view, since there exist now well defined projects concerning the radiotherapy with high LET particles as neutrons, protons, heavy ions. It is thus necessary to have a good understanding of the processes which occur in the propagation of a relativistic heavy ion beam (E{>=} 100 A.MeV) in matter. We have elaborated a three dimensional transport code, using a Monte Carlo method, in order to describe the propagation of Ne and Ar ions in water. Violent nuclear collisions giving fragmentation process have been taken into account by use of the FREESCO program. We have tested the validity of our transport model and we show an important change of the energy deposition at the vicinity of the Bragg peak; such a distortion, due mainly to fragmentation reactions, is of a great interest for biological applications. (author).

Univalents and fragments in the meiosis of mammals

International Nuclear Information System (INIS)

Vyglenov, A.

1987-01-01

The manifestation of univalents and fragments in spermatocytes in diakinese-metaphase was studied on mice, rats, Syrian hamsters and rabbits irradiated with various dose rates. It was established that the incidence of the univalents resulting from the separation of the XY and autosomic bivalents and of the fragments did not depend on the dose rate and there were no differences between the control and the irradiated animals. A species specificity was found in the manifestation of the gonosomic and to some extent of the autosomic univalents. To a certain extent the differences in the incidence of the autosomic univalents and particularly of the fragments most probably were a consequence of the various measuring methods. In comparative aspect, the investigated mammals rank as follows: with the lowest incidence of univalents and fragments was the macaque-rhesus, with higher was the rat, followed by the Syrian hamster and with very high - the mouse and rabbit

A method for three-dimensional quantitative observation of the microstructure of biological samples

Science.gov (United States)

Wang, Pengfei; Chen, Dieyan; Ma, Wanyun; Wu, Hongxin; Ji, Liang; Sun, Jialin; Lv, Danyu; Zhang, Lu; Li, Ying; Tian, Ning; Zheng, Jinggao; Zhao, Fengying

2009-07-01

Contemporary biology has developed into the era of cell biology and molecular biology, and people try to study the mechanism of all kinds of biological phenomena at the microcosmic level now. Accurate description of the microstructure of biological samples is exigent need from many biomedical experiments. This paper introduces a method for 3-dimensional quantitative observation on the microstructure of vital biological samples based on two photon laser scanning microscopy (TPLSM). TPLSM is a novel kind of fluorescence microscopy, which has excellence in its low optical damage, high resolution, deep penetration depth and suitability for 3-dimensional (3D) imaging. Fluorescent stained samples were observed by TPLSM, and afterward the original shapes of them were obtained through 3D image reconstruction. The spatial distribution of all objects in samples as well as their volumes could be derived by image segmentation and mathematic calculation. Thus the 3-dimensionally and quantitatively depicted microstructure of the samples was finally derived. We applied this method to quantitative analysis of the spatial distribution of chromosomes in meiotic mouse oocytes at metaphase, and wonderful results came out last.

Cloning and expression of cell wall acid invertase gene fragment ...

African Journals Online (AJOL)

A fragment of invertase gene containing catalytic sites of cysteine was cloned from poinsettia (Euphorbia pulcherrima wild.) by using the polymerase chain reaction (PCR) method. The length of the fragment was 521 bp, encoding 173 amino acids and containing a part of open reading frames, but no intron. It had a high ...

Effect of local automatic control rods on three-dimensional calculations of the power distribution in an RBMK

International Nuclear Information System (INIS)

Pogosbekyan, L.R.; Lysov, D.A.; Bronitskii, L.L.

1993-01-01

Numerical simulators and information systems that support nuclear reactor operators must have fast models to estimate how fuel reloads and control rod displacement affect neutron and power distributions in the core. The consequences of reloads and control rod displacement cannot be evaluated correctly without considering local automatic control-rod operations in maintaining the radial power distribution. Fast three-dimensional models to estimate the effects of reloads and displacement of the control and safety rods have already been examined. I.V. Zonov et al. used the following assumptions in their calculational model: (1) the full-scale problem could be reduced a three-dimensional fragment of a locally perturbed core, and (2) the boundary conditions of the fragment and its total power were constant. The last assumption considers approximately how local automatic control rods stabilize the radial power distribution, but three dimensional calculations with these rods are not considered. These assumptions were introduced to obtain high computational speed. I.L. Bronitskii et al. considered in more detail how moving the local automatic control rods affect the power dimensional in the three-dimensional fragment, because, with on-line monitoring of the reload process, information on control rod positions is periodically renewed, and the calculations are done in real time. This model to predict the three-dimensional power distribution to (1) do a preliminary reload analysis, and (2) prepare the core for reloading did not consider the effect of perturbations from the local automatic control rods. Here we examine a model of a stationary neutron distribution. On one hand it gives results in an acceptable computation time; on the other it is a full-scale three-dimensional model and considers how local automatic control rods affect both the radial and axial power distribution

On a novel matrix method for three-dimensional photoelasticity

International Nuclear Information System (INIS)

Theocaris, P.S.; Gdoutos, E.E.

1978-01-01

A non-destructive method for the photoelastic determination of three-dimensional stress distributions, based on the Mueller and Jones calculi, is developed. The differential equations satisfied by the Stokes and Jones vectors, when a polarized light beam passes through a photoelastic model, presenting rotation of the secondary principal stress directions, are established in matrix form. The Peano-Baker method is used for the solution of these differential equations in a matrix series form, establishing the elements of the Mueller and Jones matrices of the photoelastic model. These matrices are experimentally determined by using different wavelengths in conjunction with Jones' 'equivalence theorem'. The Neumann equations are immediately deduced from the above-mentioned differential equations. (orig.) [de

Variational Homotopy Perturbation Method for Solving Higher Dimensional Initial Boundary Value Problems

Directory of Open Access Journals (Sweden)

Muhammad Aslam Noor

2008-01-01

Full Text Available We suggest and analyze a technique by combining the variational iteration method and the homotopy perturbation method. This method is called the variational homotopy perturbation method (VHPM. We use this method for solving higher dimensional initial boundary value problems with variable coefficients. The developed algorithm is quite efficient and is practically well suited for use in these problems. The proposed scheme finds the solution without any discritization, transformation, or restrictive assumptions and avoids the round-off errors. Several examples are given to check the reliability and efficiency of the proposed technique.

Charge distribution in the ternary fragmentation of {sup 252}Cf

Energy Technology Data Exchange (ETDEWEB)

Senthil Kannan, M.T.; Balasubramaniam, M. [Bharathiar University, Department of Physics, Coimbatore (India)

2017-08-15

We present here, for the first time, a study on ternary fragmentation charge distribution of {sup 252}Cf using the convolution integral method and the statistical theory. The charge distribution for all possible charge combinations of a ternary breakup are grouped as a bin containing different mass partitions. Different bins corresponding to various third fragments with mass numbers from A{sub 3} = 16 to 84 are identified with the available experimental masses. The corresponding potential energy surfaces are calculated using the three cluster model for the two arrangements A{sub 1} + A{sub 2} + A{sub 3} and A{sub 1} + A{sub 3} + A{sub 2}. The ternary fragmentation yield values are calculated for the ternary combination from each bin possessing minimum potential energy. The yields of the resulting ternary combinations as a function of the charge numbers of the three fragments are analyzed for both the arrangements. The calculations are carried out at different excitation energies of the parent nucleus. For each excitation energy the temperature of the three fragments are iteratively computed conserving the total energy. The distribution of fragment temperatures corresponding to different excitation energies for some fixed third fragments are discussed. The presence of the closed shell nucleus Sn in the favourable ternary fragmentation is highlighted. (orig.)

Binary aspects and particle multiplicities of the fragments from sup(nat)Ag+340 MeV 40Ar deep inelastic collisions

International Nuclear Information System (INIS)

Cauvin, B.; Jared, R.C.; Russo, P.; Schmitt, R.P.; Babinet, R.; Moretto, L.G.

1978-01-01

Deep inelastic fragments from the reaction sup(nat)Ag+340MeV 40 Ar have been studied in coincidence. Charged particles (10<=Z<=32) were detected and indentified in Z by means of a ΔE-E telescope, while the complementary fragments were detected in a one-dimensional solid-state position-sensitive detector. Both in-plane and out-of-plane correlations were measured. The results confirm the binary nature of the deep inelastic process for this reaction. From the measured energies and angles of the fragments and the atomic number of one of the fragments, it was possible to determine the total mass loss due to the de-excitation of the fragments as well as the total evaporated charge at symmetry. An iterative procedure is discussed which enables one to determine the masses and kinetic energies of the fragments before evaporation, as well as the total number of particles evaporated by each fragment. The widths of the in-plane and out-of-plane correlations agree with the results of the iterative calculations, as do evaporation calculations which are based on the charge equilibrium model. The experimental results support the charge equilibrium model and indicate that thermal equilibrium is achieved between the fragments at fixed mass asymmetry. (Auth.)

Dimensional analysis and qualitative methods in problem solving: II

International Nuclear Information System (INIS)

Pescetti, D

2009-01-01

We show that the underlying mathematical structure of dimensional analysis (DA), in the qualitative methods in problem-solving context, is the algebra of the affine spaces. In particular, we show that the qualitative problem-solving procedure based on the parallel decomposition of a problem into simple special cases yields the new original mathematical concepts of special points and special representations of affine spaces. A qualitative problem-solving algorithm piloted by the mathematics of DA is illustrated by a set of examples.

Image-Based Compression Method of Three-Dimensional Range Data with Texture

OpenAIRE

Chen, Xia; Bell, Tyler; Zhang, Song

2017-01-01

Recently, high speed and high accuracy three-dimensional (3D) scanning techniques and commercially available 3D scanning devices have made real-time 3D shape measurement and reconstruction possible. The conventional mesh representation of 3D geometry, however, results in large file sizes, causing difficulties for its storage and transmission. Methods for compressing scanned 3D data therefore become desired. This paper proposes a novel compression method which stores 3D range data within the c...

Topology optimization for three-dimensional electromagnetic waves using an edge element-based finite-element method.

Science.gov (United States)

Deng, Yongbo; Korvink, Jan G

2016-05-01

This paper develops a topology optimization procedure for three-dimensional electromagnetic waves with an edge element-based finite-element method. In contrast to the two-dimensional case, three-dimensional electromagnetic waves must include an additional divergence-free condition for the field variables. The edge element-based finite-element method is used to both discretize the wave equations and enforce the divergence-free condition. For wave propagation described in terms of the magnetic field in the widely used class of non-magnetic materials, the divergence-free condition is imposed on the magnetic field. This naturally leads to a nodal topology optimization method. When wave propagation is described using the electric field, the divergence-free condition must be imposed on the electric displacement. In this case, the material in the design domain is assumed to be piecewise homogeneous to impose the divergence-free condition on the electric field. This results in an element-wise topology optimization algorithm. The topology optimization problems are regularized using a Helmholtz filter and a threshold projection method and are analysed using a continuous adjoint method. In order to ensure the applicability of the filter in the element-wise topology optimization version, a regularization method is presented to project the nodal into an element-wise physical density variable.

Multisymplectic Structure-Preserving in Simple Finite Element Method in High Dimensional Case

Institute of Scientific and Technical Information of China (English)

BAI Yong-Qiang; LIU Zhen; PEI Ming; ZHENG Zhu-Jun

2003-01-01

In this paper, we study a finite element scheme of some semi-linear elliptic boundary value problems inhigh-dimensional space. With uniform mesh, we find that, the numerical scheme derived from finite element method cankeep a preserved multisymplectic structure.

Kernel based methods for accelerated failure time model with ultra-high dimensional data

Directory of Open Access Journals (Sweden)

Jiang Feng

2010-12-01

Full Text Available Abstract Background Most genomic data have ultra-high dimensions with more than 10,000 genes (probes. Regularization methods with L1 and Lp penalty have been extensively studied in survival analysis with high-dimensional genomic data. However, when the sample size n ≪ m (the number of genes, directly identifying a small subset of genes from ultra-high (m > 10, 000 dimensional data is time-consuming and not computationally efficient. In current microarray analysis, what people really do is select a couple of thousands (or hundreds of genes using univariate analysis or statistical tests, and then apply the LASSO-type penalty to further reduce the number of disease associated genes. This two-step procedure may introduce bias and inaccuracy and lead us to miss biologically important genes. Results The accelerated failure time (AFT model is a linear regression model and a useful alternative to the Cox model for survival analysis. In this paper, we propose a nonlinear kernel based AFT model and an efficient variable selection method with adaptive kernel ridge regression. Our proposed variable selection method is based on the kernel matrix and dual problem with a much smaller n × n matrix. It is very efficient when the number of unknown variables (genes is much larger than the number of samples. Moreover, the primal variables are explicitly updated and the sparsity in the solution is exploited. Conclusions Our proposed methods can simultaneously identify survival associated prognostic factors and predict survival outcomes with ultra-high dimensional genomic data. We have demonstrated the performance of our methods with both simulation and real data. The proposed method performs superbly with limited computational studies.

Right ventricular volume determination by two-dimensional echocardiography and radiography in model hearts using a subtraction method

International Nuclear Information System (INIS)

Krebs, W.; Erbel, R.; Schweizer, P.; Richter, H.A.; Massberg, I.; Meyer, J.; Effert, S.; Henn, G.

1982-01-01

The irregularity and complexity of the right ventricle is the reason why no accurate method for right ventricular volume determination exists. A new method for right ventricular volume determination particularly for two-dimensional echocardiography was developed - it is called subtraction method - and was compared with the pyramid and Simpson's methods. The partial volume of the left ventricle and septum was subtracted from total volume of right and left ventricle including interventricular septum. Thus right ventricular volume resulted. Total and partial volume were computer-assisted calculated by use of biplane methods, preferably Simpson's rule. The method was proved with thinwall silicon-rubber model hearts of the left and right ventricle. Two orthogonal planes in the long-axis were filmed by radiography or scanned in a water bath by two-dimensional echocardiography equivalent to RAO and LAO-projections of cineangiocardiograms or to four- and two-chamber views of apical two-dimensional echocardiograms. For calculation of the major axes of the elliptical sections, summed up by Simpson's rule, they were derived from the LAO-projection and the four-chamber view, respectively, the minor axis approximated from the RAO-projection and the two-chamber view. For comparison of direct-measured volume and two-dimensional echocardiographically determined volume, regression equation was given by y = 1.01 x - 3.2, correlation-coefficient, r = 0.977, and standard error of estimate (SEE) +-10.5 ml. For radiography, regression equation was y = 0.909 x + 13.3, r = 0.983, SEE = +-8.0 ml. For pyramid method and Simpson's rule, higher standard errors and lower correlation coefficients were found. Between radiography and two-dimensional echocardiography a mean difference of 4.3 +- 13.2 ml, using subtraction method, and -10.2 +- 22.9 ml, using pyramid method, as well as -0.6 +- 18.5 ml, using Simpson's rule, were calculated for right ventricular volume measurements. (orig./APR) [de

Large scale meta-analysis of fragment-based screening campaigns: privileged fragments and complementary technologies.

Science.gov (United States)

Kutchukian, Peter S; Wassermann, Anne Mai; Lindvall, Mika K; Wright, S Kirk; Ottl, Johannes; Jacob, Jaison; Scheufler, Clemens; Marzinzik, Andreas; Brooijmans, Natasja; Glick, Meir

2015-06-01

A first step in fragment-based drug discovery (FBDD) often entails a fragment-based screen (FBS) to identify fragment "hits." However, the integration of conflicting results from orthogonal screens remains a challenge. Here we present a meta-analysis of 35 fragment-based campaigns at Novartis, which employed a generic 1400-fragment library against diverse target families using various biophysical and biochemical techniques. By statistically interrogating the multidimensional FBS data, we sought to investigate three questions: (1) What makes a fragment amenable for FBS? (2) How do hits from different fragment screening technologies and target classes compare with each other? (3) What is the best way to pair FBS assay technologies? In doing so, we identified substructures that were privileged for specific target classes, as well as fragments that were privileged for authentic activity against many targets. We also revealed some of the discrepancies between technologies. Finally, we uncovered a simple rule of thumb in screening strategy: when choosing two technologies for a campaign, pairing a biochemical and biophysical screen tends to yield the greatest coverage of authentic hits. © 2014 Society for Laboratory Automation and Screening.

Exact rebinning methods for three-dimensional PET.

Science.gov (United States)

Liu, X; Defrise, M; Michel, C; Sibomana, M; Comtat, C; Kinahan, P; Townsend, D

1999-08-01

The high computational cost of data processing in volume PET imaging is still hindering the routine application of this successful technique, especially in the case of dynamic studies. This paper describes two new algorithms based on an exact rebinning equation, which can be applied to accelerate the processing of three-dimensional (3-D) PET data. The first algorithm, FOREPROJ, is a fast-forward projection algorithm that allows calculation of the 3-D attenuation correction factors (ACF's) directly from a two-dimensional (2-D) transmission scan, without first reconstructing the attenuation map and then performing a 3-D forward projection. The use of FOREPROJ speeds up the estimation of the 3-D ACF's by more than a factor five. The second algorithm, FOREX, is a rebinning algorithm that is also more than five times faster, compared to the standard reprojection algorithm (3DRP) and does not suffer from the image distortions generated by the even faster approximate Fourier rebinning (FORE) method at large axial apertures. However, FOREX is probably not required by most existing scanners, as the axial apertures are not large enough to show improvements over FORE with clinical data. Both algorithms have been implemented and applied to data simulated for a scanner with a large axial aperture (30 degrees), and also to data acquired with the ECAT HR and the ECAT HR+ scanners. Results demonstrate the excellent accuracy achieved by these algorithms and the important speedup when the sinogram sizes are powers of two.

In silico fragment-based drug design.

Science.gov (United States)

Konteatis, Zenon D

2010-11-01

In silico fragment-based drug design (FBDD) is a relatively new approach inspired by the success of the biophysical fragment-based drug discovery field. Here, we review the progress made by this approach in the last decade and showcase how it complements and expands the capabilities of biophysical FBDD and structure-based drug design to generate diverse, efficient drug candidates. Advancements in several areas of research that have enabled the development of in silico FBDD and some applications in drug discovery projects are reviewed. The reader is introduced to various computational methods that are used for in silico FBDD, the fragment library composition for this technique, special applications used to identify binding sites on the surface of proteins and how to assess the druggability of these sites. In addition, the reader will gain insight into the proper application of this approach from examples of successful programs. In silico FBDD captures a much larger chemical space than high-throughput screening and biophysical FBDD increasing the probability of developing more diverse, patentable and efficient molecules that can become oral drugs. The application of in silico FBDD holds great promise for historically challenging targets such as protein-protein interactions. Future advances in force fields, scoring functions and automated methods for determining synthetic accessibility will all aid in delivering more successes with in silico FBDD.

The ADO-nodal method for solving two-dimensional discrete ordinates transport problems

International Nuclear Information System (INIS)

Barichello, L.B.; Picoloto, C.B.; Cunha, R.D. da

2017-01-01

Highlights: • Two-dimensional discrete ordinates neutron transport. • Analytical Discrete Ordinates (ADO) nodal method. • Heterogeneous media fixed source problems. • Local solutions. - Abstract: In this work, recent results on the solution of fixed-source two-dimensional transport problems, in Cartesian geometry, are reported. Homogeneous and heterogeneous media problems are considered in order to incorporate the idea of arbitrary number of domain division into regions (nodes) when applying the ADO method, which is a method of analytical features, to those problems. The ADO-nodal formulation is developed, for each node, following previous work devoted to heterogeneous media problem. Here, however, the numerical procedure is extended to higher number of domain divisions. Such extension leads, in some cases, to the use of an iterative method for solving the general linear system which defines the arbitrary constants of the general solution. In addition to solve alternative heterogeneous media configurations than reported in previous works, the present approach allows comparisons with results provided by other metodologies generated with refined meshes. Numerical results indicate the ADO solution may achieve a prescribed accuracy using coarser meshes than other schemes.

Experimental study on two-dimensional film flow with local measurement methods

Energy Technology Data Exchange (ETDEWEB)

Yang, Jin-Hwa, E-mail: evo03@snu.ac.kr [Nuclear Thermal-Hydraulic Engineering Laboratory, Seoul National University, Gwanak 599, Gwanak-ro, Gwanak-gu, Seoul 151-742 (Korea, Republic of); Korea Atomic Energy Research Institute, 989-111, Daedeok-daero, Yuseong-gu, Daejeon 305-600 (Korea, Republic of); Cho, Hyoung-Kyu [Nuclear Thermal-Hydraulic Engineering Laboratory, Seoul National University, Gwanak 599, Gwanak-ro, Gwanak-gu, Seoul 151-742 (Korea, Republic of); Kim, Seok [Korea Atomic Energy Research Institute, 989-111, Daedeok-daero, Yuseong-gu, Daejeon 305-600 (Korea, Republic of); Euh, Dong-Jin, E-mail: djeuh@kaeri.re.kr [Korea Atomic Energy Research Institute, 989-111, Daedeok-daero, Yuseong-gu, Daejeon 305-600 (Korea, Republic of); Park, Goon-Cherl [Nuclear Thermal-Hydraulic Engineering Laboratory, Seoul National University, Gwanak 599, Gwanak-ro, Gwanak-gu, Seoul 151-742 (Korea, Republic of)

2015-12-01

Highlights: • An experimental study on the two-dimensional film flow with lateral air injection was performed. • The ultrasonic thickness gauge was used to measure the local liquid film thickness. • The depth-averaged PIV (Particle Image Velocimetry) method was applied to measure the local liquid film velocity. • The uncertainty of the depth-averaged PIV was quantified with a validation experiment. • Characteristics of two-dimensional film flow were classified following the four different flow patterns. - Abstract: In an accident condition of a nuclear reactor, multidimensional two-phase flows may occur in the reactor vessel downcomer and reactor core. Therefore, those have been regarded as important issues for an advanced thermal-hydraulic safety analysis. In particular, the multi-dimensional two-phase flow in the upper downcomer during the reflood phase of large break loss of coolant accident appears with an interaction between a downward liquid and a transverse gas flow, which determines the bypass flow rate of the emergency core coolant and subsequently, the reflood coolant flow rate. At present, some thermal-hydraulic analysis codes incorporate multidimensional modules for the nuclear reactor safety analysis. However, their prediction capability for the two-phase cross flow in the upper downcomer has not been validated sufficiently against experimental data based on local measurements. For this reason, an experimental study was carried out for the two-phase cross flow to clarify the hydraulic phenomenon and provide local measurement data for the validation of the computational tools. The experiment was performed in a 1/10 scale unfolded downcomer of Advanced Power Reactor 1400 (APR1400). Pitot tubes, a depth-averaged PIV method and ultrasonic thickness gauge were applied for local measurement of the air velocity, the liquid film velocity and the liquid film thickness, respectively. The uncertainty of the depth-averaged PIV method for the averaged

Experimental study on two-dimensional film flow with local measurement methods

International Nuclear Information System (INIS)

Yang, Jin-Hwa; Cho, Hyoung-Kyu; Kim, Seok; Euh, Dong-Jin; Park, Goon-Cherl

2015-01-01

Highlights: • An experimental study on the two-dimensional film flow with lateral air injection was performed. • The ultrasonic thickness gauge was used to measure the local liquid film thickness. • The depth-averaged PIV (Particle Image Velocimetry) method was applied to measure the local liquid film velocity. • The uncertainty of the depth-averaged PIV was quantified with a validation experiment. • Characteristics of two-dimensional film flow were classified following the four different flow patterns. - Abstract: In an accident condition of a nuclear reactor, multidimensional two-phase flows may occur in the reactor vessel downcomer and reactor core. Therefore, those have been regarded as important issues for an advanced thermal-hydraulic safety analysis. In particular, the multi-dimensional two-phase flow in the upper downcomer during the reflood phase of large break loss of coolant accident appears with an interaction between a downward liquid and a transverse gas flow, which determines the bypass flow rate of the emergency core coolant and subsequently, the reflood coolant flow rate. At present, some thermal-hydraulic analysis codes incorporate multidimensional modules for the nuclear reactor safety analysis. However, their prediction capability for the two-phase cross flow in the upper downcomer has not been validated sufficiently against experimental data based on local measurements. For this reason, an experimental study was carried out for the two-phase cross flow to clarify the hydraulic phenomenon and provide local measurement data for the validation of the computational tools. The experiment was performed in a 1/10 scale unfolded downcomer of Advanced Power Reactor 1400 (APR1400). Pitot tubes, a depth-averaged PIV method and ultrasonic thickness gauge were applied for local measurement of the air velocity, the liquid film velocity and the liquid film thickness, respectively. The uncertainty of the depth-averaged PIV method for the averaged

Simulation of a relativistic heavy ions beam transport in the matter: contribution of the fragmentation process and biological implications

International Nuclear Information System (INIS)

Ibnouzahir, M.

1995-03-01

The study of relativistic heavy ion collisions permit an approach of the properties of dense and not hadronic matter, and an analysis of the reaction mechanisms. Such studies are also interesting on the biological point of view, since there exist now well defined projects concerning the radiotherapy with high LET particles as neutrons, protons, heavy ions. It is thus necessary to have a good understanding of the processes which occur in the propagation of a relativistic heavy ion beam (E≥ 100 A.MeV) in matter. We have elaborated a three dimensional transport code, using a Monte Carlo method, in order to describe the propagation of Ne and Ar ions in water. Violent nuclear collisions giving fragmentation process have been taken into account by use of the FREESCO program. We have tested the validity of our transport model and we show an important change of the energy deposition at the vicinity of the Bragg peak; such a distortion, due mainly to fragmentation reactions, is of a great interest for biological applications. (author)

When fragments link: a bibliometric perspective on the development of fragment-based drug discovery.

Science.gov (United States)

Romasanta, Angelo K S; van der Sijde, Peter; Hellsten, Iina; Hubbard, Roderick E; Keseru, Gyorgy M; van Muijlwijk-Koezen, Jacqueline; de Esch, Iwan J P

2018-05-05

Fragment-based drug discovery (FBDD) is a highly interdisciplinary field, rich in ideas integrated from pharmaceutical sciences, chemistry, biology, and physics, among others. To enrich our understanding of the development of the field, we used bibliometric techniques to analyze 3642 publications in FBDD, complementing accounts by key practitioners. Mapping its core papers, we found the transfer of knowledge from academia to industry. Co-authorship analysis showed that university-industry collaboration has grown over time. Moreover, we show how ideas from other scientific disciplines have been integrated into the FBDD paradigm. Keyword analysis showed that the field is organized into four interconnected practices: library design, fragment screening, computational methods, and optimization. This study highlights the importance of interactions among various individuals and institutions from diverse disciplines in newly emerging scientific fields. Copyright © 2018. Published by Elsevier Ltd.

THE FRAGMENTATION OF MAGNETIZED, MASSIVE STAR-FORMING CORES WITH RADIATIVE FEEDBACK

Energy Technology Data Exchange (ETDEWEB)

Myers, Andrew T.; McKee, Christopher F. [Department of Physics, University of California, Berkeley, Berkeley, CA 94720 (United States); Cunningham, Andrew J. [Lawrence Livermore National Laboratory, P.O. Box 808, L-23, Livermore, CA 94550 (United States); Klein, Richard I. [Department of Astronomy, University of California, Berkeley, Berkeley, CA 94720 (United States); Krumholz, Mark R., E-mail: atmyers@berkeley.edu [Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States)

2013-04-01

We present a set of three-dimensional, radiation-magnetohydrodynamic calculations of the gravitational collapse of massive (300 M{sub Sun }), star-forming molecular cloud cores. We show that the combined effects of magnetic fields and radiative feedback strongly suppress core fragmentation, leading to the production of single-star systems rather than small clusters. We find that the two processes are efficient at suppressing fragmentation in different regimes, with the feedback most effective in the dense, central region and the magnetic field most effective in more diffuse, outer regions. Thus, the combination of the two is much more effective at suppressing fragmentation than either one considered in isolation. Our work suggests that typical massive cores, which have mass-to-flux ratios of about 2 relative to critical, likely form a single-star system, but that cores with weaker fields may form a small star cluster. This result helps us understand why the observed relationship between the core mass function and the stellar initial mass function holds even for {approx}100 M{sub Sun} cores with many thermal Jeans masses of material. We also demonstrate that a {approx}40 AU Keplerian disk is able to form in our simulations, despite the braking effect caused by the strong magnetic field.

File Type Identification of File Fragments using Longest Common Subsequence (LCS)

Science.gov (United States)

Rahmat, R. F.; Nicholas, F.; Purnamawati, S.; Sitompul, O. S.

2017-01-01

Computer forensic analyst is a person in charge of investigation and evidence tracking. In certain cases, the file needed to be presented as digital evidence was deleted. It is difficult to reconstruct the file, because it often lost its header and cannot be identified while being restored. Therefore, a method is required for identifying the file type of file fragments. In this research, we propose Longest Common Subsequences that consists of three steps, namely training, testing and validation, to identify the file type from file fragments. From all testing results we can conlude that our proposed method works well and achieves 92.91% of accuracy to identify the file type of file fragment for three data types.

Fragment-based drug design.

Science.gov (United States)

Feyfant, Eric; Cross, Jason B; Paris, Kevin; Tsao, Désirée H H

2011-01-01

Fragment-based drug design (FBDD), which is comprised of both fragment screening and the use of fragment hits to design leads, began more than 15 years ago and has been steadily gaining in popularity and utility. Its origin lies on the fact that the coverage of chemical space and the binding efficiency of hits are directly related to the size of the compounds screened. Nevertheless, FBDD still faces challenges, among them developing fragment screening libraries that ensure optimal coverage of chemical space, physical properties and chemical tractability. Fragment screening also requires sensitive assays, often biophysical in nature, to detect weak binders. In this chapter we will introduce the technologies used to address these challenges and outline the experimental advantages that make FBDD one of the most popular new hit-to-lead process.

Research of nuclear fragmentation characteristics

International Nuclear Information System (INIS)

Richert, J.

1989-01-01

Motivations for the study of nuclear fragmentation are presented. Different models and methods which were developed in the past are reviewed, critically discussed and confronted in connection with the experimental information gathered over the past years. Specific aspects related to the onset of the process, its characteristics and the mechanism which governs it are discussed [fr

Improved non-dimensional dynamic influence function method for vibration analysis of arbitrarily shaped plates with clamped edges

Directory of Open Access Journals (Sweden)

Sang-Wook Kang

2016-03-01

Full Text Available A new formulation for the non-dimensional dynamic influence function method, which was developed by the authors, is proposed to efficiently extract eigenvalues and mode shapes of clamped plates with arbitrary shapes. Compared with the finite element and boundary element methods, the non-dimensional dynamic influence function method yields highly accurate solutions in eigenvalue analysis problems of plates and membranes including acoustic cavities. However, the non-dimensional dynamic influence function method requires the uneconomic procedure of calculating the singularity of a system matrix in the frequency range of interest for extracting eigenvalues because it produces a non-algebraic eigenvalue problem. This article describes a new approach that reduces the problem of free vibrations of clamped plates to an algebraic eigenvalue problem, the solution of which is straightforward. The validity and efficiency of the proposed method are illustrated through several numerical examples.

Shroud leakage flow models and a multi-dimensional coupling CFD (computational fluid dynamics) method for shrouded turbines

International Nuclear Information System (INIS)

Zou, Zhengping; Liu, Jingyuan; Zhang, Weihao; Wang, Peng

2016-01-01

Multi-dimensional coupling simulation is an effective approach for evaluating the flow and aero-thermal performance of shrouded turbines, which can balance the simulation accuracy and computing cost effectively. In this paper, 1D leakage models are proposed based on classical jet theories and dynamics equations, which can be used to evaluate most of the main features of shroud leakage flow, including the mass flow rate, radial and circumferential momentum, temperature and the jet width. Then, the 1D models are expanded to 2D distributions on the interface by using a multi-dimensional scaling method. Based on the models and multi-dimensional scaling, a multi-dimensional coupling simulation method for shrouded turbines is developed, in which, some boundary source and sink are set on the interface between the shroud and the main flow passage. To verify the precision, some simulations on the design point and off design points of a 1.5 stage turbine are conducted. It is indicated that the models and methods can give predictions with sufficient accuracy for most of the flow field features and will contribute to pursue deeper understanding and better design methods of shrouded axial turbines, which are the important devices in energy engineering. - Highlights: • Free and wall attached jet theories are used to model the leakage flow in shrouds. • Leakage flow rate is modeled by virtual labyrinth number and residual-energy factor. • A scaling method is applied to 1D model to obtain 2D distributions on interfaces. • A multi-dimensional coupling CFD method for shrouded turbines is proposed. • The proposed coupling method can give accurate predictions with low computing cost.

Inclusive characteristics of the nuclear target fragmentation products induced by relativistic particles

International Nuclear Information System (INIS)

Bogatin, V.I.; Ganza, E.A.; Lozhkin, O.V.; Murin, Yu.A.; Oplavin, V.S.; Perfilov, N.A.; Yakovlev, Yu.P.

1981-01-01

An experimental investigation of inclusive characteristics of nuclei-target fragmentation is conducted for further development and test of physical value of the earlier suggested nuclear fragmentation model based on the connection of the fragmentation with fluctuations of the quasiparticle density in the two-component quantum liquid, an experimental investigation of the inclusive characteristics of the nuclei-target fragmentation is carried out. The processes of sup(3, 4, 6, 8)He and sup(6, 7, 8, 9, 11)Li fragment formation during the interaction of relativistic protons (Esub(p)=6.7 GeV) and deutrons (Esub(d)=3.1 GeV) with 112 Sn and 124 Sn isotopes are studied by the method of semiconductive ΔE-E detectors. Differential energy spectra of fragments and isotopic ratio of cross sections of their formation as well as data on the dependence of isotopic ratios of fragmentation cross sections on the energy of incident particles and on the fragment energy are obtained. Presented is a phenomenological model of fragmentation within the frames of which the obtained experimental data are analyzed [ru

Analysis of Elastic-Plastic J Integrals for 3-Dimensional Cracks Using Finite Element Alternating Method

International Nuclear Information System (INIS)

Park, Jai Hak

2009-01-01

SGBEM(Symmetric Galerkin Boundary Element Method)-FEM alternating method has been proposed by Nikishkov, Park and Atluri. In the proposed method, arbitrarily shaped three-dimensional crack problems can be solved by alternating between the crack solution in an infinite body and the finite element solution without a crack. In the previous study, the SGBEM-FEM alternating method was extended further in order to solve elastic-plastic crack problems and to obtain elastic-plastic stress fields. For the elastic-plastic analysis the algorithm developed by Nikishkov et al. is used after modification. In the algorithm, the initial stress method is used to obtain elastic-plastic stress and strain fields. In this paper, elastic-plastic J integrals for three-dimensional cracks are obtained using the method. For that purpose, accurate values of displacement gradients and stresses are necessary on an integration path. In order to improve the accuracy of stress near crack surfaces, coordinate transformation and partitioning of integration domain are used. The coordinate transformation produces a transformation Jacobian, which cancels the singularity of the integrand. Using the developed program, simple three-dimensional crack problems are solved and elastic and elastic-plastic J integrals are obtained. The obtained J integrals are compared with the values obtained using a handbook solution. It is noted that J integrals obtained from the alternating method are close to the values from the handbook

Effectiveness in detecting fission fragments with ionization chambers

International Nuclear Information System (INIS)

Manrique Garcia, J.; Monne, G.

1991-01-01

Detection of fission fragments is important in nuclear measurements. When a high detection accuracy is required it is necessary to take in account the detection losses due to the absorption of fragments in the fissionable material. The losses corrections might change the final results in 2-3%. The traditional expression used in the calculation of the detection efficiency does not consider neither the density variation of the fissionable substance with its width, because it depends on the target material. That's why actually in many labs it is being searched new methods that allow to find the efficiency for each target. In this work a new method for determination of absorption efficiency is presented. The obtained results are analyzed

Looking for bimodal distributions in multi-fragmentation reactions

International Nuclear Information System (INIS)

Gulminelli, F.

2007-01-01

The presence of a phase transition in a finite system can be deduced, together with its order, from the form of the distribution of the order parameter. This issue has been extensively studied in multifragmentation experiments, with results that do not appear fully consistent. In this paper we discuss the effect of the statistical ensemble or sorting conditions on the form of fragment distributions, and propose a new method, which can be easily implemented experimentally, to discriminate between different fragmentation scenarios. This method, based on a re-weighting of the measured distribution to account for the experimental constraints linked to the energy deposit, is tested on different simple models, and appears to provide a powerful discrimination. (author)

Study of the dynamic fragmentation of laser shock-loaded metallic target

International Nuclear Information System (INIS)

Lescoute, E.

2010-01-01

The irradiation of a metallic target by a high power laser pulse induces a shock wave in the material. Under some conditions, it leads to the production of high velocity ejecta which can damage the optical environment (lenses, mirrors, windows, etc.). With the ongoing development of high energy laser facilities designed to achieve inertial confinement fusion, such as the Laser MegaJoule in France or the National Ignition Facility in the USA, the question of debris ejection from metallic samples subjected to intense laser irradiation has become a key issue. It is necessary to understand fragmentation processes induced by laser shock, and to anticipate and quantify generated fragments, in order to design suitable protections and experiments, and to preserve laser facilities. The main fragmentation processes which can occur in a laser-shock-loaded metallic target and generate high velocity ejecta are: (i) micro-jetting, which occurs upon reflection of the incident compressive front from the free surface, (ii) spallation, which is due to the later interaction of the release wave reflected from that surface with the incident unloading wave and (iii) dynamic punching of thin targets. Experimental campaigns have been performed on high energy laser facilities in the Centre d'Etudes Scientifiques et Techniques d'Aquitaine (CESTA, CEA, Alise facility) and in the Laboratoire pour l'Utilisation des Lasers Intenses (LULI, Ecole Polytechnique, LULI 2000 facility). Gold and aluminium have been mainly studied because they are the two main metallic components of the target which will be used to achieved the inertial confinement fusion. Specific diagnostics have been developed and used during these experiments to study the dynamic fragmentation: transverse shadowgraphy, free surface velocity measurement and recovery of generated fragments. Experimental results have been compared with numerical predictions obtained with a bi-dimensional hydrodynamic code, where a specific numerical

Distinguishing Aspartic and Isoaspartic Acids in Peptides by Several Mass Spectrometric Fragmentation Methods

Science.gov (United States)

DeGraan-Weber, Nick; Zhang, Jun; Reilly, James P.

2016-12-01

Six ion fragmentation techniques that can distinguish aspartic acid from its isomer, isoaspartic acid, were compared. MALDI post-source decay (PSD), MALDI 157 nm photodissociation, tris(2,4,6-trimethoxyphenyl)phosphonium bromide (TMPP) charge tagging in PSD and photodissociation, ESI collision-induced dissociation (CID), electron transfer dissociation (ETD), and free-radical initiated peptide sequencing (FRIPS) with CID were applied to peptides containing either aspartic or isoaspartic acid. Diagnostic ions, such as the y-46 and b+H2O, are present in PSD, photodissociation, and charge tagging. c•+57 and z-57 ions are observed in ETD and FRIPS experiments. For some molecules, aspartic and isoaspartic acid yield ion fragments with significantly different intensities. ETD and charge tagging appear to be most effective at distinguishing these residues.

A method for three-dimensional structural analysis of reinforced concrete containment

International Nuclear Information System (INIS)

Kulak, R.F.; Fiala, C.

1989-01-01

A finite element method designed to assist reactor safety analysts in the three-dimensional numerical simulation of reinforced concrete containments to normal and off-normal mechanical loadings is presented. The development of a lined reinforced concrete plate element is described in detail, and the implementation of an empirical transverse shear failure criteria is discussed. The method is applied to the analysis of a 1/6th scale reinforced concrete containment model subjected to static internal pressurization. 11 refs., 14 figs., 1 tab

Site-specific fab fragment biotinylation at the conserved nucleotide binding site for enhanced Ebola detection.

Science.gov (United States)

Mustafaoglu, Nur; Alves, Nathan J; Bilgicer, Basar

2015-07-01

The nucleotide binding site (NBS) is a highly conserved region between the variable light and heavy chains at the Fab domains of all antibodies, and a small molecule that we identified, indole-3-butyric acid (IBA), binds specifically to this site. Fab fragment, with its small size and simple production methods compared to intact antibody, is good candidate for use in miniaturized diagnostic devices and targeted therapeutic applications. However, commonly used modification techniques are not well suited for Fab fragments as they are often more delicate than intact antibodies. Fab fragments are of particular interest for sensor surface functionalization but immobilization results in damage to the antigen binding site and greatly reduced activity due to their truncated size that allows only a small area that can bind to surfaces without impeding antigen binding. In this study, we describe an NBS-UV photocrosslinking functionalization method (UV-NBS(Biotin) in which a Fab fragment is site-specifically biotinylated with an IBA-EG11-Biotin linker via UV energy exposure (1 J/cm(2)) without affecting its antigen binding activity. This study demonstrates successful immobilization of biotinylated Ebola detecting Fab fragment (KZ52 Fab fragment) via the UV-NBS(Biotin) method yielding 1031-fold and 2-fold better antigen detection sensitivity compared to commonly used immobilization methods: direct physical adsorption and NHS-Biotin functionalization, respectively. Utilization of the UV-NBS(Biotin) method for site-specific conjugation to Fab fragment represents a proof of concept use of Fab fragment for various diagnostic and therapeutic applications with numerous fluorescent probes, affinity molecules and peptides. © 2015 Wiley Periodicals, Inc.

Mathematical processing of experimental data on neutron yield from separate fission fragments

International Nuclear Information System (INIS)

Basova, B.G.; Rabinovich, A.D.; Ryazanov, D.K.

1975-01-01

The algorithm is described for processing the multi-dimensional experiments on measurements of prompt emission of neutrons from separate fission fragments. While processing the data the effect of a number of experimental corrections is correctly taken into account; random coincidence background, neutron spectrum, neutron detector efficiency, instrument angular resolution. On the basis of the described algorithm a program for BESM-4 computer is realized and the treatment of experimental data is performed according to the spontaneous fission of 252 Cf

An improved method for computer generation of three-dimensional digital holography

International Nuclear Information System (INIS)

Hu, Yanlei; Chen, Yuhang; Li, Jiawen; Huang, Wenhao; Chu, Jiaru; Ma, Jianqiang

2013-01-01

A novel method is proposed for designing optimized three-dimensional computer-generated holograms (CGHs). A series of spherical wave factors are introduced into the conventional optimal rotation angle (ORA) algorithm to achieve a varying amount of defocus along the optical axis, and the distraction terms are minimized during the iterative process. Both numerical simulation and experimental reconstructions are presented to demonstrate that this method is able to yield excellent multilayer patterns with high uniformity and signal-to-noise ratio (SNR). This method is significant for applications in laser 3D printing and multilayer data recording. (paper)

Approximate solutions for the two-dimensional integral transport equation. The critically mixed methods of resolution

International Nuclear Information System (INIS)

Sanchez, Richard.

1980-11-01

This work is divided into two part the first part (note CEA-N-2165) deals with the solution of complex two-dimensional transport problems, the second one treats the critically mixed methods of resolution. These methods are applied for one-dimensional geometries with highly anisotropic scattering. In order to simplify the set of integral equation provided by the integral transport equation, the integro-differential equation is used to obtain relations that allow to lower the number of integral equation to solve; a general mathematical and numerical study is presented [fr

Fragment-based drug discovery and its application to challenging drug targets.

Science.gov (United States)

Price, Amanda J; Howard, Steven; Cons, Benjamin D

2017-11-08

Fragment-based drug discovery (FBDD) is a technique for identifying low molecular weight chemical starting points for drug discovery. Since its inception 20 years ago, FBDD has grown in popularity to the point where it is now an established technique in industry and academia. The approach involves the biophysical screening of proteins against collections of low molecular weight compounds (fragments). Although fragments bind to proteins with relatively low affinity, they form efficient, high quality binding interactions with the protein architecture as they have to overcome a significant entropy barrier to bind. Of the biophysical methods available for fragment screening, X-ray protein crystallography is one of the most sensitive and least prone to false positives. It also provides detailed structural information of the protein-fragment complex at the atomic level. Fragment-based screening using X-ray crystallography is therefore an efficient method for identifying binding hotspots on proteins, which can then be exploited by chemists and biologists for the discovery of new drugs. The use of FBDD is illustrated here with a recently published case study of a drug discovery programme targeting the challenging protein-protein interaction Kelch-like ECH-associated protein 1:nuclear factor erythroid 2-related factor 2. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Putative in vitro expressed gene fragments unique to Mycobacterium avium subspecies para tuberculosis

DEFF Research Database (Denmark)

Nielsen, Kirstine Klitgaard; Ahrens, Peter

2002-01-01

By a suppression subtractive hybridization based method, nine novel Mycobacterium avium subsp. para tuberculosis (M. para tuberculosis) fragments of between 318 and 596 bp have been identified and characterized. Database search revealed little or no similarity with other mycobacteria. The uniquen......By a suppression subtractive hybridization based method, nine novel Mycobacterium avium subsp. para tuberculosis (M. para tuberculosis) fragments of between 318 and 596 bp have been identified and characterized. Database search revealed little or no similarity with other mycobacteria....... The uniqueness and diagnostic potential of seven of these fragments in relation to M. paratuberculosis closest relative Mycobacterium avium subsp. avium (M. avium) was confirmed by species-specific PCR and Southern blot. Furthermore, RT-PCR indicated that eight of the nine fragments originate from areas...

Fragmentation in the branching coral Acropora palmata (Lamarck): growth, survivorship, and reproduction of colonies and fragments.

Science.gov (United States)

Lirman

2000-08-23

Acropora palmata, a branching coral abundant on shallow reef environments throughout the Caribbean, is susceptible to physical disturbance caused by storms. Accordingly, the survivorship and propagation of this species are tied to its capability to recover after fragmentation. Fragments of A. palmata comprised 40% of ramets within populations that had experienced recent storms. While the survivorship of A. palmata fragments was not directly related to the size of fragments, removal of fragments from areas where they settled was influenced by size. Survivorship of fragments was also affected by type of substratum; the greatest mortality (58% loss within the first month) was observed on sand, whereas fragments placed on top of live colonies of A. palmata fused to the underlying tissue and did not experience any losses. Fragments created by Hurricane Andrew on a Florida reef in August 1992 began developing new growth (proto-branches) 7 months after the storm. The number of proto-branches on fragments was dependent on size, but growth was not affected by the size of fragments. Growth-rates of proto-branches increased exponentially with time (1.7 cm year(-1) for 1993-1994, 2.7 cm year(-1) for 1994-1995, 4.2 cm year(-1) for 1995-1996, and 6.5 cm year(-1) for 1996-1997), taking over 4 years for proto-branches to achieve rates comparable to those of adult colonies on the same reef (6.9 cm year(-1)). In addition to the initial mortality and reduced growth-rates, fragmentation resulted in a loss of reproductive potential. Neither colonies that experienced severe fragmentation nor fragments contained gametes until 4 years after the initial damage. Although A. palmata may survive periodic fragmentation, the long-term effects of this process will depend ultimately on the balance between the benefits and costs of this process.