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Sample records for affinity calculation based

  1. Fragment-based quantum mechanical calculation of protein-protein binding affinities.

    Science.gov (United States)

    Wang, Yaqian; Liu, Jinfeng; Li, Jinjin; He, Xiao

    2018-04-29

    The electrostatically embedded generalized molecular fractionation with conjugate caps (EE-GMFCC) method has been successfully utilized for efficient linear-scaling quantum mechanical (QM) calculation of protein energies. In this work, we applied the EE-GMFCC method for calculation of binding affinity of Endonuclease colicin-immunity protein complex. The binding free energy changes between the wild-type and mutants of the complex calculated by EE-GMFCC are in good agreement with experimental results. The correlation coefficient (R) between the predicted binding energy changes and experimental values is 0.906 at the B3LYP/6-31G*-D level, based on the snapshot whose binding affinity is closest to the average result from the molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) calculation. The inclusion of the QM effects is important for accurate prediction of protein-protein binding affinities. Moreover, the self-consistent calculation of PB solvation energy is required for accurate calculations of protein-protein binding free energies. This study demonstrates that the EE-GMFCC method is capable of providing reliable prediction of relative binding affinities for protein-protein complexes. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  2. Calculation of protein-ligand binding affinities.

    Science.gov (United States)

    Gilson, Michael K; Zhou, Huan-Xiang

    2007-01-01

    Accurate methods of computing the affinity of a small molecule with a protein are needed to speed the discovery of new medications and biological probes. This paper reviews physics-based models of binding, beginning with a summary of the changes in potential energy, solvation energy, and configurational entropy that influence affinity, and a theoretical overview to frame the discussion of specific computational approaches. Important advances are reported in modeling protein-ligand energetics, such as the incorporation of electronic polarization and the use of quantum mechanical methods. Recent calculations suggest that changes in configurational entropy strongly oppose binding and must be included if accurate affinities are to be obtained. The linear interaction energy (LIE) and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) methods are analyzed, as are free energy pathway methods, which show promise and may be ready for more extensive testing. Ultimately, major improvements in modeling accuracy will likely require advances on multiple fronts, as well as continued validation against experiment.

  3. Excited state electron affinity calculations for aluminum

    Science.gov (United States)

    Hussein, Adnan Yousif

    2017-08-01

    Excited states of negative aluminum ion are reviewed, and calculations of electron affinities of the states (3s^23p^2)^1D and (3s3p^3){^5}{S}° relative to the (3s^23p)^2P° and (3s3p^2)^4P respectively of the neutral aluminum atom are reported in the framework of nonrelativistic configuration interaction (CI) method. A priori selected CI (SCI) with truncation energy error (Bunge in J Chem Phys 125:014107, 2006) and CI by parts (Bunge and Carbó-Dorca in J Chem Phys 125:014108, 2006) are used to approximate the valence nonrelativistic energy. Systematic studies of convergence of electron affinity with respect to the CI excitation level are reported. The calculated value of the electron affinity for ^1D state is 78.675(3) meV. Detailed Calculations on the ^5S°c state reveals that is 1216.8166(3) meV below the ^4P state.

  4. Importance of Accurate Charges in Binding Affinity Calculations: A Case of Neuraminidase Series

    Energy Technology Data Exchange (ETDEWEB)

    Park, Kichul; Kyun, Nack Sung; Cho, Art E. [Korea Univ., Sejong (Korea, Republic of)

    2013-02-15

    It has been shown that calculating atomic charges using quantum mechanical level theory greatly improves the accuracy of docking. A protocol was developed and shown to be effective. That this protocol works is just a manifestation of the fact that electrostatic interactions are important in protein-ligand binding. In order to investigate how the same protocol helps in prediction of binding affinities, we took a series of known cocrystal structures of influenza neuraminidase inhibitors with the receptor and performed docking with Glide SP, Glide XP, and QPLD, the last being a workflow that incorporates QM/MM calculations to replace the fixed atomic charges of force fields with quantum mechanically recalculated ones at a given docking pose, and predicted the binding affinities of each cocrystal. The correlation with experimental binding affinities considerably improved with QPLD compared to Glide SP/XP yielding r{sup 2} = 0.83. The results suggest that for binding sites, such as that of neuraminidase, which are laden with hydrophilic residues, protocols such as QPLD which utilizes QM-based atomic charges can better predict the binding affinities.

  5. Permanent and induced dipole requirements in ab initio calculations of electron affinities of polar molecules

    International Nuclear Information System (INIS)

    Garrett, W.R.

    1979-01-01

    Through the use of a molecular pseudopotential method, we determine the a approximate magnitudes of errors that result when electron affinity determinations of polar negative ions are made through ab initio calculations in which the use of a given basis set yields inappropriate values for permanent and induced dipole moments of the neutral molecule. These results should prove useful in assessing the adequacy of basis sets in ab initio calculations of molecular electron affinities for simple linear polar molecules

  6. Using physics-based pose predictions and free energy perturbation calculations to predict binding poses and relative binding affinities for FXR ligands in the D3R Grand Challenge 2

    Science.gov (United States)

    Athanasiou, Christina; Vasilakaki, Sofia; Dellis, Dimitris; Cournia, Zoe

    2018-01-01

    Computer-aided drug design has become an integral part of drug discovery and development in the pharmaceutical and biotechnology industry, and is nowadays extensively used in the lead identification and lead optimization phases. The drug design data resource (D3R) organizes challenges against blinded experimental data to prospectively test computational methodologies as an opportunity for improved methods and algorithms to emerge. We participated in Grand Challenge 2 to predict the crystallographic poses of 36 Farnesoid X Receptor (FXR)-bound ligands and the relative binding affinities for two designated subsets of 18 and 15 FXR-bound ligands. Here, we present our methodology for pose and affinity predictions and its evaluation after the release of the experimental data. For predicting the crystallographic poses, we used docking and physics-based pose prediction methods guided by the binding poses of native ligands. For FXR ligands with known chemotypes in the PDB, we accurately predicted their binding modes, while for those with unknown chemotypes the predictions were more challenging. Our group ranked #1st (based on the median RMSD) out of 46 groups, which submitted complete entries for the binding pose prediction challenge. For the relative binding affinity prediction challenge, we performed free energy perturbation (FEP) calculations coupled with molecular dynamics (MD) simulations. FEP/MD calculations displayed a high success rate in identifying compounds with better or worse binding affinity than the reference (parent) compound. Our studies suggest that when ligands with chemical precedent are available in the literature, binding pose predictions using docking and physics-based methods are reliable; however, predictions are challenging for ligands with completely unknown chemotypes. We also show that FEP/MD calculations hold predictive value and can nowadays be used in a high throughput mode in a lead optimization project provided that crystal structures of

  7. Affine-Invariant Geometric Constraints-Based High Accuracy Simultaneous Localization and Mapping

    Directory of Open Access Journals (Sweden)

    Gangchen Hua

    2017-01-01

    Full Text Available In this study we describe a new appearance-based loop-closure detection method for online incremental simultaneous localization and mapping (SLAM using affine-invariant-based geometric constraints. Unlike other pure bag-of-words-based approaches, our proposed method uses geometric constraints as a supplement to improve accuracy. By establishing an affine-invariant hypothesis, the proposed method excludes incorrect visual words and calculates the dispersion of correctly matched visual words to improve the accuracy of the likelihood calculation. In addition, camera’s intrinsic parameters and distortion coefficients are adequate for this method. 3D measuring is not necessary. We use the mechanism of Long-Term Memory and Working Memory (WM to manage the memory. Only a limited size of the WM is used for loop-closure detection; therefore the proposed method is suitable for large-scale real-time SLAM. We tested our method using the CityCenter and Lip6Indoor datasets. Our proposed method results can effectively correct the typical false-positive localization of previous methods, thus gaining better recall ratios and better precision.

  8. [Affine transformation-based automatic registration for peripheral digital subtraction angiography (DSA)].

    Science.gov (United States)

    Kong, Gang; Dai, Dao-Qing; Zou, Lu-Min

    2008-07-01

    In order to remove the artifacts of peripheral digital subtraction angiography (DSA), an affine transformation-based automatic image registration algorithm is introduced here. The whole process is described as follows: First, rectangle feature templates are constructed with their centers of the extracted Harris corners in the mask, and motion vectors of the central feature points are estimated using template matching technology with the similarity measure of maximum histogram energy. And then the optimal parameters of the affine transformation are calculated with the matrix singular value decomposition (SVD) method. Finally, bilinear intensity interpolation is taken to the mask according to the specific affine transformation. More than 30 peripheral DSA registrations are performed with the presented algorithm, and as the result, moving artifacts of the images are removed with sub-pixel precision, and the time consumption is less enough to satisfy the clinical requirements. Experimental results show the efficiency and robustness of the algorithm.

  9. PRINCIPLES OF AFFINITY-BASED BIOSENSORS

    Science.gov (United States)

    Despite the amount of resources that have been invested by national and international academic, government, and commercial sectors to develop affinity-based biosensor products, little obvious success has been realized through commercialization of these devices for specific applic...

  10. Calculating the Na⁺ translocating V-ATPase catalytic site affinity for substrate binding by homology modeled NtpA monomer using molecular dynamics/free energy calculation.

    Science.gov (United States)

    Muhammed, Zahed; Arai, Satoshi; Saijo, Shinya; Yamato, Ichiro; Murata, Takeshi; Suenaga, Atsushi

    2012-07-01

    Vacuolar ATPase (V-ATPase) of Enterococcus hirae is composed of a soluble catalytic domain (V₁; NtpA₃-B₃-D-G) and an integral membrane domain (V₀; NtpI-K₁₀) connected by a central and two peripheral stalks (NtpC, NtpD-G and NtpE-F). Recently nucleotide binding of catalytic NtpA monomer has been reported (Arai et al.). In the present study, we calculated the nucleotide binding affinity of NtpA by molecular dynamics (MD) simulation/free energy calculation using MM-GBSA approach based on homology modeled structure of NtpA monomer docked with ATP analogue, adenosine 5'-[β, γ-imido] triphosphate (AMP-PNP). The calculated binding free energies showed qualitatively good agreement with experimental data. The calculation was cross-validated further by the rigorous method, thermodynamic integration (TI) simulation. Finally, the interaction between NtpA and nucleotides at the atomic level was investigated by the analyses of components of free energy and the optimized model structures obtained from MD simulations, suggesting that electrostatic contribution is responsible for the difference in nucleotide binding to NtpA monomer. This is the first observation and suggestion to explain the difference of nucleotide binding properties in V-ATPase NtpA subunit, and our method can be a valuable primary step to predict nucleotide binding affinity to other subunits (NtpAB, NtpA₃B₃) and to explore subunit interactions and eventually may help to understand energy transduction mechanism of E. hirae V-ATPase. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Electron affinities: theoretical

    International Nuclear Information System (INIS)

    Kaufman, J.J.

    1976-01-01

    A brief description is given of the conceptual background and formalism of the various ab-initio and semi-ab-initio quantum computational techniques for calculating atomic and molecular electron affinities: Hartree--Fock--Roothaan SCF, configuration interaction (CI), multiconfiguration SCF (MC-SCF), Bethe--Goldstone, superposition of configurations (SOC), ab-initio effective core model potentials, Xα-MS, plus other less common methods. Illustrative and comparative examples of electron affinities calculated by these various methods are presented

  12. Targeting Anti-Cancer Active Compounds: Affinity-Based Chromatographic Assays

    OpenAIRE

    de Moraes, Marcela Cristina; Cardoso, Carmen Lucia; Seidl, Claudia; Moaddel, Ruin; Cass, Quezia Bezerra

    2016-01-01

    Affinity-based chromatography assays encompass the use of solid supports containing immobilized biological targets to monitor binding events in the isolation , identification and/or characterization of bioactive compounds. This powerful bioanalytical technique allows the screening of potential binders through fast analyses that can be directly performed using isolated substances or complex matrices. An overview of the recent researches in frontal and zonal affinity-based chromatography screen...

  13. Molecular electron affinities

    International Nuclear Information System (INIS)

    Fukuda, E.K.

    1983-01-01

    Molecular electron affinities have historically been difficult quantities to measure accurately. These difficulties arise from differences in structure between the ion and neutral as well as the existence of excited negative ion states. To circumvent these problems, relative electron affinities were determined in this dissertation by studying equilibrium electron transfer reactions using a pulsed ion cyclotron resonance (ICR) spectrometer. Direct measurement of ion and neutral concentrations for reactions of the general type, A - + B = B - + A, allow calculation of the equilibrium constant and, therefore, the free energy change. The free energy difference is related to the difference in electron affinities between A and B. A relative electron affinity scale covering a range of about 45 kcal/mol was constructed with various substituted p-benzoquinones, nitrobenzenes, anhydrides, and benzophenones. To assign absolute electron affinities, various species with accurately known electron affinities are tied to the scale via ion-cyclotron double resonance bracketing techniques. After the relative scale is anchored to these species with well-known electron affinities, the scale is then used as a check on other electron affinity values as well as generating new electron affinity values. Many discrepancies were found between the electron affinities measured using the ICR technique and previous literature determinations

  14. Enhancing Community Detection By Affinity-based Edge Weighting Scheme

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Andy [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Sanders, Geoffrey [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Henson, Van [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Vassilevski, Panayot [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-10-05

    Community detection refers to an important graph analytics problem of finding a set of densely-connected subgraphs in a graph and has gained a great deal of interest recently. The performance of current community detection algorithms is limited by an inherent constraint of unweighted graphs that offer very little information on their internal community structures. In this paper, we propose a new scheme to address this issue that weights the edges in a given graph based on recently proposed vertex affinity. The vertex affinity quantifies the proximity between two vertices in terms of their clustering strength, and therefore, it is ideal for graph analytics applications such as community detection. We also demonstrate that the affinity-based edge weighting scheme can improve the performance of community detection algorithms significantly.

  15. Paper-based immune-affinity arrays for detection of multiple mycotoxins in cereals.

    Science.gov (United States)

    Li, Li; Chen, Hongpu; Lv, Xiaolan; Wang, Min; Jiang, Xizhi; Jiang, Yifei; Wang, Heye; Zhao, Yongfu; Xia, Liru

    2018-03-01

    Mycotoxins produced by different species of fungi may coexist in cereals and feedstuffs, and could be highly toxic for humans and animals. For quantification of multiple mycotoxins in cereals, we developed a paper-based mycotoxin immune-affinity array. First, paper-based microzone arrays were fabricated by photolithography. Then, monoclonal mycotoxin antibodies were added in a copolymerization reaction with a cross-linker to form an immune-affinity monolith on the paper-based microzone array. With use of a competitive immune-response format, paper-based mycotoxin immune-affinity arrays were successfully applied to detect mycotoxins in samples. The detection limits for deoxynivalenol, zearalenone, T-2 toxin, and HT-2 toxin were 62.7, 10.8, 0.36, and 0.23 μg·kg -1 , respectively, which meet relevant requirements for these compounds in food. The recovery rates were 81-86% for deoxynivalenol, 89-117% for zearalenone, 79-86% for T-2 toxin, and 78-83% for HT-2 toxin, and showed the paper-based immune-affinity arrays had good reproducibility. In summary, the paper-based mycotoxin immune-affinity array provides a sensitive, rapid, accurate, stable, and convenient platform for detection of multiple mycotoxins in agro-foods. Graphical abstract Paper-based immune-affinity monolithic array. DON deoxynivalenol, HT-2 HT-2 toxin, T-2 T-2 toxin, PEGDA polyethylene glycol diacrylate, ZEN zearalenone.

  16. Immobilizing affinity proteins to nitrocellulose: a toolbox for paper-based assay developers.

    Science.gov (United States)

    Holstein, Carly A; Chevalier, Aaron; Bennett, Steven; Anderson, Caitlin E; Keniston, Karen; Olsen, Cathryn; Li, Bing; Bales, Brian; Moore, David R; Fu, Elain; Baker, David; Yager, Paul

    2016-02-01

    To enable enhanced paper-based diagnostics with improved detection capabilities, new methods are needed to immobilize affinity reagents to porous substrates, especially for capture molecules other than IgG. To this end, we have developed and characterized three novel methods for immobilizing protein-based affinity reagents to nitrocellulose membranes. We have demonstrated these methods using recombinant affinity proteins for the influenza surface protein hemagglutinin, leveraging the customizability of these recombinant "flu binders" for the design of features for immobilization. The three approaches shown are: (1) covalent attachment of thiolated affinity protein to an epoxide-functionalized nitrocellulose membrane, (2) attachment of biotinylated affinity protein through a nitrocellulose-binding streptavidin anchor protein, and (3) fusion of affinity protein to a novel nitrocellulose-binding anchor protein for direct coupling and immobilization. We also characterized the use of direct adsorption for the flu binders, as a point of comparison and motivation for these novel methods. Finally, we demonstrated that these novel methods can provide improved performance to an influenza hemagglutinin assay, compared to a traditional antibody-based capture system. Taken together, this work advances the toolkit available for the development of next-generation paper-based diagnostics.

  17. DFT study on the effect of exocyclic substituents on the proton affinity of 1-methylimidazole

    International Nuclear Information System (INIS)

    Liu, Haining; Bara, Jason E.; Turner, C. Heath

    2013-01-01

    Highlights: • DFT calculations are used to predict the proton affinity of 1-methylimidazoles. • The electron-withdrawing groups dominate the predicted proton affinity. • The effects of multiple substituents on the proton affinity can be accurately predicted. • Large compound libraries can be screened for imidazoles with tailored reactivity. - Abstract: A deeper understanding of the acid/base properties of imidazole derivatives will aid the development of solvents, polymer membranes and other materials that can be used for CO 2 capture and acid gas removal. In this study, we employ density functional theory calculations to investigate the effect of various electron-donating and electron-withdrawing groups on the proton affinity of 1-methylimidazole. We find that electron-donating groups are able to increase the proton affinity relative to 1-methylimidazole, i.e., making the molecule more basic. In contrast, electron-withdrawing groups cause a decrease of the proton affinity. When multiple substituents are present, their effects on the proton affinity were found to be additive. This finding offers a quick approach for predicting and targeting the proton affinities of this series of molecules, and we show the strong correlation between the calculated proton affinities and experimental pK a values

  18. Targeting Anti-Cancer Active Compounds: Affinity-Based Chromatographic Assays

    Science.gov (United States)

    de Moraes, Marcela Cristina; Cardoso, Carmen Lucia; Seidl, Claudia; Moaddel, Ruin; Cass, Quezia Bezerra

    2016-01-01

    Affinity-based chromatography assays encompass the use of solid supports containing immobilized biological targets to monitor binding events in the isolation , identification and/or characterization of bioactive compounds. This powerful bioanalytical technique allows the screening of potential binders through fast analyses that can be directly performed using isolated substances or complex matrices. An overview of the recent researches in frontal and zonal affinity-based chromatography screening assays, which has been used as a tool in the identification and characterization of new anti-cancer agents, is discussed. In addition, a critical evaluation of the recently emerged ligands fishing assays in complex mixtures is also discussed. PMID:27306095

  19. Quantum image encryption based on generalized affine transform and logistic map

    Science.gov (United States)

    Liang, Hao-Ran; Tao, Xiang-Yang; Zhou, Nan-Run

    2016-07-01

    Quantum circuits of the generalized affine transform are devised based on the novel enhanced quantum representation of digital images. A novel quantum image encryption algorithm combining the generalized affine transform with logistic map is suggested. The gray-level information of the quantum image is encrypted by the XOR operation with a key generator controlled by the logistic map, while the position information of the quantum image is encoded by the generalized affine transform. The encryption keys include the independent control parameters used in the generalized affine transform and the logistic map. Thus, the key space is large enough to frustrate the possible brute-force attack. Numerical simulations and analyses indicate that the proposed algorithm is realizable, robust and has a better performance than its classical counterpart in terms of computational complexity.

  20. The theoretical advantage of affinity membrane-based immunoadsorption therapy of hypercholesterolemia

    International Nuclear Information System (INIS)

    Green, P.; Odell, R.; Schindhelm, K.

    1996-01-01

    Full text: Therapy of hypercholesterolemia using immunoadsorption of Low Density Lipoprotein (LDL) to a gel substrate is a current clinical technique (Bosch T., Biomat., Art. Cells and Immob. Biotech, 20: 1165- 1169, 1992). Recently, Affinity Membranes have been proposed as an alternate substrate for immunoadsorption (Brandt S and others, Bio Technology, 6:779-782, 1988). Potentially, the overall rate of adsorption to a membrane may be faster than to a gel because of the different geometry (ibid). This implies that for the same conditions, a membrane-based device will have a higher Number of Transfer Units, more efficient adsorption and a smaller device size than a gel. To test this hypothesis, we calculated two key theoretical design parameters: Separation Factor, R, and the Number of Transfer Units, N, for a functioning clinical-scale affinity membrane device: R=K d /K d +C 0 . Kd: Equilibrium Dissociation Constant (M) and Co: Feed Concentration (M) N=k a Q max V m /F. ka: Intrinsic reaction rate constant (M -1 min -1 ), Qmax: Substrate capacity (M), Vm: Membrane volume (m1) and F: Flow Rate (m1 min -1 ). We assumed 1 hr treatment time during which 1 plasma volume (3L) is treated, hence F=50 (m1 min -1 ). If we assume 2/3 of LDL is removed from an initial level of 3 g/L, we can calculate an average feed concentration Co = 2 g / L. There is some data available in the literature for typical values of Kd (10 -8 M) and ka ( 10 3 M -1 s -1 to 3 x 10 5 M -1 s -1 ) (Olsen WC and others, Molec. Immun: 26: 129-136, 1989). Since the intrinsic reaction kinetics may vary from very slow (10 3 M) to very fast (3 x 10 5 M), the Number of Transfer Units, N may vary from small (2) to large (650). Hence for a membrane device, we must select the antibody with the fastest reaction, ka, and highest capacity (Qmax) otherwise, there may be no advantage in a membrane-based device over a gel-based device

  1. Hirota's solitons in the affine and the conformal affine Toda models

    International Nuclear Information System (INIS)

    Aratyn, H.; Constantinidis, C.P.; Ferreira, L.A.; Gomes, J.F.; Zimerman, A.H.

    1993-01-01

    We use Hirota's method formulated as a recursive scheme to construct a complete set of soliton solutions for the affine Toda field theory based on an arbitrary Lie algebra. Our solutions include a new class of solitons connected with two different types of degeneracies encountered in Hirota's perturbation approach. We also derive an universal mass formula for all Hirota's solutions to the affine Toda model valid for all underlying Lie groups. Embedding of the affine Toda model in the conformal affine Toda model plays a crucial role in this analysis. (orig.)

  2. Flexible Molybdenum Electrodes towards Designing Affinity Based Protein Biosensors.

    Science.gov (United States)

    Kamakoti, Vikramshankar; Panneer Selvam, Anjan; Radha Shanmugam, Nandhinee; Muthukumar, Sriram; Prasad, Shalini

    2016-07-18

    Molybdenum electrode based flexible biosensor on porous polyamide substrates has been fabricated and tested for its functionality as a protein affinity based biosensor. The biosensor performance was evaluated using a key cardiac biomarker; cardiac Troponin-I (cTnI). Molybdenum is a transition metal and demonstrates electrochemical behavior upon interaction with an electrolyte. We have leveraged this property of molybdenum for designing an affinity based biosensor using electrochemical impedance spectroscopy. We have evaluated the feasibility of detection of cTnI in phosphate-buffered saline (PBS) and human serum (HS) by measuring impedance changes over a frequency window from 100 mHz to 1 MHz. Increasing changes to the measured impedance was correlated to the increased dose of cTnI molecules binding to the cTnI antibody functionalized molybdenum surface. We achieved cTnI detection limit of 10 pg/mL in PBS and 1 ng/mL in HS medium. The use of flexible substrates for designing the biosensor demonstrates promise for integration with a large-scale batch manufacturing process.

  3. Investigation of molybdenum-crosslinker interfaces for affinity based electrochemical biosensing applications

    Science.gov (United States)

    Kamakoti, Vikramshankar; Shanmugam, Nandhinee Radha; Tanak, Ambalika Sanjeev; Jagannath, Badrinath; Prasad, Shalini

    2018-04-01

    Molybdenum (Mo) has been investigated for implementation as an electrode material for affinity based biosensing towards devloping flexibe electronic biosensors. Treatment of the native oxide of molybdenum was investigated through two surface treatment strategies namely thiol and carbodiimide crosslinking methods. The binding interaction between cross-linker molecules and Mo electrode surface has been characterized using Fourier Transform Infrared Spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and optical microscopy. The efficacy of treatment of Mo with its native oxide using carbodiimide cross linking methodology was established. The carbodiimide cross-linking chemistry was found to possess better surface coverage and binding affinity with Molybdenum electrode surface when compared to thiol cross-linking chemistry.Electrochemical characterization of Mo electrode using Electrochemical Impedance Spectroscopy (EIS) and Cyclic Voltametry (CV) techniques was performed to evaluate the effect of ionic properties of solution buffer on the Mo electrode's performance. Affinity based biosensing of C-Reactive Protein (CRP) has been demonstrated on a flexible nanoporous polymeric substrate with detection threshold of 100 pg/ml in synthetic urine buffer medium. The biosensor has been evaluated to be developed as a dipstick based point of care device for detection of biomarkers in urine.

  4. Thermokinetic model of borosilicate glass dissolution: contextual affinity

    International Nuclear Information System (INIS)

    Advocat, T.; Vernaz, E.; Crovisier, J.L.; Fritz, B.

    1989-01-01

    Short and long-term geochemical interactions of R7T7 nuclear glass with water at 100 0 C were simulated with the DISSOL thermokinetic computer code. Both the dissolved glass quantity and the resulting water composition, saturation states and mineral quantities produced were calculated as a function of time. The rate equation used in the simulation was first proposed by Aagaard and Helgeson. It simulates a gradually diminishing dissolution rate as the reaction affinity diminishes. The best agreement with 1-year experimental data was obtained with a reaction affinity calculated from silica activity (Grambow's hypothesis) rather than taking into account the activity of all the glass components as proposed by Jantzen and Plodinec. The concept of residual affinity was introduced by Grambow to express the fact that the glass dissolution rate does not cease. We prefer to replace the term residual affinity by contextual affinity, which expresses the influence on the dissolution rate of three factors: the solution chemistry, the metastability of SiO 2 (m), and the possible precipitation of certain aluminosilicates such as zeolites. 19 refs

  5. Free energy calculations offer insights into the influence of receptor flexibility on ligand-receptor binding affinities.

    Science.gov (United States)

    Dolenc, Jožica; Riniker, Sereina; Gaspari, Roberto; Daura, Xavier; van Gunsteren, Wilfred F

    2011-08-01

    Docking algorithms for computer-aided drug discovery and design often ignore or restrain the flexibility of the receptor, which may lead to a loss of accuracy of the relative free enthalpies of binding. In order to evaluate the contribution of receptor flexibility to relative binding free enthalpies, two host-guest systems have been examined: inclusion complexes of α-cyclodextrin (αCD) with 1-chlorobenzene (ClBn), 1-bromobenzene (BrBn) and toluene (MeBn), and complexes of DNA with the minor-groove binding ligands netropsin (Net) and distamycin (Dist). Molecular dynamics simulations and free energy calculations reveal that restraining of the flexibility of the receptor can have a significant influence on the estimated relative ligand-receptor binding affinities as well as on the predicted structures of the biomolecular complexes. The influence is particularly pronounced in the case of flexible receptors such as DNA, where a 50% contribution of DNA flexibility towards the relative ligand-DNA binding affinities is observed. The differences in the free enthalpy of binding do not arise only from the changes in ligand-DNA interactions but also from changes in ligand-solvent interactions as well as from the loss of DNA configurational entropy upon restraining.

  6. Lie algebraic discussion for affinity based information diffusion in social networks

    Science.gov (United States)

    Shang, Yilun

    2017-11-01

    In this paper we develop a dynamical information diffusion model which features the affinity of people with information disseminated in social networks. Four types of agents, i.e., susceptible, informed, known, and refractory ones, are involved in the system, and the affinity mechanism composing of an affinity threshold which represents the fitness of information to be propagated is incorporated. The model can be generally described by a time-inhomogeneous Markov chain, which is governed by its master (Kolmogorov) equation. Based on the Wei-Norman method, we derive analytical solutions of the model by constructing a low-dimensional Lie algebra. Numerical examples are provided to illustrate the obtained theoretical results. This study provides useful insights into the closed-form solutions of complex social dynamics models through the Lie algebra method.

  7. Preparation of Affinity Column Based on Zr4+ Ion for Phosphoproteins Isolation

    International Nuclear Information System (INIS)

    Lee, Seon Mi; Bae, In Ae; Park, Jung Hyen; Kim, Tae Dong; Choi, Seong Ho

    2009-01-01

    This paper has described about preparation of Zr 4+ affinity column based on the poly(styreneco- glycidyl methacrylate) prepared by emulsion polymerization of styrene and glycidyl methacrylate in order to isolate phosphopeptide. The Zr 4+ ions were introduced after the phophonation of an epoxy group on polymeric microspheres. The successful preparation of Zr 4+ -immobilized polymeric microsphere stationary phase was confirmed through Fourier transform infrared spectra, optical microscopy, scanning electron microscopy, X-ray photoelectron spectra and inductively coupled plasma-atomic emission spectrometer. The separation efficiency for Zr 4+ affinity column prepared by slurry packing was tested to phosphonated casein and dephosphonated casein. The resolution time (min) of the phosphonated casein was higher than that of dephosphated casein for Zr 4+ affinity polymeric microsphere by liquid chromatography. This Zr 4+ affinity column can be used for isolation of phosphonated casein from casein using liquid chromatography

  8. Affine fractal functions as bases of continuous funtions | Navascues ...

    African Journals Online (AJOL)

    The objective of the present paper is the study of affine transformations of the plane, which provide self-affine curves as attractors. The properties of these curves depend decisively of the coefficients of the system of affinities involved. The corresponding functions are continuous on a compact interval. If the scale factors are ...

  9. Thermokinetic model of borosilicate glass dissolution: Contextual affinity

    International Nuclear Information System (INIS)

    Advocat, T.; Vernaz, E.; Crovisier, J.L.; Fritz, B.

    1990-01-01

    Short and long-term geochemical interactions of R7T7 nuclear glass with water at 100C were simulated with the DISSOL thermokinetic computer code. Both the dissolved glass quantity and the resulting water composition, saturation states and mineral quantities produced were calculated as a function of time. The rate equation used in the simulation was first proposed by Aagaard and Hegelson: v = k + · S · a( H + ) -n · (1 - e -(A/RT) ). It simulates a gradually diminishing dissolution rate as the reaction affinity diminishes. The best agreement with 1-year experimental data was obtained with a reaction affinity calculated from silica activity (Grambow's hypothesis) rather than taking into account the activity of all the glass components as proposed by Jantzen and Plodinec. The concept of residual affinity was introduced by Grambow to express the fact that the glass dissolution rate does not cease. The authors prefer to replace the term residual affinity by contextual affinity, which expresses the influence on the dissolution rate of three factors: the solution chemistry, the metastability of SiO 2 (m), and the possible precipitation of certain aluminosilicates such as zeolites

  10. The correlation of cathodic peak potentials of vitamin K(3) derivatives and their calculated electron affinities. The role of hydrogen bonding and conformational changes.

    Science.gov (United States)

    Nasiri, Hamid Reza; Panisch, Robin; Madej, M Gregor; Bats, Jan W; Lancaster, C Roy D; Schwalbe, Harald

    2009-06-01

    2-methyl-1,4-naphtoquinone 1 (vitamin K(3), menadione) derivatives with different substituents at the 3-position were synthesized to tune their electrochemical properties. The thermodynamic midpoint potential (E(1/2)) of the naphthoquinone derivatives yielding a semi radical naphthoquinone anion were measured by cyclic voltammetry in the aprotic solvent dimethoxyethane (DME). Using quantum chemical methods, a clear correlation was found between the thermodynamic midpoint potentials and the calculated electron affinities (E(A)). Comparison of calculated and experimental values allowed delineation of additional factors such as the conformational dependence of quinone substituents and hydrogen bonding which can influence the electron affinities (E(A)) of the quinone. This information can be used as a model to gain insight into enzyme-cofactor interactions, particularly for enzyme quinone binding modes and the electrochemical adjustment of the quinone motif.

  11. Statistical inference for discrete-time samples from affine stochastic delay differential equations

    DEFF Research Database (Denmark)

    Küchler, Uwe; Sørensen, Michael

    2013-01-01

    Statistical inference for discrete time observations of an affine stochastic delay differential equation is considered. The main focus is on maximum pseudo-likelihood estimators, which are easy to calculate in practice. A more general class of prediction-based estimating functions is investigated...

  12. Recognition of genetically modified product based on affinity propagation clustering and terahertz spectroscopy

    Science.gov (United States)

    Liu, Jianjun; Kan, Jianquan

    2018-04-01

    In this paper, based on the terahertz spectrum, a new identification method of genetically modified material by support vector machine (SVM) based on affinity propagation clustering is proposed. This algorithm mainly uses affinity propagation clustering algorithm to make cluster analysis and labeling on unlabeled training samples, and in the iterative process, the existing SVM training data are continuously updated, when establishing the identification model, it does not need to manually label the training samples, thus, the error caused by the human labeled samples is reduced, and the identification accuracy of the model is greatly improved.

  13. Realization of parking task based on affine system modeling

    International Nuclear Information System (INIS)

    Kim, Young Woo; Narikiyo, Tatsuo

    2007-01-01

    This paper presents a motion control system of an unmanned vehicle, where parallel parking task is realized based on a self-organizing affine system modeling and a quadratic programming based robust controller. Because of non-linearity of the vehicle system and complexity of the task to realize, control objective is not always realized with a single algorithm or control mode. This paper presents a hybrid model for parallel parking task in which seven modes for describing sub-tasks constitute an entire model

  14. Towards Automated Binding Affinity Prediction Using an Iterative Linear Interaction Energy Approach

    Directory of Open Access Journals (Sweden)

    C. Ruben Vosmeer

    2014-01-01

    Full Text Available Binding affinity prediction of potential drugs to target and off-target proteins is an essential asset in drug development. These predictions require the calculation of binding free energies. In such calculations, it is a major challenge to properly account for both the dynamic nature of the protein and the possible variety of ligand-binding orientations, while keeping computational costs tractable. Recently, an iterative Linear Interaction Energy (LIE approach was introduced, in which results from multiple simulations of a protein-ligand complex are combined into a single binding free energy using a Boltzmann weighting-based scheme. This method was shown to reach experimental accuracy for flexible proteins while retaining the computational efficiency of the general LIE approach. Here, we show that the iterative LIE approach can be used to predict binding affinities in an automated way. A workflow was designed using preselected protein conformations, automated ligand docking and clustering, and a (semi-automated molecular dynamics simulation setup. We show that using this workflow, binding affinities of aryloxypropanolamines to the malleable Cytochrome P450 2D6 enzyme can be predicted without a priori knowledge of dominant protein-ligand conformations. In addition, we provide an outlook for an approach to assess the quality of the LIE predictions, based on simulation outcomes only.

  15. Preparation of Affinity Column Based on Zr{sup 4+} Ion for Phosphoproteins Isolation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seon Mi; Bae, In Ae; Park, Jung Hyen; Kim, Tae Dong; Choi, Seong Ho [Hannam University, Daejeon (Korea, Republic of)

    2009-06-15

    This paper has described about preparation of Zr{sup 4+} affinity column based on the poly(styreneco- glycidyl methacrylate) prepared by emulsion polymerization of styrene and glycidyl methacrylate in order to isolate phosphopeptide. The Zr{sup 4+} ions were introduced after the phophonation of an epoxy group on polymeric microspheres. The successful preparation of Zr{sup 4+}-immobilized polymeric microsphere stationary phase was confirmed through Fourier transform infrared spectra, optical microscopy, scanning electron microscopy, X-ray photoelectron spectra and inductively coupled plasma-atomic emission spectrometer. The separation efficiency for Zr{sup 4+} affinity column prepared by slurry packing was tested to phosphonated casein and dephosphonated casein. The resolution time (min) of the phosphonated casein was higher than that of dephosphated casein for Zr{sup 4+} affinity polymeric microsphere by liquid chromatography. This Zr{sup 4+} affinity column can be used for isolation of phosphonated casein from casein using liquid chromatography.

  16. Improved scFv Anti-HIV-1 p17 Binding Affinity Guided from the Theoretical Calculation of Pairwise Decomposition Energies and Computational Alanine Scanning

    Directory of Open Access Journals (Sweden)

    Panthip Tue-ngeun

    2013-01-01

    Full Text Available Computational approaches have been used to evaluate and define important residues for protein-protein interactions, especially antigen-antibody complexes. In our previous study, pairwise decomposition of residue interaction energies of single chain Fv with HIV-1 p17 epitope variants has indicated the key specific residues in the complementary determining regions (CDRs of scFv anti-p17. In this present investigation in order to determine whether a specific side chain group of residue in CDRs plays an important role in bioactivity, computational alanine scanning has been applied. Molecular dynamics simulations were done with several complexes of original scFv anti-p17 and scFv anti-p17mutants with HIV-1 p17 epitope variants with a production run up to 10 ns. With the combination of pairwise decomposition residue interaction and alanine scanning calculations, the point mutation has been initially selected at the position MET100 to improve the residue binding affinity. The calculated docking interaction energy between a single mutation from methionine to either arginine or glycine has shown the improved binding affinity, contributed from the electrostatic interaction with the negative favorably interaction energy, compared to the wild type. Theoretical calculations agreed well with the results from the peptide ELISA results.

  17. High-throughput and multiplexed regeneration buffer scouting for affinity-based interactions

    NARCIS (Netherlands)

    Geuijen, K.P.M.; Schasfoort, R.B.; Wijffels, R.H.; Eppink, M.H.M.

    2014-01-01

    Affinity-based analyses on biosensors depend partly on regeneration between measurements. Regeneration is performed with a buffer that efficiently breaks all interactions between ligand and analyte while maintaining the active binding site of the ligand. We demonstrated a regeneration buffer

  18. Capillary electrophoresis-based assessment of nanobody affinity and purity

    NARCIS (Netherlands)

    Haselberg, Rob; Oliveira, Sabrina; van der Meel, Roy; Somsen, Govert W; de Jong, Gerhardus J

    2014-01-01

    Drug purity and affinity are essential attributes during development and production of therapeutic proteins. In this work, capillary electrophoresis (CE) was used to determine both the affinity and composition of the biotechnologically produced "nanobody" EGa1, the binding fragment of a

  19. Electrostatics Explains the Position-Dependent Effect of G⋅U Wobble Base Pairs on the Affinity of RNA Kissing Complexes.

    Science.gov (United States)

    Abi-Ghanem, Josephine; Rabin, Clémence; Porrini, Massimiliano; Dausse, Eric; Toulmé, Jean-Jacques; Gabelica, Valérie

    2017-10-06

    In the RNA realm, non-Watson-Crick base pairs are abundant and can affect both the RNA 3D structure and its function. Here, we investigated the formation of RNA kissing complexes in which the loop-loop interaction is modulated by non-Watson-Crick pairs. Mass spectrometry, surface plasmon resonance, and UV-melting experiments show that the G⋅U wobble base pair favors kissing complex formation only when placed at specific positions. We tried to rationalize this effect by molecular modeling, including molecular mechanics Poisson-Boltzmann surface area (MMPBSA) thermodynamics calculations and PBSA calculations of the electrostatic potential surfaces. Modeling reveals that the G⋅U stabilization is due to a specific electrostatic environment defined by the base pairs of the entire loop-loop region. The loop is not symmetric, and therefore the identity and position of each base pair matters. Predicting and visualizing the electrostatic environment created by a given sequence can help to design specific kissing complexes with high affinity, for potential therapeutic, nanotechnology or analytical applications. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Affine and quasi-affine frames for rational dilations

    DEFF Research Database (Denmark)

    Bownik, Marcin; Lemvig, Jakob

    2011-01-01

    In this paper we extend the investigation of quasi-affine systems, which were originally introduced by Ron and Shen [J. Funct. Anal. 148 (1997), 408-447] for integer, expansive dilations, to the class of rational, expansive dilations. We show that an affine system is a frame if, and only if......, the corresponding family of quasi-affine systems are frames with uniform frame bounds. We also prove a similar equivalence result between pairs of dual affine frames and dual quasi-affine frames. Finally, we uncover some fundamental differences between the integer and rational settings by exhibiting an example...

  1. A Quick and Affine Invariance Matching Method for Oblique Images

    Directory of Open Access Journals (Sweden)

    XIAO Xiongwu

    2015-04-01

    Full Text Available This paper proposed a quick, affine invariance matching method for oblique images. It calculated the initial affine matrix by making full use of the two estimated camera axis orientation parameters of an oblique image, then recovered the oblique image to a rectified image by doing the inverse affine transform, and left over by the SIFT method. We used the nearest neighbor distance ratio(NNDR, normalized cross correlation(NCC measure constraints and consistency check to get the coarse matches, then used RANSAC method to calculate the fundamental matrix and the homography matrix. And we got the matches that they were interior points when calculating the homography matrix, then calculated the average value of the matches' principal direction differences. During the matching process, we got the initial matching features by the nearest neighbor(NN matching strategy, then used the epipolar constrains, homography constrains, NCC measure constrains and consistency check of the initial matches' principal direction differences with the calculated average value of the interior matches' principal direction differences to eliminate false matches. Experiments conducted on three pairs of typical oblique images demonstrate that our method takes about the same time as SIFT to match a pair of oblique images with a plenty of corresponding points distributed evenly and an extremely low mismatching rate.

  2. Self-affinity and nonextensivity of sunspots

    International Nuclear Information System (INIS)

    Moret, M.A.

    2014-01-01

    In this paper we study the time series of sunspots by using two different approaches, analyzing its self-affine behavior and studying its distribution. The long-range correlation exponent α has been calculated via Detrended Fluctuation Analysis and the power law vanishes to values greater than 11 years. On the other hand, the distribution of the sunspots obeys a q-exponential decay that suggests a non-extensive behavior. This observed characteristic seems to take an alternative interpretation of the sunspots dynamics. The present findings suggest us to propose a dynamic model of sunspots formation based on a nonlinear Fokker–Planck equation. Therefore its dynamic process follows the generalized thermostatistical formalism.

  3. Momentum conserving defects in affine Toda field theories

    Energy Technology Data Exchange (ETDEWEB)

    Bristow, Rebecca; Bowcock, Peter [Department of Mathematical Sciences, Durham University,Durham, DH1 3LE (United Kingdom)

    2017-05-30

    Type II integrable defects with more than one degree of freedom at the defect are investigated. A condition on the form of the Lagrangian for such defects is found which ensures the existence of a conserved momentum in the presence of the defect. In addition it is shown that for any Lagrangian satisfying this condition, the defect equations of motion, when taken to hold everywhere, can be extended to give a Bäcklund transformation between the bulk theories on either side of the defect. This strongly suggests that such systems are integrable. Momentum conserving defects and Bäcklund transformations for affine Toda field theories based on the A{sub n}, B{sub n}, C{sub n} and D{sub n} series of Lie algebras are found. The defect associated with the D{sub 4} affine Toda field theory is examined in more detail. In particular classical time delays for solitons passing through the defect are calculated.

  4. PANDA: Protein function prediction using domain architecture and affinity propagation.

    Science.gov (United States)

    Wang, Zheng; Zhao, Chenguang; Wang, Yiheng; Sun, Zheng; Wang, Nan

    2018-02-22

    We developed PANDA (Propagation of Affinity and Domain Architecture) to predict protein functions in the format of Gene Ontology (GO) terms. PANDA at first executes profile-profile alignment algorithm to search against PfamA, KOG, COG, and SwissProt databases, and then launches PSI-BLAST against UniProt for homologue search. PANDA integrates a domain architecture inference algorithm based on the Bayesian statistics that calculates the probability of having a GO term. All the candidate GO terms are pooled and filtered based on Z-score. After that, the remaining GO terms are clustered using an affinity propagation algorithm based on the GO directed acyclic graph, followed by a second round of filtering on the clusters of GO terms. We benchmarked the performance of all the baseline predictors PANDA integrates and also for every pooling and filtering step of PANDA. It can be found that PANDA achieves better performances in terms of area under the curve for precision and recall compared to the baseline predictors. PANDA can be accessed from http://dna.cs.miami.edu/PANDA/ .

  5. Two-parameter quantum affine algebra Ur,s(sln-circumflex), Drinfeld realization and quantum affine Lyndon basis

    International Nuclear Information System (INIS)

    Hu Naihong; Rosso, M.; Zhang Honglian

    2006-12-01

    We further find the defining structure of a two-parameter quantum affine algebra U r,s (sl n -circumflex) (n > 2) in the sense of Benkart-Witherspoon [BW1] after the work of [BGH1], [HS] and [BH], which turns out to be a Drinfeld double. Of more importance for the 'affine' cases is that we work out the compatible two-parameter version of the Drinfeld realization as a quantum affinization of U r,s (sl n ) and establish the Drinfeld isomorphism Theorem in the two-parameter setting via developing a new remarkable combinatorial approach - quantum 'affine' Lyndon basis with an explicit valid algorithm, based on the Drinfeld realization. (author)

  6. Proton Affinities of Anionic Bases:  Trends Across the Periodic Table, Structural Effects, and DFT Validation.

    Science.gov (United States)

    Swart, Marcel; Bickelhaupt, F Matthias

    2006-03-01

    We have carried out an extensive exploration of the gas-phase basicity of archetypal anionic bases across the periodic system using the generalized gradient approximation of density functional theory (DFT) at BP86/QZ4P//BP86/TZ2P. First, we validate DFT as a reliable tool for computing proton affinities and related thermochemical quantities:  BP86/QZ4P//BP86/TZ2P is shown to yield a mean absolute deviation of 1.6 kcal/mol for the proton affinity at 0 K with respect to high-level ab initio benchmark data. The main purpose of this work is to provide the proton affinities (and corresponding entropies) at 298 K of the anionic conjugate bases of all main-group-element hydrides of groups 14-17 and periods 2-6. We have also studied the effect of stepwise methylation of the protophilic center of the second- and third-period bases.

  7. Unexpected DNA affinity and sequence selectivity through core rigidity in guanidinium-based minor groove binders.

    Science.gov (United States)

    Nagle, Padraic S; McKeever, Caitriona; Rodriguez, Fernando; Nguyen, Binh; Wilson, W David; Rozas, Isabel

    2014-09-25

    In this paper we report the design and biophysical evaluation of novel rigid-core symmetric and asymmetric dicationic DNA binders containing 9H-fluorene and 9,10-dihydroanthracene cores as well as the synthesis of one of these fluorene derivatives. First, the affinity toward particular DNA sequences of these compounds and flexible core derivatives was evaluated by means of surface plasmon resonance and thermal denaturation experiments finding that the position of the cations significantly influence the binding strength. Then their affinity and mode of binding were further studied by performing circular dichroism and UV studies and the results obtained were rationalized by means of DFT calculations. We found that the fluorene derivatives prepared have the ability to bind to the minor groove of certain DNA sequences and intercalate to others, whereas the dihydroanthracene compounds bind via intercalation to all the DNA sequences studied here.

  8. Whole-heart coronary MRA with 3D affine motion correction using 3D image-based navigation.

    Science.gov (United States)

    Henningsson, Markus; Prieto, Claudia; Chiribiri, Amedeo; Vaillant, Ghislain; Razavi, Reza; Botnar, René M

    2014-01-01

    Robust motion correction is necessary to minimize respiratory motion artefacts in coronary MR angiography (CMRA). The state-of-the-art method uses a 1D feet-head translational motion correction approach, and data acquisition is limited to a small window in the respiratory cycle, which prolongs the scan by a factor of 2-3. The purpose of this work was to implement 3D affine motion correction for Cartesian whole-heart CMRA using a 3D navigator (3D-NAV) to allow for data acquisition throughout the whole respiratory cycle. 3D affine transformations for different respiratory states (bins) were estimated by using 3D-NAV image acquisitions which were acquired during the startup profiles of a steady-state free precession sequence. The calculated 3D affine transformations were applied to the corresponding high-resolution Cartesian image acquisition which had been similarly binned, to correct for respiratory motion between bins. Quantitative and qualitative comparisons showed no statistical difference between images acquired with the proposed method and the reference method using a diaphragmatic navigator with a narrow gating window. We demonstrate that 3D-NAV and 3D affine correction can be used to acquire Cartesian whole-heart 3D coronary artery images with 100% scan efficiency with similar image quality as with the state-of-the-art gated and corrected method with approximately 50% scan efficiency. Copyright © 2013 Wiley Periodicals, Inc.

  9. Engineering of bispecific affinity proteins with high affinity for ERBB2 and adaptable binding to albumin.

    Directory of Open Access Journals (Sweden)

    Johan Nilvebrant

    Full Text Available The epidermal growth factor receptor 2, ERBB2, is a well-validated target for cancer diagnostics and therapy. Recent studies suggest that the over-expression of this receptor in various cancers might also be exploited for antibody-based payload delivery, e.g. antibody drug conjugates. In such strategies, the full-length antibody format is probably not required for therapeutic effect and smaller tumor-specific affinity proteins might be an alternative. However, small proteins and peptides generally suffer from fast excretion through the kidneys, and thereby require frequent administration in order to maintain a therapeutic concentration. In an attempt aimed at combining ERBB2-targeting with antibody-like pharmacokinetic properties in a small protein format, we have engineered bispecific ERBB2-binding proteins that are based on a small albumin-binding domain. Phage display selection against ERBB2 was used for identification of a lead candidate, followed by affinity maturation using second-generation libraries. Cell surface display and flow-cytometric sorting allowed stringent selection of top candidates from pools pre-enriched by phage display. Several affinity-matured molecules were shown to bind human ERBB2 with sub-nanomolar affinity while retaining the interaction with human serum albumin. Moreover, parallel selections against ERBB2 in the presence of human serum albumin identified several amino acid substitutions that dramatically modulate the albumin affinity, which could provide a convenient means to control the pharmacokinetics. The new affinity proteins competed for ERBB2-binding with the monoclonal antibody trastuzumab and recognized the native receptor on a human cancer cell line. Hence, high affinity tumor targeting and tunable albumin binding were combined in one small adaptable protein.

  10. Surface sensitization mechanism on negative electron affinity p-GaN nanowires

    Science.gov (United States)

    Diao, Yu; Liu, Lei; Xia, Sihao; Feng, Shu; Lu, Feifei

    2018-03-01

    The surface sensitization is the key to prepare negative electron affinity photocathode. The thesis emphasizes on the study of surface sensitization mechanism of p-type doping GaN nanowires utilizing first principles based on density function theory. The adsorption energy, work function, dipole moment, geometry structure, electronic structure and optical properties of Mg-doped GaN nanowires surfaces with various coverages of Cs atoms are investigated. The GaN nanowire with Mg doped in core position is taken as the sensitization base. At the initial stage of sensitization, the best adsorption site for Cs atom on GaN nanowire surface is BN, the bridge site of two adjacent N atoms. Surface sensitization generates a p-type internal surface with an n-type surface state, introducing a band bending region which can help reduce surface barrier and work function. With increasing Cs coverage, work functions decrease monotonously and the "Cs-kill" phenomenon disappears. For Cs coverage of 0.75 ML and 1 ML, the corresponding sensitization systems reach negative electron affinity state. Through surface sensitization, the absorption curves are red shifted and the absorption coefficient is cut down. All theoretical calculations can guide the design of negative electron affinity Mg doped GaN nanowires photocathode.

  11. Representations of affine Hecke algebras

    CERN Document Server

    Xi, Nanhua

    1994-01-01

    Kazhdan and Lusztig classified the simple modules of an affine Hecke algebra Hq (q E C*) provided that q is not a root of 1 (Invent. Math. 1987). Ginzburg had some very interesting work on affine Hecke algebras. Combining these results simple Hq-modules can be classified provided that the order of q is not too small. These Lecture Notes of N. Xi show that the classification of simple Hq-modules is essentially different from general cases when q is a root of 1 of certain orders. In addition the based rings of affine Weyl groups are shown to be of interest in understanding irreducible representations of affine Hecke algebras. Basic knowledge of abstract algebra is enough to read one third of the book. Some knowledge of K-theory, algebraic group, and Kazhdan-Lusztig cell of Cexeter group is useful for the rest

  12. A mix-and-read drop-based in vitro two-hybrid method for screening high-affinity peptide binders

    Science.gov (United States)

    Cui, Naiwen; Zhang, Huidan; Schneider, Nils; Tao, Ye; Asahara, Haruichi; Sun, Zhiyi; Cai, Yamei; Koehler, Stephan A.; de Greef, Tom F. A.; Abbaspourrad, Alireza; Weitz, David A.; Chong, Shaorong

    2016-01-01

    Drop-based microfluidics have recently become a novel tool by providing a stable linkage between phenotype and genotype for high throughput screening. However, use of drop-based microfluidics for screening high-affinity peptide binders has not been demonstrated due to the lack of a sensitive functional assay that can detect single DNA molecules in drops. To address this sensitivity issue, we introduced in vitro two-hybrid system (IVT2H) into microfluidic drops and developed a streamlined mix-and-read drop-IVT2H method to screen a random DNA library. Drop-IVT2H was based on the correlation between the binding affinity of two interacting protein domains and transcriptional activation of a fluorescent reporter. A DNA library encoding potential peptide binders was encapsulated with IVT2H such that single DNA molecules were distributed in individual drops. We validated drop-IVT2H by screening a three-random-residue library derived from a high-affinity MDM2 inhibitor PMI. The current drop-IVT2H platform is ideally suited for affinity screening of small-to-medium-sized libraries (103–106). It can obtain hits within a single day while consuming minimal amounts of reagents. Drop-IVT2H simplifies and accelerates the drop-based microfluidics workflow for screening random DNA libraries, and represents a novel alternative method for protein engineering and in vitro directed protein evolution. PMID:26940078

  13. A rhodium(III) complex for high-affinity DNA base-pair mismatch recognition

    Science.gov (United States)

    Junicke, Henrik; Hart, Jonathan R.; Kisko, Jennifer; Glebov, Oleg; Kirsch, Ilan R.; Barton, Jacqueline K.

    2003-01-01

    A rhodium(III) complex, rac-[Rh(bpy)2phzi]3+ (bpy, 2,2′-bipyridine; phzi, benzo[a]phenazine-5,6-quinone diimine) has been designed as a sterically demanding intercalator targeted to destabilized mismatched sites in double-helical DNA. The complex is readily synthesized by condensation of the phenazine quinone with the corresponding diammine complex. Upon photoactivation, the complex promotes direct strand scission at single-base mismatch sites within the DNA duplex. As with the parent mismatch-specific reagent, [Rh(bpy)2(chrysi)]3+ [chrysene-5,6-quinone diimine (chrysi)], mismatch selectivity depends on the helix destabilization associated with mispairing. Unlike the parent chrysi complex, the phzi analogue binds and cleaves with high affinity and efficiency. The specific binding constants for CA, CC, and CT mismatches within a 31-mer oligonucleotide duplex are 0.3, 1, and 6 × 107 M−1, respectively; site-specific photocleavage is evident at nanomolar concentrations. Moreover, the specificity, defined as the ratio in binding affinities for mispaired vs. well paired sites, is maintained. The increase in affinity is attributed to greater stability in the mismatched site associated with stacking by the heterocyclic aromatic ligand. The high-affinity complex is also applied in the differential cleavage of DNA obtained from cell lines deficient in mismatch repair vs. those proficient in mismatch repair. Agreement is found between photocleavage by the mismatch-specific probes and deficiency in mismatch repair. This mismatch-specific targeting, therefore, offers a potential strategy for new chemotherapeutic design. PMID:12610209

  14. Polynomials associated with equilibria of affine Toda-Sutherland systems

    International Nuclear Information System (INIS)

    Odake, S; Sasaki, R

    2004-01-01

    An affine Toda-Sutherland system is a quasi-exactly solvable multi-particle dynamics based on an affine simple root system. It is a 'cross' between two well-known integrable multi-particle dynamics, an affine Toda molecule (exponential potential, periodic nearest-neighbour interaction) and a Sutherland system (inverse sine-square interaction). Polynomials describing the equilibrium positions of affine Toda-Sutherland systems are determined for all affine simple root systems

  15. Affinity-based screening of combinatorial libraries using automated, serial-column chromatography

    Energy Technology Data Exchange (ETDEWEB)

    Evans, D.M.; Williams, K.P.; McGuinness, B. [PerSeptive Biosystems, Framingham, MA (United States)] [and others

    1996-04-01

    The authors have developed an automated serial chromatographic technique for screening a library of compounds based upon their relative affinity for a target molecule. A {open_quotes}target{close_quotes} column containing the immobilized target molecule is set in tandem with a reversed-phase column. A combinatorial peptide library is injected onto the target column. The target-bound peptides are eluted from the first column and transferred automatically to the reversed-phase column. The target-specific peptide peaks from the reversed-phase column are identified and sequenced. Using a monoclonal antibody (3E-7) against {beta}-endorphin as a target, we selected a single peptide with sequence YGGFL from approximately 5800 peptides present in a combinatorial library. We demonstrated the applicability of the technology towards selection of peptides with predetermined affinity for bacterial lipopolysaccharide (LPS, endotoxin). We expect that this technology will have broad applications for high throughput screening of chemical libraries or natural product extracts. 21 refs., 4 figs.

  16. The utility of affine variables and affine coherent states

    International Nuclear Information System (INIS)

    Klauder, John R

    2012-01-01

    Affine coherent states are generated by affine kinematical variables much like canonical coherent states are generated by canonical kinematical variables. Although all classical and quantum formalisms normally entail canonical variables, it is shown that affine variables can serve equally well for many classical and quantum studies. This general purpose analysis provides tools to discuss two major applications: (1) the completely successful quantization of a nonrenormalizable scalar quantum field theory by affine techniques, in complete contrast to canonical techniques which only offer triviality; and (2) a formulation of the kinematical portion of quantum gravity that favors affine kinematical variables over canonical kinematical variables, and which generates a framework in which a favorable analysis of the constrained dynamical issues can take place. All this is possible because of the close connection between the affine and the canonical stories, while the few distinctions can be used to advantage when appropriate. This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to ‘Coherent states: mathematical and physical aspects’. (review)

  17. Alternative affinity tools: more attractive than antibodies?

    NARCIS (Netherlands)

    Ruigrok, V.J.B.; Levisson, M.; Eppink, M.H.M.; Smidt, H.; Oost, van der J.

    2011-01-01

    Antibodies are the most successful affinity tools used today, in both fundamental and applied research (diagnostics, purification and therapeutics). Nonetheless, antibodies do have their limitations, including high production costs and low stability. Alternative affinity tools based on nucleic acids

  18. Affine stochastic mortality

    NARCIS (Netherlands)

    Schrager, D.F.

    2006-01-01

    We propose a new model for stochastic mortality. The model is based on the literature on affine term structure models. It satisfies three important requirements for application in practice: analytical tractibility, clear interpretation of the factors and compatibility with financial option pricing

  19. Electrochemical Affinity Biosensors Based on Disposable Screen-Printed Electrodes for Detection of Food Allergens

    Science.gov (United States)

    Vasilescu, Alina; Nunes, Gilvanda; Hayat, Akhtar; Latif, Usman; Marty, Jean-Louis

    2016-01-01

    Food allergens are proteins from nuts and tree nuts, fish, shellfish, wheat, soy, eggs or milk which trigger severe adverse reactions in the human body, involving IgE-type antibodies. Sensitive detection of allergens in a large variety of food matrices has become increasingly important considering the emergence of functional foods and new food manufacturing technologies. For example, proteins such as casein from milk or lysozyme and ovalbumin from eggs are sometimes used as fining agents in the wine industry. Nonetheless, allergen detection in processed foods is a challenging endeavor, as allergen proteins are degraded during food processing steps involving heating or fermentation. Detection of food allergens was primarily achieved via Enzyme-Linked Immuno Assay (ELISA) or by chromatographic methods. With the advent of biosensors, electrochemical affinity-based biosensors such as those incorporating antibodies and aptamers as biorecognition elements were also reported in the literature. In this review paper, we highlight the success achieved in the design of electrochemical affinity biosensors based on disposable screen-printed electrodes towards detection of protein allergens. We will discuss the analytical figures of merit for various disposable screen-printed affinity sensors in relation to methodologies employed for immobilization of bioreceptors on transducer surface. PMID:27827963

  20. Affinity Strings: Enterprise Data for Resource Recommendations

    Directory of Open Access Journals (Sweden)

    Shane Nackerud

    2008-12-01

    Full Text Available The University of Minnesota Libraries have created a MyLibrary portal, with databases and e-journals targeted to users, based on their affiliations. The University's enterprise authentication system provides an "affinity string", now used to personalize the MyLibrary portal. This affinity string automates discovery of a user's relationship to the University--describing a user's academic department and degree program or position at the University. Affinity strings also provide the Libraries with an anonymized view of resource usage, allowing data collection that respects users' privacy and lays the groundwork for automated recommendation of relevant resources based on the practices and habits of their peers.

  1. Integrable deformations of affine Toda theories and duality

    International Nuclear Information System (INIS)

    Fateev, V.A.

    1996-01-01

    We introduce and study five series of one-parameter families of two-dimensional integrable quantum field theories. These theories have a Lagrangian description in terms of the massive Thirring model coupled with non-simply laced affine Toda theories. Perturbative calculations, analysis of the factorized scattering theory and the Bethe ansatz technique are used to show that these field theories possess the dual representation available for the perturbative analysis in the strong coupling limit. The dual theory can be formulated as the non-linear sigma model with Witten's Euclidean black hole metric (complex sinh-Gordon theory) coupled with non-simply laced affine Toda theories. Lie algebras associated with these ''dual'' Toda theories belong to the dual series of affine algebras but have a smaller rank. The exact relation between coupling constants in the dual theories is conjectured. (orig.)

  2. Report: Affinity Chromatography.

    Science.gov (United States)

    Walters, Rodney R.

    1985-01-01

    Supports, affinity ligands, immobilization, elution methods, and a number of applications are among the topics considered in this discussion of affinity chromatography. An outline of the basic principles of affinity chromatography is included. (JN)

  3. Lactosylamidine-based affinity purification for cellulolytic enzymes EG I and CBH I from Hypocrea jecorina and their properties.

    Science.gov (United States)

    Ogata, Makoto; Kameshima, Yumiko; Hattori, Takeshi; Michishita, Kousuke; Suzuki, Tomohiro; Kawagishi, Hirokazu; Totani, Kazuhide; Hiratake, Jun; Usui, Taichi

    2010-12-10

    Selective adsorption and separation of β-glucosidase, endo-acting endo-β-(1→4)-glucanase I (EG I), and exo-acting cellobiohydrolase I (CBH I) were achieved by affinity chromatography with β-lactosylamidine as ligand. A crude cellulase preparation from Hypocrea jecorina served as the source of enzyme. When crude cellulase was applied to the lactosylamidine-based affinity column, β-glucosidase appeared in the unbound fraction. By contrast, EG I and CBH I were retained on the column and then separated from each other by appropriately adjusting the elution conditions. The relative affinities of the enzymes, based on their column elution conditions, were strongly dependent on the ligand. The highly purified EG I and CBH I, obtained by affinity chromatography, were further purified by Mono P and DEAE chromatography, respectively. EG I and CBH I cleave only at the phenolic bond in p-nitrophenyl glycosides with lactose and N-acetyllactosamine (LacNAc). By contrast, both scissile bonds in p-nitrophenyl glycosides with cellobiose were subject to hydrolysis although with important differences in their kinetic parameters. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Approximate convex hull of affine iterated function system attractors

    International Nuclear Information System (INIS)

    Mishkinis, Anton; Gentil, Christian; Lanquetin, Sandrine; Sokolov, Dmitry

    2012-01-01

    Highlights: ► We present an iterative algorithm to approximate affine IFS attractor convex hull. ► Elimination of the interior points significantly reduces the complexity. ► To optimize calculations, we merge the convex hull images at each iteration. ► Approximation by ellipses increases speed of convergence to the exact convex hull. ► We present a method of the output convex hull simplification. - Abstract: In this paper, we present an algorithm to construct an approximate convex hull of the attractors of an affine iterated function system (IFS). We construct a sequence of convex hull approximations for any required precision using the self-similarity property of the attractor in order to optimize calculations. Due to the affine properties of IFS transformations, the number of points considered in the construction is reduced. The time complexity of our algorithm is a linear function of the number of iterations and the number of points in the output approximate convex hull. The number of iterations and the execution time increases logarithmically with increasing accuracy. In addition, we introduce a method to simplify the approximate convex hull without loss of accuracy.

  5. PHARMACEUTICAL AND BIOMEDICAL APPLICATIONS OF AFFINITY CHROMATOGRAPHY: RECENT TRENDS AND DEVELOPMENTS

    Science.gov (United States)

    Hage, David S.; Anguizola, Jeanethe A.; Bi, Cong; Li, Rong; Matsuda, Ryan; Papastavros, Efthimia; Pfaunmiller, Erika; Vargas, John; Zheng, Xiwei

    2012-01-01

    Affinity chromatography is a separation technique that has become increasingly important in work with biological samples and pharmaceutical agents. This method is based on the use of a biologically-related agent as a stationary phase to selectively retain analytes or to study biological interactions. This review discusses the basic principles behind affinity chromatography and examines recent developments that have occurred in the use of this method for biomedical and pharmaceutical analysis. Techniques based on traditional affinity supports are discussed, but an emphasis is placed on methods in which affinity columns are used as part of HPLC systems or in combination with other analytical methods. General formats for affinity chromatography that are considered include step elution schemes, weak affinity chromatography, affinity extraction and affinity depletion. Specific separation techniques that are examined include lectin affinity chromatography, boronate affinity chromatography, immunoaffinity chromatography, and immobilized metal ion affinity chromatography. Approaches for the study of biological interactions by affinity chromatography are also presented, such as the measurement of equilibrium constants, rate constants, or competition and displacement effects. In addition, related developments in the use of immobilized enzyme reactors, molecularly imprinted polymers, dye ligands and aptamers are briefly considered. PMID:22305083

  6. Methyl cation affinities of neutral and anionic maingroup-element hydrides: trends across the periodic table and correlation with proton affinities.

    Science.gov (United States)

    Mulder, R Joshua; Guerra, Célia Fonseca; Bickelhaupt, F Matthias

    2010-07-22

    We have computed the methyl cation affinities in the gas phase of archetypal anionic and neutral bases across the periodic table using ZORA-relativistic density functional theory (DFT) at BP86/QZ4P//BP86/TZ2P. The main purpose of this work is to provide the methyl cation affinities (and corresponding entropies) at 298 K of all anionic (XH(n-1)(-)) and neutral bases (XH(n)) constituted by maingroup-element hydrides of groups 14-17 and the noble gases (i.e., group 18) along the periods 2-6. The cation affinity of the bases decreases from H(+) to CH(3)(+). To understand this trend, we have carried out quantitative bond energy decomposition analyses (EDA). Quantitative correlations are established between the MCA and PA values.

  7. The Cutting Edge of Affinity Electrophoresis Technology.

    Science.gov (United States)

    Kinoshita, Eiji; Kinoshita-Kikuta, Emiko; Koike, Tohru

    2015-03-18

    Affinity electrophoresis is an important technique that is widely used to separate and analyze biomolecules in the fields of biology and medicine. Both quantitative and qualitative information can be gained through affinity electrophoresis. Affinity electrophoresis can be applied through a variety of strategies, such as mobility shift electrophoresis, charge shift electrophoresis or capillary affinity electrophoresis. These strategies are based on changes in the electrophoretic patterns of biological macromolecules that result from interactions or complex-formation processes that induce changes in the size or total charge of the molecules. Nucleic acid fragments can be characterized through their affinity to other molecules, for example transcriptional factor proteins. Hydrophobic membrane proteins can be identified by means of a shift in the mobility induced by a charged detergent. The various strategies have also been used in the estimation of association/disassociation constants. Some of these strategies have similarities to affinity chromatography, in that they use a probe or ligand immobilized on a supported matrix for electrophoresis. Such methods have recently contributed to profiling of major posttranslational modifications of proteins, such as glycosylation or phosphorylation. Here, we describe advances in analytical techniques involving affinity electrophoresis that have appeared during the last five years.

  8. Simulating the influence of plasma protein on measured receptor affinity in biochemical assays reveals the utility of Schild analysis for estimating compound affinity for plasma proteins.

    Science.gov (United States)

    Blakeley, D; Sykes, D A; Ensor, P; Bertran, E; Aston, P J; Charlton, S J

    2015-11-01

    Plasma protein binding (PPB) influences the free fraction of drug available to bind to its target and is therefore an important consideration in drug discovery. While traditional methods for assessing PPB (e.g. rapid equilibrium dialysis) are suitable for comparing compounds with relatively weak PPB, they are not able to accurately discriminate between highly bound compounds (typically >99.5%). The aim of the present work was to use mathematical modelling to explore the potential utility of receptor binding and cellular functional assays to estimate the affinity of compounds for plasma proteins. Plasma proteins are routinely added to in vitro assays, so a secondary goal was to investigate the effect of plasma proteins on observed ligand-receptor interactions. Using the principle of conservation of mass and the law of mass action, a cubic equation was derived describing the ligand-receptor complex [LR] in the presence of plasma protein at equilibrium. The model demonstrates the profound influence of PPB on in vitro assays and identifies the utility of Schild analysis, which is usually applied to determine receptor-antagonist affinities, for calculating affinity at plasma proteins (termed KP ). We have also extended this analysis to functional effects using operational modelling and demonstrate that these approaches can also be applied to cell-based assay systems. These mathematical models can potentially be used in conjunction with experimental data to estimate drug-plasma protein affinities in the earliest phases of drug discovery programmes. © 2015 The British Pharmacological Society.

  9. Linear Interaction Energy Based Prediction of Cytochrome P450 1A2 Binding Affinities with Reliability Estimation.

    Directory of Open Access Journals (Sweden)

    Luigi Capoferri

    Full Text Available Prediction of human Cytochrome P450 (CYP binding affinities of small ligands, i.e., substrates and inhibitors, represents an important task for predicting drug-drug interactions. A quantitative assessment of the ligand binding affinity towards different CYPs can provide an estimate of inhibitory activity or an indication of isoforms prone to interact with the substrate of inhibitors. However, the accuracy of global quantitative models for CYP substrate binding or inhibition based on traditional molecular descriptors can be limited, because of the lack of information on the structure and flexibility of the catalytic site of CYPs. Here we describe the application of a method that combines protein-ligand docking, Molecular Dynamics (MD simulations and Linear Interaction Energy (LIE theory, to allow for quantitative CYP affinity prediction. Using this combined approach, a LIE model for human CYP 1A2 was developed and evaluated, based on a structurally diverse dataset for which the estimated experimental uncertainty was 3.3 kJ mol-1. For the computed CYP 1A2 binding affinities, the model showed a root mean square error (RMSE of 4.1 kJ mol-1 and a standard error in prediction (SDEP in cross-validation of 4.3 kJ mol-1. A novel approach that includes information on both structural ligand description and protein-ligand interaction was developed for estimating the reliability of predictions, and was able to identify compounds from an external test set with a SDEP for the predicted affinities of 4.6 kJ mol-1 (corresponding to 0.8 pKi units.

  10. Fan Affinity Laws from a Collision Model

    Science.gov (United States)

    Bhattacharjee, Shayak

    2012-01-01

    The performance of a fan is usually estimated using hydrodynamical considerations. The calculations are long and involved and the results are expressed in terms of three affinity laws. In this paper we use kinetic theory to attack this problem. A hard sphere collision model is used, and subsequently a correction to account for the flow behaviour…

  11. Spectral affinity in protein networks.

    Science.gov (United States)

    Voevodski, Konstantin; Teng, Shang-Hua; Xia, Yu

    2009-11-29

    Protein-protein interaction (PPI) networks enable us to better understand the functional organization of the proteome. We can learn a lot about a particular protein by querying its neighborhood in a PPI network to find proteins with similar function. A spectral approach that considers random walks between nodes of interest is particularly useful in evaluating closeness in PPI networks. Spectral measures of closeness are more robust to noise in the data and are more precise than simpler methods based on edge density and shortest path length. We develop a novel affinity measure for pairs of proteins in PPI networks, which uses personalized PageRank, a random walk based method used in context-sensitive search on the Web. Our measure of closeness, which we call PageRank Affinity, is proportional to the number of times the smaller-degree protein is visited in a random walk that restarts at the larger-degree protein. PageRank considers paths of all lengths in a network, therefore PageRank Affinity is a precise measure that is robust to noise in the data. PageRank Affinity is also provably related to cluster co-membership, making it a meaningful measure. In our experiments on protein networks we find that our measure is better at predicting co-complex membership and finding functionally related proteins than other commonly used measures of closeness. Moreover, our experiments indicate that PageRank Affinity is very resilient to noise in the network. In addition, based on our method we build a tool that quickly finds nodes closest to a queried protein in any protein network, and easily scales to much larger biological networks. We define a meaningful way to assess the closeness of two proteins in a PPI network, and show that our closeness measure is more biologically significant than other commonly used methods. We also develop a tool, accessible at http://xialab.bu.edu/resources/pnns, that allows the user to quickly find nodes closest to a queried vertex in any protein

  12. Transformations Based on Continuous Piecewise-Affine Velocity Fields

    DEFF Research Database (Denmark)

    Freifeld, Oren; Hauberg, Søren; Batmanghelich, Kayhan

    2017-01-01

    We propose novel finite-dimensional spaces of well-behaved transformations. The latter are obtained by (fast and highly-accurate) integration of continuous piecewise-affine velocity fields. The proposed method is simple yet highly expressive, effortlessly handles optional constraints (e.g., volum...

  13. The Cutting Edge of Affinity Electrophoresis Technology

    Science.gov (United States)

    Kinoshita, Eiji; Kinoshita-Kikuta, Emiko; Koike, Tohru

    2015-01-01

    Affinity electrophoresis is an important technique that is widely used to separate and analyze biomolecules in the fields of biology and medicine. Both quantitative and qualitative information can be gained through affinity electrophoresis. Affinity electrophoresis can be applied through a variety of strategies, such as mobility shift electrophoresis, charge shift electrophoresis or capillary affinity electrophoresis. These strategies are based on changes in the electrophoretic patterns of biological macromolecules that result from interactions or complex-formation processes that induce changes in the size or total charge of the molecules. Nucleic acid fragments can be characterized through their affinity to other molecules, for example transcriptional factor proteins. Hydrophobic membrane proteins can be identified by means of a shift in the mobility induced by a charged detergent. The various strategies have also been used in the estimation of association/disassociation constants. Some of these strategies have similarities to affinity chromatography, in that they use a probe or ligand immobilized on a supported matrix for electrophoresis. Such methods have recently contributed to profiling of major posttranslational modifications of proteins, such as glycosylation or phosphorylation. Here, we describe advances in analytical techniques involving affinity electrophoresis that have appeared during the last five years. PMID:28248262

  14. Experimental and theoretical binding affinity between polyvinylpolypyrrolidone and selected phenolic compounds from food matrices.

    Science.gov (United States)

    Durán-Lara, Esteban F; López-Cortés, Xaviera A; Castro, Ricardo I; Avila-Salas, Fabián; González-Nilo, Fernando D; Laurie, V Felipe; Santos, Leonardo S

    2015-02-01

    Polyvinylpolypyrrolidone (PVPP) is a fining agent, widely used in winemaking and brewing, whose mode of action in removing phenolic compounds has not been fully characterised. The aim of this study was to evaluate the experimental and theoretical binding affinity of PVPP towards six phenolic compounds representing different types of phenolic species. The interaction between PVPP and phenolics was evaluated in model solutions, where hydroxyl groups, hydrophobic bonding and steric hindrance were characterised. The results of the study indicated that PVPP exhibits high affinity for quercetin and catechin, moderate affinity for epicatechin, gallic acid and lower affinity for 4-methylcatechol and caffeic acid. The affinity has a direct correlation with the hydroxylation degree of each compound. The results show that the affinity of PVPP towards phenols is related with frontier orbitals. This work demonstrates a direct correlation between the experimental affinity and the interaction energy calculations obtained through computational chemistry methods. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. The solutions of affine and conformal affine Toda field theory

    International Nuclear Information System (INIS)

    Papadopoulos, G.; Spence, B.

    1994-02-01

    We give new formulations of the solutions of the field equations of the affine Toda and conformal affine Toda theories on a cylinder and two-dimensional Minkowski space-time. These solutions are parameterised in terms of initial data and the resulting covariant phase spaces are diffeomorphic to the Hamiltonian ones. We derive the fundamental Poisson brackets of the parameters of the solutions and give the general static solutions for the affine theory. (authors). 10 refs

  16. Computational prediction of binding affinity for CYP1A2-ligand complexes using empirical free energy calculations

    DEFF Research Database (Denmark)

    Poongavanam, Vasanthanathan; Olsen, Lars; Jørgensen, Flemming Steen

    2010-01-01

    , and methods based on statistical mechanics. In the present investigation, we started from an LIE model to predict the binding free energy of structurally diverse compounds of cytochrome P450 1A2 ligands, one of the important human metabolizing isoforms of the cytochrome P450 family. The data set includes both...... substrates and inhibitors. It appears that the electrostatic contribution to the binding free energy becomes negligible in this particular protein and a simple empirical model was derived, based on a training set of eight compounds. The root mean square error for the training set was 3.7 kJ/mol. Subsequent......Predicting binding affinities for receptor-ligand complexes is still one of the challenging processes in computational structure-based ligand design. Many computational methods have been developed to achieve this goal, such as docking and scoring methods, the linear interaction energy (LIE) method...

  17. Affinity improvement of a therapeutic antibody by structure-based computational design: generation of electrostatic interactions in the transition state stabilizes the antibody-antigen complex.

    Directory of Open Access Journals (Sweden)

    Masato Kiyoshi

    Full Text Available The optimization of antibodies is a desirable goal towards the development of better therapeutic strategies. The antibody 11K2 was previously developed as a therapeutic tool for inflammatory diseases, and displays very high affinity (4.6 pM for its antigen the chemokine MCP-1 (monocyte chemo-attractant protein-1. We have employed a virtual library of mutations of 11K2 to identify antibody variants of potentially higher affinity, and to establish benchmarks in the engineering of a mature therapeutic antibody. The most promising candidates identified in the virtual screening were examined by surface plasmon resonance to validate the computational predictions, and to characterize their binding affinity and key thermodynamic properties in detail. Only mutations in the light-chain of the antibody are effective at enhancing its affinity for the antigen in vitro, suggesting that the interaction surface of the heavy-chain (dominated by the hot-spot residue Phe101 is not amenable to optimization. The single-mutation with the highest affinity is L-N31R (4.6-fold higher affinity than wild-type antibody. Importantly, all the single-mutations showing increase affinity incorporate a charged residue (Arg, Asp, or Glu. The characterization of the relevant thermodynamic parameters clarifies the energetic mechanism. Essentially, the formation of new electrostatic interactions early in the binding reaction coordinate (transition state or earlier benefits the durability of the antibody-antigen complex. The combination of in silico calculations and thermodynamic analysis is an effective strategy to improve the affinity of a matured therapeutic antibody.

  18. Lectin affinity electrophoresis.

    Science.gov (United States)

    Kobayashi, Yuka

    2014-01-01

    An interaction or a binding event typically changes the electrophoretic properties of a molecule. Affinity electrophoresis methods detect changes in the electrophoretic pattern of molecules (mainly macromolecules) that occur as a result of biospecific interactions or complex formation. Lectin affinity electrophoresis is a very effective method for the detection and analysis of trace amounts of glycobiological substances. It is particularly useful for isolating and separating the glycoisomers of target molecules. Here, we describe a sensitive technique for the detection of glycoproteins separated by agarose gel-lectin affinity electrophoresis that uses antibody-affinity blotting. The technique is tested using α-fetoprotein with lectin (Lens culinaris agglutinin and Phaseolus vulgaris agglutinin)-agarose gels.

  19. Novel trends in affinity biosensors: current challenges and perspectives

    International Nuclear Information System (INIS)

    Arugula, Mary A; Simonian, Aleksandr

    2014-01-01

    Molecular biorecognition processes facilitate physical and biochemical interactions between molecules in all crucial metabolic pathways. Perhaps the target analyte and the biorecognition element interactions have the most impactful use in biosensing applications. Traditional analytical sensing systems offer excellent biorecognition elements with the ability to detect and determine the presence of analytes. High affinity antibodies and DNA play an important role in the development of affinity biosensors based on electrochemical, optical and mass sensitive approaches. Advancements in this area routinely employ labels, label free, nanoparticles, multifunctional matrices, carbon nanotubes and other methods to meet the requirements of its own application. However, despite increasing affinity ceilings for conventional biosensors, the field draws back in meeting specifically important demands, such as long-term stability, ultrasensitivity, rapid detection, extreme selectivity, strong biological base, calibration, in vivo measurements, regeneration, satisfactory performance and ease of production. Nevertheless, recent efforts through this line have produced novel high-tech nanosensing systems such as ‘aptamers’ and ‘phages’ which exhibit high-throughput sensing. Aptamers and phages are powerful tools that excel over antibodies in sensibility, stability, multi-detection, in vivo measurements and regeneration. Phages are superior in stability, screening for affinity-based target molecules ranging from small to proteins and even cells, and easy production. In this review, we focus mainly on recent developments in affinity-based biosensors such as immunosensors, DNA sensors, emphasizing aptasensors and phage-based biosensors basing on novel electrochemical, optical and mass sensitive detection techniques. We also address enzyme inhibition-based biosensors and the current problems associated with the above sensors and their future perspectives. (topical review)

  20. Methyl Cation Affinities of Neutral and Anionic Maingroup-Element Hydrides: Trends Across the Periodic Table and Correlation with Proton Affinities

    NARCIS (Netherlands)

    Mulder, R. Joshua; Guerra, Celia Fonseca; Bickelhaupt, F. Matthias

    2010-01-01

    We have computed the methyl cation affinities in the gas phase of archetypal anionic and neutral bases across the periodic table using ZORA-relativistic density functional theory (DFT) at BP86/QZ4P//BP86/TZ2P. The main purpose of this work is to provide the methyl cation affinities (and

  1. Development of immobilized membrane-based affinity columns for use in the online characterization of membrane bound proteins and for targeted affinity isolations

    International Nuclear Information System (INIS)

    Moaddel, Ruin; Wainer, Irving W.

    2006-01-01

    Membranes obtained from cell lines that express or do not express a target membrane bound protein have been immobilized on a silica-based liquid chromatographic support or on the surface of an activated glass capillary. The resulting chromatographic columns have been placed in liquid chromatographic systems and used to characterize the target proteins and to identify small molecules that bind to the target. Membranes containing ligand gated ion channels, G-protein coupled receptors and drug transporters have been prepared and characterized. If a marker ligand has been identified for the target protein, frontal or zonal displacement chromatographic techniques can be used to determine binding affinities (K d values) and non-linear chromatography can be used to assess the association (k on ) and dissociation (k off ) rate constants and the thermodynamics of the binding process. Membrane-based affinity columns have been created using membranes from a cell line that does not express the target protein (control) and the same cell line that expresses the target protein (experimental) after genomic transfection. The resulting columns can be placed in a parallel chromatography system and the differential retention between the control and experimental columns can be used to identify small molecules and protein that bind to the target protein. These applications will be illustrated using columns created using cellular membranes containing nicotinic acetylcholine receptors and the drug transporter P-glycoprotein

  2. Development of immobilized membrane-based affinity columns for use in the online characterization of membrane bound proteins and for targeted affinity isolations

    Energy Technology Data Exchange (ETDEWEB)

    Moaddel, Ruin [Gerontology Research Center, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224-6825 (United States); Wainer, Irving W. [Gerontology Research Center, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224-6825 (United States)]. E-mail: Wainerir@grc.nia.nih.gov

    2006-03-30

    Membranes obtained from cell lines that express or do not express a target membrane bound protein have been immobilized on a silica-based liquid chromatographic support or on the surface of an activated glass capillary. The resulting chromatographic columns have been placed in liquid chromatographic systems and used to characterize the target proteins and to identify small molecules that bind to the target. Membranes containing ligand gated ion channels, G-protein coupled receptors and drug transporters have been prepared and characterized. If a marker ligand has been identified for the target protein, frontal or zonal displacement chromatographic techniques can be used to determine binding affinities (K {sub d} values) and non-linear chromatography can be used to assess the association (k {sub on}) and dissociation (k {sub off}) rate constants and the thermodynamics of the binding process. Membrane-based affinity columns have been created using membranes from a cell line that does not express the target protein (control) and the same cell line that expresses the target protein (experimental) after genomic transfection. The resulting columns can be placed in a parallel chromatography system and the differential retention between the control and experimental columns can be used to identify small molecules and protein that bind to the target protein. These applications will be illustrated using columns created using cellular membranes containing nicotinic acetylcholine receptors and the drug transporter P-glycoprotein.

  3. Spectral affinity in protein networks

    Directory of Open Access Journals (Sweden)

    Teng Shang-Hua

    2009-11-01

    Full Text Available Abstract Background Protein-protein interaction (PPI networks enable us to better understand the functional organization of the proteome. We can learn a lot about a particular protein by querying its neighborhood in a PPI network to find proteins with similar function. A spectral approach that considers random walks between nodes of interest is particularly useful in evaluating closeness in PPI networks. Spectral measures of closeness are more robust to noise in the data and are more precise than simpler methods based on edge density and shortest path length. Results We develop a novel affinity measure for pairs of proteins in PPI networks, which uses personalized PageRank, a random walk based method used in context-sensitive search on the Web. Our measure of closeness, which we call PageRank Affinity, is proportional to the number of times the smaller-degree protein is visited in a random walk that restarts at the larger-degree protein. PageRank considers paths of all lengths in a network, therefore PageRank Affinity is a precise measure that is robust to noise in the data. PageRank Affinity is also provably related to cluster co-membership, making it a meaningful measure. In our experiments on protein networks we find that our measure is better at predicting co-complex membership and finding functionally related proteins than other commonly used measures of closeness. Moreover, our experiments indicate that PageRank Affinity is very resilient to noise in the network. In addition, based on our method we build a tool that quickly finds nodes closest to a queried protein in any protein network, and easily scales to much larger biological networks. Conclusion We define a meaningful way to assess the closeness of two proteins in a PPI network, and show that our closeness measure is more biologically significant than other commonly used methods. We also develop a tool, accessible at http://xialab.bu.edu/resources/pnns, that allows the user to

  4. Color-weak compensation using local affine isometry based on discrimination threshold matching

    OpenAIRE

    Mochizuki, Rika; Kojima, Takanori; Lenz, Reiner; Chao, Jinhui

    2015-01-01

    We develop algorithms for color-weak compensation and color-weak simulation based on Riemannian geometry models of color spaces. The objective function introduced measures the match of color discrimination thresholds of average normal observers and a color-weak observer. The developed matching process makes use of local affine maps between color spaces of color-normal and color-weak observers. The method can be used to generate displays of images that provide color-normal and color-weak obser...

  5. Lp-dual affine surface area

    Science.gov (United States)

    Wei, Wang; Binwu, He

    2008-12-01

    According to the notion of Lp-affine surface area by Lutwak, in this paper, we introduce the concept of Lp-dual affine surface area. Further, we establish the affine isoperimetric inequality and the Blaschke-Santaló inequality for Lp-dual affine surface area. Besides, the dual Brunn-Minkowski inequality for Lp-dual affine surface area is presented.

  6. Application of affinity propagation algorithm based on manifold distance for transformer PD pattern recognition

    Science.gov (United States)

    Wei, B. G.; Huo, K. X.; Yao, Z. F.; Lou, J.; Li, X. Y.

    2018-03-01

    It is one of the difficult problems encountered in the research of condition maintenance technology of transformers to recognize partial discharge (PD) pattern. According to the main physical characteristics of PD, three models of oil-paper insulation defects were set up in laboratory to study the PD of transformers, and phase resolved partial discharge (PRPD) was constructed. By using least square method, the grey-scale images of PRPD were constructed and features of each grey-scale image were 28 box dimensions and 28 information dimensions. Affinity propagation algorithm based on manifold distance (AP-MD) for transformers PD pattern recognition was established, and the data of box dimension and information dimension were clustered based on AP-MD. Study shows that clustering result of AP-MD is better than the results of affinity propagation (AP), k-means and fuzzy c-means algorithm (FCM). By choosing different k values of k-nearest neighbor, we find clustering accuracy of AP-MD falls when k value is larger or smaller, and the optimal k value depends on sample size.

  7. Affine.m—Mathematica package for computations in representation theory of finite-dimensional and affine Lie algebras

    Science.gov (United States)

    Nazarov, Anton

    2012-11-01

    In this paper we present Affine.m-a program for computations in representation theory of finite-dimensional and affine Lie algebras and describe implemented algorithms. The algorithms are based on the properties of weights and Weyl symmetry. Computation of weight multiplicities in irreducible and Verma modules, branching of representations and tensor product decomposition are the most important problems for us. These problems have numerous applications in physics and we provide some examples of these applications. The program is implemented in the popular computer algebra system Mathematica and works with finite-dimensional and affine Lie algebras. Catalogue identifier: AENA_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AENB_v1_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, UK Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 24 844 No. of bytes in distributed program, including test data, etc.: 1 045 908 Distribution format: tar.gz Programming language: Mathematica. Computer: i386-i686, x86_64. Operating system: Linux, Windows, Mac OS, Solaris. RAM: 5-500 Mb Classification: 4.2, 5. Nature of problem: Representation theory of finite-dimensional Lie algebras has many applications in different branches of physics, including elementary particle physics, molecular physics, nuclear physics. Representations of affine Lie algebras appear in string theories and two-dimensional conformal field theory used for the description of critical phenomena in two-dimensional systems. Also Lie symmetries play a major role in a study of quantum integrable systems. Solution method: We work with weights and roots of finite-dimensional and affine Lie algebras and use Weyl symmetry extensively. Central problems which are the computations of weight multiplicities, branching and fusion coefficients are solved using one general recurrent

  8. Development of an aptamer-based affinity purification method for vascular endothelial growth factor

    Directory of Open Access Journals (Sweden)

    Maren Lönne

    2015-12-01

    Full Text Available Since aptamers bind their targets with high affinity and specificity, they are promising alternative ligands in protein affinity purification. As aptamers are chemically synthesized oligonucleotides, they can be easily produced in large quantities regarding GMP conditions allowing their application in protein production for therapeutic purposes. Several advantages of aptamers compared to antibodies are described in general within this paper. Here, an aptamer directed against the human Vascular Endothelial Growth Factor (VEGF was used as affinity ligand for establishing a purification platform for VEGF in small scale. The aptamer was covalently immobilized on magnetic beads in a controlled orientation resulting in a functional active affinity matrix. Target binding was optimized by introduction of spacer molecules and variation of aptamer density. Further, salt-induced target elution was demonstrated as well as VEGF purification from a complex protein mixture proving the specificity of protein-aptamer binding.

  9. Variational predictions of transition energies and electron affinities: He and Li ground states and Li, Be, and Mg core-excited states

    International Nuclear Information System (INIS)

    Fischer, C.F.

    1990-01-01

    Variational procedures for predicting energy differences of many-electron systems are investigated. Several different calculations for few-electron systems are considered that illustrate the problems encountered when a many-electron system is modeled as a core plus outer electrons. It is shown that sequences of increasingly more accurate calculations for outer correlation may converge yielding wrong transition energies. At the same time, accurate core-polarization calculations overestimate the binding energy, requiring a core-valence correction. For the high-spin, core-excited states of Li, it was found that outer correlation only predicted electron affinities as accurately as full-correlation studies. This observation suggested a prediction of the core-excited 4 P endash 4 S transition in Be - , based on observed 3 P 0 endash 3 P transition energies of the neutral species, predicted electron affinities including only outer correlation, and a core-valence correction, that is shown to be in good agreement with experiment. A similar calculation for Mg - predicts a wavelength of 2895.1 A for this transition

  10. Structure-based engineering to restore high affinity binding of an isoform-selective anti-TGFβ1 antibody

    Science.gov (United States)

    Honey, Denise M.; Best, Annie; Qiu, Huawei

    2018-01-01

    ABSTRACT Metelimumab (CAT192) is a human IgG4 monoclonal antibody developed as a TGFβ1-specific antagonist. It was tested in clinical trials for the treatment of scleroderma but later terminated due to lack of efficacy. Subsequent characterization of CAT192 indicated that its TGFβ1 binding affinity was reduced by ∼50-fold upon conversion from the parental single-chain variable fragment (scFv) to IgG4. We hypothesized this result was due to decreased conformational flexibility of the IgG that could be altered via engineering. Therefore, we designed insertion mutants in the elbow region and screened for binding and potency. Our results indicated that increasing the elbow region linker length in each chain successfully restored the isoform-specific and high affinity binding of CAT192 to TGFβ1. The crystal structure of the high binding affinity mutant displays large conformational rearrangements of the variable domains compared to the wild-type antigen-binding fragment (Fab) and the low binding affinity mutants. Insertion of two glycines in both the heavy and light chain elbow regions provided sufficient flexibility for the variable domains to extend further apart than the wild-type Fab, and allow the CDR3s to make additional interactions not seen in the wild-type Fab structure. These interactions coupled with the dramatic conformational changes provide a possible explanation of how the scFv and elbow-engineered Fabs bind TGFβ1 with high affinity. This study demonstrates the benefits of re-examining both structure and function when converting scFv to IgG molecules, and highlights the potential of structure-based engineering to produce fully functional antibodies. PMID:29333938

  11. A “Swingable” straight-chain affinity molecule immobilized on a semi-conductor electrode for photo-excited current-based molecular sensing

    International Nuclear Information System (INIS)

    Takatsuji, Yoshiyuki; Wakabayashi, Ryo; Sakakura, Tatsuya; Haruyama, Tetsuya

    2015-01-01

    The molecular affinities of biomolecules have found applications in the areas of clinical diagnostics, drug discovery, as well as allied fields of study. An affinity sensor is a unique in situ assay tool, which is valuable and convenient in practical situations. In this study, we designed a photo-excitable molecular interface with an affinity domain and fabricated with a “swingable” straight-chain affinity molecule immobilized on a semi-conductor electrode (SCE). The straight-chain affinity molecule possessed a photo-excitable dye at one end and was bound to the SCE surface at the other by the EC tag method, which was developed previously. A straight-chain molecule is too long to transfer electrons from the photo-excited dye to the conduction band of the SCE. However, the straight-chain molecule was designed with a “swing” structure, which made the transfer of electrons possible. The central region of the chain molecule has an affinity to the activated estrogen receptor (ER). When the activated ER bound to the affinity region, the molecular lost its swingable function, the electron transfer from the photo-excited dye to the SCE was consequently suppressed. Based on the unique swingable molecular interface, the affinity sensor can be used to determine the in situ concentration of endocrine disrupter ESTROGEN (17β-estradiol) at concentrations ranging from 2 to 10 nM with very good reproducibility. The superior assay reproducibility is responsible for the success of the EC tag method, which is a quantitative method for immobilizing molecules on SCE.

  12. Affine pairings on ARM

    NARCIS (Netherlands)

    Acar, T.; Lauter, K.; Naehrig, M.; Shumow, D.; Abdalla, M.; Lange, T.

    2013-01-01

    We report on relative performance numbers for affine and projective pairings on a dual-core Cortex A9 ARM processor. Using a fast inversion in the base field and doing inversion in extension fields by using the norm map to reduce to inversions in smaller fields, we find a very low ratio of

  13. Affine coherent states and Toeplitz operators

    Science.gov (United States)

    Hutníková, Mária; Hutník, Ondrej

    2012-06-01

    We study a parameterized family of Toeplitz operators in the context of affine coherent states based on the Calderón reproducing formula (= resolution of unity on L_2( {R})) and the specific admissible wavelets (= affine coherent states in L_2( {R})) related to Laguerre functions. Symbols of such Calderón-Toeplitz operators as individual coordinates of the affine group (= upper half-plane with the hyperbolic geometry) are considered. In this case, a certain class of pseudo-differential operators, their properties and their operator algebras are investigated. As a result of this study, the Fredholm symbol algebras of the Calderón-Toeplitz operator algebras for these particular cases of symbols are described. This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to ‘Coherent states: mathematical and physical aspects’.

  14. Exact-exchange-based quasiparticle calculations

    International Nuclear Information System (INIS)

    Aulbur, Wilfried G.; Staedele, Martin; Goerling, Andreas

    2000-01-01

    One-particle wave functions and energies from Kohn-Sham calculations with the exact local Kohn-Sham exchange and the local density approximation (LDA) correlation potential [EXX(c)] are used as input for quasiparticle calculations in the GW approximation (GWA) for eight semiconductors. Quasiparticle corrections to EXX(c) band gaps are small when EXX(c) band gaps are close to experiment. In the case of diamond, quasiparticle calculations are essential to remedy a 0.7 eV underestimate of the experimental band gap within EXX(c). The accuracy of EXX(c)-based GWA calculations for the determination of band gaps is as good as the accuracy of LDA-based GWA calculations. For the lowest valence band width a qualitatively different behavior is observed for medium- and wide-gap materials. The valence band width of medium- (wide-) gap materials is reduced (increased) in EXX(c) compared to the LDA. Quasiparticle corrections lead to a further reduction (increase). As a consequence, EXX(c)-based quasiparticle calculations give valence band widths that are generally 1-2 eV smaller (larger) than experiment for medium- (wide-) gap materials. (c) 2000 The American Physical Society

  15. Testing Affine Term Structure Models in Case of Transaction Costs

    NARCIS (Netherlands)

    Driessen, J.J.A.G.; Melenberg, B.; Nijman, T.E.

    1999-01-01

    In this paper we empirically analyze the impact of transaction costs on the performance of affine interest rate models. We test the implied (no arbitrage) Euler restrictions, and we calculate the specification error bound of Hansen and Jagannathan to measure the extent to which a model is

  16. Development of a nonlinear model for the prediction of response times of glucose affinity sensors using concanavalin A and dextran and the development of a differential osmotic glucose affinity sensor

    Science.gov (United States)

    Reis, Louis G.

    With the increasing prevalence of diabetes in the United States and worldwide, blood glucose monitoring must be accurate and reliable. Current enzymatic sensors have numerous disadvantages that make them unreliable and unfavorable among patients. Recent research in glucose affinity sensors correct some of the problems that enzymatic sensors experience. Dextran and concanavalin A are two of the more common components used in glucose affinity sensors. When these sensors were first explored, a model was derived to predict the response time of a glucose affinity sensor using concanavalin A and dextran. However, the model assumed the system was linear and fell short of calculating times representative of the response times determined through experimental tests with the sensors. In this work, a new model that uses the Stokes-Einstein Equation to demonstrate the nonlinear behavior of the glucose affinity assay was developed to predict the response times of similar glucose affinity sensors. In addition to the device tested by the original linear model, additional devices were identified and tested with the proposed model. The nonlinear model was designed to accommodate the many different variations between systems. The proposed model was able to accurately calculate response times for sensors using the concanavalin A-dextran affinity assay with respect to the experimentally reported times by the independent research groups. Parameter studies using the nonlinear model were able to identify possible setbacks that could compromise the response of thesystem. Specifically, the model showed that the improper use of asymmetrical membranes could increase the response time by as little as 20% or more as the device is miniaturized. The model also demonstrated that systems using the concanavalin Adextran assay would experience higher response times in the hypoglycemic range. This work attempted to replicate and improve an osmotic glucose affinity sensor. The system was designed to

  17. Affinity-based biosensors as promising tools for gene doping detection.

    Science.gov (United States)

    Minunni, Maria; Scarano, Simona; Mascini, Marco

    2008-05-01

    Innovative bioanalytical approaches can be foreseen as interesting means for solving relevant emerging problems in anti-doping control. Sport authorities fear that the newer form of doping, so-called gene doping, based on a misuse of gene therapy, will be undetectable and thus much less preventable. The World Anti-Doping Agency has already asked scientists to assist in finding ways to prevent and detect this newest kind of doping. In this Opinion article we discuss the main aspects of gene doping, from the putative target analytes to suitable sampling strategies. Moreover, we discuss the potential application of affinity sensing in this field, which so far has been successfully applied to a variety of analytical problems, from clinical diagnostics to food and environmental analysis.

  18. Mathematical analysis of frontal affinity chromatography in particle and membrane configurations.

    Science.gov (United States)

    Tejeda-Mansir, A; Montesinos, R M; Guzmán, R

    2001-10-30

    The scaleup and optimization of large-scale affinity-chromatographic operations in the recovery, separation and purification of biochemical components is of major industrial importance. The development of mathematical models to describe affinity-chromatographic processes, and the use of these models in computer programs to predict column performance is an engineering approach that can help to attain these bioprocess engineering tasks successfully. Most affinity-chromatographic separations are operated in the frontal mode, using fixed-bed columns. Purely diffusive and perfusion particles and membrane-based affinity chromatography are among the main commercially available technologies for these separations. For a particular application, a basic understanding of the main similarities and differences between particle and membrane frontal affinity chromatography and how these characteristics are reflected in the transport models is of fundamental relevance. This review presents the basic theoretical considerations used in the development of particle and membrane affinity chromatography models that can be applied in the design and operation of large-scale affinity separations in fixed-bed columns. A transport model for column affinity chromatography that considers column dispersion, particle internal convection, external film resistance, finite kinetic rate, plus macropore and micropore resistances is analyzed as a framework for exploring further the mathematical analysis. Such models provide a general realistic description of almost all practical systems. Specific mathematical models that take into account geometric considerations and transport effects have been developed for both particle and membrane affinity chromatography systems. Some of the most common simplified models, based on linear driving-force (LDF) and equilibrium assumptions, are emphasized. Analytical solutions of the corresponding simplified dimensionless affinity models are presented. Particular

  19. High affinity binding of [3H]cocaine to rat liver microsomes

    International Nuclear Information System (INIS)

    El-Maghrabi, E.A.; Calligaro, D.O.; Eldefrawi, M.E.

    1988-01-01

    ] 3 H]cocaine bound reversible, with high affinity and stereospecificity to rat liver microsomes. Little binding was detected in the lysosomal, mitochondrial and nuclear fractions. The binding kinetics were slow and the kinetically calculated K/sub D/ was 2 nM. Induction of mixed function oxidases by phenobarbital did not produce significant change in [ 3 H]cocaine binding. On the other hand, chronic administration of cocaine reduced [ 3 H]cocaine binding drastically. Neither treatment affected the affinity of the liver binding protein for cocaine. Microsomes from mouse and human livers had less cocaine-binding protein and lower affinity for cocaine than those from rat liver. Binding of [ 3 H]cocaine to rat liver microsomes was insensitive to monovalent cations and > 10 fold less sensitive to biogenic amines than the cocaine receptor in rat striatum. However, the liver protein had higher affinity for cocaine and metabolites except for norcocaine. Amine uptake inhibitors displaced [ 3 H]cocaine binding to liver with a different rank order of potency than their displacement of [ 3 H]cocaine binding to striatum. This high affinity [ 3 H]cocaine binding protein in liver is not likely to be monooxygenase, but may have a role in cocaine-induced hepatotoxicity

  20. Continuous affine processes

    DEFF Research Database (Denmark)

    Buchardt, Kristian

    2016-01-01

    Affine processes possess the property that expectations of exponential affine transformations are given by a set of Riccati differential equations, which is the main feature of this popular class of processes. In this paper we generalise these results for expectations of more general transformati...

  1. Affinity in electrophoresis.

    Science.gov (United States)

    Heegaard, Niels H H

    2009-06-01

    The journal Electrophoresis has greatly influenced my approaches to biomolecular affinity studies. The methods that I have chosen as my main tools to study interacting biomolecules--native gel and later capillary zone electrophoresis--have been the topic of numerous articles in Electrophoresis. Below, the role of the journal in the development and dissemination of these techniques and applications reviewed. Many exhaustive reviews on affinity electrophoresis and affinity CE have been published in the last few years and are not in any way replaced by the present deliberations that are focused on papers published by the journal.

  2. Affinity of antibody secreted by a single cell

    International Nuclear Information System (INIS)

    Doran, D.M.

    1978-01-01

    It was the intention of this research to measure the affinity of antibody secreted by a single cell, and to describe the spectrum of affinities displayed in response to antigenic stimulation. The single cell secreting specific antibody was isolated by means of the hemolytic plaque assay. The amount of antibody secreted by the cell was to be measured through the use of a solid phase radioimmunoassay. The affinity of the antibody would be estimated by comparing the diameter of the plaque, and the amount of antibody secreted, with a mathematical theory of the formation of a plaque in agar. As a test system, a solid phase radioimmunoassay was developed for human serum albumin using antibody coupled to Sephadex. A sensitivity of 1 nanogram was attained with this assay. A solid phase radioimmunoassay for mouse immunoglobulin M was developed, using antibody coupled to Sepharose. The sensitivity attained with this assay was only on the order of 10 micrograms. The mouse immunoglobulin M radioimmunoassay was not sensitive enough to measure the amount of antibody secreted by a single cell. From a theoretical equation, the relationship between antibody affinity, plaque diameter and antibody secretion rate was calculated for the experimental conditions used in this research. By assuming a constant antibody secretion rate, an effective binding constant for the antibody was estimated from the average plaque diameters. This effective binding constant was observed to increase during the immune response

  3. The metric-affine gravitational theory as the gauge theory of the affine group

    International Nuclear Information System (INIS)

    Lord, E.A.

    1978-01-01

    The metric-affine gravitational theory is shown to be the gauge theory of the affine group, or equivalently, the gauge theory of the group GL(4,R) of tetrad deformations in a space-time with a locally Minkowskian metric. The identities of the metric-affine theory, and the relationship between them and those of general relativity and Sciama-Kibble theory, are derived. (Auth.)

  4. A Generalized Affine Isoperimetric Inequality

    OpenAIRE

    Chen, Wenxiong; Howard, Ralph; Lutwak, Erwin; Yang, Deane; Zhang, Gaoyong

    2004-01-01

    A purely analytic proof is given for an inequality that has as a direct consequence the two most important affine isoperimetric inequalities of plane convex geometry: The Blaschke-Santalo inequality and the affine isoperimetric inequality of affine differential geometry.

  5. Compound immobilization and drug-affinity chromatography.

    Science.gov (United States)

    Rix, Uwe; Gridling, Manuela; Superti-Furga, Giulio

    2012-01-01

    Bioactive small molecules act through modulating a yet unpredictable number of targets. It is therefore of critical importance to define the cellular target proteins of a compound as an entry point to understanding its mechanism of action. Often, this can be achieved in a direct fashion by chemical proteomics. As with any affinity chromatography, immobilization of the bait to a solid support is one of the earliest and most crucial steps in the process. Interfering with structural features that are important for identification of a target protein will be detrimental to binding affinity. Also, many molecules are sensitive to heat or to certain chemicals, such as acid or base, and might be destroyed during the process of immobilization, which therefore needs to be not only efficient, but also mild. The subsequent affinity chromatography step needs to preserve molecular and conformational integrity of both bait compound and proteins in order to result in the desired specific enrichment while ensuring a high level of compatibility with downstream analysis by mass spectrometry. Thus, the right choice of detergent, buffer, and protease inhibitors is also essential. This chapter describes a widely applicable procedure for the immobilization of small molecule drugs and for drug-affinity chromatography with subsequent protein identification by mass spectrometry.

  6. Fatty acid and drug binding to a low-affinity component of human serum albumin, purified by affinity chromatography

    DEFF Research Database (Denmark)

    Vorum, H; Pedersen, A O; Honoré, B

    1992-01-01

    Binding equilibria for decanoate to a defatted, commercially available human serum albumin preparation were investigated by dialysis exchange rate determinations. The binding isotherm could not be fitted by the general binding equation. It was necessary to assume that the preparation was a mixture...... of two albumin components about 40% of the albumin having high affinity and about 60% having low affinity. By affinity chromatography we succeeded in purifying the low-affinity component from the mixture. The high-affinity component, however, could not be isolated. We further analyzed the fatty acid...... and drug binding abilities of the low-affinity component. The fatty acids decanoate, laurate, myristate and palmitate were bound with higher affinity to the mixture than to the low-affinity component. Diazepam was bound with nearly the same affinity to the low-affinity component as to the albumin mixture...

  7. Quantitative relationship between antibody affinity and antibody avidity

    International Nuclear Information System (INIS)

    Griswold, W.R.

    1987-01-01

    The relationship between antibody avidity, measured by the dissociation of the antigen-antibody bond in antigen excess, and antibody affinity was studied. Complexes of radiolabelled antigen and antibody of known affinity were prepared in vitro and allowed to stand for seven days to reach equilibrium. Then nonlabelled antigen in one hundred fold excess was added to dissociate the complexes. After an appropriate incubation the fraction of antigen bound to antibody was measured by the ammonium sulfate precipitation method. The dissociation index was the fraction bound in the experimental sample divided by the fraction bound in the control. The correlation coefficient between the dissociation index and the antibody binding constant was 0.92 for early dissociation and 0.98 for late dissociation. The regression equation relating the binding constant to the dissociation index was K = 6.4(DI) + 6.25, where DI is the late dissociation index and K is the logarithm to the base 10 of the binding constant. There is a high correlation between avidity and affinity of antibody. Antibody affinity can be estimated from avidity data. The stability of antigen-antibody complexes can be predicted from antibody affinity

  8. Affine group formulation of the Standard Model coupled to gravity

    Energy Technology Data Exchange (ETDEWEB)

    Chou, Ching-Yi, E-mail: l2897107@mail.ncku.edu.tw [Department of Physics, National Cheng Kung University, Taiwan (China); Ita, Eyo, E-mail: ita@usna.edu [Department of Physics, US Naval Academy, Annapolis, MD (United States); Soo, Chopin, E-mail: cpsoo@mail.ncku.edu.tw [Department of Physics, National Cheng Kung University, Taiwan (China)

    2014-04-15

    In this work we apply the affine group formalism for four dimensional gravity of Lorentzian signature, which is based on Klauder’s affine algebraic program, to the formulation of the Hamiltonian constraint of the interaction of matter and all forces, including gravity with non-vanishing cosmological constant Λ, as an affine Lie algebra. We use the hermitian action of fermions coupled to gravitation and Yang–Mills theory to find the density weight one fermionic super-Hamiltonian constraint. This term, combined with the Yang–Mills and Higgs energy densities, are composed with York’s integrated time functional. The result, when combined with the imaginary part of the Chern–Simons functional Q, forms the affine commutation relation with the volume element V(x). Affine algebraic quantization of gravitation and matter on equal footing implies a fundamental uncertainty relation which is predicated upon a non-vanishing cosmological constant. -- Highlights: •Wheeler–DeWitt equation (WDW) quantized as affine algebra, realizing Klauder’s program. •WDW formulated for interaction of matter and all forces, including gravity, as affine algebra. •WDW features Hermitian generators in spite of fermionic content: Standard Model addressed. •Constructed a family of physical states for the full, coupled theory via affine coherent states. •Fundamental uncertainty relation, predicated on non-vanishing cosmological constant.

  9. Lp-mixed affine surface area

    Science.gov (United States)

    Wang, Weidong; Leng, Gangsong

    2007-11-01

    According to the three notions of mixed affine surface area, Lp-affine surface area and Lp-mixed affine surface area proposed by Lutwak, in this article, we give the concept of ith Lp-mixed affine surface area such that the first and second notions of Lutwak are its special cases. Further, some Lutwak's results are extended associated with this concept. Besides, applying this concept, we establish an inequality for the volumes and dual quermassintegrals of a class of star bodies.

  10. Visual and Plasmon Resonance Absorption Sensor for Adenosine Triphosphate Based on the High Affinity between Phosphate and Zr(IV)

    OpenAIRE

    Qi, Wenjing; Liu, Zhongyuan; Zhang, Wei; Halawa, Mohamed Ibrahim; Xu, Guobao

    2016-01-01

    Zr(IV) can form phosphate and Zr(IV) (?PO3 2??Zr4+?) complex owing to the high affinity between Zr(IV) with phosphate. Zr(IV) can induce the aggregation of gold nanoparticles (AuNPs), while adenosine triphosphate(ATP) can prevent Zr(IV)-induced aggregation of AuNPs. Herein, a visual and plasmon resonance absorption (PRA)sensor for ATP have been developed using AuNPs based on the high affinity between Zr(IV)with ATP. AuNPs get aggregated in the presence of certain concentrations of Zr(IV). Aft...

  11. Surface Plasmon Resonance Biosensor Method for Palytoxin Detection Based on Na+,K+-ATPase Affinity

    Science.gov (United States)

    Alfonso, Amparo; Pazos, María-José; Fernández-Araujo, Andrea; Tobio, Araceli; Alfonso, Carmen; Vieytes, Mercedes R.; Botana, Luis M.

    2013-01-01

    Palytoxin (PLTX), produced by dinoflagellates from the genus Ostreopsis was first discovered, isolated, and purified from zoanthids belonging to the genus Palythoa. The detection of this toxin in contaminated shellfish is essential for human health preservation. A broad range of studies indicate that mammalian Na+,K+-ATPase is a high affinity cellular receptor for PLTX. The toxin converts the pump into an open channel that stimulates sodium influx and potassium efflux. In this work we develop a detection method for PLTX based on its binding to the Na+,K+-ATPase. The method was developed by using the phenomenon of surface plasmon resonance (SPR) to monitor biomolecular reactions. This technique does not require any labeling of components. The interaction of PLTX over immobilized Na+,K+-ATPase is quantified by injecting different concentrations of toxin in the biosensor and checking the binding rate constant (kobs). From the representation of kobs versus PLTX concentration, the kinetic equilibrium dissociation constant (KD) for the PLTX-Na+,K+-ATPase association can be calculated. The value of this constant is KD = 6.38 × 10−7 ± 6.67 × 10−8 M PLTX. In this way the PLTX-Na+,K+-ATPase association was used as a suitable method for determination of the toxin concentration in a sample. This method represents a new and useful approach to easily detect the presence of PLTX-like compounds in marine products using the mechanism of action of these toxins and in this way reduce the use of other more expensive and animal based methods. PMID:24379088

  12. Surface plasmon resonance biosensor method for palytoxin detection based on Na+,K+-ATPase affinity.

    Science.gov (United States)

    Alfonso, Amparo; Pazos, María-José; Fernández-Araujo, Andrea; Tobio, Araceli; Alfonso, Carmen; Vieytes, Mercedes R; Botana, Luis M

    2013-12-27

    Palytoxin (PLTX), produced by dinoflagellates from the genus Ostreopsis was first discovered, isolated, and purified from zoanthids belonging to the genus Palythoa. The detection of this toxin in contaminated shellfish is essential for human health preservation. A broad range of studies indicate that mammalian Na+,K+-ATPase is a high affinity cellular receptor for PLTX. The toxin converts the pump into an open channel that stimulates sodium influx and potassium efflux. In this work we develop a detection method for PLTX based on its binding to the Na+,K+-ATPase. The method was developed by using the phenomenon of surface plasmon resonance (SPR) to monitor biomolecular reactions. This technique does not require any labeling of components. The interaction of PLTX over immobilized Na+,K+-ATPase is quantified by injecting different concentrations of toxin in the biosensor and checking the binding rate constant (Kobs). From the representation of Kobs versus PLTX concentration, the kinetic equilibrium dissociation constant (K(D)) for the PLTX-Na+,K+-ATPase association can be calculated. The value of this constant is K(D) = 6.38 × 10-7 ± 6.67 × 10-8 M PLTX. In this way the PLTX-Na+,K+-ATPase association was used as a suitable method for determination of the toxin concentration in a sample. This method represents a new and useful approach to easily detect the presence of PLTX-like compounds in marine products using the mechanism of action of these toxins and in this way reduce the use of other more expensive and animal based methods.

  13. Surface Plasmon Resonance Biosensor Method for Palytoxin Detection Based on Na+,K+-ATPase Affinity

    Directory of Open Access Journals (Sweden)

    Amparo Alfonso

    2013-12-01

    Full Text Available Palytoxin (PLTX, produced by dinoflagellates from the genus Ostreopsis was first discovered, isolated, and purified from zoanthids belonging to the genus Palythoa. The detection of this toxin in contaminated shellfish is essential for human health preservation. A broad range of studies indicate that mammalian Na+,K+-ATPase is a high affinity cellular receptor for PLTX. The toxin converts the pump into an open channel that stimulates sodium influx and potassium efflux. In this work we develop a detection method for PLTX based on its binding to the Na+,K+-ATPase. The method was developed by using the phenomenon of surface plasmon resonance (SPR to monitor biomolecular reactions. This technique does not require any labeling of components. The interaction of PLTX over immobilized Na+,K+-ATPase is quantified by injecting different concentrations of toxin in the biosensor and checking the binding rate constant (kobs. From the representation of kobs versus PLTX concentration, the kinetic equilibrium dissociation constant (KD for the PLTX-Na+,K+-ATPase association can be calculated. The value of this constant is KD = 6.38 × 10−7 ± 6.67 × 10−8 M PLTX. In this way the PLTX-Na+,K+-ATPase association was used as a suitable method for determination of the toxin concentration in a sample. This method represents a new and useful approach to easily detect the presence of PLTX-like compounds in marine products using the mechanism of action of these toxins and in this way reduce the use of other more expensive and animal based methods.

  14. Self-affine roughness effects on the contact area between elastic bodies

    NARCIS (Netherlands)

    Palasantzas, G; De Hosson, JTM

    2003-01-01

    We have calculated the real contact area between elastic bodies with self-affine rough surfaces, which are described in terms of analytical correlation models in Fourier space. It is found that the roughness has a strong influence on the real contact area A(lambda) at lateral length scales lambda

  15. Affinity-based, biophysical methods to detect and analyze ligand binding to recombinant proteins: matching high information content with high throughput.

    Science.gov (United States)

    Holdgate, Geoff A; Anderson, Malcolm; Edfeldt, Fredrik; Geschwindner, Stefan

    2010-10-01

    Affinity-based technologies have become impactful tools to detect, monitor and characterize molecular interactions using recombinant target proteins. This can aid the understanding of biological function by revealing mechanistic details, and even more importantly, enables the identification of new improved ligands that can modulate the biological activity of those targets in a desired fashion. The selection of the appropriate technology is a key step in that process, as each one of the currently available technologies offers a characteristic type of biophysical information about the ligand-binding event. Alongside the indisputable advantages of each of those technologies they naturally display diverse restrictions that are quite frequently related to the target system to be studied but also to the affinity, solubility and molecular size of the ligands. This paper discusses some of the theoretical and experimental aspects of the most common affinity-based methods, what type of information can be gained from each one of those approaches, and what requirements as well as limitations are expected from working with recombinant proteins on those platforms and how those can be optimally addressed.

  16. An Affine Invariant Bivariate Version of the Sign Test.

    Science.gov (United States)

    1987-06-01

    words: affine invariance, bivariate quantile, bivariate symmetry, model,. generalized median, influence function , permutation test, normal efficiency...calculate a bivariate version of the influence function , and the resulting form is bounded, as is the case for the univartate sign test, and shows the...terms of a blvariate analogue of IHmpel’s (1974) influence function . The latter, though usually defined as a von-Mises derivative of certain

  17. Mapping Affinities in Academic Organizations

    Directory of Open Access Journals (Sweden)

    Dario Rodighiero

    2018-02-01

    Full Text Available Scholarly affinities are one of the most fundamental hidden dynamics that drive scientific development. Some affinities are actual, and consequently can be measured through classical academic metrics such as co-authoring. Other affinities are potential, and therefore do not leave visible traces in information systems; for instance, some peers may share interests without actually knowing it. This article illustrates the development of a map of affinities for academic collectives, designed to be relevant to three audiences: the management, the scholars themselves, and the external public. Our case study involves the School of Architecture, Civil and Environmental Engineering of EPFL, hereinafter ENAC. The school consists of around 1,000 scholars, 70 laboratories, and 3 institutes. The actual affinities are modeled using the data available from the information systems reporting publications, teaching, and advising scholars, whereas the potential affinities are addressed through text mining of the publications. The major challenge for designing such a map is to represent the multi-dimensionality and multi-scale nature of the information. The affinities are not limited to the computation of heterogeneous sources of information; they also apply at different scales. The map, thus, shows local affinities inside a given laboratory, as well as global affinities among laboratories. This article presents a graphical grammar to represent affinities. Its effectiveness is illustrated by two actualizations of the design proposal: an interactive online system in which the map can be parameterized, and a large-scale carpet of 250 square meters. In both cases, we discuss how the materiality influences the representation of data, in particular the way key questions could be appropriately addressed considering the three target audiences: the insights gained by the management and their consequences in terms of governance, the understanding of the scholars’ own

  18. Improving binding mode and binding affinity predictions of docking by ligand-based search of protein conformations: evaluation in D3R grand challenge 2015

    Science.gov (United States)

    Xu, Xianjin; Yan, Chengfei; Zou, Xiaoqin

    2017-08-01

    The growing number of protein-ligand complex structures, particularly the structures of proteins co-bound with different ligands, in the Protein Data Bank helps us tackle two major challenges in molecular docking studies: the protein flexibility and the scoring function. Here, we introduced a systematic strategy by using the information embedded in the known protein-ligand complex structures to improve both binding mode and binding affinity predictions. Specifically, a ligand similarity calculation method was employed to search a receptor structure with a bound ligand sharing high similarity with the query ligand for the docking use. The strategy was applied to the two datasets (HSP90 and MAP4K4) in recent D3R Grand Challenge 2015. In addition, for the HSP90 dataset, a system-specific scoring function (ITScore2_hsp90) was generated by recalibrating our statistical potential-based scoring function (ITScore2) using the known protein-ligand complex structures and the statistical mechanics-based iterative method. For the HSP90 dataset, better performances were achieved for both binding mode and binding affinity predictions comparing with the original ITScore2 and with ensemble docking. For the MAP4K4 dataset, although there were only eight known protein-ligand complex structures, our docking strategy achieved a comparable performance with ensemble docking. Our method for receptor conformational selection and iterative method for the development of system-specific statistical potential-based scoring functions can be easily applied to other protein targets that have a number of protein-ligand complex structures available to improve predictions on binding.

  19. Binding free energy calculations to rationalize the interactions of huprines with acetylcholinesterase.

    Science.gov (United States)

    Nascimento, Érica C M; Oliva, Mónica; Andrés, Juan

    2018-05-01

    In the present study, the binding free energy of a family of huprines with acetylcholinesterase (AChE) is calculated by means of the free energy perturbation method, based on hybrid quantum mechanics and molecular mechanics potentials. Binding free energy calculations and the analysis of the geometrical parameters highlight the importance of the stereochemistry of huprines in AChE inhibition. Binding isotope effects are calculated to unravel the interactions between ligands and the gorge of AChE. New chemical insights are provided to explain and rationalize the experimental results. A good correlation with the experimental data is found for a family of inhibitors with moderate differences in the enzyme affinity. The analysis of the geometrical parameters and interaction energy per residue reveals that Asp72, Glu199, and His440 contribute significantly to the network of interactions between active site residues, which stabilize the inhibitors in the gorge. It seems that a cooperative effect of the residues of the gorge determines the affinity of the enzyme for these inhibitors, where Asp72, Glu199, and His440 make a prominent contribution.

  20. Binding free energy calculations to rationalize the interactions of huprines with acetylcholinesterase

    Science.gov (United States)

    Nascimento, Érica C. M.; Oliva, Mónica; Andrés, Juan

    2018-05-01

    In the present study, the binding free energy of a family of huprines with acetylcholinesterase (AChE) is calculated by means of the free energy perturbation method, based on hybrid quantum mechanics and molecular mechanics potentials. Binding free energy calculations and the analysis of the geometrical parameters highlight the importance of the stereochemistry of huprines in AChE inhibition. Binding isotope effects are calculated to unravel the interactions between ligands and the gorge of AChE. New chemical insights are provided to explain and rationalize the experimental results. A good correlation with the experimental data is found for a family of inhibitors with moderate differences in the enzyme affinity. The analysis of the geometrical parameters and interaction energy per residue reveals that Asp72, Glu199, and His440 contribute significantly to the network of interactions between active site residues, which stabilize the inhibitors in the gorge. It seems that a cooperative effect of the residues of the gorge determines the affinity of the enzyme for these inhibitors, where Asp72, Glu199, and His440 make a prominent contribution.

  1. Fundamentals of affinity cell separations.

    Science.gov (United States)

    Zhang, Ye; Lyons, Veronica; Pappas, Dimitri

    2018-03-01

    Cell separations using affinity methods continue to be an enabling science for a wide variety of applications. In this review, we discuss the fundamental aspects of affinity separation, including the competing forces for cell capture and elution, cell-surface interactions, and models for cell adhesion. Factors affecting separation performance such as bond affinity, contact area, and temperature are presented. We also discuss and demonstrate the effects of nonspecific binding on separation performance. Metrics for evaluating cell separations are presented, along with methods of comparing separation techniques for cell isolation using affinity capture. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Genetically based low oxygen affinities of felid hemoglobins: lack of biochemical adaptation to high-altitude hypoxia in the snow leopard

    Science.gov (United States)

    Janecka, Jan E.; Nielsen, Simone S. E.; Andersen, Sidsel D.; Hoffmann, Federico G.; Weber, Roy E.; Anderson, Trevor; Storz, Jay F.; Fago, Angela

    2015-01-01

    ABSTRACT Genetically based modifications of hemoglobin (Hb) function that increase blood–O2 affinity are hallmarks of hypoxia adaptation in vertebrates. Among mammals, felid Hbs are unusual in that they have low intrinsic O2 affinities and reduced sensitivities to the allosteric cofactor 2,3-diphosphoglycerate (DPG). This combination of features compromises the acclimatization capacity of blood–O2 affinity and has led to the hypothesis that felids have a restricted physiological niche breadth relative to other mammals. In seeming defiance of this conjecture, the snow leopard (Panthera uncia) has an extraordinarily broad elevational distribution and occurs at elevations above 6000 m in the Himalayas. Here, we characterized structural and functional variation of big cat Hbs and investigated molecular mechanisms of Hb adaptation and allosteric regulation that may contribute to the extreme hypoxia tolerance of the snow leopard. Experiments revealed that purified Hbs from snow leopard and African lion exhibited equally low O2 affinities and DPG sensitivities. Both properties are primarily attributable to a single amino acid substitution, β2His→Phe, which occurred in the common ancestor of Felidae. Given the low O2 affinity and reduced regulatory capacity of feline Hbs, the extreme hypoxia tolerance of snow leopards must be attributable to compensatory modifications of other steps in the O2-transport pathway. PMID:26246610

  3. Exploring Girls' Science Affinities Through an Informal Science Education Program

    Science.gov (United States)

    Todd, Brandy; Zvoch, Keith

    2017-10-01

    This study examines science interests, efficacy, attitudes, and identity—referred to as affinities, in the context of an informal science outreach program for girls. A mixed methods design was used to explore girls' science affinities before, during, and after participation in a cohort-based summer science camp. Multivariate analysis of survey data revealed that girls' science affinities varied as a function of the joint relationship between family background and number of years in the program, with girls from more affluent families predicted to increase affinities over time and girls from lower income families to experience initial gains in affinities that diminish over time. Qualitative examination of girls' perspectives on gender and science efficacy, attitudes toward science, and elements of science identities revealed a complex interplay of gendered stereotypes of science and girls' personal desires to prove themselves knowledgeable and competent scientists. Implications for the best practice in fostering science engagement and identities in middle school-aged girls are discussed.

  4. A Novel Affinity Tag, ABTAG, and Its Application to the Affinity Screening of Single-Domain Antibodies Selected by Phage Display

    Directory of Open Access Journals (Sweden)

    Greg Hussack

    2017-10-01

    Full Text Available ABTAG is a camelid single-domain antibody (sdAb that binds to bovine serum albumin (BSA with low picomolar affinity. In surface plasmon resonance (SPR analyses using BSA surfaces, bound ABTAG can be completely dissociated from the BSA surfaces at low pH, over multiple cycles, without any reduction in the capacity of the BSA surfaces to bind ABTAG. A moderate throughput, SPR-based, antibody screening assay exploiting the unique features of ABTAG is described. Anti-carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6 sdAbs were isolated from a phage-displayed sdAb library derived from the heavy chain antibody repertoire of a llama immunized with CEACAM6. Following one or two rounds of panning, enriched clones were expressed as ABTAG fusions in microtiter plate cultures. The sdAb-ABTAG fusions from culture supernatants were captured on BSA surfaces and CEACAM6 antigen was then bound to the captured molecules. The SPR screening method gives a read-out of relative expression levels of the fusion proteins and kinetic and affinity constants for CEACAM6 binding by the captured molecules. The library was also panned and screened by conventional methods and positive clones were subcloned and expressed for SPR analysis. Compared to conventional panning and screening, the SPR-based ABTAG method yielded a considerably higher diversity of binders, some with affinities that were three orders of magnitude higher affinity than those identified by conventional panning.

  5. Novel and high affinity fluorescent ligands for the serotonin transporter based on (s)-citalopram

    DEFF Research Database (Denmark)

    Kumar, Vivek; Rahbek-Clemmensen, Troels; Billesbølle, Christian B

    2014-01-01

    Novel rhodamine-labeled ligands, based on (S)-citalopram, were synthesized and evaluated for uptake inhibition at the human serotonin, dopamine, and norepinephrine transporters (hSERT, hDAT, and hNET, respectively) and for binding at SERT, in transiently transfected COS7 cells. Compound 14 demons...... demonstrated high affinity binding and selectivity for SERT (K i = 3 nM). Visualization of SERT, using confocal laser scanning microscopy, validated compound 14 as a novel tool for studying SERT expression and distribution in living cells....

  6. Translation of Bernstein Coefficients Under an Affine Mapping of the Unit Interval

    Science.gov (United States)

    Alford, John A., II

    2012-01-01

    We derive an expression connecting the coefficients of a polynomial expanded in the Bernstein basis to the coefficients of an equivalent expansion of the polynomial under an affine mapping of the domain. The expression may be useful in the calculation of bounds for multi-variate polynomials.

  7. Machine-learning scoring functions to improve structure-based binding affinity prediction and virtual screening.

    Science.gov (United States)

    Ain, Qurrat Ul; Aleksandrova, Antoniya; Roessler, Florian D; Ballester, Pedro J

    2015-01-01

    Docking tools to predict whether and how a small molecule binds to a target can be applied if a structural model of such target is available. The reliability of docking depends, however, on the accuracy of the adopted scoring function (SF). Despite intense research over the years, improving the accuracy of SFs for structure-based binding affinity prediction or virtual screening has proven to be a challenging task for any class of method. New SFs based on modern machine-learning regression models, which do not impose a predetermined functional form and thus are able to exploit effectively much larger amounts of experimental data, have recently been introduced. These machine-learning SFs have been shown to outperform a wide range of classical SFs at both binding affinity prediction and virtual screening. The emerging picture from these studies is that the classical approach of using linear regression with a small number of expert-selected structural features can be strongly improved by a machine-learning approach based on nonlinear regression allied with comprehensive data-driven feature selection. Furthermore, the performance of classical SFs does not grow with larger training datasets and hence this performance gap is expected to widen as more training data becomes available in the future. Other topics covered in this review include predicting the reliability of a SF on a particular target class, generating synthetic data to improve predictive performance and modeling guidelines for SF development. WIREs Comput Mol Sci 2015, 5:405-424. doi: 10.1002/wcms.1225 For further resources related to this article, please visit the WIREs website.

  8. Oxygen affinity and acid-base status of human blood during exposure to hypoxia and carbon monoxide

    Energy Technology Data Exchange (ETDEWEB)

    Mulhausen, R.O.; Astrup, P.; Mellemgaard, K.

    1968-01-01

    Eight individuals exposed to hypoxia at altitude or simulated altitude in hypobaric chamber had hemoglobin with a decreased affinity for O/sub 2/ as shown by a shift in the dissociation curve to the right (about 4 mm at 3450 m). Acid-base changes could not explain shift. Intermittent CO doses to maintain approx. 15% carboxyhemoglobin produced the typical shift to the left. Acid-base changes were insignificant. Proposed adaptation mechanism for combating hypoxia does not work for CO poisoning.

  9. Thermal-depth matching in dynamic scene based on affine projection and feature registration

    Science.gov (United States)

    Wang, Hongyu; Jia, Tong; Wu, Chengdong; Li, Yongqiang

    2018-03-01

    This paper aims to study the construction of 3D temperature distribution reconstruction system based on depth and thermal infrared information. Initially, a traditional calibration method cannot be directly used, because the depth and thermal infrared camera is not sensitive to the color calibration board. Therefore, this paper aims to design a depth and thermal infrared camera calibration board to complete the calibration of the depth and thermal infrared camera. Meanwhile a local feature descriptors in thermal and depth images is proposed. The belief propagation matching algorithm is also investigated based on the space affine transformation matching and local feature matching. The 3D temperature distribution model is built based on the matching of 3D point cloud and 2D thermal infrared information. Experimental results show that the method can accurately construct the 3D temperature distribution model, and has strong robustness.

  10. Affine field theories

    International Nuclear Information System (INIS)

    Cadavid, A.C.

    1989-01-01

    The author constructs a non-Abelian field theory by gauging a Kac-Moody algebra, obtaining an infinite tower of interacting vector fields and associated ghosts, that obey slightly modified Feynman rules. She discusses the spontaneous symmetry breaking of such theory via the Higgs mechanism. If the Higgs particle lies in the Cartan subalgebra of the Kac-Moody algebra, the previously massless vectors acquire a mass spectrum that is linear in the Kac-Moody index and has additional fine structure depending on the associated Lie algebra. She proceeds to show that there is no obstacle in implementing the affine extension of supersymmetric Yang-Mills theories. The result is valid in four, six and ten space-time dimensions. Then the affine extension of supergravity is investigated. She discusses only the loop algebra since the affine extension of the super-Poincare algebra appears inconsistent. The construction of the affine supergravity theory is carried out by the group manifold method and leads to an action describing infinite towers of spin 2 and spin 3/2 fields that interact subject to the symmetries of the loop algebra. The equations of motion satisfy the usual consistency check. Finally, she postulates a theory in which both the vector and scalar fields lie in the loop algebra of SO(3). This theory has an expanded soliton sector, and corresponding to the original 't Hooft-Polyakov solitonic solutions she now finds an infinite family of exact, special solutions of the new equations. She also proposes a perturbation method for obtaining an arbitrary solution of those equations for each level of the affine index

  11. Gene Therapy Vectors with Enhanced Transfection Based on Hydrogels Modified with Affinity Peptides

    Science.gov (United States)

    Shepard, Jaclyn A.; Wesson, Paul J.; Wang, Christine E.; Stevans, Alyson C.; Holland, Samantha J.; Shikanov, Ariella; Grzybowski, Bartosz A.; Shea, Lonnie D.

    2011-01-01

    Regenerative strategies for damaged tissue aim to present biochemical cues that recruit and direct progenitor cell migration and differentiation. Hydrogels capable of localized gene delivery are being developed to provide a support for tissue growth, and as a versatile method to induce the expression of inductive proteins; however, the duration, level, and localization of expression isoften insufficient for regeneration. We thus investigated the modification of hydrogels with affinity peptides to enhance vector retention and increase transfection within the matrix. PEG hydrogels were modified with lysine-based repeats (K4, K8), which retained approximately 25% more vector than control peptides. Transfection increased 5- to 15-fold with K8 and K4 respectively, over the RDG control peptide. K8- and K4-modified hydrogels bound similar quantities of vector, yet the vector dissociation rate was reduced for K8, suggesting excessive binding that limited transfection. These hydrogels were subsequently applied to an in vitro co-culture model to induce NGF expression and promote neurite outgrowth. K4-modified hydrogels promoted maximal neurite outgrowth, likely due to retention of both the vector and the NGF. Thus, hydrogels modified with affinity peptides enhanced vector retention and increased gene delivery, and these hydrogels may provide a versatile scaffold for numerous regenerative medicine applications. PMID:21514659

  12. k-Schur functions and affine Schubert calculus

    CERN Document Server

    Lam, Thomas; Morse, Jennifer; Schilling, Anne; Shimozono, Mark; Zabrocki, Mike

    2014-01-01

    This book gives an introduction to the very active field of combinatorics of affine Schubert calculus, explains the current state of the art, and states the current open problems. Affine Schubert calculus lies at the crossroads of combinatorics, geometry, and representation theory. Its modern development is motivated by two seemingly unrelated directions. One is the introduction of k-Schur functions in the study of Macdonald polynomial positivity, a mostly combinatorial branch of symmetric function theory. The other direction is the study of the Schubert bases of the (co)homology of the affine Grassmannian, an algebro-topological formulation of a problem in enumerative geometry. This is the first introductory text on this subject. It contains many examples in Sage, a free open source general purpose mathematical software system, to entice the reader to investigate the open problems. This book is written for advanced undergraduate and graduate students, as well as researchers, who want to become familiar with ...

  13. Supramolecular Affinity Chromatography for Methylation-Targeted Proteomics.

    Science.gov (United States)

    Garnett, Graham A E; Starke, Melissa J; Shaurya, Alok; Li, Janessa; Hof, Fraser

    2016-04-05

    Proteome-wide studies of post-translationally methylated species using mass spectrometry are complicated by high sample diversity, competition for ionization among peptides, and mass redundancies. Antibody-based enrichment has powered methylation proteomics until now, but the reliability, pan-specificity, polyclonal nature, and stability of the available pan-specific antibodies are problematic and do not provide a standard, reliable platform for investigators. We have invented an anionic supramolecular host that can form host-guest complexes selectively with methyllysine-containing peptides and used it to create a methylysine-affinity column. The column resolves peptides on the basis of methylation-a feat impossible with a comparable commercial cation-exchange column. A proteolyzed nuclear extract was separated on the methyl-affinity column prior to standard proteomics analysis. This experiment demonstrates that such chemical methyl-affinity columns are capable of enriching and improving the analysis of methyllysine residues from complex protein mixtures. We discuss the importance of this advance in the context of biomolecule-driven enrichment methods.

  14. Hemoglobin affinity in Andean rodents

    Directory of Open Access Journals (Sweden)

    HRVOJ OSTOJIC

    2002-01-01

    Full Text Available Blood hemoglobin oxygen affinity (P50 was measured in three Andean species and in the laboratory rat (control, all raised near sea level. Chinchilla lanigera (Molina, 1792 has an altitudinal habitat range from low Andean slopes up to 3000 m., while Chinchilla brevicaudata (Waterhouse, 1848 has an altitudinal range from 3000 to 5000 m. The laboratory type guinea pig, wild type guinea pig (Cavia porcellus, (Waterhouse, 1748, and laboratory rat (Rattus norvegicus were also raised at sea level. The Andean species had high hemoglobin oxygen affinities (low P50 compared with the rat. Chinchilla brevicaudata had a higher affinity than Chinchilla lanigera. The wild type guinea pig had a higher affinity than the laboratory type. As has been shown in other species, this is another example of an inverse correlation between the altitude level and the P50 values. This is the first hemoglobin oxygen affinity study in Chinchilla brevicaudata.

  15. Enzyme activity assay of glycoprotein enzymes based on a boronate affinity molecularly imprinted 96-well microplate.

    Science.gov (United States)

    Bi, Xiaodong; Liu, Zhen

    2014-12-16

    Enzyme activity assay is an important method in clinical diagnostics. However, conventional enzyme activity assay suffers from apparent interference from the sample matrix. Herein, we present a new format of enzyme activity assay that can effectively eliminate the effects of the sample matrix. The key is a 96-well microplate modified with molecularly imprinted polymer (MIP) prepared according to a newly proposed method called boronate affinity-based oriented surface imprinting. Alkaline phosphatase (ALP), a glycoprotein enzyme that has been routinely used as an indicator for several diseases in clinical tests, was taken as a representative target enzyme. The prepared MIP exhibited strong affinity toward the template enzyme (with a dissociation constant of 10(-10) M) as well as superb tolerance for interference. Thus, the enzyme molecules in a complicated sample matrix could be specifically captured and cleaned up for enzyme activity assay, which eliminated the interference from the sample matrix. On the other hand, because the boronate affinity MIP could well retain the enzymatic activity of glycoprotein enzymes, the enzyme captured by the MIP was directly used for activity assay. Thus, additional assay time and possible enzyme or activity loss due to an enzyme release step required by other methods were avoided. Assay of ALP in human serum was successfully demonstrated, suggesting a promising prospect of the proposed method in real-world applications.

  16. Alkali Metal Cation versus Proton and Methyl Cation Affinities: Structure and Bonding Mechanism.

    Science.gov (United States)

    Boughlala, Zakaria; Fonseca Guerra, Célia; Bickelhaupt, F Matthias

    2016-06-01

    We have analyzed the structure and bonding of gas-phase Cl-X and [HCl-X](+) complexes for X(+)= H(+), CH3 (+), Li(+), and Na(+), using relativistic density functional theory (DFT). We wish to establish a quantitative trend in affinities of the anionic and neutral Lewis bases Cl(-) and HCl for the various cations. The Cl-X bond becomes longer and weaker along X(+) = H(+), CH3 (+), Li(+), and Na(+). Our main purpose is to understand the heterolytic bonding mechanism behind the intrinsic (i.e., in the absence of solvent) alkali metal cation affinities (AMCA) and how this compares with and differs from those of the proton affinity (PA) and methyl cation affinity (MCA). Our analyses are based on Kohn-Sham molecular orbital (KS-MO) theory in combination with a quantitative energy decomposition analysis (EDA) that pinpoints the importance of the different features in the bonding mechanism. Orbital overlap appears to play an important role in determining the trend in cation affinities.

  17. Cost Function Network-based Design of Protein-Protein Interactions: predicting changes in binding affinity.

    Science.gov (United States)

    Viricel, Clément; de Givry, Simon; Schiex, Thomas; Barbe, Sophie

    2018-02-20

    Accurate and economic methods to predict change in protein binding free energy upon mutation are imperative to accelerate the design of proteins for a wide range of applications. Free energy is defined by enthalpic and entropic contributions. Following the recent progresses of Artificial Intelligence-based algorithms for guaranteed NP-hard energy optimization and partition function computation, it becomes possible to quickly compute minimum energy conformations and to reliably estimate the entropic contribution of side-chains in the change of free energy of large protein interfaces. Using guaranteed Cost Function Network algorithms, Rosetta energy functions and Dunbrack's rotamer library, we developed and assessed EasyE and JayZ, two methods for binding affinity estimation that ignore or include conformational entropic contributions on a large benchmark of binding affinity experimental measures. If both approaches outperform most established tools, we observe that side-chain conformational entropy brings little or no improvement on most systems but becomes crucial in some rare cases. as open-source Python/C ++ code at sourcesup.renater.fr/projects/easy-jayz. thomas.schiex@inra.fr and sophie.barbe@insa-toulouse.fr. Supplementary data are available at Bioinformatics online.

  18. Validation of tautomeric and protomeric binding modes by free energy calculations. A case study for the structure based optimization of d-amino acid oxidase inhibitors

    Science.gov (United States)

    Orgován, Zoltán; Ferenczy, György G.; Steinbrecher, Thomas; Szilágyi, Bence; Bajusz, Dávid; Keserű, György M.

    2018-02-01

    Optimization of fragment size d-amino acid oxidase (DAAO) inhibitors was investigated using a combination of computational and experimental methods. Retrospective free energy perturbation (FEP) calculations were performed for benzo[d]isoxazole derivatives, a series of known inhibitors with two potential binding modes derived from X-ray structures of other DAAO inhibitors. The good agreement between experimental and computed binding free energies in only one of the hypothesized binding modes strongly support this bioactive conformation. Then, a series of 1-H-indazol-3-ol derivatives formerly not described as DAAO inhibitors was investigated. Binding geometries could be reliably identified by structural similarity to benzo[d]isoxazole and other well characterized series and FEP calculations were performed for several tautomers of the deprotonated and protonated compounds since all these forms are potentially present owing to the experimental pKa values of representative compounds in the series. Deprotonated compounds are proposed to be the most important bound species owing to the significantly better agreement between their calculated and measured affinities compared to the protonated forms. FEP calculations were also used for the prediction of the affinities of compounds not previously tested as DAAO inhibitors and for a comparative structure-activity relationship study of the benzo[d]isoxazole and indazole series. Selected indazole derivatives were synthesized and their measured binding affinity towards DAAO was in good agreement with FEP predictions.

  19. Poly(hydroxyethyl methacrylate) based affinity membranes for in vitro removal of anti-dsDNA antibodies from SLE plasma.

    Science.gov (United States)

    Uzun, Lokman; Yavuz, Handan; Osman, Bilgen; Celik, Hamdi; Denizli, Adil

    2010-07-01

    The preparation of polymeric membrane using affinity technology for application in blood filtration devices is described here. DNA attached poly(hydroxyethyl methacrylate) (PHEMA) based microporous affinity membrane was prepared for selective removal of anti-dsDNA antibodies from systemic lupus erythematosus (SLE) patient plasma in in vitro. In order to further increase blood-compatibility of affinity membrane, aminoacid based comonomer N-methacryloyl-L-alanine (MAAL) was included in the polymerization recipe. PHEMAAL membrane was produced by a photopolymerization technique and then characterized by swelling tests and scanning electron microscope (SEM) studies. Blood-compatibility tests were also performed. The water swelling ratio of PHEMAAL membrane increased significantly (133.2%) compared with PHEMA (58%). PHEMAAL membrane has large pores around in the range of 5-10 microm. All the clotting times increased when compared with PHEMA membrane. Loss of platelets and leukocytes was very low. DNA loading was 7.8 mg/g. There was a very low anti-dsDNA-antibody adsorption onto the plain PHEMAAL membrane, about 78 IU/g. The PHEMAAL-DNA membrane adsorbed anti-dsDNA-antibody in the range of 10-68 x 10(3)IU/g from SLE plasma. Anti-dsDNA-antibody concentration decreased significantly from 875 to 144 IU/ml with the time. Anti-dsDNA-antibodies could be repeatedly adsorbed and eluted without noticeable loss in the anti-dsDNA-antibody adsorption amount. (c) 2010 Elsevier B.V. All rights reserved.

  20. Vertex operators, semiclassical limit for soliton S-matrices and the number of bound states in Affine Toda Field Theories

    International Nuclear Information System (INIS)

    Kneipp, Marco A.C.

    1999-10-01

    Soliton time delays and the semiclassical limit for soliton S-matrices are calculated for non-simply laced Affine Toda Field Theories. The phase shift is written as a sum over bilinears on the soliton conserved charges. The results apply to any two solitons of any Affine Toda Field Theory. As a by-product, a general expression for the number of bound states and the values of the coupling in which the S-matrix can be diagonal are obtained. In order to arrive at these results, a vertex operator is constructed, in the principal gradation, for non-simply laced affine Lie algebras, extending the previous constructions for simply laced and twisted affine Lie algebras. (author)

  1. Fractal-based exponential distribution of urban density and self-affine fractal forms of cities

    International Nuclear Information System (INIS)

    Chen Yanguang; Feng Jian

    2012-01-01

    Highlights: ► The model of urban population density differs from the common exponential function. ► Fractal landscape influences the exponential distribution of urban density. ► The exponential distribution of urban population suggests a self-affine fractal. ► Urban space can be divided into three layers with scaling and non-scaling regions. ► The dimension of urban form with characteristic scale can be treated as 2. - Abstract: Urban population density always follows the exponential distribution and can be described with Clark’s model. Because of this, the spatial distribution of urban population used to be regarded as non-fractal pattern. However, Clark’s model differs from the exponential function in mathematics because that urban population is distributed on the fractal support of landform and land-use form. By using mathematical transform and empirical evidence, we argue that there are self-affine scaling relations and local power laws behind the exponential distribution of urban density. The scale parameter of Clark’s model indicating the characteristic radius of cities is not a real constant, but depends on the urban field we defined. So the exponential model suggests local fractal structure with two kinds of fractal parameters. The parameters can be used to characterize urban space filling, spatial correlation, self-affine properties, and self-organized evolution. The case study of the city of Hangzhou, China, is employed to verify the theoretical inference. Based on the empirical analysis, a three-ring model of cities is presented and a city is conceptually divided into three layers from core to periphery. The scaling region and non-scaling region appear alternately in the city. This model may be helpful for future urban studies and city planning.

  2. 2017 Guralp Affinity Digitizer Evaluation.

    Energy Technology Data Exchange (ETDEWEB)

    Merchant, Bion J.

    2018-03-01

    Sandia National Laboratories has tested and evaluated two Guralp Affinity digitizers. The Affinity digitizers are intended to record sensor output for seismic and infrasound monitoring applications. The purpose of this digitizer evaluation is to measure the performance characteristics in such areas as power consumption, input impedance, sensitivity, full scale, self- noise, dynamic range, system noise, response, passband, and timing. The Affinity digitizers are being evaluated for potential use in the International Monitoring System (IMS) of the Comprehensive Nuclear Test-Ban-Treaty Organization (CTBTO).

  3. Electrochemical affinity biosensors for detection of mycotoxins: A review.

    Science.gov (United States)

    Vidal, Juan C; Bonel, Laura; Ezquerra, Alba; Hernández, Susana; Bertolín, Juan R; Cubel, Carlota; Castillo, Juan R

    2013-11-15

    This review discusses the current state of electrochemical biosensors in the determination of mycotoxins in foods. Mycotoxins are highly toxic secondary metabolites produced by molds. The acute toxicity of these results in serious human and animal health problems, although it has been only since early 1960s when the first studied aflatoxins were found to be carcinogenic. Mycotoxins affect a broad range of agricultural products, most important cereals and cereal-based foods. A majority of countries, mentioning especially the European Union, have established preventive programs to control contamination and strict laws of the permitted levels in foods. Official methods of analysis of mycotoxins normally requires sophisticated instrumentation, e.g. liquid chromatography with fluorescence or mass detectors, combined with extraction procedures for sample preparation. For about sixteen years, the use of simpler and faster analytical procedures based on affinity biosensors has emerged in scientific literature as a very promising alternative, particularly electrochemical (i.e., amperometric, impedance, potentiometric or conductimetric) affinity biosensors due to their simplicity and sensitivity. Typically, electrochemical biosensors for mycotoxins use specific antibodies or aptamers as affinity ligands, although recombinant antibodies, artificial receptors and molecular imprinted polymers show potential utility. This article deals with recent advances in electrochemical affinity biosensors for mycotoxins and covers complete literature from the first reports about sixteen years ago. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. A rapid solution-based method for determining the affinity of heroin hapten-induced antibodies to heroin, its metabolites, and other opioids.

    Science.gov (United States)

    Torres, Oscar B; Duval, Alexander J; Sulima, Agnieszka; Antoline, Joshua F G; Jacobson, Arthur E; Rice, Kenner C; Alving, Carl R; Matyas, Gary R

    2018-06-01

    We describe for the first time a method that utilizes microscale thermophoresis (MST) technology to determine polyclonal antibody affinities to small molecules. Using a novel type of heterologous MST, we have accurately measured a solution-based binding affinity of serum antibodies to heroin which was previously impossible with other currently available methods. Moreover, this mismatch approach (i.e., using a cross-reactive hapten tracer) has never been reported in the literature. When compared with equilibrium dialysis combined with ultra-performance liquid chromatography/tandem mass spectrometry (ED-UPLC/MS/MS), this novel MST method yields similar binding affinity values for polyclonal antibodies to the major heroin metabolites 6-AM and morphine. Additionally, we herein report the method of synthesis of this novel cross-reactive hapten, MorHap-acetamide-a useful analog for the study of heroin hapten-antibody interactions. Using heterologous MST, we were able to determine the affinities, down to nanomolar accuracies, of polyclonal antibodies to various abused opioids. While optimizing this method, we further discovered that heroin is protected from serum esterase degradation by the presence of these antibodies in a concentration-dependent manner. Lastly, using affinity data for a number of structurally different opioids, we were able to dissect the moieties that are crucial to antibody binding. The novel MST method that is presented herein can be extended to the analysis of any ligand that is prone to degradation and can be applied not only to the development of vaccines to substances of abuse but also to the analysis of small molecule/protein interactions in the presence of serum. Graphical abstract Strategy for the determination of hapten-induced antibody affinities using Microscale thermophoresis.

  5. High affinity hemoglobin and Parkinson's disease.

    Science.gov (United States)

    Graham, Jeffrey; Hobson, Douglas; Ponnampalam, Arjuna

    2014-12-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN) region of the midbrain. Oxidative damage in this region has been shown to play an important role in the pathogenesis of this disease. Human neurons have been discovered to contain hemoglobin, with an increased concentration seen in the neurons of the SN. High affinity hemoglobin is a clinical entity resulting from mutations that create a functional increase in the binding of hemoglobin to oxygen and an inability to efficiently unload it to tissues. This can result in a number of metabolic compensatory changes, including an elevation in circulating hemoglobin and an increase in the molecule 2,3-diphosphoglycerate (2,3-DPG). Population based studies have revealed that patients with PD have elevated hemoglobin as well as 2,3-DPG levels. Based on these observations, we hypothesize that the oxidative damage seen in PD is related to an underlying high affinity hemoglobin subtype. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Sparse Adaptive Channel Estimation Based on lp-Norm-Penalized Affine Projection Algorithm

    Directory of Open Access Journals (Sweden)

    Yingsong Li

    2014-01-01

    Full Text Available We propose an lp-norm-penalized affine projection algorithm (LP-APA for broadband multipath adaptive channel estimations. The proposed LP-APA is realized by incorporating an lp-norm into the cost function of the conventional affine projection algorithm (APA to exploit the sparsity property of the broadband wireless multipath channel, by which the convergence speed and steady-state performance of the APA are significantly improved. The implementation of the LP-APA is equivalent to adding a zero attractor to its iterations. The simulation results, which are obtained from a sparse channel estimation, demonstrate that the proposed LP-APA can efficiently improve channel estimation performance in terms of both the convergence speed and steady-state performance when the channel is exactly sparse.

  7. Fibrin matrices with affinity-based delivery systems and neurotrophic factors promote functional nerve regeneration.

    Science.gov (United States)

    Wood, Matthew D; MacEwan, Matthew R; French, Alexander R; Moore, Amy M; Hunter, Daniel A; Mackinnon, Susan E; Moran, Daniel W; Borschel, Gregory H; Sakiyama-Elbert, Shelly E

    2010-08-15

    Glial-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) have both been shown to enhance peripheral nerve regeneration following injury and target different neuronal populations. The delivery of either growth factor at the site of injury may, therefore, result in quantitative differences in motor nerve regeneration and functional recovery. In this study we evaluated the effect of affinity-based delivery of GDNF or NGF from fibrin-filled nerve guidance conduits (NGCs) on motor nerve regeneration and functional recovery in a 13 mm rat sciatic nerve defect. Seven experimental groups were evaluated consisting of GDNF or NGF and the affinity-based delivery system (DS) within NGCs, control groups excluding the DS and/or growth factor, and nerve isografts. Groups with growth factor in the conduit demonstrated equivalent or superior performance in behavioral tests and relative muscle mass measurements compared to isografts at 12 weeks. Additionally, groups with GDNF demonstrated greater specific twitch and tetanic force production in extensor digitorum longus (EDL) muscle than the isograft control, while groups with NGF produced demonstrated similar force production compared to the isograft control. Assessment of motor axon regeneration by retrograde labeling further revealed that the number of ventral horn neurons regenerating across NGCs containing GDNF and NGF DS was similar to the isograft group and these counts were greater than the groups without growth factor. Overall, the GDNF DS group demonstrated superior functional recovery and equivalent motor nerve regeneration compared to the isograft control, suggesting it has potential as a treatment for motor nerve injury.

  8. Antisymmetric tensor generalizations of affine vector fields.

    Science.gov (United States)

    Houri, Tsuyoshi; Morisawa, Yoshiyuki; Tomoda, Kentaro

    2016-02-01

    Tensor generalizations of affine vector fields called symmetric and antisymmetric affine tensor fields are discussed as symmetry of spacetimes. We review the properties of the symmetric ones, which have been studied in earlier works, and investigate the properties of the antisymmetric ones, which are the main theme in this paper. It is shown that antisymmetric affine tensor fields are closely related to one-lower-rank antisymmetric tensor fields which are parallelly transported along geodesics. It is also shown that the number of linear independent rank- p antisymmetric affine tensor fields in n -dimensions is bounded by ( n + 1)!/ p !( n - p )!. We also derive the integrability conditions for antisymmetric affine tensor fields. Using the integrability conditions, we discuss the existence of antisymmetric affine tensor fields on various spacetimes.

  9. Manifolds with integrable affine shape operator

    Directory of Open Access Journals (Sweden)

    Daniel A. Joaquín

    2005-05-01

    Full Text Available This work establishes the conditions for the existence of vector fields with the property that theirs covariant derivative, with respect to the affine normal connection, be the affine shape operatorS in hypersurfaces. Some results are obtained from this property and, in particular, for some kind of affine decomposable hypersurfaces we explicitely get the actual vector fields.

  10. Identification of an adeno-associated virus binding epitope for AVB sepharose affinity resin

    Directory of Open Access Journals (Sweden)

    Qiang Wang

    Full Text Available Recent successes of adeno-associated virus (AAV–based gene therapy have created a demand for large-scale AAV vector manufacturing and purification techniques for use in clinical trials and beyond. During the development of purification protocols for rh.10, hu.37, AAV8, rh.64R1, AAV3B, and AAV9 vectors, based on a widely used affinity resin, AVB sepharose (GE, we found that, under the same conditions, different serotypes have different affinities to the resin, with AAV3B binding the best and AAV9 the poorest. Further analysis revealed a surface-exposed residue (amino acid number 665 in AAV8 VP1 numbering differs between the high-affinity AAV serotypes (serine in AAV3B, rh.10, and hu.37 and the low-affinity ones (asparagine in AAV8, rh.64R1, and AAV9. The residue locates within a surface-exposed, variable epitope flanked by highly conserved residues. The substitution of the epitope in AAV8, rh.64R1, and AAV9 with the corresponding epitope of AAV3B (SPAKFA resulted in greatly increased affinity to AVB sepharose with no reduction in the vectors’ in vitro potency. The presence of the newly identified AVB-binding epitope will be useful for affinity resin selection for the purification of novel AAV serotypes. It also suggests the possibility of vector engineering to yield a universal affinity chromatography purification method for multiple AAV serotypes.

  11. High Performance Affinity Chromatography of Antithrombin III Based on Monodisperse Poly (glycidyl methacrylate) Beads

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A new approach for the separation of antithrombin III with high performance affinity chromatography (HPAC) was described. A novel monodisperse,non-porous,cross-linked poly (glycidyl methacrylate) beads (PGMA) were used as the affinity support. With the water-soluble carbodiimide,heparin was linked covalently to amino-PGMA-beads,which was prepared by amination of PGMA. The adsorbent obtained exhibits high binding activity to antithrombin III (ATIII),good resolution and excellent mechanical properties and can be used under high flow rate.

  12. S-Boxes Based on Affine Mapping and Orbit of Power Function

    Science.gov (United States)

    Khan, Mubashar; Azam, Naveed Ahmed

    2015-06-01

    The demand of data security against computational attacks such as algebraic, differential, linear and interpolation attacks has been increased as a result of rapid advancement in the field of computation. It is, therefore, necessary to develop such cryptosystems which can resist current cryptanalysis and more computational attacks in future. In this paper, we present a multiple S-boxes scheme based on affine mapping and orbit of the power function used in Advanced Encryption Standard (AES). The proposed technique results in 256 different S-boxes named as orbital S-boxes. Rigorous tests and comparisons are performed to analyse the cryptographic strength of each of the orbital S-boxes. Furthermore, gray scale images are encrypted by using multiple orbital S-boxes. Results and simulations show that the encryption strength of the orbital S-boxes against computational attacks is better than that of the existing S-boxes.

  13. Synthesis of new isoxazoline-based acidic amino acids and investigation of their affinity and selectivity profile at ionotropic glutamate receptors

    DEFF Research Database (Denmark)

    Pinto, Andrea; Conti, Paola; Grazioso, Giovanni

    2011-01-01

    The synthesis of four new isoxazoline-based amino acids being analogues of previously described glutamate receptor ligands is reported and their affinity for ionotropic glutamate receptors is analyzed in comparison with that of selected model compounds. Molecular modelling investigations have been...

  14. 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.

  15. Affine LIBOR Models with Multiple Curves

    DEFF Research Database (Denmark)

    Grbac, Zorana; Papapantoleon, Antonis; Schoenmakers, John

    2015-01-01

    are specified following the methodology of the affine LIBOR models and are driven by the wide and flexible class of affine processes. The affine property is preserved under forward measures, which allows us to derive Fourier pricing formulas for caps, swaptions, and basis swaptions. A model specification...... with dependent LIBOR rates is developed that allows for an efficient and accurate calibration to a system of caplet prices....

  16. Genetic affinities of north and northeastern populations of India: inference from HLA-based study.

    Science.gov (United States)

    Agrawal, S; Srivastava, S K; Borkar, M; Chaudhuri, T K

    2008-08-01

    India is like a microcosm of the world in terms of its diversity; religion, climate and ethnicity which leads to genetic variations in the populations. As a highly polymorphic marker, the human leukocyte antigen (HLA) system plays an important role in the genetic differentiation studies. To assess the genetic diversity of HLA class II loci, we studied a total of 1336 individuals from north India using DNA-based techniques. The study included four endogamous castes (Kayastha, Mathurs, Rastogies and Vaishyas), two inbreeding Muslim populations (Shias and Sunnis) from north India and three northeast Indian populations (Lachung, Mech and Rajbanshi). A total of 36 alleles were observed at DRB1 locus in both Hindu castes and Muslims from north, while 21 alleles were seen in northeast Indians. At the DQA1 locus, the number of alleles ranged from 11 to 17 in the studied populations. The total number of alleles at DQB1 was 19, 12 and 20 in the studied castes, Muslims and northeastern populations, respectively. The most frequent haplotypes observed in all the studied populations were DRB1*0701-DQA1*0201-DQB1*0201 and DRB1*1501-DQA1*0103-DQB1*0601. Upon comparing our results with other world populations, we observed the presence of Caucasoid element in north Indian population. However, differential admixturing among Sunnis and Shias with the other north Indians was evident. Northeastern populations showed genetic affinity with Mongoloids from southeast Asia. When genetic distances were calculated, we found the north Indians and northeastern populations to be markedly unrelated.

  17. Affinity Programs and the Real Estate Brokerage Industry

    OpenAIRE

    G Stacy Sirmans; David A. Macpherson

    2001-01-01

    This study surveys active real estate brokers obtaining information on involvement in affinity programs and referral/relocation networks. Some results regarding affinity involvement are: (a) 13% of respondents reported affinity affilliations, 75% reported no affiliations, and 12% indicated plans to become involved within the next year; (b) about half having affinity affiliations were involved with 2-4 groups; (c) affinity relationships were most often with membership organizations, corporatio...

  18. Isolation of a new ssDNA aptamer against staphylococcal enterotoxin B based on CNBr-activated sepharose-4B affinity chromatography.

    Science.gov (United States)

    Hedayati Ch, Mojtaba; Amani, Jafar; Sedighian, Hamid; Amin, Mohsen; Salimian, Jafar; Halabian, Raheleh; Imani Fooladi, Abbas Ali

    2016-09-01

    Staphylococcus aureus are potent human pathogens possessing arsenal of virulence factors. Staphylococcal food poisoning (SFP) and respiratory infections mediated by staphylococcal enterotoxin B (SEB) are common clinical manifestations. Many diagnostic techniques are based on serological detection and quantification of SEB in different food and clinical samples. Aptamers are known as new therapeutic and detection tools which are available in different ssDNA, dsDNA and protein structures. In this study, we used a new set of ssDNA aptamers against SEB. The methods used included preparation of a dsDNA library using standard SEB protein as the target analyte, affinity chromatography matrix in microfuge tubes, SELEX procedures to isolate specific ssDNA-aptamer as an affinity ligand, aptamer purification using ethanol precipitation method, affinity binding assay using ELISA, aptamer cloning and specificity test. Among 12 readable sequences, three of them were selected as the most appropriate aptamer because of their affinity and specificity to SEB. This study presents a new set of ssDNA aptamer with favorable selectivity to SEB through 12 rounds of SELEX. Selected aptamers were used to detect SEB in infected serum samples. Results showed that SEB c1 aptamer (2 µg SEB/100 nM aptamer) had favorable specificity to SEB (kd  = 2.3 × 10(-11) ). In conclusion, aptamers can be considered as useful tools for detecting and evaluating SEB. The results showed that affinity chromatography was an affordable assay with acceptable accuracy to isolate sensitive and selective novel aptamers. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  19. Dependence of the reactivity of five-remembered aromatic heterocycles on their structure. 2. Effect of aza substitution on the proton affinity of aminofurans

    International Nuclear Information System (INIS)

    Shokhen, M.A.; Andrianov, V.G.; Eremeev, A.V.; Barmina, S.V.

    1987-01-01

    The proton affinities of a series of aminofurans and their aza derivatives were calculated by a nonempirical method in the STO-3G basis set. A correlation was established between the proton affinities and the position of the heteroatoms in the ring. The calculation was performed by means of the Gaussian-76 program in the STO-3G basis set with the use of the geometric parameters obtained with full optimization of the molecular geometry in terms of the semiempirical MNDO method

  20. An MHC-restricted antibody-based chimeric antigen receptor requires TCR-like affinity to maintain antigen specificity

    Directory of Open Access Journals (Sweden)

    Marcela V Maus

    2016-01-01

    Full Text Available Chimeric antigen receptors (CARs are synthetic receptors that usually redirect T cells to surface antigens independent of human leukocyte antigen (HLA. Here, we investigated a T cell receptor-like CAR based on an antibody that recognizes HLA-A*0201 presenting a peptide epitope derived from the cancer-testis antigen NY-ESO-1. We hypothesized that this CAR would efficiently redirect transduced T cells in an HLA-restricted, antigen-specific manner. However, we found that despite the specificity of the soluble Fab, the same antibody in the form of a CAR caused moderate lysis of HLA-A2 expressing targets independent of antigen owing to T cell avidity. We hypothesized that lowering the affinity of the CAR for HLA-A2 would improve its specificity. We undertook a rational approach of mutating residues that, in the crystal structure, were predicted to stabilize binding to HLA-A2. We found that one mutation (DN lowered the affinity of the Fab to T cell receptor-range and restored the epitope specificity of the CAR. DN CAR T cells lysed native tumor targets in vitro, and, in a xenogeneic mouse model implanted with two human melanoma lines (A2+/NYESO+ and A2+/NYESO−, DN CAR T cells specifically migrated to, and delayed progression of, only the HLA-A2+/NY-ESO-1+ melanoma. Thus, although maintaining MHC-restricted antigen specificity required T cell receptor-like affinity that decreased potency, there is exciting potential for CARs to expand their repertoire to include a broad range of intracellular antigens.

  1. Using Affinity Diagrams to Evaluate Interactive Prototypes

    DEFF Research Database (Denmark)

    Lucero, Andrés

    2015-01-01

    our particular use of affinity diagramming in prototype evaluations. We reflect on a decade’s experience using affinity diagramming across a number of projects, both in industry and academia. Our affinity diagramming process in interaction design has been tailored and consists of four stages: creating...

  2. Writing in the Wild: Writers' Motivation in Fan-Based Affinity Spaces

    Science.gov (United States)

    Curwood, Jen Scott; Magnifico, Alecia Marie; Lammers, Jayne C.

    2013-01-01

    In order to understand the culture of the physical, virtual, and blended spheres that adolescents inhabit, we build on Gee's concept of affinity spaces. Drawing on our ethnographic research of adolescent literacies related to The Hunger Games novels, the Neopets online game, and The Sims videogames, this article explores the nature of…

  3. Can free energy calculations be fast and accurate at the same time? Binding of low-affinity, non-peptide inhibitors to the SH2 domain of the src protein

    Science.gov (United States)

    Chipot, Christophe; Rozanska, Xavier; Dixit, Surjit B.

    2005-11-01

    The usefulness of free-energy calculations in non-academic environments, in general, and in the pharmaceutical industry, in particular, is a long-time debated issue, often considered from the angle of cost/performance criteria. In the context of the rational drug design of low-affinity, non-peptide inhibitors to the SH2 domain of the pp60src tyrosine kinase, the continuing difficulties encountered in an attempt to obtain accurate free-energy estimates are addressed. free-energy calculations can provide a convincing answer, assuming that two key-requirements are fulfilled: (i) thorough sampling of the configurational space is necessary to minimize the statistical error, hence raising the question: to which extent can we sacrifice the computational effort, yet without jeopardizing the precision of the free-energy calculation? (ii) the sensitivity of binding free-energies to the parameters utilized imposes an appropriate parametrization of the potential energy function, especially for non-peptide molecules that are usually poorly described by multipurpose macromolecular force fields. Employing the free-energy perturbation method, accurate ranking, within ±0.7 kcal/mol, is obtained in the case of four non-peptide mimes of a sequence recognized by the pp60src SH2 domain.

  4. Single-step affinity purification for fungal proteomics.

    Science.gov (United States)

    Liu, Hui-Lin; Osmani, Aysha H; Ukil, Leena; Son, Sunghun; Markossian, Sarine; Shen, Kuo-Fang; Govindaraghavan, Meera; Varadaraj, Archana; Hashmi, Shahr B; De Souza, Colin P; Osmani, Stephen A

    2010-05-01

    A single-step protein affinity purification protocol using Aspergillus nidulans is described. Detailed protocols for cell breakage, affinity purification, and depending on the application, methods for protein release from affinity beads are provided. Examples defining the utility of the approaches, which should be widely applicable, are included.

  5. Extraction of trace nitrophenols in environmental water samples using boronate affinity sorbent

    International Nuclear Information System (INIS)

    Zhang, Yong; Mei, Meng; Huang, Xiaojia; Yuan, Dongxing

    2015-01-01

    In this research, the applicability of a new sorbent based on boronate affinity material is demonstrated. For this purpose, six strong polar nitrophenols were selected as models which are difficult to be extracted in neutral form (only based on hydrophobic interactions). The extracted nitrophenols were separated and determined by high-performance liquid chromatography with diode array detection. The sorbent was synthesized by in situ copolymerization of 3-acrylamidophenylboronic acid and divinylbenzene using dimethyl sulfoxide and azobisisobutyronitrile as porogen solvent and initiator, respectively. The effect of the preparation parameters in the polymerization mixture on extraction performance was investigated in detail. The size and morphology of the sorbent have been characterized via different techniques such as infrared spectroscopy, elemental analysis, scanning electron microscopy and mercury intrusion porosimetry. The important parameters influencing the extraction efficiency were studied and optimized thoroughly. Under the optimum extraction conditions, the limits of detection (S/N = 3) and limits of quantification (S/N = 10) for the target nitrophenols were 0.097–0.28 and 0.32–0.92 μg/L, respectively. The precision of the proposed method was evaluated in terms of intra- and inter-assay variability calculated as RSD, and it was found that the RSDs were all below 9%. Finally, the developed method was successfully applied for environmental water samples such as wastewater, tap, lake and river water. The recoveries varied within the range of 71.2–115% with RSD below 11% in all cases. The results well demonstrate that the new boronate affinity sorbent can extract nitrophenols effectively through multi-interactions including boron–nitrogen coordination, hydrogen-bond and hydrophobic interactions between sorbent and analytes. - Highlights: • A new boronate affinity sorbent (BAS) was prepared. • The BAS was used as the extractive medium of stir

  6. Study of the affinity between the protein kinase PKA and homoarginine-containing peptides derived from kemptide: Free energy perturbation (FEP) calculations.

    Science.gov (United States)

    Mena-Ulecia, Karel; Gonzalez-Norambuena, Fabian; Vergara-Jaque, Ariela; Poblete, Horacio; Tiznado, William; Caballero, Julio

    2018-02-05

    Protein kinases (PKs) discriminate between closely related sequences that contain serine, threonine, and/or tyrosine residues. Such specificity is defined by the amino acid sequence surrounding the phosphorylatable residue, so that it is possible to identify an optimal recognition motif (ORM) for each PK. The ORM for the protein kinase A (PKA), a well-known member of the PK family, is the sequence RRX(S/T)X, where arginines at the -3 and -2 positions play a key role with respect to the primed phosphorylation site. In this work, differential affinities of PKA for the peptide substrate Kemptide (LRRASLG) and mutants that substitute the arginine residues by the unnatural peptide homoarginine were evaluated through molecular dynamics (MD) and free energy perturbation (FEP) calculations. The FEP study for the homoarginine mutants required previous elaboration of a CHARMM "arginine to homoarginine" (R2B) hybrid topology file which is available in this manuscript as Supporting Information. Mutants substituting the arginine residues by alanine, lysine, and histidine were also considered in the comparison by using the same protocol. FEP calculations allowed estimating the free energy changes from the free PKA to PKA-substrate complex (ΔΔG E→ES ) when Kemptide structure was mutated. Both ΔΔG S→ES values for homoarginine mutants were predicted with a difference below 1 kcal/mol. In addition, FEP correctly predicted that all the studied mutations decrease the catalytic efficiency of Kemptide for PKA. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  7. Connections between quantized affine algebras and superalgebras

    International Nuclear Information System (INIS)

    Zhang, R.B.

    1992-08-01

    Every affine superalgebra with a symmetrizable Cartan matrix is closely related to an ordinary affine algebra with the same Cartan matrix. It is shown that the quantum supergroup associated with the former is essentially isomorphic to the quantum group associated with the latter in an appropriate class of representations. At the classical level, each integrable irreducible highest weight representation of the affine superalgebra has a corresponding irreducible representation of the affine algebra, which has the same weight space decomposition. (author). 5 refs, 3 tabs

  8. Mobile Technology Affinity in Renal Transplant Recipients.

    Science.gov (United States)

    Reber, S; Scheel, J; Stoessel, L; Schieber, K; Jank, S; Lüker, C; Vitinius, F; Grundmann, F; Eckardt, K-U; Prokosch, H-U; Erim, Y

    Medication nonadherence is a common problem in renal transplant recipients (RTRs). Mobile health approaches to improve medication adherence are a current trend, and several medication adherence apps are available. However, it is unknown whether RTRs use these technologies and to what extent. In the present study, the mobile technology affinity of RTRs was analyzed. We hypothesized significant age differences in mobile technology affinity and that mobile technology affinity is associated with better cognitive functioning as well as higher educational level. A total of 109 RTRs (63% male) participated in the cross-sectional study, with an overall mean age of 51.8 ± 14.2 years. The study included the Technology Experience Questionnaire (TEQ) for the assessment of mobile technology affinity, a cognitive test battery, and sociodemographic data. Overall, 57.4% of the patients used a smartphone or tablet and almost 45% used apps. The TEQ sum score was 20.9 in a possible range from 6 (no affinity to technology) to 30 (very high affinity). Younger patients had significantly higher scores in mobile technology affinity. The only significant gender difference was found in having fun with using electronic devices: Men enjoyed technology more than women did. Mobile technology affinity was positively associated with cognitive functioning and educational level. Young adult patients might profit most from mobile health approaches. Furthermore, high educational level and normal cognitive functioning promote mobile technology affinity. This should be kept in mind when designing mobile technology health (mHealth) interventions for RTRs. For beneficial mHealth interventions, further research on potential barriers and desired technologic features is necessary to adapt apps to patients' needs. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Calculation of the uptake of CO into the human blood

    Energy Technology Data Exchange (ETDEWEB)

    Zankl, J.G.

    1981-01-01

    CO is a toxic substance mainly because, due to its high hemoglobin affinity, it inhibits oxygen transport in the human blood. This process must be quantified in order to establish limiting CO concentrations for garages, road tunnels, places of work, and for purpose of accident analysis. The medical information given is based on literature and is considered only as an introduction for non-experts. The emphasis of the work was on the development of a computer program by which the influence also of variable air CO concentrations and sea levels can be calculated. The program is available at the author's institute along with detailed calculations and results not considered in this publication.

  10. Color and Contrast Enhancement by Controlled Piecewise Affine Histogram Equalization

    Directory of Open Access Journals (Sweden)

    Jose-Luis Lisani

    2012-10-01

    Full Text Available This paper presents a simple contrast enhancement algorithm based on histogram equalization (HE. The proposed algorithm performs a piecewise affine transform of the intensity levels of a digital image such that the new cumulative distribution function will be approximately uniform (as with HE, but where the stretching of the range is locally controlled to avoid brutal noise enhancement. We call this algorithm Piecewise Affine Equalization (PAE. Several experiments show that, in general, the new algorithm improves HE results.

  11. Affinity and specificity of serine endopeptidase-protein inhibitor interactions. Empirical free energy calculations based on X-ray crystallographic structures.

    Science.gov (United States)

    Krystek, S; Stouch, T; Novotny, J

    1993-12-05

    An empirical function was used to calculate free energy change (delta G) of complex formation between the following inhibitors and enzymes: Kunitz inhibitor (BPTI) with trypsin, trypsinogen and kallikrein; turkey ovomucoid 3rd domain (OMTKY3) with alpha-chymotrypsin and the Streptomyces griseus protease B; the potato chymotrypsin inhibitor with the protease B; and the barely chymotrypsin inhibitor and eglin-c with subtilisin and thermitase. Using X-ray coordinates of the nine complexes, we estimated the contributions that hydrophobic effect, electrostatic interactions and side-chain conformational entropy make towards the stability of the complexes. The calculated delta G values showed good agreement with the experimentally measured ones, the only exception being the kallikrein/BPTI complex whose X-ray structure was solved at an exceptionally low pH. In complexes with different enzymes, the same inhibitor residues contributed identically towards complex formation (delta G(residue) Spearman rank correlation coefficient 0.7 to 1.0). The most productive enzyme-contacting residues in OMTKY3, eglin-c, and the chymotrypsin inhibitors were found in analogous positions on their respective binding loops; thus, our calculations identified a functional (energetic) motif that parallels the well-known structural similarity of the binding loops. The delta G values calculated for BPTI complexed with trypsin (-21.7 kcal) and trypsinogen (-23.4 kcal) were similar and close to the experimental delta G value of the trypsin/BPTI complex (-18.1 kcal), lending support to the suggestion that the 10(7) difference in the observed stabilities (KA) of these two complexes reflects the energetic cost of conformational changes induced in trypsinogen during the pre-equilibrium stages of complex formation. In almost all of the complexes studied, the stabilization free energy contributed by the inhibitors was larger than that donated by the enzymes. In the trypsin-BPTI complex, the calculated

  12. Identification of Thioredoxin Target Disulfides Using Isotope-Coded Affinity Tags

    DEFF Research Database (Denmark)

    Hägglund, Per; Bunkenborg, Jakob; Maeda, Kenji

    2014-01-01

    Thioredoxins (Trx) are small redox proteins that reduce disulfide bonds in various target proteins and maintain cellular thiol redox control. Here, a thiol-specific labeling and affinity enrichment approach for identification and relative quantification of Trx target disulfides in complex protein...... reduction is determined by LC-MS/MS-based quantification of tryptic peptides labeled with "light" (12C) and "heavy" (13C) ICAT reagents. The methodology can be adapted to monitor the effect of different reductants or oxidants on the redox status of thiol/disulfide proteomes in biological systems....... extracts is described. The procedure utilizes the isotope-coded affinity tag (ICAT) reagents containing a thiol reactive iodoacetamide group and a biotin affinity tag to target peptides containing reduced cysteine residues. The identification of substrates for Trx and the extent of target disulfide...

  13. Affinity Crystallography: A New Approach to Extracting High-Affinity Enzyme Inhibitors from Natural Extracts.

    Science.gov (United States)

    Aguda, Adeleke H; Lavallee, Vincent; Cheng, Ping; Bott, Tina M; Meimetis, Labros G; Law, Simon; Nguyen, Nham T; Williams, David E; Kaleta, Jadwiga; Villanueva, Ivan; Davies, Julian; Andersen, Raymond J; Brayer, Gary D; Brömme, Dieter

    2016-08-26

    Natural products are an important source of novel drug scaffolds. The highly variable and unpredictable timelines associated with isolating novel compounds and elucidating their structures have led to the demise of exploring natural product extract libraries in drug discovery programs. Here we introduce affinity crystallography as a new methodology that significantly shortens the time of the hit to active structure cycle in bioactive natural product discovery research. This affinity crystallography approach is illustrated by using semipure fractions of an actinomycetes culture extract to isolate and identify a cathepsin K inhibitor and to compare the outcome with the traditional assay-guided purification/structural analysis approach. The traditional approach resulted in the identification of the known inhibitor antipain (1) and its new but lower potency dehydration product 2, while the affinity crystallography approach led to the identification of a new high-affinity inhibitor named lichostatinal (3). The structure and potency of lichostatinal (3) was verified by total synthesis and kinetic characterization. To the best of our knowledge, this is the first example of isolating and characterizing a potent enzyme inhibitor from a partially purified crude natural product extract using a protein crystallographic approach.

  14. Affine Fullerene C60 in a GS-Quasigroup

    Directory of Open Access Journals (Sweden)

    Vladimir Volenec

    2014-01-01

    Full Text Available It will be shown that the affine fullerene C60, which is defined as an affine image of buckminsterfullerene C60, can be obtained only by means of the golden section. The concept of the affine fullerene C60 will be constructed in a general GS-quasigroup using the statements about the relationships between affine regular pentagons and affine regular hexagons. The geometrical interpretation of all discovered relations in a general GS-quasigroup will be given in the GS-quasigroup C(1/2(1+5.

  15. Programmable calculator: alternative to minicomputer-based analyzer

    International Nuclear Information System (INIS)

    Hochel, R.C.

    1979-01-01

    Described are a number of typical field and laboratory counting systems that use standard stand-alone multichannel analyzers (MCA) interfaced to a Hewlett-Packard Company (HP 9830) programmable calculator. Such systems can offer significant advantages in cost and flexibility over a minicomputyr-based system. Because most laboratories tend to accumulate MCA's over the years, the programmable calculator also offers an easy way to upgrade the laboratory while making optimum use of existing systems. Software programs are easily tailored to fit a variety of general or specific applications. The only disadvantage of the calculator vs a computer-based system is in speed of analyses; however, for most applications this handicap is minimal. Applications discussed give a brief overview of the power and flexibility of the MCA-calculator approach to automated counting and data reduction

  16. Assessment of Density-Functional Tight-Binding Ionization Potentials and Electron Affinities of Molecules of Interest for Organic Solar Cells Against First-Principles GW Calculations

    Directory of Open Access Journals (Sweden)

    Ala Aldin M. H. M. Darghouth

    2015-12-01

    Full Text Available Ionization potentials (IPs and electron affinities (EAs are important quantities input into most models for calculating the open-circuit voltage (Voc of organic solar cells. We assess the semi-empirical density-functional tight-binding (DFTB method with the third-order self-consistent charge (SCC correction and the 3ob parameter set (the third-order DFTB (DFTB3 organic and biochemistry parameter set against experiments (for smaller molecules and against first-principles GW (Green’s function, G, times the screened potential, W calculations (for larger molecules of interest in organic electronics for the calculation of IPs and EAs. Since GW calculations are relatively new for molecules of this size, we have also taken care to validate these calculations against experiments. As expected, DFTB is found to behave very much like density-functional theory (DFT, but with some loss of accuracy in predicting IPs and EAs. For small molecules, the best results were found with ΔSCF (Δ self-consistent field SCC-DFTB calculations for first IPs (good to ± 0.649 eV. When considering several IPs of the same molecule, it is convenient to use the negative of the orbital energies (which we refer to as Koopmans’ theorem (KT IPs as an indication of trends. Linear regression analysis shows that KT SCC-DFTB IPs are nearly as accurate as ΔSCF SCC-DFTB eigenvalues (± 0.852 eV for first IPs, but ± 0.706 eV for all of the IPs considered here for small molecules. For larger molecules, SCC-DFTB was also the ideal choice with IP/EA errors of ± 0.489/0.740 eV from ΔSCF calculations and of ± 0.326/0.458 eV from (KT orbital energies. Interestingly, the linear least squares fit for the KT IPs of the larger molecules also proves to have good predictive value for the lower energy KT IPs of smaller molecules, with significant deviations appearing only for IPs of 15–20 eV or larger. We believe that this quantitative analysis of errors in SCC-DFTB IPs and EAs may be of

  17. Affinity Spaces and 21st Century Learning

    Science.gov (United States)

    Gee, James Paul

    2017-01-01

    This article discusses video games as "attractors" to "affinity spaces." It argues that affinity spaces are key sites today where people teach and learn 21st Century skills. While affinity spaces are proliferating on the Internet as interest-and-passion-driven sites devoted to a common set of endeavors, they are not new, just…

  18. Proton affinity of diastereoisomers of modified prolines using the kinetic method and density functional theory calculations: role of the cis/trans substituent on the endo/exo ring conformation.

    Science.gov (United States)

    Mezzache, S; Pepe, C; Karoyan, P; Fournier, F; Tabet, J-C

    2005-01-01

    The proton affinity (PA) of cis/trans-3-prolinoleucines and cis/trans-3-prolinoglutamic acids have been studied by the kinetic method and density functional theory (DFT) calculations. Several conformations of the neutral and the protonated modified prolines, in particular the endo and exo ring conformations, were analyzed with respect to their contribution to the PA values. When the substituent is an alkyl, both the diastereoisomers have the same PA value. However, the PA values for the diastereoisomers are different when the substituted chain contains functional groups (e.g. a carboxyl group). This variation in PA values could be attributed to the existence of intramolecular hydrogen bonds. Copyright (c) 2005 John Wiley & Sons, Ltd.

  19. Binding affinity toward human prion protein of some anti-prion compounds - Assessment based on QSAR modeling, molecular docking and non-parametric ranking.

    Science.gov (United States)

    Kovačević, Strahinja; Karadžić, Milica; Podunavac-Kuzmanović, Sanja; Jevrić, Lidija

    2018-01-01

    The present study is based on the quantitative structure-activity relationship (QSAR) analysis of binding affinity toward human prion protein (huPrP C ) of quinacrine, pyridine dicarbonitrile, diphenylthiazole and diphenyloxazole analogs applying different linear and non-linear chemometric regression techniques, including univariate linear regression, multiple linear regression, partial least squares regression and artificial neural networks. The QSAR analysis distinguished molecular lipophilicity as an important factor that contributes to the binding affinity. Principal component analysis was used in order to reveal similarities or dissimilarities among the studied compounds. The analysis of in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) parameters was conducted. The ranking of the studied analogs on the basis of their ADMET parameters was done applying the sum of ranking differences, as a relatively new chemometric method. The main aim of the study was to reveal the most important molecular features whose changes lead to the changes in the binding affinities of the studied compounds. Another point of view on the binding affinity of the most promising analogs was established by application of molecular docking analysis. The results of the molecular docking were proven to be in agreement with the experimental outcome. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. On the structure of self-affine convex bodies

    Energy Technology Data Exchange (ETDEWEB)

    Voynov, A S [M. V. Lomonosov Moscow State University, Faculty of Mechanics and Mathematics, Moscow (Russian Federation)

    2013-08-31

    We study the structure of convex bodies in R{sup d} that can be represented as a union of their affine images with no common interior points. Such bodies are called self-affine. Vallet's conjecture on the structure of self-affine bodies was proved for d = 2 by Richter in 2011. In the present paper we disprove the conjecture for all d≥3 and derive a detailed description of self-affine bodies in R{sup 3}. Also we consider the relation between properties of self-affine bodies and functional equations with a contraction of an argument. Bibliography: 10 titles.

  1. Simple Calculation Programs for Biology Immunological Methods

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Simple Calculation Programs for Biology Immunological Methods. Computation of Ab/Ag Concentration from EISA data. Graphical Method; Raghava et al., 1992, J. Immuno. Methods 153: 263. Determination of affinity of Monoclonal Antibody. Using non-competitive ...

  2. Affinity functions for modeling glass dissolution rates

    Energy Technology Data Exchange (ETDEWEB)

    Bourcier, W.L. [Lawrence Livermore National Lab., CA (United States)

    1997-07-01

    Glass dissolution rates decrease dramatically as glass approach ''saturation'' with respect to the leachate solution. Most repository sites are chosen where water fluxes are minimal, and therefore the waste glass is most likely to dissolve under conditions close to ''saturation''. The key term in the rate expression used to predict glass dissolution rates close to ''saturation'' is the affinity term, which accounts for saturation effects on dissolution rates. Interpretations of recent experimental data on the dissolution behaviour of silicate glasses and silicate minerals indicate the following: 1) simple affinity control does not explain the observed dissolution rate for silicate minerals or glasses; 2) dissolution rates can be significantly modified by dissolved cations even under conditions far from saturation where the affinity term is near unity; 3) the effects of dissolved species such as Al and Si on the dissolution rate vary with pH, temperature, and saturation state; and 4) as temperature is increased, the effect of both pH and temperature on glass and mineral dissolution rates decrease, which strongly suggests a switch in rate control from surface reaction-based to diffusion control. Borosilicate glass dissolution models need to be upgraded to account for these recent experimental observations. (A.C.)

  3. Specific capture of uranyl protein targets by metal affinity chromatography

    International Nuclear Information System (INIS)

    Basset, C.; Dedieu, A.; Guerin, P.; Quemeneur, E.; Meyer, D.; Vidaud, C.

    2008-01-01

    To improve general understanding of biochemical mechanisms in the field of uranium toxicology, the identification of protein targets needs to be intensified. Immobilized metal affinity chromatography (IMAC) has been widely developed as a powerful tool for capturing metal binding proteins from biological extracts. However uranyl cations (UO 2 2+ ) have particular physico-chemical characteristics which prevent them from being immobilized on classical metal chelating supports. We report here on the first development of an immobilized uranyl affinity chromatography method, based on the cation-exchange properties of amino-phosphonate groups for uranyl binding. The cation distribution coefficient and loading capacity on the support were determined. Then the stability of the uranyl-bonded phase under our chromatographic conditions was optimized to promote affinity mechanisms. The successful enrichment of uranyl binding proteins from human serum was then proven using proteomic and mass spectral analysis. (authors)

  4. Binding Affinity of a Highly Sensitive Au/Ag/Au/Chitosan-Graphene Oxide Sensor Based on Direct Detection of Pb2+ and Hg2+ Ions

    Directory of Open Access Journals (Sweden)

    Nur Hasiba Kamaruddin

    2017-10-01

    Full Text Available The study of binding affinity is essential in surface plasmon resonance (SPR sensing because it allows researchers to quantify the affinity between the analyte and immobilised ligands of an SPR sensor. In this study, we demonstrate the derivation of the binding affinity constant, K, for Pb2+ and Hg2+ ions according to their SPR response using a gold/silver/gold/chitosan–graphene oxide (Au/Ag/Au/CS–GO sensor for the concentration range of 0.1–5 ppm. The higher affinity of Pb2+ to binding with the CS–GO sensor explains the outstanding sensitivity of 2.05 °ppm−1 against 1.66 °ppm−1 of Hg2+. The maximum signal-to-noise ratio (SNR upon detection of Pb2+ is 1.53, and exceeds the suggested logical criterion of an SNR. The Au/Ag/Au/CS–GO SPR sensor also exhibits excellent repeatability in Pb2+ due to the strong bond between its functional groups and this cation. The adsorption data of Pb2+ and Hg2+ on the CS–GO sensor fits well with the Langmuir isotherm model where the affinity constant, K, of Pb2+ and Hg2+ ions is computed. The affinity of Pb2+ ions to the Au/Ag/Au/CS–GO sensor is significantly higher than that of Hg2+ based on the value of K, 7 × 105 M−1 and 4 × 105 M−1, respectively. The higher shift in SPR angles due to Pb2+ and Hg2+ compared to Cr3+, Cu2+ and Zn2+ ions also reveals the greater affinity of the CS–GO SPR sensor to them, thus supporting the rationale for obtaining K for these two heavy metals. This study provides a better understanding on the sensing performance of such sensors in detecting heavy metal ions.

  5. Different endothelin receptor affinities in dog tissues

    International Nuclear Information System (INIS)

    Loeffler, B.M.L.; Loehrer, W.

    1991-01-01

    Endothelin (ET) is a long-lasting potent vasoconstrictor-peptide. Here the authors report different binding affinities of endothelin-1 (ET-1) to ET-receptors of various dog tissues. Crude microsomal fractions were prepared after homogenisation of dog tissues in 50 mM Tris/HCl, 20 mM MnCl2, 1 mM EDTA, pH 7.4 by differential centrifugation. Aliquots of microsomal fractions (70 micrograms of protein) were incubated at 25 degrees C for 180 min in the presence of 20 pM 125I-ET-1 and various concentrations of cold ET-1. Four different ET-1 receptor binding affinities were found: adrenals, cerebrum, liver, heart, skeletal muscle and stomach microsomal membranes contained high affinity binding sites (Kd 50 - 80 pM, Bmax 60 - 250 fmol/mg). In cerebellum and spleen medium affinity ET-1 receptors (Kd 350 pM, Bmax 880 and 1200 fmol/mg respectively) were present. In comparison lung and kidney microsomes contained a low affinity ET-1 receptor (Kd 800 and 880 pM, Bmax 1600 and 350 fmol/mg). Receptors of even lower affinity were present in heart, intestine and liver microsomes with Kd values of 3 - 6 nM

  6. Duals of Affine Grassmann Codes and Their Relatives

    DEFF Research Database (Denmark)

    Beelen, P.; Ghorpade, S. R.; Hoholdt, T.

    2012-01-01

    Affine Grassmann codes are a variant of generalized Reed-Muller codes and are closely related to Grassmann codes. These codes were introduced in a recent work by Beelen Here, we consider, more generally, affine Grassmann codes of a given level. We explicitly determine the dual of an affine...... Grassmann code of any level and compute its minimum distance. Further, we ameliorate the results by Beelen concerning the automorphism group of affine Grassmann codes. Finally, we prove that affine Grassmann codes and their duals have the property that they are linear codes generated by their minimum......-weight codewords. This provides a clean analogue of a corresponding result for generalized Reed-Muller codes....

  7. A Novel Vertex Affinity for Community Detection

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Andy [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Sanders, Geoffrey [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Henson, Van [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Vassilevski, Panayot [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-10-05

    We propose a novel vertex affinity measure in this paper. The new vertex affinity quantifies the proximity between two vertices in terms of their clustering strength and is ideal for such graph analytics applications as community detection. We also developed a framework that combines simple graph searches and resistance circuit formulas to compute the vertex affinity efficiently. We study the properties of the new affinity measure empirically in comparison to those of other popular vertex proximity metrics. Our results show that the existing metrics are ill-suited for community detection due to their lack of fundamental properties that are essential for correctly capturing inter- and intra-cluster vertex proximity.

  8. Peptide nucleic acid probe for protein affinity purification based on biotin-streptavidin interaction and peptide nucleic acid strand hybridization.

    Science.gov (United States)

    Tse, Jenny; Wang, Yuanyuan; Zengeya, Thomas; Rozners, Eriks; Tan-Wilson, Anna

    2015-02-01

    We describe a new method for protein affinity purification that capitalizes on the high affinity of streptavidin for biotin but does not require dissociation of the biotin-streptavidin complex for protein retrieval. Conventional reagents place both the selectively reacting group (the "warhead") and the biotin on the same molecule. We place the warhead and the biotin on separate molecules, each linked to a short strand of peptide nucleic acid (PNA), synthetic polymers that use the same bases as DNA but attached to a backbone that is resistant to attack by proteases and nucleases. As in DNA, PNA strands with complementary base sequences hybridize. In conditions that favor PNA duplex formation, the warhead strand (carrying the tagged protein) and the biotin strand form a complex that is held onto immobilized streptavidin. As in DNA, the PNA duplex dissociates at moderately elevated temperature; therefore, retrieval of the tagged protein is accomplished by a brief exposure to heat. Using iodoacetate as the warhead, 8-base PNA strands, biotin, and streptavidin-coated magnetic beads, we demonstrate retrieval of the cysteine protease papain. We were also able to use our iodoacetyl-PNA:PNA-biotin probe for retrieval and identification of a thiol reductase and a glutathione transferase from soybean seedling cotyledons. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Quantifying high-affinity binding of hydrophobic ligands by isothermal titration calorimetry.

    Science.gov (United States)

    Krainer, Georg; Broecker, Jana; Vargas, Carolyn; Fanghänel, Jörg; Keller, Sandro

    2012-12-18

    A fast and reliable quantification of the binding thermodynamics of hydrophobic high-affinity ligands employing a new calorimetric competition experiment is described. Although isothermal titration calorimetry is the method of choice for a quantitative characterization of intermolecular interactions in solution, a reliable determination of a dissociation constant (K(D)) is typically limited to the range 100 μM > K(D) > 1 nM. Interactions displaying higher or lower K(D) values can be assessed indirectly, provided that a suitable competing ligand is available whose K(D) falls within the directly accessible affinity window. This established displacement assay, however, requires the high-affinity ligand to be soluble at high concentrations in aqueous buffer and, consequently, poses serious problems in the study of protein binding involving small-molecule ligands dissolved in organic solvents--a familiar case in many drug-discovery projects relying on compound libraries. The calorimetric competition assay introduced here overcomes this limitation, thus allowing for a detailed thermodynamic description of high-affinity receptor-ligand interactions involving poorly water-soluble compounds. Based on a single titration of receptor into a dilute mixture of the two competing ligands, this competition assay provides accurate and precise values for the dissociation constants and binding enthalpies of both high- and moderate-affinity ligands. We discuss the theoretical background underlying the approach, demonstrate its practical application to metal ion chelation and high-affinity protein-inhibitor interactions, and explore its potential and limitations with the aid of simulations and statistical analyses.

  10. On affine non-negative matrix factorization

    DEFF Research Database (Denmark)

    Laurberg, Hans; Hansen, Lars Kai

    2007-01-01

    We generalize the non-negative matrix factorization (NMF) generative model to incorporate an explicit offset. Multiplicative estimation algorithms are provided for the resulting sparse affine NMF model. We show that the affine model has improved uniqueness properties and leads to more accurate id...

  11. Improving image segmentation by learning region affinities

    Energy Technology Data Exchange (ETDEWEB)

    Prasad, Lakshman [Los Alamos National Laboratory; Yang, Xingwei [TEMPLE UNIV.; Latecki, Longin J [TEMPLE UNIV.

    2010-11-03

    We utilize the context information of other regions in hierarchical image segmentation to learn new regions affinities. It is well known that a single choice of quantization of an image space is highly unlikely to be a common optimal quantization level for all categories. Each level of quantization has its own benefits. Therefore, we utilize the hierarchical information among different quantizations as well as spatial proximity of their regions. The proposed affinity learning takes into account higher order relations among image regions, both local and long range relations, making it robust to instabilities and errors of the original, pairwise region affinities. Once the learnt affinities are obtained, we use a standard image segmentation algorithm to get the final segmentation. Moreover, the learnt affinities can be naturally unutilized in interactive segmentation. Experimental results on Berkeley Segmentation Dataset and MSRC Object Recognition Dataset are comparable and in some aspects better than the state-of-art methods.

  12. F+ and F⁻ affinities of simple N(x)F(y) and O(x)F(y) compounds.

    Science.gov (United States)

    Grant, Daniel J; Wang, Tsang-Hsiu; Vasiliu, Monica; Dixon, David A; Christe, Karl O

    2011-03-07

    Atomization energies at 0 K and heats of formation at 0 and 298 K are predicted for the neutral and ionic N(x)F(y) and O(x)F(y) systems using coupled cluster theory with single and double excitations and including a perturbative triples correction (CCSD(T)) method with correlation consistent basis sets extrapolated to the complete basis set (CBS) limit. To achieve near chemical accuracy (±1 kcal/mol), three corrections to the electronic energy were added to the frozen core CCSD(T)/CBS binding energies: corrections for core-valence, scalar relativistic, and first order atomic spin-orbit effects. Vibrational zero point energies were computed at the CCSD(T) level of theory where possible. The calculated heats of formation are in good agreement with the available experimental values, except for FOOF because of the neglect of higher order correlation corrections. The F(+) affinity in the N(x)F(y) series increases from N(2) to N(2)F(4) by 63 kcal/mol, while that in the O(2)F(y) series decreases by 18 kcal/mol from O(2) to O(2)F(2). Neither N(2) nor N(2)F(4) is predicted to bind F(-), and N(2)F(2) is a very weak Lewis acid with an F(-) affinity of about 10 kcal/mol for either the cis or trans isomer. The low F(-) affinities of the nitrogen fluorides explain why, in spite of the fact that many stable nitrogen fluoride cations are known, no nitrogen fluoride anions have been isolated so far. For example, the F(-) affinity of NF is predicted to be only 12.5 kcal/mol which explains the numerous experimental failures to prepare NF(2)(-) salts from the well-known strong acid HNF(2). The F(-) affinity of O(2) is predicted to have a small positive value and increases for O(2)F(2) by 23 kcal/mol, indicating that the O(2)F(3)(-) anion might be marginally stable at subambient temperatures. The calculated adiabatic ionization potentials and electron affinities are in good agreement with experiment considering that many of the experimental values are for vertical processes. © 2011

  13. Selection of imprinted nanoparticles by affinity chromatography.

    Science.gov (United States)

    Guerreiro, António R; Chianella, Iva; Piletska, Elena; Whitcombe, Michael J; Piletsky, Sergey A

    2009-04-15

    Soluble molecularly imprinted nanoparticles were synthesised via iniferter initiated polymerisation and separated by size via gel permeation chromatography. Subsequent fractionation of these particles by affinity chromatography allowed the separation of high affinity fractions from the mixture of nanoparticles. Fractions selected this way possess affinity similar to that of natural antibodies (K(d) 6.6x10(-8)) M and were also able to discriminate between related functional analogues of the template.

  14. Data base to compare calculations and observations

    International Nuclear Information System (INIS)

    Tichler, J.L.

    1985-01-01

    Meteorological and climatological data bases were compared with known tritium release points and diffusion calculations to determine if calculated concentrations could replace measure concentrations at the monitoring stations. Daily tritium concentrations were monitored at 8 stations and 16 possible receptors. Automated data retrieval strategies are listed

  15. Object matching using a locally affine invariant and linear programming techniques.

    Science.gov (United States)

    Li, Hongsheng; Huang, Xiaolei; He, Lei

    2013-02-01

    In this paper, we introduce a new matching method based on a novel locally affine-invariant geometric constraint and linear programming techniques. To model and solve the matching problem in a linear programming formulation, all geometric constraints should be able to be exactly or approximately reformulated into a linear form. This is a major difficulty for this kind of matching algorithm. We propose a novel locally affine-invariant constraint which can be exactly linearized and requires a lot fewer auxiliary variables than other linear programming-based methods do. The key idea behind it is that each point in the template point set can be exactly represented by an affine combination of its neighboring points, whose weights can be solved easily by least squares. Errors of reconstructing each matched point using such weights are used to penalize the disagreement of geometric relationships between the template points and the matched points. The resulting overall objective function can be solved efficiently by linear programming techniques. Our experimental results on both rigid and nonrigid object matching show the effectiveness of the proposed algorithm.

  16. High-affinity RNA aptamers to C-reactive protein (CRP): newly developed pre-elution methods for aptamer selection

    International Nuclear Information System (INIS)

    Orito, N; Umekage, S; Sakai, E; Tanaka, T; Kikuchi, Y; Sato, K; Kawauchi, S; Tanaka, H

    2012-01-01

    We have developed a modified SELEX (systematic evolution of ligands by exponential enrichment) method to obtain RNA aptamers with high affinity to C-reactive protein (CRP). CRP is a clinical biomarker present in plasma, the level of which increases in response to infections and noninfectious inflammation. The CRP level is also an important prognostic indicator in patients with several syndromes. At present, CRP content in blood is measured immunochemically using antibodies. To develop a more sensitive method using RNA aptamers, we have attempted to obtain high-affinity RNA aptamers to CRP. We succeeded in obtaining an RNA aptamer with high affinity to CRP using a CRP-immobilized Sepharose column and pre-elution procedure. Pre-elution is a method that removes the weak binding portion from a selected RNA population by washing for a short time with buffer containing CRP. By surface plasmon-resonance (SPR) analysis, the affinity constant of this aptamer for CRP was calculated to be K D = 2.25x10 -9 (M). The secondary structure, contact sites with CRP protein, and application of this aptamer will be described.

  17. Affinity for a malignant tumor and organs at the elements in group VIII of the periodic table

    International Nuclear Information System (INIS)

    Ando, Atsushi; Hisada, Kinichi; Ando, Itsuko.

    1975-01-01

    In order to investigate the tumor affinity of the radioisotopes, iron(Fe-59), cobalt(Co-58), ruthenium(Ru-103), palladium(Pd-103), osmium(Os-185+191) and iridium(Ir-192), the elements of group VIII in the periodic table were examined, using rats which were subcutaneously transplanted with Yoshida sarcoma. Six preparations, 59 Fe-chloride, 58 Co-chloride, 103 Ru-chloride, 103 Pd-chloride, 185+191 Os-hexachlorosmic acid and 192 Ir-hexachloriridic acid were injected intravenously in to each group of tumor bearing rats. These rats were sacrificed at various periods after injection of each preparation: 3 hours, 24 hours and 48 hours in all preparations, except 59 Fe-chloride with 30 minutes, 3 hours, 24 hours and 48 hours. The radioactivities of the tumor, blood muscle, liver, kidney and spleen were measured by a well-type scintillation counter, and retention values (in every tissue including the tumor were calculated in percent of administered dose per g-tissue weight). 185+191 Os-hexachlorosmic acid had a considerably strong affinity for the malignant tumor. 59 Fe-chloride, 58 Co-chloride, 103 Ru-chloride, 103 Pd-chloride and 192 Ir-hexachloriridic acid did not have any affinity for the malignant tumor. However 59 Fe-chloride had a very strong affinity for blood corpuscles. 103 Pd-chloride had a fairly strong affinity for the kidney and liver, 58 Co-chloride had a fairly affinity for the liver, 103 Ru-chloride, 185+191 Os-hexachlorosmic acid and 192 Ir-hexachloriridic acid had a fairly strong affinity for the kidney. (Evans, J.)

  18. Contractions of affine spherical varieties

    International Nuclear Information System (INIS)

    Arzhantsev, I V

    1999-01-01

    The language of filtrations and contractions is used to describe the class of G-varieties obtainable as the total spaces of the construction of contraction applied to affine spherical varieties, which is well-known in invariant theory. These varieties are local models for arbitrary affine G-varieties of complexity 1 with a one-dimensional categorical quotient. As examples, reductive algebraic semigroups and three-dimensional SL 2 -varieties are considered

  19. On-bead chemical synthesis and display of phosphopeptides for affinity pull-down proteomics

    DEFF Research Database (Denmark)

    Malene, Brandt; Madsen, Jens C.; Bunkenborg, Jakob

    2006-01-01

    We describe a new method for phosphopeptide proteomics based on the solid-phase synthesis of phosphopeptides on beads suitable for affinity pull-down experiments. Peptide sequences containing the Bad Ser112 and Ser136 phosphorylation motifs were used as bait in affinity pull-down experiments...... (aldehyde) at the C terminus for potential activity-based proteomics. The synthetic support-bound Bad phosphopeptides were able to pull down 14-3-3zeta. Furthermore, Bad phosphopeptides bound endogenous 14-3-3 proteins, and all seven members of the 14-3-3 family were identified by mass spectrometry....... In control experiments, none of the unphosphorylated Bad peptides bound transfected 14-3-3zeta or endogenous 14-3-3. We conclude that the combined synthesis and display of phosphopeptides on-bead is a fast and efficient method for affinity pull-down proteomics....

  20. Providing affinity

    DEFF Research Database (Denmark)

    Guglielmi, Michel; Johannesen, Hl

    2004-01-01

    , Essex, Hertfordshire, Norfolk and Suffolk. Research found that there was a lack of identity or sense of belonging and nothing anchoring people to the region as a whole. Common affinity is somehow forced to the people of East England and thereby we came to the conclusion that a single landmark...... and potential situations but also virtual events that calls for an undeterminated process of resolution. This process is activated by the user who co-produces the actualisation as an answer to a virtual reality that we defined at the first place. The potential situations or the possible it is a fantomatic real....... The possible is like the real. It is determinated and it only lakes existence. While the possible is already made, the virtual is like a problematic which needs to be resolved and actualized. Our installations are based on high tech interactivity where we use sensors and remote communication to offer a sense...

  1. Floristic affinities of the lowland savannahs of Belize and southern Mexico.

    Science.gov (United States)

    Canché-Estrada, Idalia Arely; Ortiz-Díaz, Juan Javier; Tun-Garrido, Juan

    2018-01-01

    Environmental heterogeneity of Belize and southern Mexico savannahs as well as their geographical location suggest that these plant communities share floristic elements, making them conducive to a phytogeographical analysis. The aim of this study was to analyse the floristic affinities of nine savannahs of Belize and southern Mexico and to explain the similarities and differences amongst them. A binary data matrix containing 915 species was built based on the authors' own collections and on nine floristic lists already published. A second data matrix, consisting of 113 species representing trees, was also used since most literature on neotropical savannahs has focused on this life form. In addition, the ten most species-rich families as well as the characteristic species present in more than five savannahs were analysed. Floristic similarities were calculated using the Jaccard index. Dendrograms obtained in both types of analysis showed clusters with low similarity values, corresponding to geographic locations formed by the savannahs of Belize-Tabasco and the Yucatan Peninsula. The floristic affinities of the savannahs may be explained in terms of heterogeneity in climate and physiography. The Yucatan Peninsula and Belize-Tabasco groups have differences in climate type and the amount of rainfall. In addition, the Yucatan Peninsula savannahs are established at the bottom of karstic valleys, while the Belize and Tabasco savannahs develop on extensive flatlands. The savannahs of Oaxaca have the same climate type and amount of rainfall as those of the Yucatan Peninsula but they are distributed along peaks and the slopes of shale hills. Fabaceae and Poaceae mainly dominated the local floras with 121 and 116 species each; remarkably, Melastomataceae was absent in the Yucatan Peninsula and Oaxaca. Nine species occurred in five to seven savannahs, confirming that they are widespread in both Belize and southern Mexico, and the Neotropics. Geographic location and floristic

  2. Sperm cell purification from mock forensic swabs using SOMAmer™ affinity reagents.

    Science.gov (United States)

    Katilius, Evaldas; Carmel, Andrew B; Koss, Heidi; O'Connell, Dan; Smith, Breanna C; Sanders, Glenn M; LaBerge, Greggory S

    2018-03-27

    We have demonstrated a proof of concept with affinity-based purification of sperm cells from mock forensic samples using SOMAmer™ reagents, DNA-based affinity reagents developed by SomaLogic, Inc. SOMAmer reagents were selected in vitro using whole-cell SELEX to bind specifically with intact, detergent-treated sperm cells. Successful separation of sperm from epithelial cells and their debris was demonstrated using buccal swabs with added semen. Primarily male DNA profiles were generated from sperm cells eluted from the types of cotton swabs typically used for rape kit evidence collection. The quality of sperm DNA isolated from samples purified using SOMAmers is comparable to existing commercially available differential extraction-based methods at higher sperm concentrations. This purification method is simple, offers relatively rapid (forensic casework. Copyright © 2018. Published by Elsevier B.V.

  3. The spectrum of the conserved charges in affine Toda theories

    International Nuclear Information System (INIS)

    Niedermaier, M.R.

    1992-07-01

    A vertex operator construction for the phase of the minimal form factor is used to predict the exact spectrum of the infinite set of conserved charges on the multi-particle states in affine Toda theories from the bootstrap S-matrix. Conversely, the scattering phase can be recovered from the spectral information. The result is checed against the classical spectrum which is calculated ab-initio using the τ-function formalism. The latter is shown to provide a considerable shortcut compared to the traditional use of the inverse scattering transform. (orig.)

  4. Actinide-lanthanide separation by bipyridyl-based ligands. DFT calculations and experimental results

    International Nuclear Information System (INIS)

    Borisova, Nataliya E.; Eroshkina, Elizaveta A.; Korotkov, Leonid A.; Ustynyuk, Yuri A.; Alyapyshev, Mikhail Yu.; Eliseev, Ivan I.; Babain, Vasily A.

    2011-01-01

    In order to gain insights into effect of substituents on selectivity of Am/Eu separation, the synthesis and extractions tests were undertaken on the series of bipyridyl-based ligands (amides of 2,2'-bipyridyl-6,6'-dicarboxylic acid: L Ph - N,N'-diethyl-N,N'-diphenyl amide; L Bu2 - tetrabutyl amide; L Oct2 - tetraoctyl amide; L 3FPh - N,N'-diethyl-N,N'-bis-(3-fluorophenyl) amide; as well as N,N'-diethyl-N,N'-diphenyl amide of 4,4'-dibrom-2,2'-bipyridyl-6,6'-dicarboxylic acid and N,N'-diethyl-N,N'-diphenyl amide of 4,4'-dinitro-2,2'-bipyridyl-6,6'-dicarboxylic acid) as well as structure and stability of their complexes with lanthanides and actinides were studied. The extraction tests were performed for Am, lanthanide series and transition metals in polar diluents in presence of chlorinated cobalt dicarbolide and have shown high distribution coefficients for Am. Also was found that the type of substituents on amidic nitrogen exerts great influence on the extraction of light lanthanides. For understanding of the nature of this effect we made QC-calculations at DFT level, binding constants determination and X-Ray structure determination of the complexes. The UV/VIS titration performed show that the composition of all complexes of the amides with lanthanides in solution is 1:1. In spite of the binding constants are high (lgβ about 6-7 in acetonitrile solution), lanthanide ions have binding constants with the same order of magnitude for dialkyl substituted extractants. The X-Ray structures of the complexes of bipyridyl-based amides show the composition of 1:1 and the coordination number of the ions being 10. The DFT optimized structures of the compounds are in good agreement with that obtained by X-Ray. The gas phase affinity of the amides to lanthanides shows strong correlation with the distribution ratios. We can infer that the bipyridyl-based amides form complexes with metal nitrates which have similar structure in solid and gas phases and in solution, and the DFT

  5. Calculation of electromagnetic parameter based on interpolation algorithm

    International Nuclear Information System (INIS)

    Zhang, Wenqiang; Yuan, Liming; Zhang, Deyuan

    2015-01-01

    Wave-absorbing material is an important functional material of electromagnetic protection. The wave-absorbing characteristics depend on the electromagnetic parameter of mixed media. In order to accurately predict the electromagnetic parameter of mixed media and facilitate the design of wave-absorbing material, based on the electromagnetic parameters of spherical and flaky carbonyl iron mixture of paraffin base, this paper studied two different interpolation methods: Lagrange interpolation and Hermite interpolation of electromagnetic parameters. The results showed that Hermite interpolation is more accurate than the Lagrange interpolation, and the reflectance calculated with the electromagnetic parameter obtained by interpolation is consistent with that obtained through experiment on the whole. - Highlights: • We use interpolation algorithm on calculation of EM-parameter with limited samples. • Interpolation method can predict EM-parameter well with different particles added. • Hermite interpolation is more accurate than Lagrange interpolation. • Calculating RL based on interpolation is consistent with calculating RL from experiment

  6. Identification of Thioredoxin Disulfide Targets Using a Quantitative Proteomics Approach Based on Isotope-Coded Affinity Tags

    DEFF Research Database (Denmark)

    Hägglund, Per; Bunkenborg, Jakob; Maeda, Kenji

    2008-01-01

    Thioredoxin (Trx) is a ubiquitous protein disulfide reductase involved in a wide range of cellular redox processes. A large number of putative target proteins have been identified using proteomics approaches, but insight into target specificity at the molecular level is lacking since the reactivity...... of Trx toward individual disulfides has not been quantified. Here, a novel proteomics procedure is described for quantification of Trx-mediated target disulfide reduction based on thiol-specific differential labeling with the iodoacetamide-based isotope-coded affinity tag (ICAT) reagents. Briefly......, protein extract of embryos from germinated barley seeds was treated +/- Trx, and thiols released from target protein disulfides were irreversibly blocked with iodoacetamide. The remaining cysteine residues in the Trx-treated and the control (-Trx) samples were then chemically reduced and labeled...

  7. Non-affine fields in solid-solid transformations: the structure and stability of a product droplet.

    Science.gov (United States)

    Paul, Arya; Sengupta, Surajit; Rao, Madan

    2014-01-08

    We describe the microstructure, morphology, and dynamics of growth of a droplet of martensite nucleating in a parent austenite during a solid-solid transformation, using a Landau theory written in terms of both conventional affine elastic deformations and non-affine deformations. Non-affineness, φ, serves as a source of strain incompatibility and screens long-ranged elastic interactions. It is produced wherever the local stress exceeds a threshold and anneals diffusively thereafter. Using a variational calculation, we find three types of stable solution (labeled I, II, and III) for the structure of the product droplet, depending on the stress threshold and the scaled mobilities of φ parallel and perpendicular to the parent-product interface. The profile of the non-affine field φ is different in these three solutions: I is characterized by a vanishingly small φ, II admits large values of φ localized in regions of high stress within the parent-product interface, and III is a structure in which φ completely wets the parent-product interface. The width l and size W of the twins follow the relation l is proportional to √W in solution I; this relation does not hold for II or III. We obtain a dynamical phase diagram featuring these solutions, and argue that they represent specific solid-state microstructures.

  8. Environment-based pin-power reconstruction method for homogeneous core calculations

    International Nuclear Information System (INIS)

    Leroyer, H.; Brosselard, C.; Girardi, E.

    2012-01-01

    Core calculation schemes are usually based on a classical two-step approach associated with assembly and core calculations. During the first step, infinite lattice assemblies calculations relying on a fundamental mode approach are used to generate cross-sections libraries for PWRs core calculations. This fundamental mode hypothesis may be questioned when dealing with loading patterns involving several types of assemblies (UOX, MOX), burnable poisons, control rods and burn-up gradients. This paper proposes a calculation method able to take into account the heterogeneous environment of the assemblies when using homogeneous core calculations and an appropriate pin-power reconstruction. This methodology is applied to MOX assemblies, computed within an environment of UOX assemblies. The new environment-based pin-power reconstruction is then used on various clusters of 3x3 assemblies showing burn-up gradients and UOX/MOX interfaces, and compared to reference calculations performed with APOLLO-2. The results show that UOX/MOX interfaces are much better calculated with the environment-based calculation scheme when compared to the usual pin-power reconstruction method. The power peak is always better located and calculated with the environment-based pin-power reconstruction method on every cluster configuration studied. This study shows that taking into account the environment in transport calculations can significantly improve the pin-power reconstruction so far as it is consistent with the core loading pattern. (authors)

  9. Schubert calculus and threshold polynomials of affine fusion

    International Nuclear Information System (INIS)

    Irvine, S.E.; Walton, M.A.

    2000-01-01

    We show how the threshold level of affine fusion, the fusion of Wess-Zumino-Witten (WZW) conformal field theories, fits into the Schubert calculus introduced by Gepner. The Pieri rule can be modified in a simple way to include the threshold level, so that calculations may be done for all (non-negative integer) levels at once. With the usual Giambelli formula, the modified Pieri formula deforms the tensor product coefficients (and the fusion coefficients) into what we call threshold polynomials. We compare them with the q-deformed tensor product coefficients and fusion coefficients that are related to q-deformed weight multiplicities. We also discuss the meaning of the threshold level in the context of paths on graphs

  10. A Novel Fast and Robust Binary Affine Invariant Descriptor for Image Matching

    Directory of Open Access Journals (Sweden)

    Xiujie Qu

    2014-01-01

    Full Text Available As the current binary descriptors have disadvantages of high computational complexity, no affine invariance, and the high false matching rate with viewpoint changes, a new binary affine invariant descriptor, called BAND, is proposed. Different from other descriptors, BAND has an irregular pattern, which is based on local affine invariant region surrounding a feature point, and it has five orientations, which are obtained by LBP effectively. Ultimately, a 256 bits binary string is computed by simple random sampling pattern. Experimental results demonstrate that BAND has a good matching result in the conditions of rotating, image zooming, noising, lighting, and small-scale perspective transformation. It has better matching performance compared with current mainstream descriptors, while it costs less time.

  11. Global affine differential geometry of hypersurfaces

    CERN Document Server

    Li, An-Min; Zhao, Guosong; Hu, Zejun

    2015-01-01

    This book draws a colorful and widespread picture of global affine hypersurface theory up to the most recent state. Moreover, the recent development revealed that affine differential geometry- as differential geometry in general- has an exciting intersection area with other fields of interest, like partial differential equations, global analysis, convex geometry and Riemann surfaces.

  12. Passive Fault Tolerant Control of Piecewise Affine Systems Based on H Infinity Synthesis

    DEFF Research Database (Denmark)

    Gholami, Mehdi; Cocquempot, vincent; Schiøler, Henrik

    2011-01-01

    In this paper we design a passive fault tolerant controller against actuator faults for discretetime piecewise affine (PWA) systems. By using dissipativity theory and H analysis, fault tolerant state feedback controller design is expressed as a set of Linear Matrix Inequalities (LMIs). In the cur...

  13. CaFE: a tool for binding affinity prediction using end-point free energy methods.

    Science.gov (United States)

    Liu, Hui; Hou, Tingjun

    2016-07-15

    Accurate prediction of binding free energy is of particular importance to computational biology and structure-based drug design. Among those methods for binding affinity predictions, the end-point approaches, such as MM/PBSA and LIE, have been widely used because they can achieve a good balance between prediction accuracy and computational cost. Here we present an easy-to-use pipeline tool named Calculation of Free Energy (CaFE) to conduct MM/PBSA and LIE calculations. Powered by the VMD and NAMD programs, CaFE is able to handle numerous static coordinate and molecular dynamics trajectory file formats generated by different molecular simulation packages and supports various force field parameters. CaFE source code and documentation are freely available under the GNU General Public License via GitHub at https://github.com/huiliucode/cafe_plugin It is a VMD plugin written in Tcl and the usage is platform-independent. tingjunhou@zju.edu.cn. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. New unitary affine-Virasoro constructions

    International Nuclear Information System (INIS)

    Halpern, M.B.; Kiritsis, E.; Obers, N.A.; Poratti, M.; Yamron, J.P.

    1990-01-01

    This paper reports on a quasi-systematic investigation of the Virasoro master equation. The space of all affine-Virasoro constructions is organized by K-conjugation into affine-Virasoro nests, and an estimate of the dimension of the space shows that most solutions await discovery. With consistent ansatze for the master equation, large classes of new unitary nests are constructed, including quadratic deformation nests with continuous conformal weights, and unitary irrational central charge nests, which may dominate unitary rational central charge on compact g

  15. Maximum-Entropy Models of Sequenced Immune Repertoires Predict Antigen-Antibody Affinity.

    Directory of Open Access Journals (Sweden)

    Lorenzo Asti

    2016-04-01

    Full Text Available The immune system has developed a number of distinct complex mechanisms to shape and control the antibody repertoire. One of these mechanisms, the affinity maturation process, works in an evolutionary-like fashion: after binding to a foreign molecule, the antibody-producing B-cells exhibit a high-frequency mutation rate in the genome region that codes for the antibody active site. Eventually, cells that produce antibodies with higher affinity for their cognate antigen are selected and clonally expanded. Here, we propose a new statistical approach based on maximum entropy modeling in which a scoring function related to the binding affinity of antibodies against a specific antigen is inferred from a sample of sequences of the immune repertoire of an individual. We use our inference strategy to infer a statistical model on a data set obtained by sequencing a fairly large portion of the immune repertoire of an HIV-1 infected patient. The Pearson correlation coefficient between our scoring function and the IC50 neutralization titer measured on 30 different antibodies of known sequence is as high as 0.77 (p-value 10-6, outperforming other sequence- and structure-based models.

  16. Staircase Models from Affine Toda Field Theory

    CERN Document Server

    Dorey, P; Dorey, Patrick; Ravanini, Francesco

    1993-01-01

    We propose a class of purely elastic scattering theories generalising the staircase model of Al. B. Zamolodchikov, based on the affine Toda field theories for simply-laced Lie algebras g=A,D,E at suitable complex values of their coupling constants. Considering their Thermodynamic Bethe Ansatz equations, we give analytic arguments in support of a conjectured renormalisation group flow visiting the neighbourhood of each W_g minimal model in turn.

  17. In search for an optimal methodology to calculate the valence electron affinities of temporary anions.

    Science.gov (United States)

    Puiatti, Marcelo; Vera, D Mariano A; Pierini, Adriana B

    2009-10-28

    Recently, we have proposed an approach for finding the valence anion ground state, based on the stabilization exerted by a polar solvent; the methodology used standard DFT methods and relatively inexpensive basis sets and yielded correct electron affinity (EA) values by gradually decreasing the dielectric constant of the medium. In order to address the overall performance of the new methodology, to find the best conditions for stabilizing the valence state and to evaluate its scope and limitations, we gathered a pool of 60 molecules, 25 of them bearing the conventional valence state as the ground anion and 35 for which the lowest anion state found holds the extra electron in a diffuse orbital around the molecule (non valence state). The results obtained by testing this representative set suggest a very good performance for most species having an experimental EA less negative than -3.0 eV; the correlation at the B3LYP/6-311+G(2df,p) level being y = 1.01x + 0.06, with a correlation index of 0.985. As an alternative, the time dependent DFT (TD-DFT) approach was also tested with both B3LYP and PBE0 functionals. The methodology we proposed shows a comparable or better accuracy with respect to TD-DFT, although the TD-DFT approach with the PBE0 functional is suggested as a suitable estimate for species with the most negative EAs (ca.-2.5 to -3.5 eV), for which stabilization strategies can hardly reach the valence state. As an application, a pool of 8 compounds of key biological interest with EAs which remain unknown or unclear were predicted using the new methodology.

  18. Rank Two Affine Manifolds in Genus 3

    OpenAIRE

    Aulicino, David; Nguyen, Duc-Manh

    2016-01-01

    We complete the classification of rank two affine manifolds in the moduli space of translation surfaces in genus three. Combined with a recent result of Mirzakhani and Wright, this completes the classification of higher rank affine manifolds in genus three.

  19. Food and value motivation: Linking consumer affinities to different types of food products.

    Science.gov (United States)

    de Boer, Joop; Schösler, Hanna

    2016-08-01

    This study uses the consumer affinity concept to examine the multiple motives that may shape consumers' relationships with food. The concept was applied in a study on four broad product types in the Netherlands, which cover a wide range of the market and may each appeal to consumers with different affinities towards foods. These product types may be denoted as 'conventional', 'efficient', 'gourmet' and 'pure'. A comparative analysis, based on Higgins' Regulatory Focus Theory, was performed to examine whether food-related value motivations could explain different consumer affinities for these product types. The affinities of consumers were measured by means of a non-verbal, visual presentation of four samples of food products in a nationwide survey (n = 742) among consumers who were all involved in food purchasing and/or cooking. The affinities found could be predicted fairly well from a number of self-descriptions relating to food and eating, which expressed different combinations of type of value motivation and involvement with food. The analysis demonstrated the contrasting role of high and low involvement as well as the potential complementarity of promotion- and prevention-focused value motivation. It is suggested that knowledge of the relationships between product types, consumer affinities and value motivation can help improve the effectiveness of interventions that seek to promote healthy and sustainable diets in developed countries. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. A novel lentiviral scFv display library for rapid optimization and selection of high affinity antibodies.

    Science.gov (United States)

    Qudsia, Sehar; Merugu, Siva B; Mangukiya, Hitesh B; Hema, Negi; Wu, Zhenghua; Li, Dawei

    2018-04-30

    Antibody display libraries have become a popular technique to screen monoclonal antibodies for therapeutic purposes. An important aspect of display technology is to generate an optimization library by changing antibody affinity to antigen through mutagenesis and screening the high affinity antibody. In this study, we report a novel lentivirus display based optimization library antibody in which Agtuzumab scFv is displayed on cell membrane of HEK-293T cells. To generate an optimization library, hotspot mutagenesis was performed to achieve diverse antibody library. Based on sequence analysis of randomly selected clones, library size was estimated approximately to be 1.6 × 10 6 . Lentivirus display vector was used to display scFv antibody on cell surface and flow cytometery was performed to check the antibody affinity to antigen. Membrane bound scFv antibodies were then converted to secreted antibody through cre/loxP recombination. One of the mutant clones, M8 showed higher affinity to antigen in flow cytometery analysis. Further characterization of cellular and secreted scFv through western blot showed that antibody affinity was increased by three fold after mutagenesis. This study shows successful construction of a novel antibody library and suggests that hotspot mutagenesis could prove a useful and rapid optimization tool to generate similar libraries with various degree of antigen affinity. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Membrane Affinity of Platensimycin and Its Dialkylamine Analogs

    Directory of Open Access Journals (Sweden)

    Ian Rowe

    2015-08-01

    Full Text Available Membrane permeability is a desired property in drug design, but there have been difficulties in quantifying the direct drug partitioning into native membranes. Platensimycin (PL is a new promising antibiotic whose biosynthetic production is costly. Six dialkylamine analogs of PL were synthesized with identical pharmacophores but different side chains; five of them were found inactive. To address the possibility that their activity is limited by the permeation step, we calculated polarity, measured surface activity and the ability to insert into the phospholipid monolayers. The partitioning of PL and the analogs into the cytoplasmic membrane of E. coli was assessed by activation curve shifts of a re-engineered mechanosensitive channel, MscS, in patch-clamp experiments. Despite predicted differences in polarity, the affinities to lipid monolayers and native membranes were comparable for most of the analogs. For PL and the di-myrtenyl analog QD-11, both carrying bulky sidechains, the affinity for the native membrane was lower than for monolayers (half-membranes, signifying that intercalation must overcome the lateral pressure of the bilayer. We conclude that the biological activity among the studied PL analogs is unlikely to be limited by their membrane permeability. We also discuss the capacity of endogenous tension-activated channels to detect asymmetric partitioning of exogenous substances into the native bacterial membrane and the different contributions to the thermodynamic force which drives permeation.

  2. Affinity-based biosensors in sport medicine and doping control analysis.

    Science.gov (United States)

    Mazzei, Franco; Antiochia, Riccarda; Botrè, Francesco; Favero, Gabriele; Tortolini, Cristina

    2014-01-01

    Affinity-based biosensors (ABBs) have started to be considered in sport medicine and doping control analysis because they are cheap, easy to use and sufficiently selective analytical devices, characterized by a reversible interaction with the analyte under investigation allowing the use of the same sensor for multiple analyses. In this review we describe the main categories of substances reported in the World Anti-Doping Agency Prohibited List and how ABBs may contribute to their detection. Although several ABBs proposed in the last few years display limit of detections that are in principle matching the World Anti-Doping Agency requirements, their application in the framework of 'traditional' antidoping tests seems quite unlikely, mainly because of the still insufficient selectivity especially in the case of 'pseudo-endogenous' compounds, and on the lack of complete information regarding potential matrix effects in real samples and following their routine use. At the same time, ABBs could contribute to fill a significant information gap concerning complementary evidence that can be obtained from their use 'on the spot', as well as to preselect a risk population of individuals to be targeted for a full antidoping test; while in sport medicine they could contribute to obtaining analytical information of physiological relevance from the measurement of specific parameters or markers before, during and after physical exercise.

  3. Dynamics of Open Systems with Affine Maps

    International Nuclear Information System (INIS)

    Zhang Da-Jian; Liu Chong-Long; Tong Dian-Min

    2015-01-01

    Many quantum systems of interest are initially correlated with their environments and the reduced dynamics of open systems are an interesting while challenging topic. Affine maps, as an extension of completely positive maps, are a useful tool to describe the reduced dynamics of open systems with initial correlations. However, it is unclear what kind of initial state shares an affine map. In this study, we give a sufficient condition of initial states, in which the reduced dynamics can always be described by an affine map. Our result shows that if the initial states of the combined system constitute a convex set, and if the correspondence between the initial states of the open system and those of the combined system, defined by taking the partial trace, is a bijection, then the reduced dynamics of the open system can be described by an affine map. (paper)

  4. USING MICROSCALE THERMOPHORESIS TO EASILY MEASURE BINDING AFFINITY

    Directory of Open Access Journals (Sweden)

    Dennis Breitsprecher*

    2018-03-01

    Full Text Available While it’s very common for biologists and chemists to test whether or not two molecules interact with each other, it’s much more useful to gather information on the nature of that interaction. How strong is it? How long will it last? What does that mean for its biological function? One way to answer these questions is to study affinity. Binding affinity is defined as the strength of the binding interaction between a single biomolecule to its binding partner, or ligand, and it can be quantifiably measured, providing information on whether or not molecules are interacting, as well as assigning a value to the affinity. When measuring binding affinity, there are several parameters to look at, but the dissociation constant (Kd, which defines the likelihood that an interaction between two molecules will break, is a very common measurement. The smaller the dissociation constant, the more tightly bound the ligand is, and the higher the affinity is between the two molecules.

  5. Affinity capillary electrophoresis and quantum mechanical calculations applied to investigation of [Gly(6)]-antamanide binding with sodium and potassium ions

    Czech Academy of Sciences Publication Activity Database

    Pangavhane, Sachin; Böhm, S.; Makrlík, E.; Ruzza, P.; Kašička, Václav

    2017-01-01

    Roč. 38, č. 12 (2017), s. 1551-1559 ISSN 0173-0835 R&D Projects: GA ČR(CZ) GA15-01948S Institutional support: RVO:61388963 Keywords : affinity capillary electrophoresis * density functional theory * [Gly(6)]-antamanide * peptide complex * stability constant Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 2.744, year: 2016

  6. Single-Step Affinity Purification for Fungal Proteomics ▿ †

    OpenAIRE

    Liu, Hui-Lin; Osmani, Aysha H.; Ukil, Leena; Son, Sunghun; Markossian, Sarine; Shen, Kuo-Fang; Govindaraghavan, Meera; Varadaraj, Archana; Hashmi, Shahr B.; De Souza, Colin P.; Osmani, Stephen A.

    2010-01-01

    A single-step protein affinity purification protocol using Aspergillus nidulans is described. Detailed protocols for cell breakage, affinity purification, and depending on the application, methods for protein release from affinity beads are provided. Examples defining the utility of the approaches, which should be widely applicable, are included.

  7. An analytical fuzzy-based approach to ?-gain optimal control of input-affine nonlinear systems using Newton-type algorithm

    Science.gov (United States)

    Milic, Vladimir; Kasac, Josip; Novakovic, Branko

    2015-10-01

    This paper is concerned with ?-gain optimisation of input-affine nonlinear systems controlled by analytic fuzzy logic system. Unlike the conventional fuzzy-based strategies, the non-conventional analytic fuzzy control method does not require an explicit fuzzy rule base. As the first contribution of this paper, we prove, by using the Stone-Weierstrass theorem, that the proposed fuzzy system without rule base is universal approximator. The second contribution of this paper is an algorithm for solving a finite-horizon minimax problem for ?-gain optimisation. The proposed algorithm consists of recursive chain rule for first- and second-order derivatives, Newton's method, multi-step Adams method and automatic differentiation. Finally, the results of this paper are evaluated on a second-order nonlinear system.

  8. The Structure of Affine Buildings

    CERN Document Server

    Weiss, Richard M

    2009-01-01

    In The Structure of Affine Buildings, Richard Weiss gives a detailed presentation of the complete proof of the classification of Bruhat-Tits buildings first completed by Jacques Tits in 1986. The book includes numerous results about automorphisms, completions, and residues of these buildings. It also includes tables correlating the results in the locally finite case with the results of Tits's classification of absolutely simple algebraic groups defined over a local field. A companion to Weiss's The Structure of Spherical Buildings, The Structure of Affine Buildings is organized around the clas

  9. A high affinity monoclonal antibody recognizing the light chain of human coagulating factor VII.

    Science.gov (United States)

    Sarial, Sheila; Asadi, Farzad; Jeddi-Tehrani, Mahmood; Hadavi, Reza; Bayat, Ali Ahmad; Mahmoudian, Jafar; Taghizadeh-Jahed, Masoud; Shokri, Fazel; Rabbani, Hodjattallah

    2012-12-01

    Factor VII (FVII) is a serine protease-coagulating element responsible for the initiation of an extrinsic pathway of clot formation. Here we generated and characterized a high affinity monoclonal antibody that specifically recognizes human FVII. Recombinant human FVII (rh-FVII) was used for the production of a monoclonal antibody using BALB/c mice. The specificity of the antibody was determined by Western blot using plasma samples from human, mouse, sheep, goat, bovine, rabbit, and rat. Furthermore, the antibody was used to detect transiently expressed rh-FVII in BHK21 cell line using Western blot and sandwich ELISA. A mouse IgG1 (kappa chain) monoclonal antibody clone 1F1-B11 was produced against rh-FVII. The affinity constant (K(aff)) of the antibody was calculated to be 6.4×10(10) M(-1). The antibody could specifically recognize an epitope on the light chain of hFVII, with no reactivity with factor VII from several other animals. In addition, transiently expressed rh-FVII in BHK21 cells was recognized by 1F1-B11. The high affinity as well as the specificity of 1F1-B11 for hFVII will facilitate the affinity purification of hFVII and also production of FVII deficient plasma and minimizes the risk of bovine FVII contamination when fetal bovine serum-supplemented media are used for production and subsequent purification of rh-FVII.

  10. Characterization of the somatogenic receptor in rat liver. Hydrodynamic properties and affinity cross-linking

    International Nuclear Information System (INIS)

    Husman, B.; Haldosen, L.A.; Andersson, G.; Gustafsson, J.A.

    1988-01-01

    Rat liver somatogenic receptors have been characterized by gel permeation chromatography, sucrose density gradients in H 2 O and D 2 O, and affinity cross-linking using 125 I-bovine growth hormone (bGH) as a specific somatogenic receptor ligand. Cross-linking of 125 I-bovine growth hormone to a Triton X-100-treated low density fraction isolated from livers of late pregnant rats followed by sodium dodecylsulfate-polyacrylamide gel electrophoresis under reducing conditions showed three major binders with Mr 95,000, 86,000, and 43,000 and a minor binder of Mr 55,000, after correction for bound ligand assuming a 1:1 binding ratio of ligand-receptor. The Mr 86,000, 55,000, and 43,000 species were recovered in the detergent-soluble supernatant after high-speed centrifugation, whereas the Mr 95,000 species remained Triton X-100 insoluble. Detergent-soluble 125 I-bGH-receptor complexes were further analyzed by sedimentation into sucrose density gradients. The sedimentation coefficient was S20,w = 5.2 S and the partial specific volume v = 0.72 ml/g. Gel permeation chromatography on a Sepharose S-400 column indicated a Stokes radius of 61 A for the 125 I-bGH-receptor-Triton X-100 complex. Based on these figures, the molecular weight of the complex was calculated as 131,100. The molecular weight of the ligand-free receptor-Triton X-100 complex was calculated as Mr 109,100. Affinity cross-linking and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the 61 A peak from Sephacryl S-400 chromatography (cf. above) showed two binding entities, one major and one minor with Mr values 86,000 and 43,000, respectively, in the absence of reductant. When electrophoresis was run in the presence of reductant the Mr 43,000 species was the major binding entity

  11. G2(+)M study on N-alkylamino cation affinities of neutral main-group element hydrides: trends across the periodic table.

    Science.gov (United States)

    Geng, Song; Wu, Ding-Lu; Yang, Jing; Wei, Xi-Guang; Zhu, Jun; Zhang, Hai-Bo; Ren, Yi; Lau, Kai-Chung

    2014-05-08

    We have made an extensive theoretical exploration of gas-phase N-alkylamino cation affinities (NAAMCA), including amino cation affinities (AMCA) and N-dimethylamino cation affinities (NDMAMCA), of neutral main-group element hydrides of groups 15-17 and periods 2-4 in the periodic table by using the G2(+)M method. Some similarities and differences are found between NAAMCA and the corresponding alkyl cation affinities (ACA) of H(n)X. Our calculations show that the AMCA and NDMAMCA are systematically lower than the corresponding proton affinities (PA) for H(n)X. In general, there is no linear correlation between NAAMCA and PA of H(n)X. Instead, the correlations exist only within the central elements X in period 2, or periods 3-4, which is significantly different from the reasonable correlations between ACA and PA for all H(n)X. NAAMCA (H(n)X) are weaker than NAAMCA (H(n-1)X(-)) by more than 700 kJ/mol and generally stronger than ACA (H(n)X), with three exceptions: H2ONR2(+)(R = H, Me) and HFNH2(+). These new findings can be rationalized by the negative hyperconjugation and Pauli repulsion.

  12. Aspects of affine Toda field theory

    International Nuclear Information System (INIS)

    Braden, H.W.; Corrigan, E.; Dorey, P.E.; Sasaki, R.

    1990-05-01

    The report is devoted to properties of the affine Toda field theory, the intention being to highlight a selection of curious properties that should be explicable in terms of the underlying group theory but for which in most cases there are no explanation. The motivation for exploring the ideas contained in this report came principally from the recent work of Zamolodchikov concerning the two dimensional Ising model at critical temperature perturbed by a magnetic field. Hollowood and Mansfield pointed out that since Toda field theory is conformal the perturbation considered by Zamolodchikov might well be best regarded as a perturbation of a Toda field theory. This work made it seem plausible that the theory sought by Zamolodchikov was actually affine E 8 Toda field theory. However, this connection required an imaginary value of the coupling constant. Investigations here concerning exact S-matrices use a perturbative approach based on real coupling and the results differ in various ways from those thought to correspond to perturbed conformal field theory. A further motivation is to explore the connection between conformal and perturbed conformal field theories in other contexts using similar ideas. (N.K.)

  13. The dynamics of metric-affine gravity

    International Nuclear Information System (INIS)

    Vitagliano, Vincenzo; Sotiriou, Thomas P.; Liberati, Stefano

    2011-01-01

    Highlights: → The role and the dynamics of the connection in metric-affine theories is explored. → The most general second order action does not lead to a dynamical connection. → Including higher order invariants excites new degrees of freedom in the connection. → f(R) actions are also discussed and shown to be a non- representative class. - Abstract: Metric-affine theories of gravity provide an interesting alternative to general relativity: in such an approach, the metric and the affine (not necessarily symmetric) connection are independent quantities. Furthermore, the action should include covariant derivatives of the matter fields, with the covariant derivative naturally defined using the independent connection. As a result, in metric-affine theories a direct coupling involving matter and connection is also present. The role and the dynamics of the connection in such theories is explored. We employ power counting in order to construct the action and search for the minimal requirements it should satisfy for the connection to be dynamical. We find that for the most general action containing lower order invariants of the curvature and the torsion the independent connection does not carry any dynamics. It actually reduces to the role of an auxiliary field and can be completely eliminated algebraically in favour of the metric and the matter field, introducing extra interactions with respect to general relativity. However, we also show that including higher order terms in the action radically changes this picture and excites new degrees of freedom in the connection, making it (or parts of it) dynamical. Constructing actions that constitute exceptions to this rule requires significant fine tuned and/or extra a priori constraints on the connection. We also consider f(R) actions as a particular example in order to show that they constitute a distinct class of metric-affine theories with special properties, and as such they cannot be used as representative toy

  14. Multiprocessor Real-Time Scheduling with Hierarchical Processor Affinities

    OpenAIRE

    Bonifaci , Vincenzo; Brandenburg , Björn; D'Angelo , Gianlorenzo; Marchetti-Spaccamela , Alberto

    2016-01-01

    International audience; Many multiprocessor real-time operating systems offer the possibility to restrict the migrations of any task to a specified subset of processors by setting affinity masks. A notion of " strong arbitrary processor affinity scheduling " (strong APA scheduling) has been proposed; this notion avoids schedulability losses due to overly simple implementations of processor affinities. Due to potential overheads, strong APA has not been implemented so far in a real-time operat...

  15. Rational design of peptide affinity ligands for the purification of therapeutic enzymes.

    Science.gov (United States)

    Trasatti, John P; Woo, James; Ladiwala, Asif; Cramer, Steven; Karande, Pankaj

    2018-04-25

    Non-mAb biologics represent a growing class of therapeutics under clinical development. Although affinity chromatography is a potentially attractive approach for purification, the development of platform technologies, such as Protein A for mAbs, has been challenging due to the inherent chemical and structural diversity of these molecules. Here, we present our studies on the rapid development of peptide affinity ligands for the purification of biologics using a prototypical enzyme therapeutic in clinical use. Employing a suite of de novo rational and combinatorial design strategies we designed and screened a library of peptides on microarray platforms for their ability to bind to the target with high affinity and selectivity in cell culture fluid. Lead peptides were evaluated on resin in batch conditions and compared with a commercially available resin to evaluate their efficacy. Two lead candidates identified from microarray studies provided high binding capacity to the target while demonstrating high selectivity against culture contaminants and product variants compared to a commercial resin system. These findings provide a proof-of-concept for developing affinity peptide-based bioseparations processes for a target biologic. Peptide affinity ligand design and screening approaches presented in this work can also be easily translated to other biologics of interest. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018. © 2018 American Institute of Chemical Engineers.

  16. Comparative analysis the binding affinity of mycophenolic sodium and meprednisone with human serum albumin: Insight by NMR relaxation data and docking simulation.

    Science.gov (United States)

    Ma, Xiaoli; He, Jiawei; Yan, Jin; Wang, Qing; Li, Hui

    2016-03-25

    Mycophenolic sodium is an immunosuppressive agent that is always combined administration with corticosteroid in clinical practice. Considering the distribution and side-effect of the drug may change when co-administrated drug exist, this paper comparatively analyzed the binding ability of mycophenolic sodium and meprednisone toward human serum albumin by nuclear magnetic resonance relaxation data and docking simulation. The nuclear magnetic resonance approach was based on the analysis of proton selective and non-selective relaxation rate enhancement of the ligand in the absence and presence of macromolecules. The contribution of the bound ligand fraction to the observed relaxation rate in relation to protein concentration allowed the calculation of the affinity index. This approach allowed the comparison of the binding affinity of mycophenolic sodium and meprednisone. Molecular modeling was operated to simulate the binding model of ligand and albumin through Autodock 4.2.5. Competitive binding of mycophenolic sodium and meprednisone was further conducted through fluorescence spectroscopy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Content-Based High-Resolution Remote Sensing Image Retrieval via Unsupervised Feature Learning and Collaborative Affinity Metric Fusion

    Directory of Open Access Journals (Sweden)

    Yansheng Li

    2016-08-01

    Full Text Available With the urgent demand for automatic management of large numbers of high-resolution remote sensing images, content-based high-resolution remote sensing image retrieval (CB-HRRS-IR has attracted much research interest. Accordingly, this paper proposes a novel high-resolution remote sensing image retrieval approach via multiple feature representation and collaborative affinity metric fusion (IRMFRCAMF. In IRMFRCAMF, we design four unsupervised convolutional neural networks with different layers to generate four types of unsupervised features from the fine level to the coarse level. In addition to these four types of unsupervised features, we also implement four traditional feature descriptors, including local binary pattern (LBP, gray level co-occurrence (GLCM, maximal response 8 (MR8, and scale-invariant feature transform (SIFT. In order to fully incorporate the complementary information among multiple features of one image and the mutual information across auxiliary images in the image dataset, this paper advocates collaborative affinity metric fusion to measure the similarity between images. The performance evaluation of high-resolution remote sensing image retrieval is implemented on two public datasets, the UC Merced (UCM dataset and the Wuhan University (WH dataset. Large numbers of experiments show that our proposed IRMFRCAMF can significantly outperform the state-of-the-art approaches.

  18. Modeling DNA affinity landscape through two-round support vector regression with weighted degree kernels

    KAUST Repository

    Wang, Xiaolei

    2014-12-12

    Background: A quantitative understanding of interactions between transcription factors (TFs) and their DNA binding sites is key to the rational design of gene regulatory networks. Recent advances in high-throughput technologies have enabled high-resolution measurements of protein-DNA binding affinity. Importantly, such experiments revealed the complex nature of TF-DNA interactions, whereby the effects of nucleotide changes on the binding affinity were observed to be context dependent. A systematic method to give high-quality estimates of such complex affinity landscapes is, thus, essential to the control of gene expression and the advance of synthetic biology. Results: Here, we propose a two-round prediction method that is based on support vector regression (SVR) with weighted degree (WD) kernels. In the first round, a WD kernel with shifts and mismatches is used with SVR to detect the importance of subsequences with different lengths at different positions. The subsequences identified as important in the first round are then fed into a second WD kernel to fit the experimentally measured affinities. To our knowledge, this is the first attempt to increase the accuracy of the affinity prediction by applying two rounds of string kernels and by identifying a small number of crucial k-mers. The proposed method was tested by predicting the binding affinity landscape of Gcn4p in Saccharomyces cerevisiae using datasets from HiTS-FLIP. Our method explicitly identified important subsequences and showed significant performance improvements when compared with other state-of-the-art methods. Based on the identified important subsequences, we discovered two surprisingly stable 10-mers and one sensitive 10-mer which were not reported before. Further test on four other TFs in S. cerevisiae demonstrated the generality of our method. Conclusion: We proposed in this paper a two-round method to quantitatively model the DNA binding affinity landscape. Since the ability to modify

  19. Antibody Affinity Maturation in Fishes—Our Current Understanding

    Directory of Open Access Journals (Sweden)

    Brad G. Magor

    2015-07-01

    Full Text Available It has long been believed that fish lack antibody affinity maturation, in part because they were thought to lack germinal centers. Recent research done on sharks and bony fishes indicates that these early vertebrates are able to affinity mature their antibodies. This article reviews the functionality of the fish homologue of the immunoglobulin (Ig mutator enzyme activation-induced cytidine deaminase (AID. We also consider the protein and molecular evidence for Ig somatic hypermutation and antibody affinity maturation. In the context of recent evidence for a putative proto-germinal center in fishes we propose some possible reasons that observed affinity maturation in fishes often seems lacking and propose future work that might shed further light on this process in fishes.

  20. Large scale free energy calculations for blind predictions of protein-ligand binding: the D3R Grand Challenge 2015.

    Science.gov (United States)

    Deng, Nanjie; Flynn, William F; Xia, Junchao; Vijayan, R S K; Zhang, Baofeng; He, Peng; Mentes, Ahmet; Gallicchio, Emilio; Levy, Ronald M

    2016-09-01

    We describe binding free energy calculations in the D3R Grand Challenge 2015 for blind prediction of the binding affinities of 180 ligands to Hsp90. The present D3R challenge was built around experimental datasets involving Heat shock protein (Hsp) 90, an ATP-dependent molecular chaperone which is an important anticancer drug target. The Hsp90 ATP binding site is known to be a challenging target for accurate calculations of ligand binding affinities because of the ligand-dependent conformational changes in the binding site, the presence of ordered waters and the broad chemical diversity of ligands that can bind at this site. Our primary focus here is to distinguish binders from nonbinders. Large scale absolute binding free energy calculations that cover over 3000 protein-ligand complexes were performed using the BEDAM method starting from docked structures generated by Glide docking. Although the ligand dataset in this study resembles an intermediate to late stage lead optimization project while the BEDAM method is mainly developed for early stage virtual screening of hit molecules, the BEDAM binding free energy scoring has resulted in a moderate enrichment of ligand screening against this challenging drug target. Results show that, using a statistical mechanics based free energy method like BEDAM starting from docked poses offers better enrichment than classical docking scoring functions and rescoring methods like Prime MM-GBSA for the Hsp90 data set in this blind challenge. Importantly, among the three methods tested here, only the mean value of the BEDAM binding free energy scores is able to separate the large group of binders from the small group of nonbinders with a gap of 2.4 kcal/mol. None of the three methods that we have tested provided accurate ranking of the affinities of the 147 active compounds. We discuss the possible sources of errors in the binding free energy calculations. The study suggests that BEDAM can be used strategically to discriminate

  1. Relative binding affinity prediction of farnesoid X receptor in the D3R Grand Challenge 2 using FEP+

    Science.gov (United States)

    Schindler, Christina; Rippmann, Friedrich; Kuhn, Daniel

    2018-01-01

    Physics-based free energy simulations have increasingly become an important tool for predicting binding affinity and the recent introduction of automated protocols has also paved the way towards a more widespread use in the pharmaceutical industry. The D3R 2016 Grand Challenge 2 provided an opportunity to blindly test the commercial free energy calculation protocol FEP+ and assess its performance relative to other affinity prediction methods. The present D3R free energy prediction challenge was built around two experimental data sets involving inhibitors of farnesoid X receptor (FXR) which is a promising anticancer drug target. The FXR binding site is predominantly hydrophobic with few conserved interaction motifs and strong induced fit effects making it a challenging target for molecular modeling and drug design. For both data sets, we achieved reasonable prediction accuracy (RMSD ≈ 1.4 kcal/mol, rank 3-4 according to RMSD out of 20 submissions) comparable to that of state-of-the-art methods in the field. Our D3R results boosted our confidence in the method and strengthen our desire to expand its applications in future in-house drug design projects.

  2. Relative binding affinity prediction of farnesoid X receptor in the D3R Grand Challenge 2 using FEP.

    Science.gov (United States)

    Schindler, Christina; Rippmann, Friedrich; Kuhn, Daniel

    2018-01-01

    Physics-based free energy simulations have increasingly become an important tool for predicting binding affinity and the recent introduction of automated protocols has also paved the way towards a more widespread use in the pharmaceutical industry. The D3R 2016 Grand Challenge 2 provided an opportunity to blindly test the commercial free energy calculation protocol FEP+ and assess its performance relative to other affinity prediction methods. The present D3R free energy prediction challenge was built around two experimental data sets involving inhibitors of farnesoid X receptor (FXR) which is a promising anticancer drug target. The FXR binding site is predominantly hydrophobic with few conserved interaction motifs and strong induced fit effects making it a challenging target for molecular modeling and drug design. For both data sets, we achieved reasonable prediction accuracy (RMSD ≈ 1.4 kcal/mol, rank 3-4 according to RMSD out of 20 submissions) comparable to that of state-of-the-art methods in the field. Our D3R results boosted our confidence in the method and strengthen our desire to expand its applications in future in-house drug design projects.

  3. Affinity between information retrieval system and search topic

    International Nuclear Information System (INIS)

    Ebinuma, Yukio

    1979-01-01

    Ten search profiles are tested on the INIS system at the Japan Atomic Energy Research Institute. The results are plotted on recall-precision chart ranging from 100% recall to 100% precision. The curves are not purely systems-dependent nor search-dependent, and are determined substantially by the ''affinity'' between the system and the search topic. The curves are named ''Affinity curves of search topics with information retrieval systems'', and hence retrieval affinity factors are derived. They are obtained not only for individual search topics but also for averages in the system. By such a quantitative examination, the difference of affinity among search topics in a given system, that of the same search topic among various systems, and that of systems to the same group of search topics can be compared reasonably. (author)

  4. Can we beat the biotin-avidin pair?: cucurbit[7]uril-based ultrahigh affinity host-guest complexes and their applications.

    Science.gov (United States)

    Shetty, Dinesh; Khedkar, Jayshree K; Park, Kyeng Min; Kim, Kimoon

    2015-12-07

    The design of synthetic, monovalent host-guest molecular recognition pairs is still challenging and of particular interest to inquire into the limits of the affinity that can be achieved with designed systems. In this regard, cucurbit[7]uril (CB[7]), an important member of the host family cucurbit[n]uril (CB[n], n = 5-8, 10, 14), has attracted much attention because of its ability to form ultra-stable complexes with multiple guests. The strong hydrophobic effect between the host cavity and guests, ion-dipole and dipole-dipole interactions of guests with CB portals helps in cooperative and multiple noncovalent interactions that are essential for realizing such strong complexations. These highly selective, strong yet dynamic interactions can be exploited in many applications including affinity chromatography, biomolecule immobilization, protein isolation, biological catalysis, and sensor technologies. In this review, we summarize the progress in the development of high affinity guests for CB[7], factors affecting the stability of complexes, theoretical insights, and the utility of these high affinity pairs in different challenging applications.

  5. Protein-protein interaction site prediction in Homo sapiens and E. coli using an interaction-affinity based membership function in fuzzy SVM.

    Science.gov (United States)

    Sriwastava, Brijesh Kumar; Basu, Subhadip; Maulik, Ujjwal

    2015-10-01

    Protein-protein interaction (PPI) site prediction aids to ascertain the interface residues that participate in interaction processes. Fuzzy support vector machine (F-SVM) is proposed as an effective method to solve this problem, and we have shown that the performance of the classical SVM can be enhanced with the help of an interaction-affinity based fuzzy membership function. The performances of both SVM and F-SVM on the PPI databases of the Homo sapiens and E. coli organisms are evaluated and estimated the statistical significance of the developed method over classical SVM and other fuzzy membership-based SVM methods available in the literature. Our membership function uses the residue-level interaction affinity scores for each pair of positive and negative sequence fragments. The average AUC scores in the 10-fold cross-validation experiments are measured as 79.94% and 80.48% for the Homo sapiens and E. coli organisms respectively. On the independent test datasets, AUC scores are obtained as 76.59% and 80.17% respectively for the two organisms. In almost all cases, the developed F-SVM method improves the performances obtained by the corresponding classical SVM and the other classifiers, available in the literature.

  6. Solitons, τ-functions and hamiltonian reduction for non-Abelian conformal affine Toda theories

    Science.gov (United States)

    Ferreira, L. A.; Miramontes, J. Luis; Guillén, Joaquín Sánchez

    1995-02-01

    We consider the Hamiltonian reduction of the "two-loop" Wess-Zumino-Novikov-Witten model (WZNW) based on an untwisted affine Kac-Moody algebra G. The resulting reduced models, called Generalized Non-Abelian Conformal Affine Toda (G-CAT), are conformally invariant and a wide class of them possesses soliton solutions; these models constitute non-Abelian generalizations of the conformal affine Toda models. Their general solution is constructed by the Leznov-Saveliev method. Moreover, the dressing transformations leading to the solutions in the orbit of the vacuum are considered in detail, as well as the τ-functions, which are defined for any integrable highest weight representation of G, irrespectively of its particular realization. When the conformal symmetry is spontaneously broken, the G-CAT model becomes a generalized affine Toda model, whose soliton solutions are constructed. Their masses are obtained exploring the spontaneous breakdown of the conformal symmetry, and their relation to the fundamental particle masses is discussed. We also introduce what we call the two-loop Virasoro algebra, describing extended symmetries of the two-loop WZNW models.

  7. Calculations of accelerator-based neutron sources characteristics

    International Nuclear Information System (INIS)

    Tertytchnyi, R.G.; Shorin, V.S.

    2000-01-01

    Accelerator-based quasi-monoenergetic neutron sources (T(p,n), D(d;n), T(d;n) and Li (p,n)-reactions) are widely used in experiments on measuring the interaction cross-sections of fast neutrons with nuclei. The present work represents the code for calculation of the yields and spectra of neutrons generated in (p, n)- and ( d; n)-reactions on some targets of light nuclei (D, T; 7 Li). The peculiarities of the stopping processes of charged particles (with incident energy up to 15 MeV) in multilayer and multicomponent targets are taken into account. The code version is made in terms of the 'SOURCE,' a subroutine for the well-known MCNP code. Some calculation results for the most popular accelerator- based neutron sources are given. (authors)

  8. A Kinetic Model Explains Why Shorter and Less Affine Enzyme-recruiting Oligonucleotides Can Be More Potent

    Directory of Open Access Journals (Sweden)

    Lykke Pedersen

    2014-01-01

    Full Text Available Antisense oligonucleotides complementary to RNA targets promise generality and ease of drug design. The first systemically administered antisense drug was recently approved for treatment and others are in clinical development. Chemical modifications that increase the hybridization affinity of oligonucleotides are reasoned to confer higher potency, i.e., modified oligonucleotides can be dosed at lower concentrations to achieve the same effect. Surprisingly, shorter and less affine oligonucleotides sometimes display increased potency. To explain this apparent contradiction, increased uptake or decreased propensity to form structures have been suggested as possible mechanisms. Here, we provide an alternative explanation that invokes only the kinetics behind oligonucleotide-mediated cleavage of RNA targets. A model based on the law of mass action predicts, and experiments support, the existence of an optimal binding affinity. Exaggerated affinity, and not length per se, is detrimental to potency. This finding clarifies how to optimally apply high-affinity modifications in the discovery of potent antisense oligonucleotide drugs.

  9. Statistical removal of background signals from high-throughput 1H NMR line-broadening ligand-affinity screens

    International Nuclear Information System (INIS)

    Worley, Bradley; Sisco, Nicholas J.; Powers, Robert

    2015-01-01

    NMR ligand-affinity screens are vital to drug discovery, are routinely used to screen fragment-based libraries, and used to verify chemical leads from high-throughput assays and virtual screens. NMR ligand-affinity screens are also a highly informative first step towards identifying functional epitopes of unknown proteins, as well as elucidating the biochemical functions of protein–ligand interaction at their binding interfaces. While simple one-dimensional 1 H NMR experiments are capable of indicating binding through a change in ligand line shape, they are plagued by broad, ill-defined background signals from protein 1 H resonances. We present an uncomplicated method for subtraction of protein background in high-throughput ligand-based affinity screens, and show that its performance is maximized when phase-scatter correction is applied prior to subtraction

  10. [Affinity of the elements in group VI of the periodic table to tumors and organs].

    Science.gov (United States)

    Ando, A; Hisada, K; Ando, I

    1976-10-01

    In order to investigate the tumor affinity radioisotopes, chromium (51Cr), molybdenum (99Mo), tungsten (181W), selenium (75Se) and tellurium (127mTe)--the elements of group VI in the periodic table--were examined, using the rats which were subcutaneously transplanted with Yoshida sarcoma. Seven preprarations, sodium chromate (Na251CrO4), chromium chloride (51CrCl3), normal ammonium molybdate ((NH4)299MoO7), sodium tungstate (Na2181WO4), sodium selenate (Na275SeO4), sodium selenite (Na275SeO3) and tellurous acid (H2127mTeO3) were injected intravenously to each group of tumor bearing rats. These rats were sacrificed at various periods after injection of each preparation: 3 hours, 24 hours and 48 hours in all preparations. The radioactivities of the tumor, blood, muscle, liver, kidney and spleen were measured by a well-type scintillation counter, and retention values (in every tissue including the tumor) were calculated in percent of administered dose per g-tissue weight. All of seven preparations did not have any affinity for malignant tumor. Na251CrO4 and H2127mTeO3 had some affinity for the kidneys, and Na275SeO3 had some affinity for the liver. Na2181WO4 and (NH4)299MoO4 disappeared very rapidly from the blood and soft tissue, and about seventy-five percent of radioactivity was excreted in urine within first 3 hours.

  11. Biotin-tagged proteins: Reagents for efficient ELISA-based serodiagnosis and phage display-based affinity selection.

    Science.gov (United States)

    Verma, Vaishali; Kaur, Charanpreet; Grover, Payal; Gupta, Amita; Chaudhary, Vijay K

    2018-01-01

    The high-affinity interaction between biotin and streptavidin has opened avenues for using recombinant proteins with site-specific biotinylation to achieve efficient and directional immobilization. The site-specific biotinylation of proteins carrying a 15 amino acid long Biotin Acceptor Peptide tag (BAP; also known as AviTag) is effected on a specific lysine either by co-expressing the E. coli BirA enzyme in vivo or by using purified recombinant E. coli BirA enzyme in the presence of ATP and biotin in vitro. In this paper, we have designed a T7 promoter-lac operator-based expression vector for rapid and efficient cloning, and high-level cytosolic expression of proteins carrying a C-terminal BAP tag in E. coli with TEV protease cleavable N-terminal deca-histidine tag, useful for initial purification. Furthermore, a robust three-step purification pipeline integrated with well-optimized protocols for TEV protease-based H10 tag removal, and recombinant BirA enzyme-based site-specific in vitro biotinylation is described to obtain highly pure biotinylated proteins. Most importantly, the paper demonstrates superior sensitivities in indirect ELISA with directional and efficient immobilization of biotin-tagged proteins on streptavidin-coated surfaces in comparison to passive immobilization. The use of biotin-tagged proteins through specific immobilization also allows more efficient selection of binders from a phage-displayed naïve antibody library. In addition, for both these applications, specific immobilization requires much less amount of protein as compared to passive immobilization and can be easily multiplexed. The simplified strategy described here for the production of highly pure biotin-tagged proteins will find use in numerous applications, including those, which may require immobilization of multiple proteins simultaneously on a solid surface.

  12. Stream cipher based on pseudorandom number generation using optical affine transformation

    Science.gov (United States)

    Sasaki, Toru; Togo, Hiroyuki; Tanida, Jun; Ichioka, Yoshiki

    2000-07-01

    We propose a new stream cipher technique for 2D image data which can be implemented by iterative optical transformation. The stream cipher uses a pseudo-random number generator (PRNG) to generate pseudo-random bit sequence. The proposed method for the PRNG is composed of iterative operation of 2D affine transformation achieved by optical components, and modulo-n addition of the transformed images. The method is expected to be executed efficiently by optical parallel processing. We verify performance of the proposed method in terms of security strength and clarify problems on optical implementation by the optical fractal synthesizer.

  13. [Ecological affinity and current distribution of primates (Cebidae) in Campeche, Mexico].

    Science.gov (United States)

    Navarro Fernández, Eloísa; Pozo de la Tijera, Carmen; Escobedo Cabrera, Enrique

    2003-06-01

    We carried out surveys realized field work from March to September 2000 to get the current distribution of Cebids in the state of Campeche, Mexico. Based on interviews and direct observations. We defined the distribution of Ateles geoffroyi yucatanensis and Alouatta pigra and we documented the first time localities where Allouata palliata is found in the state. We made distributional maps of each species using vegetation overlays from Inventario Nacional Forestal (Inv For) and each point documented during fieldwork. We presented the distribution of species according to confiability of the verified or expected data. Using the attributes table of Inv For, we calculated the areas of distribution which were 22,735 km2 for Alouatta sp. and 18,501 km2 for A. g. yucatanensis. We also presented the area occupied by each species according to vegetation types and the relative proportion of these vegetation types in the state. We confirmed the ability of Alouatta sp. to survive in disturbed environments produced by habitat fragmentation, and the affinity of A. g. yucatanesis to well preserved habitats.

  14. Fault detection for piecewise affine systems with application to ship propulsion systems.

    Science.gov (United States)

    Yang, Ying; Linlin, Li; Ding, Steven X; Qiu, Jianbin; Peng, Kaixiang

    2017-09-09

    In this paper, the design approach of non-synchronized diagnostic observer-based fault detection (FD) systems is investigated for piecewise affine processes via continuous piecewise Lyapunov functions. Considering that the dynamics of piecewise affine systems in different regions can be considerably different, the weighting matrices are used to weight the residual of each region, so as to optimize the fault detectability. A numerical example and a case study on a ship propulsion system are presented in the end to demonstrate the effectiveness of the proposed results. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

  15. Projections of climate-driven changes in tuna vertical habitat based on species-specific differences in blood oxygen affinity.

    Science.gov (United States)

    Mislan, K A S; Deutsch, Curtis A; Brill, Richard W; Dunne, John P; Sarmiento, Jorge L

    2017-10-01

    Oxygen concentrations are hypothesized to decrease in many areas of the ocean as a result of anthropogenically driven climate change, resulting in habitat compression for pelagic animals. The oxygen partial pressure, pO 2 , at which blood is 50% saturated (P 50 ) is a measure of blood oxygen affinity and a gauge of the tolerance of animals for low ambient oxygen. Tuna species display a wide range of blood oxygen affinities (i.e., P 50 values) and therefore may be differentially impacted by habitat compression as they make extensive vertical movements to forage on subdaily time scales. To project the effects of end-of-the-century climate change on tuna habitat, we calculate tuna P 50 depths (i.e., the vertical position in the water column at which ambient pO 2 is equal to species-specific blood P 50 values) from 21st century Earth System Model (ESM) projections included in the fifth phase of the Climate Model Intercomparison Project (CMIP5). Overall, we project P 50 depths to shoal, indicating likely habitat compression for tuna species due to climate change. Tunas that will be most impacted by shoaling are Pacific and southern bluefin tunas-habitat compression is projected for the entire geographic range of Pacific bluefin tuna and for the spawning region of southern bluefin tuna. Vertical shifts in P 50 depths will potentially influence resource partitioning among Pacific bluefin, bigeye, yellowfin, and skipjack tunas in the northern subtropical and eastern tropical Pacific Ocean, the Arabian Sea, and the Bay of Bengal. By establishing linkages between tuna physiology and environmental conditions, we provide a mechanistic basis to project the effects of anthropogenic climate change on tuna habitats. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  16. THE ACCOUNTING POSTEMPLOYMENT BENEFITS BASED ON ACTUARIAL CALCULATIONS

    Directory of Open Access Journals (Sweden)

    Anna CEBOTARI

    2017-11-01

    Full Text Available The accounting post-employment benefits, based on actuarial calculations, at present remains a subject studied in Moldova only theoretically. Applying actuarial calculations of accounting in fact denotes its character of evolving. Because national accounting standards have been adapted to international, which, in turn, require the valuation of assets and debts at fair value, there is a need to draw up exact calculations on which stands the theory of probability and mathematical statistics. One of the main objectives of accounting information is reflected in its financial situations and providing internal and external users of the entity. Hence, arises the need to reflect highly reliable information that can be provided by applying actuarial calculations.

  17. Specificity and affinity motifs for Grb2 SH2-ligand interactions

    NARCIS (Netherlands)

    Kessels, Helmut W. H. G.; Ward, Alister C.; Schumacher, Ton N. M.

    2002-01-01

    Protein-protein interactions are often mediated by the recognition of short continuous amino acid stretches on target proteins by specific binding domains. Affinity-based selection strategies have successfully been used to define recognition motifs for a large series of such protein domains.

  18. ASIFT: An Algorithm for Fully Affine Invariant Comparison

    Directory of Open Access Journals (Sweden)

    Guoshen Yu

    2011-02-01

    Full Text Available If a physical object has a smooth or piecewise smooth boundary, its images obtained by cameras in varying positions undergo smooth apparent deformations. These deformations are locally well approximated by affine transforms of the image plane. In consequence the solid object recognition problem has often been led back to the computation of affine invariant image local features. The similarity invariance (invariance to translation, rotation, and zoom is dealt with rigorously by the SIFT method The method illustrated and demonstrated in this work, Affine-SIFT (ASIFT, simulates a set of sample views of the initial images, obtainable by varying the two camera axis orientation parameters, namely the latitude and the longitude angles, which are not treated by the SIFT method. Then it applies the SIFT method itself to all images thus generated. Thus, ASIFT covers effectively all six parameters of the affine transform.

  19. Affinity selection-mass spectrometry and its emerging application to the high throughput screening of G protein-coupled receptors.

    Science.gov (United States)

    Whitehurst, Charles E; Annis, D Allen

    2008-07-01

    Advances in combinatorial chemistry and genomics have inspired the development of novel affinity selection-based screening techniques that rely on mass spectrometry to identify compounds that preferentially bind to a protein target. Of the many affinity selection-mass spectrometry techniques so far documented, only a few solution-based implementations that separate target-ligand complexes away from unbound ligands persist today as routine high throughput screening platforms. Because affinity selection-mass spectrometry techniques do not rely on radioactive or fluorescent reporters or enzyme activities, they can complement traditional biochemical and cell-based screening assays and enable scientists to screen targets that may not be easily amenable to other methods. In addition, by employing mass spectrometry for ligand detection, these techniques enable high throughput screening of massive library collections of pooled compound mixtures, vastly increasing the chemical space that a target can encounter during screening. Of all drug targets, G protein coupled receptors yield the highest percentage of therapeutically effective drugs. In this manuscript, we present the emerging application of affinity selection-mass spectrometry to the high throughput screening of G protein coupled receptors. We also review how affinity selection-mass spectrometry can be used as an analytical tool to guide receptor purification, and further used after screening to characterize target-ligand binding interactions, enabling the classification of orthosteric and allosteric binders.

  20. Femtomolar Ln(III) affinity in peptide-based ligands containing unnatural chelating amino acids.

    Science.gov (United States)

    Niedźwiecka, Agnieszka; Cisnetti, Federico; Lebrun, Colette; Delangle, Pascale

    2012-05-07

    The incorporation of unnatural chelating amino acids in short peptide sequences leads to lanthanide-binding peptides with a higher stability than sequences built exclusively from natural residues. In particular, the hexadentate peptide P(22), which incorporates two unnatural amino acids Ada(2) with aminodiacetate chelating arms, showed picomolar affinity for Tb(3+). To design peptides with higher denticity, expected to show higher affinity for Ln(3+), we synthesized the novel unnatural amino acid Ed3a(2) which carries an ethylenediamine triacetate side-chain and affords a pentadentate coordination site. The synthesis of the derivative Fmoc-Ed3a(2)(tBu)(3)-OH, with appropriate protecting groups for direct use in the solid phase peptide synthesis (Fmoc strategy), is described. The two high denticity peptides P(HD2) (Ac-Trp-Ed3a(2)-Pro-Gly-Ada(2)-Gly-NH(2)) and P(HD5) (Ac-Trp-Ada(2)-Pro-Gly-Ed3a(2)-Gly-NH(2)) led to octadentate Tb(3+) complexes with femtomolar stability in water. The position of the high denticity amino acid Ed3a(2) in the hexapeptide sequence appears to be critical for the control of the metal complex speciation. Whereas P(HD5) promotes the formation of polymetallic species in excess of Ln(3+), P(HD2) forms exclusively the mononuclear complex. The octadentate coordination of Tb(3+) by both P(HD) leads to total dehydration of the metal ion in the mononuclear complexes with long luminescence lifetimes (>2 ms). Hence, we demonstrated that unnatural amino acids carrying polyaminocarboxylate side-chains are interesting building blocks to design high affinity Ln-binding peptides. In particular the novel peptide P(HD2) forms a unique octadentate Tb(3+) complex with femtomolar stability in water and an improvement of the luminescence properties with respect to the trisaquo TbP(22) complex by a factor of 4.

  1. Applications of Affine and Weyl geometry

    CERN Document Server

    García-Río, Eduardo; Nikcevic, Stana

    2013-01-01

    Pseudo-Riemannian geometry is, to a large extent, the study of the Levi-Civita connection, which is the unique torsion-free connection compatible with the metric structure. There are, however, other affine connections which arise in different contexts, such as conformal geometry, contact structures, Weyl structures, and almost Hermitian geometry. In this book, we reverse this point of view and instead associate an auxiliary pseudo-Riemannian structure of neutral signature to certain affine connections and use this correspondence to study both geometries. We examine Walker structures, Riemannia

  2. Novel variable structure control for the temperature of PEM fuel cell stack based on the dynamic thermal affine model

    International Nuclear Information System (INIS)

    Li Xi; Deng Zhonghua; Wei Dong; Xu Chunshan; Cao Guangyi

    2011-01-01

    Highlights: → The affine state space control-oriented model is designed and realized for the variant structure control (VSC) strategy. → The VSC with rapid-smooth reaching law and rapid-convergent sliding mode is presented for the PEMFC stack temperature. → Numerical results show that the method can control the operating temperature to reach the target value satisfactorily. - Abstract: Dynamic thermal management of proton exchange membrane fuel cell stack (PEMFC) is a very important aspect, which plays an important role on electro-reaction. Its variation also has a significant influence on the performance and lifespan of PEMFC stack. The temperature of stack should be controlled efficiently, which has great impacts on the performance of PEMFC due to the thermal variation. Based on the control-oriented dynamic thermal affine model identified by optimization algorithm, a novel variable structures control (VSC) with rapid-smooth reaching law (RSRL) and rapid-convergent sliding mode (FCSM) is presented for the temperature control system of PEMFC stack. Numerical test results show that the method can control the operating temperature to reach the target value satisfactorily, which proves the effectiveness and robustness of the algorithm.

  3. Theoretical determination of proton affinity differences in zeolites

    NARCIS (Netherlands)

    Kramer, G.J.; Santen, van R.A.

    1993-01-01

    An important factor in zeolite catalysis is the proton affinity, i.e., the energy required to remove a proton from the zeolite lattice. Differences in proton affinity are expected to influence the catalytic activity of acid sites, making the catalytically active sites inhomogeneous (within one

  4. Pseudo-affinity chromatography of rumen microbial cellulase on ...

    African Journals Online (AJOL)

    Pseudo-affinity chromatography of rumen microbial cellulase on Sepharose- Cibacron Blue F3GA. ... African Journal of Biotechnology ... Pseudo affinity adsorption of bioproducts on Sepharose-cibacron blue F3-GA was subjected to rumen microbial enzyme evaluation through batch binding and column chromatography of ...

  5. Volatility Components, Affine Restrictions and Non-Normal Innovations

    DEFF Research Database (Denmark)

    Christoffersen, Peter; Jacobs, Kris; Dorian, Christian

    Recent work by Engle and Lee (1999) shows that allowing for long-run and short-run components greatly enhances a GARCH model's ability fit daily equity return dynamics. Using the risk-neutralization in Duan (1995), we assess the option valuation performance of the Engle-Lee model and compare...... models to four conditionally non-normal versions. As in Hsieh and Ritchken (2005), we find that non-affine models dominate affine models both in terms of fitting return and in terms of option valuation. For the affine models we find strong evidence in favor of the component structure for both returns...

  6. Realization of Robertson-Walker spacetimes as affine hypersurfaces

    International Nuclear Information System (INIS)

    Chen Bangyen

    2007-01-01

    Due to the growing interest in embeddings of spacetimes in higher dimensional spaces, we consider a special type of embedding. We prove that Robertson-Walker spacetimes can be embedded as centroaffine hypersurfaces and graph hypersurfaces in some affine spaces in such a way that the induced relative metrics are exactly the Lorentzian metrics on the Robertson-Walker spacetimes. Such realizations allow us to view Robertson-Walker spacetimes and their submanifolds as affine submanifolds in a natural way. Consequently, our realizations make it possible to apply the tools of affine differential geometry to study Robertson-Walker spacetimes and their submanifolds

  7. Affinity Purification and Comparative Biosensor Analysis of Citrulline-Peptide-Specific Antibodies in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Eszter Szarka

    2018-01-01

    Full Text Available Background: In rheumatoid arthritis (RA, anti-citrullinated protein/peptide antibodies (ACPAs are responsible for disease onset and progression, however, our knowledge is limited on ligand binding affinities of autoantibodies with different citrulline-peptide specificity. Methods: Citrulline-peptide-specific ACPA IgGs were affinity purified and tested by ELISA. Binding affinities of ACPA IgGs and serum antibodies were compared by surface plasmon resonance (SPR analysis. Bifunctional nanoparticles harboring a multi-epitope citrulline-peptide and a complement-activating peptide were used to induce selective depletion of ACPA-producing B cells. Results: KD values of affinity-purified ACPA IgGs varied between 10−6 and 10−8 M and inversely correlated with disease activity. Based on their cross-reaction with citrulline-peptides, we designed a novel multi-epitope peptide, containing Cit-Gly and Ala-Cit motifs in two–two copies, separated with a short, neutral spacer. This peptide detected antibodies in RA sera with 66% sensitivity and 98% specificity in ELISA and was recognized by 90% of RA sera, while none of the healthy samples in SPR. When coupled to nanoparticles, the multi-epitope peptide specifically targeted and depleted ACPA-producing B cells ex vivo. Conclusions: The unique multi-epitope peptide designed based on ACPA cross-reactivity might be suitable to develop better diagnostics and novel therapies for RA.

  8. Calculations with the quasirelativistic local-spin-density-functional theory for high-Z atoms

    International Nuclear Information System (INIS)

    Guo, Y.; Whitehead, M.A.

    1988-01-01

    The generalized-exchange local-spin-density-functional theory (LSD-GX) with relativistic corrections of the mass velocity and Darwin terms has been used to calculate statistical total energies for the neutral atoms, the positive ions, and the negative ions for high-Z elements. The effect of the correlation and relaxation correction on the statistical total energy is discussed. Comparing the calculated results for the ionization potentials and electron affinities for the atoms (atomic number Z from 37 to 56 and 72 to 80) with experiment, shows that for the atoms rubidium to barium both the LSD-GX and the quasirelativistic LSD-GX, with self-interaction correction, Gopinathan, Whitehead, and Bogdanovic's Fermi-hole parameters [Phys. Rev. A 14, 1 (1976)], and Vosko, Wilk, and Nusair's correlation correction [Can. J. Phys. 58, 1200 (1980)], are very good methods for calculating ionization potentials and electron affinities. For the atoms hafnium to mercury the relativistic effect has to be considered

  9. PLASS: Protein-ligand affinity statistical score a knowledge-based force-field model of interaction derived from the PDB

    Science.gov (United States)

    Ozrin, V. D.; Subbotin, M. V.; Nikitin, S. M.

    2004-04-01

    We have developed PLASS (Protein-Ligand Affinity Statistical Score), a pair-wise potential of mean-force for rapid estimation of the binding affinity of a ligand molecule to a protein active site. This scoring function is derived from the frequency of occurrence of atom-type pairs in crystallographic complexes taken from the Protein Data Bank (PDB). Statistical distributions are converted into distance-dependent contributions to the Gibbs free interaction energy for 10 atomic types using the Boltzmann hypothesis, with only one adjustable parameter. For a representative set of 72 protein-ligand structures, PLASS scores correlate well with the experimentally measured dissociation constants: a correlation coefficient R of 0.82 and RMS error of 2.0 kcal/mol. Such high accuracy results from our novel treatment of the volume correction term, which takes into account the inhomogeneous properties of the protein-ligand complexes. PLASS is able to rank reliably the affinity of complexes which have as much diversity as in the PDB.

  10. Accurate determination of the oxidative phosphorylation affinity for ADP in isolated mitochondria.

    Directory of Open Access Journals (Sweden)

    Gilles Gouspillou

    Full Text Available BACKGROUND: Mitochondrial dysfunctions appear strongly implicated in a wide range of pathologies. Therefore, there is a growing need in the determination of the normal and pathological integrated response of oxidative phosphorylation to cellular ATP demand. The present study intends to address this issue by providing a method to investigate mitochondrial oxidative phosphorylation affinity for ADP in isolated mitochondria. METHODOLOGY/PRINCIPAL FINDINGS: The proposed method is based on the simultaneous monitoring of substrate oxidation (determined polarographically and phosphorylation (determined using the glucose-hexokinase glucose-6-phosphate dehydrogenase-NADP(+ enzymatic system rates, coupled to the determination of actual ADP and ATP concentrations by bioluminescent assay. This enzymatic system allows the study of oxidative phosphorylation during true steady states in a wide range of ADP concentrations. We demonstrate how the application of this method allows an accurate determination of mitochondrial affinity for ADP from both oxidation (K(mVox and phosphorylation (K(mVp rates. We also demonstrate that determination of K(mVox leads to an important overestimation of the mitochondrial affinity for ADP, indicating that mitochondrial affinity for ADP should be determined using phosphorylation rate. Finally, we show how this method allows the direct and precise determination of the mitochondrial coupling efficiency. Data obtained from rat skeletal muscle and liver mitochondria illustrate the discriminating capabilities of this method. CONCLUSIONS/SIGNIFICANCE: Because the proposed method allows the accurate determination of mitochondrial oxidative phosphorylation affinity for ADP in isolated mitochondria, it also opens the route to a better understanding of functional consequences of mitochondrial adaptations/dysfunctions arising in various physiological/pathophysiological conditions.

  11. Generalized Warburg impedance on realistic self-affine fractals ...

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... We analyse the problem of impedance for a diffusion controlled charge transfer process across an irregular interface. These interfacial irregularities are characterized as two class of random fractals: (i) a statistically isotropic self-affine fractals and (ii) a statistically corrugated self-affine fractals.

  12. Weak affinity chromatography for evaluation of stereoisomers in early drug discovery.

    Science.gov (United States)

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

    2013-07-01

    In early drug discovery (e.g., in fragment screening), recognition of stereoisomeric structures is valuable and guides medicinal chemists to focus only on useful configurations. In this work, we concurrently screened mixtures of stereoisomers and estimated their affinities to a protein target (thrombin) using weak affinity chromatography-mass spectrometry (WAC-MS). Affinity determinations by WAC showed that minor changes in stereoisomeric configuration could have a major impact on affinity. The ability of WAC-MS to provide instant information about stereoselectivity and binding affinities directly from analyte mixtures is a great advantage in fragment library screening and drug lead development.

  13. Affinity purification combined with mass spectrometry to identify herpes simplex virus protein-protein interactions.

    Science.gov (United States)

    Meckes, David G

    2014-01-01

    The identification and characterization of herpes simplex virus protein interaction complexes are fundamental to understanding the molecular mechanisms governing the replication and pathogenesis of the virus. Recent advances in affinity-based methods, mass spectrometry configurations, and bioinformatics tools have greatly increased the quantity and quality of protein-protein interaction datasets. In this chapter, detailed and reliable methods that can easily be implemented are presented for the identification of protein-protein interactions using cryogenic cell lysis, affinity purification, trypsin digestion, and mass spectrometry.

  14. Alkali Metal Cation Affinities of Anionic Main Group-Element Hydrides Across the Periodic Table.

    Science.gov (United States)

    Boughlala, Zakaria; Fonseca Guerra, Célia; Bickelhaupt, F Matthias

    2017-10-05

    We have carried out an extensive exploration of gas-phase alkali metal cation affinities (AMCA) of archetypal anionic bases across the periodic system using relativistic density functional theory at ZORA-BP86/QZ4P//ZORA-BP86/TZ2P. AMCA values of all bases were computed for the lithium, sodium, potassium, rubidium and cesium cations and compared with the corresponding proton affinities (PA). One purpose of this work is to provide an intrinsically consistent set of values of the 298 K AMCAs of all anionic (XH n-1 - ) constituted by main group-element hydrides of groups 14-17 along the periods 2-6. In particular, we wish to establish the trend in affinity for a cation as the latter varies from proton to, and along, the alkali cations. Our main purpose is to understand these trends in terms of the underlying bonding mechanism using Kohn-Sham molecular orbital theory together with a quantitative bond energy decomposition analyses (EDA). © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Coupled Cluster Studies of Ionization Potentials and Electron Affinities of Single-Walled Carbon Nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Bo; Govind, Niranjan; Apra, Edoardo; Klemm, Michael; Hammond, Jeff R.; Kowalski, Karol

    2017-02-03

    In this paper we apply equation-of-motion coupled cluster (EOMCC) methods in studies of vertical ionization potentials (IP) and electron affinities (EA) for sin- gled walled carbon nanotubes. EOMCC formulations for ionization potentials and electron affinities employing excitation manifolds spanned by single and double ex- citations (IP/EA-EOMCCSD) are used to study IPs and EAs of nanotubes as a function of nanotube length. Several armchair nanotubes corresponding to C20nH20 models with n = 2 - 6 have been used in benchmark calculations. In agreement with previous studies, we demonstrate that the electronegativity of C20nH20 systems remains, to a large extent, independent of nanotube length. We also compare IP/EA- EOMCCSD results with those obtained with the coupled cluster models with single and double excitations corrected by perturbative triples, CCSD(T), and density func- tional theory (DFT) using global and range-separated hybrid exchange-correlation functionals.

  16. Multicomponent Density Functional Theory: Impact of Nuclear Quantum Effects on Proton Affinities and Geometries.

    Science.gov (United States)

    Brorsen, Kurt R; Yang, Yang; Hammes-Schiffer, Sharon

    2017-08-03

    Nuclear quantum effects such as zero point energy play a critical role in computational chemistry and often are included as energetic corrections following geometry optimizations. The nuclear-electronic orbital (NEO) multicomponent density functional theory (DFT) method treats select nuclei, typically protons, quantum mechanically on the same level as the electrons. Electron-proton correlation is highly significant, and inadequate treatments lead to highly overlocalized nuclear densities. A recently developed electron-proton correlation functional, epc17, has been shown to provide accurate nuclear densities for molecular systems. Herein, the NEO-DFT/epc17 method is used to compute the proton affinities for a set of molecules and to examine the role of nuclear quantum effects on the equilibrium geometry of FHF - . The agreement of the computed results with experimental and benchmark values demonstrates the promise of this approach for including nuclear quantum effects in calculations of proton affinities, pK a 's, optimized geometries, and reaction paths.

  17. Generalized Warburg impedance on realistic self-affine fractals

    Indian Academy of Sciences (India)

    We analyse the problem of impedance for a diffusion controlled charge transfer process across an irregular interface. These interfacial irregularities are characterized as two class of random fractals: (i) a statistically isotropic self-affine fractals and (ii) a statistically corrugated self-affine fractals. The information about the ...

  18. Genetic affinities between endogamous and inbreeding populations of Uttar Pradesh.

    Science.gov (United States)

    Khan, Faisal; Pandey, Atul Kumar; Tripathi, Manorma; Talwar, Sudha; Bisen, Prakash S; Borkar, Minal; Agrawal, Suraksha

    2007-04-07

    India has experienced several waves of migration since the Middle Paleolithic. It is believed that the initial demic movement into India was from Africa along the southern coastal route, approximately 60,000-85,000 years before present (ybp). It has also been reported that there were two other major colonization which included eastward diffusion of Neolithic farmers (Elamo Dravidians) from Middle East sometime between 10,000 and 7,000 ybp and a southern dispersal of Indo Europeans from Central Asia 3,000 ybp. Mongol entry during the thirteenth century A.D. as well as some possible minor incursions from South China 50,000 to 60,000 ybp may have also contributed to cultural, linguistic and genetic diversity in India. Therefore, the genetic affinity and relationship of Indians with other world populations and also within India are often contested. In the present study, we have attempted to offer a fresh and immaculate interpretation on the genetic relationships of different North Indian populations with other Indian and world populations. We have first genotyped 20 tetra-nucleotide STR markers among 1800 north Indian samples of nine endogamous populations belonging to three different socio-cultural strata. Genetic distances (Nei's DA and Reynold's Fst) were calculated among the nine studied populations, Caucasians and East Asians. This analysis was based upon the allelic profile of 20 STR markers to assess the genetic similarity and differences of the north Indian populations. North Indians showed a stronger genetic relationship with the Europeans (DA 0.0341 and Fst 0.0119) as compared to the Asians (DA 0.1694 and Fst - 0.0718). The upper caste Brahmins and Muslims were closest to Caucasians while middle caste populations were closer to Asians. Finally, three phylogenetic assessments based on two different NJ and ML phylogenetic methods and PC plot analysis were carried out using the same panel of 20 STR markers and 20 geo-ethnic populations. The three phylogenetic

  19. Genetic affinities between endogamous and inbreeding populations of Uttar Pradesh

    Directory of Open Access Journals (Sweden)

    Borkar Minal

    2007-04-01

    Full Text Available Abstract Background India has experienced several waves of migration since the Middle Paleolithic. It is believed that the initial demic movement into India was from Africa along the southern coastal route, approximately 60,000–85,000 years before present (ybp. It has also been reported that there were two other major colonization which included eastward diffusion of Neolithic farmers (Elamo Dravidians from Middle East sometime between 10,000 and 7,000 ybp and a southern dispersal of Indo Europeans from Central Asia 3,000 ybp. Mongol entry during the thirteenth century A.D. as well as some possible minor incursions from South China 50,000 to 60,000 ybp may have also contributed to cultural, linguistic and genetic diversity in India. Therefore, the genetic affinity and relationship of Indians with other world populations and also within India are often contested. In the present study, we have attempted to offer a fresh and immaculate interpretation on the genetic relationships of different North Indian populations with other Indian and world populations. Results We have first genotyped 20 tetra-nucleotide STR markers among 1800 north Indian samples of nine endogamous populations belonging to three different socio-cultural strata. Genetic distances (Nei's DA and Reynold's Fst were calculated among the nine studied populations, Caucasians and East Asians. This analysis was based upon the allelic profile of 20 STR markers to assess the genetic similarity and differences of the north Indian populations. North Indians showed a stronger genetic relationship with the Europeans (DA 0.0341 and Fst 0.0119 as compared to the Asians (DA 0.1694 and Fst – 0.0718. The upper caste Brahmins and Muslims were closest to Caucasians while middle caste populations were closer to Asians. Finally, three phylogenetic assessments based on two different NJ and ML phylogenetic methods and PC plot analysis were carried out using the same panel of 20 STR markers and 20

  20. Traceless affinity labeling of endogenous proteins for functional analysis in living cells.

    Science.gov (United States)

    Hayashi, Takahiro; Hamachi, Itaru

    2012-09-18

    Protein labeling and imaging techniques have provided tremendous opportunities to study the structure, function, dynamics, and localization of individual proteins in the complex environment of living cells. Molecular biology-based approaches, such as GFP-fusion tags and monoclonal antibodies, have served as important tools for the visualization of individual proteins in cells. Although these techniques continue to be valuable for live cell imaging, they have a number of limitations that have only been addressed by recent progress in chemistry-based approaches. These chemical approaches benefit greatly from the smaller probe sizes that should result in fewer perturbations to proteins and to biological systems as a whole. Despite the research in this area, so far none of these labeling techniques permit labeling and imaging of selected endogenous proteins in living cells. Researchers have widely used affinity labeling, in which the protein of interest is labeled by a reactive group attached to a ligand, to identify and characterize proteins. Since the first report of affinity labeling in the early 1960s, efforts to fine-tune the chemical structures of both the reactive group and ligand have led to protein labeling with excellent target selectivity in the whole proteome of living cells. Although the chemical probes used for affinity labeling generally inactivate target proteins, this strategy holds promise as a valuable tool for the labeling and imaging of endogenous proteins in living cells and by extension in living animals. In this Account, we summarize traceless affinity labeling, a technique explored mainly in our laboratory. In our overview of the different labeling techniques, we emphasize the challenge of designing chemical probes that allow for dissociation of the affinity module (often a ligand) after the labeling reaction so that the labeled protein retains its native function. This feature distinguishes the traceless labeling approach from the traditional

  1. Affine pairings on ARM

    NARCIS (Netherlands)

    Acar, T.; Lauter, K.; Naehrig, M.; Shumow, D.

    2011-01-01

    Pairings on elliptic curves are being used in an increasing number of cryptographic applications on many different devices and platforms, but few performance numbers for cryptographic pairings have been reported on embedded and mobile devices. In this paper we give performance numbers for affine and

  2. Detection of Waterborne Viruses Using High Affinity Molecularly Imprinted Polymers.

    Science.gov (United States)

    Altintas, Zeynep; Gittens, Micah; Guerreiro, Antonio; Thompson, Katy-Anne; Walker, Jimmy; Piletsky, Sergey; Tothill, Ibtisam E

    2015-07-07

    Molecularly imprinted polymers (MIPs) are artificial receptor ligands which can recognize and specifically bind to a target molecule. They are more resistant to chemical and biological damage and inactivation than antibodies. Therefore, target specific-MIP nanoparticles are aimed to develop and implemented to biosensors for the detection of biological toxic agents such as viruses, bacteria, and fungi toxins that cause many diseases and death due to the environmental contamination. For the first time, a molecularly imprinted polymer (MIP) targeting the bacteriophage MS2 as the template was investigated using a novel solid-phase synthesis method to obtain the artificial affinity ligand for the detection and removal of waterborne viruses through optical-based sensors. A high affinity between the artificial ligand and the target was found, and a regenerative MIP-based virus detection assay was successfully developed using a new surface plasmon resonance (SPR)-biosensor which provides an alternative technology for the specific detection and removal of waterborne viruses that lead to high disease and death rates all over the world.

  3. Classically integrable boundary conditions for affine Toda field theories

    International Nuclear Information System (INIS)

    Bowcock, P.; Corrigan, E.; Dorey, P.E.; Rietdijk, R.H.

    1995-01-01

    Boundary conditions compatible with classical integrability are studied both directly, using an approach based on the explicit construction of conserved quantities, and indirectly by first developing a generalisation of the Lax pair idea. The latter approach is closer to the spirit of earlier work by Sklyanin and yields a complete set of conjectures for permissible boundary conditions for any affine Toda field theory. (orig.)

  4. Affinity of serum apolipoproteins for lipid monolayers

    International Nuclear Information System (INIS)

    Ibdah, J.A.

    1987-01-01

    The effects of lipid composition and packing as well as the structure of the protein on the affinities of apolipoproteins for lipid monolayers have been investigated. The adsorption of 14 C-reductively methylated human apolipoproteins A-I and A-II at saturating subphase concentrations to monolayers prepared with synthetic lipids or lipoprotein surface lipids spread at various initial surface pressures has been studied. The adsorption of apolipoproteins is monitored by following the surface radioactivity using a gas flow counter and Wilhelmy plate, respectively. The physical states of the lipid monolayers are evaluated by measurement of the surface pressure-molecular area isotherms using a Langmuir-Adam surface balance. The probable helical regions in various apolipoproteins have been predicted using a secondary structure analysis computer program. The mean residue hydrophobicity and mean residue hydrophobic moment for the predicted helical segments have been calculated. The surface properties of synthetic peptides which are amphipathic helix analogs have been investigated at the air-water and lipid-water interfaces

  5. Single-experiment displacement assay for quantifying high-affinity binding by isothermal titration calorimetry.

    Science.gov (United States)

    Krainer, Georg; Keller, Sandro

    2015-04-01

    Isothermal titration calorimetry (ITC) is the gold standard for dissecting the thermodynamics of a biomolecular binding process within a single experiment. However, reliable determination of the dissociation constant (KD) from a single titration is typically limited to the range 100 μM>KD>1 nM. Interactions characterized by a lower KD can be assessed indirectly by so-called competition or displacement assays, provided that a suitable competitive ligand is available whose KD falls within the directly accessible window. However, this protocol is limited by the fact that it necessitates at least two titrations to characterize one high-affinity inhibitor, resulting in considerable consumption of both sample material and time. Here, we introduce a fast and efficient ITC displacement assay that allows for the simultaneous characterization of both a high-affinity ligand and a moderate-affinity ligand competing for the same binding site on a receptor within a single experiment. The protocol is based on a titration of the high-affinity ligand into a solution containing the moderate-affinity ligand bound to the receptor present in excess. The resulting biphasic binding isotherm enables accurate and precise determination of KD values and binding enthalpies (ΔH) of both ligands. We discuss the theoretical background underlying the approach, demonstrate its practical application to metal ion chelation, explore its potential and limitations with the aid of simulations and statistical analyses, and elaborate on potential applications to protein-inhibitor interactions. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. ODE/IM correspondence and modified affine Toda field equations

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Katsushi; Locke, Christopher

    2014-08-15

    We study the two-dimensional affine Toda field equations for affine Lie algebra g{sup ^} modified by a conformal transformation and the associated linear equations. In the conformal limit, the associated linear problem reduces to a (pseudo-)differential equation. For classical affine Lie algebra g{sup ^}, we obtain a (pseudo-)differential equation corresponding to the Bethe equations for the Langlands dual of the Lie algebra g, which were found by Dorey et al. in study of the ODE/IM correspondence.

  7. A single base-pair change in 2009 H1N1 hemagglutinin increases human receptor affinity and leads to efficient airborne viral transmission in ferrets.

    Directory of Open Access Journals (Sweden)

    Akila Jayaraman

    2011-03-01

    Full Text Available The 2009 H1N1 influenza A virus continues to circulate among the human population as the predominant H1N1 subtype. Epidemiological studies and airborne transmission studies using the ferret model have shown that the transmission efficiency of 2009 H1N1 viruses is lower than that of previous seasonal strains and the 1918 pandemic H1N1 strain. We recently correlated this reduced transmission efficiency to the lower binding affinity of the 2009 H1N1 hemagglutinin (HA to α2→6 sialylated glycan receptors (human receptors. Here we report that a single point mutation (Ile219→Lys; a base pair change in the glycan receptor-binding site (RBS of a representative 2009 H1N1 influenza A virus, A/California/04/09 or CA04/09, quantitatively increases its human receptor-binding affinity. The increased human receptor-affinity is in the same range as that of the HA from highly transmissible seasonal and 1918 pandemic H1N1 viruses. Moreover, a 2009 H1N1 virus carrying this mutation in the RBS (generated using reverse genetics transmits efficiently in ferrets by respiratory droplets thereby reestablishing our previously observed correlation between human receptor-binding affinity and transmission efficiency. These findings are significant in the context of monitoring the evolution of the currently circulating 2009 H1N1 viruses.

  8. Assessing the stability of free-energy perturbation calculations by performing variations in the method

    Science.gov (United States)

    Manzoni, Francesco; Ryde, Ulf

    2018-03-01

    We have calculated relative binding affinities for eight tetrafluorophenyl-triazole-thiogalactoside inhibitors of galectin-3 with the alchemical free-energy perturbation approach. We obtain a mean absolute deviation from experimental estimates of only 2-3 kJ/mol and a correlation coefficient (R 2) of 0.5-0.8 for seven relative affinities spanning a range of up to 11 kJ/mol. We also studied the effect of using different methods to calculate the charges of the inhibitor and different sizes of the perturbed group (the atoms that are described by soft-core potentials and are allowed to have differing coordinates). However, the various approaches gave rather similar results and it is not possible to point out one approach as consistently and significantly better than the others. Instead, we suggest that such small and reasonable variations in the computational method can be used to check how stable the calculated results are and to obtain a more accurate estimate of the uncertainty than if performing only one calculation with a single computational setup.

  9. Characterization of self-affinity in the global regime

    Science.gov (United States)

    Neimark, Alexander V.

    1994-11-01

    Methods for characterization of self-affine surfaces and measurements of their roughness exponents H are developed. It is shown that for smoothed surfaces, which underwent particular coarse graining or averaging of the small-scale fluctuations, the excess surface area Sex and the mean square root radius of curvature ac are related by two distinct asymptotic power laws if ac is well below or well above a certain crossover scale acr. In the local regime of self-affinity, when acSex~(ac/acr)-(1-H). In the global regime of self-affinity, when ac>>acr, Sex~(ac/acr)-2(1-H)/(2-H). The former scaling relationship is consistent with the well known definition of local fractal dimensions dloc=dtop+1-H. The latter scaling relationship offers alternatives for characterization of self-affinity over large scales by means of excess dimensions defined as dex=dtop+2(1-H)/(2-H) and can be used for determination of roughness exponents from the measurements provided in the global regime. The thermodynamic method of fractal analysis, proposed earlier for self-similar surfaces (A.V. Neimark, Pis'ma Zh. Eksp. Teor. Fiz. 51, 535 (1990) [JETP Lett. 51, 607 (1990)]; Physica A 191, 258 (1992)), is extended for self-affine surfaces for determination of fractal dimensions and roughness exponents from adsorption and capillary experimental data.

  10. Fluorescence and computational studies of thymidine phosphorylase affinity toward lipidated 5-FU derivatives

    Science.gov (United States)

    Lettieri, R.; D'Abramo, M.; Stella, L.; La Bella, A.; Leonelli, F.; Giansanti, L.; Venanzi, M.; Gatto, E.

    2018-04-01

    Thymidine phosphorylase (TP) is an enzyme that is up-regulated in a wide variety of solid tumors, including breast and colorectal cancers. It is involved in tumor growth and metastasis, for this reason it is one of the key enzyme to be inhibited, in an attempt to prevent tumor proliferation. However, it also plays an active role in cancer treatment, through its contribution in the conversion of the anti-cancer drug 5-fluorouracil (5-FU) to an irreversible inhibitor of thymidylate synthase (TS), responsible of the inhibition of the DNA synthesis. In this work, the intrinsic TP fluorescence has been investigated for the first time and exploited to study TP binding affinity for the unsubstituted 5-FU and for two 5-FU derivatives, designed to expose this molecule on liposomal membranes. These molecules were obtained by functionalizing the nitrogen atom with a chain consisting of six (1) or seven (2) units of glycol, linked to an alkyl moiety of 12 carbon atoms. Derivatives (1) and (2) exhibited an affinity for TP in the micromolar range, 10 times higher than the parent compound, irrespective of the length of the polyoxyethylenic spacer. This high affinity was maintained also when the compounds were anchored in liposomal membranes. Experimental results were supported by molecular dynamics simulations and docking calculations, supporting a feasible application of the designed supramolecular lipid structure in selective targeting of TP, to be potentially used as a drug delivery system or sensor device.

  11. Inhaled nitric oxide augments nitric oxide transport on sickle cell hemoglobin without affecting oxygen affinity

    OpenAIRE

    Gladwin, Mark T.; Schechter, Alan N.; Shelhamer, James H.; Pannell, Lewis K.; Conway, Deirdre A.; Hrinczenko, Borys W.; Nichols, James S.; Pease-Fye, Margaret E.; Noguchi, Constance T.; Rodgers, Griffin P.; Ognibene, Frederick P.

    1999-01-01

    Nitric oxide (NO) inhalation has been reported to increase the oxygen affinity of sickle cell erythrocytes. Also, proposed allosteric mechanisms for hemoglobin, based on S-nitrosation of β-chain cysteine 93, raise the possibilty of altering the pathophysiology of sickle cell disease by inhibiting polymerization or by increasing NO delivery to the tissue. We studied the effects of a 2-hour treatment, using varying concentrations of inhaled NO. Oxygen affinity, as measured by P50, did not respo...

  12. Class of the affine line is a zero divisor in the Grothendieck ring

    OpenAIRE

    Borisov, Lev

    2014-01-01

    We show that the class of the affine line is a zero divisor in the Grothendieck ring of algebraic varieties over complex numbers. The argument is based on the Pfaffian-Grassmannian double mirror correspondence.

  13. DAYA ANTIBAKTERI EKSTRAK ETANOL DAUN SENGGANI (Melastoma affine D. Don

    Directory of Open Access Journals (Sweden)

    Ika Trisharyanti Dian Kusumowati

    2014-08-01

    Full Text Available Melastoma affine D. Don had some activities such as anthelmintic, antibacteria, antiinfiammation, antifungal, and antitumor. The aims of this research was determine antibacteria activity of ethanolic extract of Melastoma affine D. Don. The antimicrobial activity was tested by solid dilution method to get Minimum Inhibition Concentration (MIC. The compounds in Melastoma affine D. Don was analyzed by tube test method and Thin Layer Chromatography (TLC with chloroform : methanol : formic acid (8,5:1,5:0,5 as mobile phase and silica gel GF254 as stationary phase. The result showed ethanolic extract of Melastoma affine D. Don contains alkaloid, polyphenol, fiavonoid, saponin, and essential oil. The MIC of Senggani against Staphylococcus aureus was 2% and 3% against Escherichia coli and the extract could not inhibit Staphylococcus aureus and Escherichia coli multiresistant until concentration 7% extract ethanol. Keywords: Melastoma affine D. Don, Staphylococcus aureus, Escherichia coli

  14. Computation of piecewise affine terminal cost functions for model predictive control

    NARCIS (Netherlands)

    Brunner, F.D.; Lazar, M.; Allgöwer, F.; Fränzle, Martin; Lygeros, John

    2014-01-01

    This paper proposes a method for the construction of piecewise affine terminal cost functions for model predictive control (MPC). The terminal cost function is constructed on a predefined partition by solving a linear program for a given piecewise affine system, a stabilizing piecewise affine

  15. Affinity-Selected Filamentous Bacteriophage as a Probe for Acoustic Wave Biodetectors of Salmonella typhimurium

    National Research Council Canada - National Science Library

    Olsen, Eric V; Sorokulova, Iryna B; Petrenko, Valery A; Chen, I-Hsuan; Barbaree, James M; Vodyanoy, Vitaly J

    2005-01-01

    Proof-in-concept biosensors were prepared for the rapid detection of Salmonella typhimurium in solution, based on affinity-selected filamentous phage prepared as probes physically adsorbed to piezoelectric transducers...

  16. Accurate and Reliable Prediction of the Binding Affinities of Macrocycles to Their Protein Targets.

    Science.gov (United States)

    Yu, Haoyu S; Deng, Yuqing; Wu, Yujie; Sindhikara, Dan; Rask, Amy R; Kimura, Takayuki; Abel, Robert; Wang, Lingle

    2017-12-12

    Macrocycles have been emerging as a very important drug class in the past few decades largely due to their expanded chemical diversity benefiting from advances in synthetic methods. Macrocyclization has been recognized as an effective way to restrict the conformational space of acyclic small molecule inhibitors with the hope of improving potency, selectivity, and metabolic stability. Because of their relatively larger size as compared to typical small molecule drugs and the complexity of the structures, efficient sampling of the accessible macrocycle conformational space and accurate prediction of their binding affinities to their target protein receptors poses a great challenge of central importance in computational macrocycle drug design. In this article, we present a novel method for relative binding free energy calculations between macrocycles with different ring sizes and between the macrocycles and their corresponding acyclic counterparts. We have applied the method to seven pharmaceutically interesting data sets taken from recent drug discovery projects including 33 macrocyclic ligands covering a diverse chemical space. The predicted binding free energies are in good agreement with experimental data with an overall root-mean-square error (RMSE) of 0.94 kcal/mol. This is to our knowledge the first time where the free energy of the macrocyclization of linear molecules has been directly calculated with rigorous physics-based free energy calculation methods, and we anticipate the outstanding accuracy demonstrated here across a broad range of target classes may have significant implications for macrocycle drug discovery.

  17. On Affine Fusion and the Phase Model

    Directory of Open Access Journals (Sweden)

    Mark A. Walton

    2012-11-01

    Full Text Available A brief review is given of the integrable realization of affine fusion discovered recently by Korff and Stroppel. They showed that the affine fusion of the su(n Wess-Zumino-Novikov-Witten (WZNW conformal field theories appears in a simple integrable system known as the phase model. The Yang-Baxter equation leads to the construction of commuting operators as Schur polynomials, with noncommuting hopping operators as arguments. The algebraic Bethe ansatz diagonalizes them, revealing a connection to the modular S matrix and fusion of the su(n WZNW model. The noncommutative Schur polynomials play roles similar to those of the primary field operators in the corresponding WZNW model. In particular, their 3-point functions are the su(n fusion multiplicities. We show here how the new phase model realization of affine fusion makes obvious the existence of threshold levels, and how it accommodates higher-genus fusion.

  18. Specificity and affinity quantification of protein-protein interactions.

    Science.gov (United States)

    Yan, Zhiqiang; Guo, Liyong; Hu, Liang; Wang, Jin

    2013-05-01

    Most biological processes are mediated by the protein-protein interactions. Determination of the protein-protein structures and insight into their interactions are vital to understand the mechanisms of protein functions. Currently, compared with the isolated protein structures, only a small fraction of protein-protein structures are experimentally solved. Therefore, the computational docking methods play an increasing role in predicting the structures and interactions of protein-protein complexes. The scoring function of protein-protein interactions is the key responsible for the accuracy of the computational docking. Previous scoring functions were mostly developed by optimizing the binding affinity which determines the stability of the protein-protein complex, but they are often lack of the consideration of specificity which determines the discrimination of native protein-protein complex against competitive ones. We developed a scoring function (named as SPA-PP, specificity and affinity of the protein-protein interactions) by incorporating both the specificity and affinity into the optimization strategy. The testing results and comparisons with other scoring functions show that SPA-PP performs remarkably on both predictions of binding pose and binding affinity. Thus, SPA-PP is a promising quantification of protein-protein interactions, which can be implemented into the protein docking tools and applied for the predictions of protein-protein structure and affinity. The algorithm is implemented in C language, and the code can be downloaded from http://dl.dropbox.com/u/1865642/Optimization.cpp.

  19. Constrained quadratic stabilization of discrete-time uncertain nonlinear multi-model systems using piecewise affine state-feedback

    Directory of Open Access Journals (Sweden)

    Olav Slupphaug

    1999-07-01

    Full Text Available In this paper a method for nonlinear robust stabilization based on solving a bilinear matrix inequality (BMI feasibility problem is developed. Robustness against model uncertainty is handled. In different non-overlapping regions of the state-space called clusters the plant is assumed to be an element in a polytope which vertices (local models are affine systems. In the clusters containing the origin in their closure, the local models are restricted to be linear systems. The clusters cover the region of interest in the state-space. An affine state-feedback is associated with each cluster. By utilizing the affinity of the local models and the state-feedback, a set of linear matrix inequalities (LMIs combined with a single nonconvex BMI are obtained which, if feasible, guarantee quadratic stability of the origin of the closed-loop. The feasibility problem is attacked by a branch-and-bound based global approach. If the feasibility check is successful, the Liapunov matrix and the piecewise affine state-feedback are given directly by the feasible solution. Control constraints are shown to be representable by LMIs or BMIs, and an application of the control design method to robustify constrained nonlinear model predictive control is presented. Also, the control design method is applied to a simple example.

  20. Learning a peptide-protein binding affinity predictor with kernel ridge regression

    Science.gov (United States)

    2013-01-01

    Background The cellular function of a vast majority of proteins is performed through physical interactions with other biomolecules, which, most of the time, are other proteins. Peptides represent templates of choice for mimicking a secondary structure in order to modulate protein-protein interaction. They are thus an interesting class of therapeutics since they also display strong activity, high selectivity, low toxicity and few drug-drug interactions. Furthermore, predicting peptides that would bind to a specific MHC alleles would be of tremendous benefit to improve vaccine based therapy and possibly generate antibodies with greater affinity. Modern computational methods have the potential to accelerate and lower the cost of drug and vaccine discovery by selecting potential compounds for testing in silico prior to biological validation. Results We propose a specialized string kernel for small bio-molecules, peptides and pseudo-sequences of binding interfaces. The kernel incorporates physico-chemical properties of amino acids and elegantly generalizes eight kernels, comprised of the Oligo, the Weighted Degree, the Blended Spectrum, and the Radial Basis Function. We provide a low complexity dynamic programming algorithm for the exact computation of the kernel and a linear time algorithm for it’s approximation. Combined with kernel ridge regression and SupCK, a novel binding pocket kernel, the proposed kernel yields biologically relevant and good prediction accuracy on the PepX database. For the first time, a machine learning predictor is capable of predicting the binding affinity of any peptide to any protein with reasonable accuracy. The method was also applied to both single-target and pan-specific Major Histocompatibility Complex class II benchmark datasets and three Quantitative Structure Affinity Model benchmark datasets. Conclusion On all benchmarks, our method significantly (p-value ≤ 0.057) outperforms the current state-of-the-art methods at predicting

  1. Screening for Natural Inhibitors of Topoisomerases I from Rhamnus davurica by Affinity Ultrafiltration and High-Performance Liquid Chromatography–Mass Spectrometry

    Science.gov (United States)

    Chen, Guilin; Guo, Mingquan

    2017-01-01

    Topoisomerase I (Topo I) catalyzes topological interconversion of duplex DNA during DNA replication and transcription, and has been deemed as important antineoplastic targets. In this study, the fraction R.d-60 from ethyl acetate extracts of Rhamnus davurica showed higher inhibitory rates against SGC-7901 and HT-29 compared with the R.d-30 fraction in vitro. However, the specific active components of R.d-60 fraction remain elusive. To this end, a method based on bio-affinity ultrafiltration and high performance liquid chromatography/electrospray mass spectrometry (HPLC- ESI-MS/MS) was developed to rapidly screen and identify the Topo I inhibitors in this fraction. The enrichment factors (EFs) were calculated to evaluate the binding affinities between the bioactive constituents and Topo I. As a result, eight ligands were identified and six of which with higher EFs showed more potential antitumor activity. Furthermore, antiproliferative assays in vitro (IC50 values) with two representative candidates (apigenin, quercetin) against SGC-7901, HT-29 and Hep G2 cells were conducted and further validated. Finally, the structure-activity relationships revealed that flavones contain a C2-C3 double bond of C ring exhibited higher bio-affinities to Topo I than those without it. This integrated method combining Topo I ultrafiltration with HPLC-MS/MS proved to be very efficient in rapid screening and identification of potential Topo I inhibitors from the complex extracts of medicinal plants, and could be further explored as a valuable high-throughput screening platform in the early drug discovery stage. PMID:28919906

  2. Calculation for Primary Combustion Characteristics of Boron-Based Fuel-Rich Propellant Based on BP Neural Network

    Directory of Open Access Journals (Sweden)

    Wu Wan'e

    2012-01-01

    Full Text Available A practical scheme for selecting characterization parameters of boron-based fuel-rich propellant formulation was put forward; a calculation model for primary combustion characteristics of boron-based fuel-rich propellant based on backpropagation neural network was established, validated, and then was used to predict primary combustion characteristics of boron-based fuel-rich propellant. The results show that the calculation error of burning rate is less than ±7.3%; in the formulation range (hydroxyl-terminated polybutadiene 28%–32%, ammonium perchlorate 30%–35%, magnalium alloy 4%–8%, catocene 0%–5%, and boron 30%, the variation of the calculation data is consistent with the experimental results.

  3. [Cell-ELA-based determination of binding affinity of DNA aptamer against U87-EGFRvIII cell].

    Science.gov (United States)

    Tan, Yan; Liang, Huiyu; Wu, Xidong; Gao, Yubo; Zhang, Xingmei

    2013-05-01

    A15, a DNA aptamer with binding specificity for U87 glioma cells stably overexpressing the epidermal growth factor receptor variant III (U87-EGFRvIII), was generated by cell systematic evolution of ligands by exponential enrichment (cell-SELEX) using a random nucleotide library. Subsequently, we established a cell enzyme-linked assay (cell-ELA) to detect the affinity of A15 compared to an EGFR antibody. We used A15 as a detection probe and cultured U87-EGFRvIII cells as targets. Our data indicate that the equilibrium dissociation constants (K(d)) for A15 were below 100 nmol/L and had similar affinity compared to an EGFR antibody for U87-EGFRvIII. We demonstrated that the cell-ELA was a useful method to determine the equilibrium dissociation constants (K(d)) of aptamers generated by cell-SELEX.

  4. Affine planes, ternary rings, and examples of non-Desarguesian planes

    OpenAIRE

    Ivanov, Nikolai V.

    2016-01-01

    The paper is devoted to a detailed self-contained exposition of a part of the theory of affine planes leading to a construction of affine (or, equivalently, projective) planes not satisfying the Desarques axiom. It is intended to complement the introductory expositions of the theory of affine and projective planes. A novelty of our exposition is a new notation for the ternary operation in a ternary ring, much more suggestive than the standard one.

  5. Automatic detection of arterial input function in dynamic contrast enhanced MRI based on affinity propagation clustering.

    Science.gov (United States)

    Shi, Lin; Wang, Defeng; Liu, Wen; Fang, Kui; Wang, Yi-Xiang J; Huang, Wenhua; King, Ann D; Heng, Pheng Ann; Ahuja, Anil T

    2014-05-01

    To automatically and robustly detect the arterial input function (AIF) with high detection accuracy and low computational cost in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). In this study, we developed an automatic AIF detection method using an accelerated version (Fast-AP) of affinity propagation (AP) clustering. The validity of this Fast-AP-based method was proved on two DCE-MRI datasets, i.e., rat kidney and human head and neck. The detailed AIF detection performance of this proposed method was assessed in comparison with other clustering-based methods, namely original AP and K-means, as well as the manual AIF detection method. Both the automatic AP- and Fast-AP-based methods achieved satisfactory AIF detection accuracy, but the computational cost of Fast-AP could be reduced by 64.37-92.10% on rat dataset and 73.18-90.18% on human dataset compared with the cost of AP. The K-means yielded the lowest computational cost, but resulted in the lowest AIF detection accuracy. The experimental results demonstrated that both the AP- and Fast-AP-based methods were insensitive to the initialization of cluster centers, and had superior robustness compared with K-means method. The Fast-AP-based method enables automatic AIF detection with high accuracy and efficiency. Copyright © 2013 Wiley Periodicals, Inc.

  6. Fermionic construction of vertex operators for twisted affine algebras

    International Nuclear Information System (INIS)

    Frappat, L.; Sorba, P.; Sciarrino, A.

    1988-03-01

    We construct vertex operator representations of the twisted affine algebras in terms of fermionic (or parafermionic in some cases) elementary fields. The folding method applied to the extended Dynkin diagrams of the affine algebras allows us to determine explicitly these fermionic fields as vertex operators

  7. Affine-projective field laws

    International Nuclear Information System (INIS)

    Murphy, G.L.

    1975-01-01

    The general topic of geometric unified field theories is discussed in the first section. Some reasons are given for pursuing such theories, and some criticisms are considered. The second section develops the fundamental equations of a purely affine theory which is invariant under projective transformations of the affine connection. This theory is a generalization of that of Schrodinger. Possible identifications for the space-time metric are considered in Sec. III. Sections IV and V deal with the limits of pure gravitation and electrodynamics. In the symmetric limit, Einstein's vacuum equations with cosmological term are recovered. The theory also contains a generalized electrodynamic set of equations which is very similar to the Born-Infeld set. In the weak-field approximation, a finite mass must be attributed to the photon. The problem of motion for charges is discussed here, and it is argued that criticisms of unified field theories because of a supposed inability to produce the Lorentz force law are probably not justified. Three more speculative sections deal with possible explanations of nuclear forces, the spin-torsion relation, and particle structure

  8. Polynomial Primal-Dual Cone Affine Scaling for Semidefinite Programming

    NARCIS (Netherlands)

    A.B. Berkelaar (Arjan); J.F. Sturm; S. Zhang (Shuzhong)

    1996-01-01

    textabstractIn this paper we generalize the primal--dual cone affine scaling algorithm of Sturm and Zhang to semidefinite programming. We show in this paper that the underlying ideas of the cone affine scaling algorithm can be naturely applied to semidefinite programming, resulting in a new

  9. Control and estimation of piecewise affine systems

    CERN Document Server

    Xu, Jun

    2014-01-01

    As a powerful tool to study nonlinear systems and hybrid systems, piecewise affine (PWA) systems have been widely applied to mechanical systems. Control and Estimation of Piecewise Affine Systems presents several research findings relating to the control and estimation of PWA systems in one unified view. Chapters in this title discuss stability results of PWA systems, using piecewise quadratic Lyapunov functions and piecewise homogeneous polynomial Lyapunov functions. Explicit necessary and sufficient conditions for the controllability and reachability of a class of PWA systems are

  10. Fragment screening for drug leads by weak affinity chromatography (WAC-MS).

    Science.gov (United States)

    Ohlson, Sten; Duong-Thi, Minh-Dao

    2018-02-23

    Fragment-based drug discovery is an important tool for design of small molecule hit-to-lead compounds against various biological targets. Several approved drugs have been derived from an initial fragment screen and many such candidates are in various stages of clinical trials. Finding fragment hits, that are suitable for optimisation by medicinal chemists, is still a challenge as the binding between the small fragment and its target is weak in the range of mM to µM of K d and irrelevant non-specific interactions are abundant in this area of transient interactions. Fortunately, there are methods that can study weak interactions quite efficiently of which NMR, surface plasmon resonance (SPR) and X-ray crystallography are the most prominent. Now, a new technology based on zonal affinity chromatography, weak affinity chromatography (WAC), has been introduced which has remedied many of the problems with other technologies. By combining WAC with mass spectrometry (WAC-MS), it is a powerful tool to identify binders quantitatively in terms of affinity and kinetics either from fragment libraries or from complex mixtures of biological extracts. As WAC-MS can be multiplexed by analysing mixtures of fragments (20-100 fragments) in one sample, this approach yields high throughput, where a whole library of e.g. >2000 fragments can be analysed quantitatively within a day. WAC-MS is easy to perform, where the robustness and quality of HPLC is fully utilized. This review will highlight the rationale behind the application of WAC-MS for fragment screening in drug discovery. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Beyond Helper Phage: Using "Helper Cells" to Select Peptide Affinity Ligands.

    Directory of Open Access Journals (Sweden)

    M Lisa Phipps

    Full Text Available Peptides are important affinity ligands for microscopy, biosensing, and targeted delivery. However, because they can have low affinity for their targets, their selection from large naïve libraries can be challenging. When selecting peptidic ligands from display libraries, it is important to: 1 ensure efficient display; 2 maximize the ability to select high affinity ligands; and 3 minimize the effect of the display context on binding. The "helper cell" packaging system has been described as a tool to produce filamentous phage particles based on phagemid constructs with varying display levels, while remaining free of helper phage contamination. Here we report on the first use of this system for peptide display, including the systematic characterization and optimization of helper cells, their inefficient use in antibody display and their use in creating and selecting from a set of phage display peptide libraries. Our libraries were analyzed with unprecedented precision by standard or deep sequencing, and shown to be superior in quality than commercial gold standards. Using our helper cell libraries, we have obtained ligands recognizing Yersinia pestis surface antigen F1V and L-glutamine-binding periplasmic protein QBP. In the latter case, unlike any of the peptide library selections described so far, we used a combination of phage and yeast display to select intriguing peptide ligands. Based on the success of our selections we believe that peptide libraries obtained with helper cells are not only suitable, but preferable to traditional phage display libraries for selection of peptidic ligands.

  12. 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.

  13. Software-Based Visual Loan Calculator For Banking Industry

    Science.gov (United States)

    Isizoh, A. N.; Anazia, A. E.; Okide, S. O. 3; Onyeyili, T. I.; Okwaraoka, C. A. P.

    2012-03-01

    industry is very necessary in modern day banking system using many design techniques for security reasons. This paper thus presents the software-based design and implementation of a Visual Loan calculator for banking industry using Visual Basic .Net (VB.Net). The fundamental approach to this is to develop a Graphical User Interface (GUI) using VB.Net operating tools, and then developing a working program which calculates the interest of any loan obtained. The VB.Net programming was done, implemented and the software proved satisfactory.

  14. Non-contact adhesion to self-affine surfaces: A theoretical model

    Energy Technology Data Exchange (ETDEWEB)

    Makeev, Maxim A., E-mail: makeev@umich.edu

    2013-11-22

    Strength of adhesion between materials is known to be strongly influenced by interface irregularities. In this work, I devise a perturbative approach to describe the effect of self-affine roughness on non-contact adhesive interactions. The hierarchy of the obtained analytical solutions is the following. First, analytical formulae are deduced to describe roughness corrections to the van der Waals interaction energies between a hemi-space adherend, bounded by a self-affine surface, and a point-like adherent. Second, the problem of two hemi-spaces, one of which has a planar surface, and the other is bounded by a self-affine surface, is solved analytically. In the latter case, a numerical analysis is performed to delineate the behavior of the roughness corrections as a function of the parameters, characterizing self-affine fractal surface roughness. The problem of two hemi-spaces, both bounded by self-affine fractal surfaces, is also addressed in this work. The model's predictions are compared with previously reported theoretical results and available experimental data.

  15. Detection-Guided Fast Affine Projection Channel Estimator for Speech Applications

    Directory of Open Access Journals (Sweden)

    Yan Wu Jennifer

    2007-04-01

    Full Text Available In various adaptive estimation applications, such as acoustic echo cancellation within teleconferencing systems, the input signal is a highly correlated speech. This, in general, leads to extremely slow convergence of the NLMS adaptive FIR estimator. As a result, for such applications, the affine projection algorithm (APA or the low-complexity version, the fast affine projection (FAP algorithm, is commonly employed instead of the NLMS algorithm. In such applications, the signal propagation channel may have a relatively low-dimensional impulse response structure, that is, the number m of active or significant taps within the (discrete-time modelled channel impulse response is much less than the overall tap length n of the channel impulse response. For such cases, we investigate the inclusion of an active-parameter detection-guided concept within the fast affine projection FIR channel estimator. Simulation results indicate that the proposed detection-guided fast affine projection channel estimator has improved convergence speed and has lead to better steady-state performance than the standard fast affine projection channel estimator, especially in the important case of highly correlated speech input signals.

  16. Affinity for a malignant tumor and organs of sup(99m)Tc-citrate complex

    Energy Technology Data Exchange (ETDEWEB)

    Ando, A; Sanada, S; Hiraki, T [Kanazawa Univ. (Japan). School of Paramedicine; Hisada, K; Nakazawa, N

    1976-12-01

    In order to investigate the tumor affinity of sup(99m)Tc-citrate complex, it was synthesized in three different ways. By (1) reducing sup(99m)TcO/sub 4//sup -/ with FeCl/sub 3//sup -/ ascorbic acid in 0.15 M sodium citrate, (2) reducing sup(99m)TcO/sub 4//sup -/ with SnCl/sub 2/ solution in 0.15 M sodium citrate, and (3) reducing sup(99m)TcO/sub 4//sup -/ with NaBH/sub 4/ in 0.45 sodium citrate. It was presumed from thinlayer chromatography that the sup(99m)Tc-citrate complexes synthesized in three ways were chemically different. These sup(99m)Tc-citrate complexes were injected intravenously into the rats subcutaneously transplanted with Yoshida sarcoma. These rats were sacrificed at one hour and three hours after injection. The radioactivity of the tumor, blood, muscle, liver, kidney, spleen and urine was measured by well-type scintillation counter. The retention values in these organs and the excretion rates in the urine were calculated. sup(99m)Tc-citrate complex synthesized by reducing sup(99m)TcO/sub 4//sup -/ with SnCl/sub 2/ solution had very strong affinity for the malignant tumor but the other two sup(99m)Tc-citrate complexes had no affinity to the malignant tumor. Excretion rates (% dose) of sup(99m)Tc-citrate complexes in one hour were from 65% to 75%.

  17. Self-affine roughness influence on redox reaction charge admittance

    NARCIS (Netherlands)

    Palasantzas, G

    2005-01-01

    In this work we investigate the influence of self-affine electrode roughness on the admittance of redox reactions during facile charge transfer kinetics. The self-affine roughness is characterized by the rms roughness amplitude w, the correlation length xi and the roughness exponent H (0

  18. Affine Toda equations and solutions in the homogeneous grading

    Czech Academy of Sciences Publication Activity Database

    Zuevsky, Alexander

    2018-01-01

    Roč. 542, April 1 (2018), s. 149-161 ISSN 0024-3795 Institutional support: RVO:67985840 Keywords : affine Lie gebras * affine Toda modes * solitons Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 0.973, year: 2016 https://www.sciencedirect.com/science/article/pii/S0024379517302100

  19. Binding affinities of anti-acetylcholine receptor autoantibodies in myasthenia gravis

    Energy Technology Data Exchange (ETDEWEB)

    Bray, J.J.; Drachman, D.B.

    1982-01-01

    Antibodies directed against acetylcholine (ACh) receptors are present in the sera of nearly 90% of patients with myasthenia gravis (MG), and are involved in the pathogenesis of this autoimmune disease. However, the antibody titers measured by the standard radioimmunoassay correspond poorly with the clinical severity of the disease. To determine whether this disparity could be accounted for by differences in the binding affinities of anti-ACh receptor antibodies in different patients, we have measured the binding affinities of these autoantibodies in 15 sera from MG patients. The affinity constants (K/sub o/), as determined by Scatchard analysis, were all in the range of 10/sup 10/ M/sup -1/, comparable to the highest values reported in immunized animals. The affinity constants were truly representative of the population of autoantibodies detected by the radioimmunoassay, as shown by the remarkable linearity of the Scatchard plots (r/sup 2/>0.90) and the close correlation between the antibody titers determined by extrapolation of the Scatchard plots and by saturation analysis (r = 0.99; p < 0.001). There was only a 6-fold variation in affinity constants measured in this series of patients despite widely differing antibody titers and severity of the disease. Factors other than the titer and affinity of anti-ACh receptor antibodies may correlate better with the clinical manifestations of MG.

  20. Calculation for Primary Combustion Characteristics of Boron-Based Fuel-Rich Propellant Based on BP Neural Network

    OpenAIRE

    Wan'e, Wu; Zuoming, Zhu

    2012-01-01

    A practical scheme for selecting characterization parameters of boron-based fuel-rich propellant formulation was put forward; a calculation model for primary combustion characteristics of boron-based fuel-rich propellant based on backpropagation neural network was established, validated, and then was used to predict primary combustion characteristics of boron-based fuel-rich propellant. The results show that the calculation error of burning rate is less than ± 7 . 3 %; in the formulation rang...

  1. Toward Fast and Accurate Binding Affinity Prediction with pmemdGTI: An Efficient Implementation of GPU-Accelerated Thermodynamic Integration.

    Science.gov (United States)

    Lee, Tai-Sung; Hu, Yuan; Sherborne, Brad; Guo, Zhuyan; York, Darrin M

    2017-07-11

    We report the implementation of the thermodynamic integration method on the pmemd module of the AMBER 16 package on GPUs (pmemdGTI). The pmemdGTI code typically delivers over 2 orders of magnitude of speed-up relative to a single CPU core for the calculation of ligand-protein binding affinities with no statistically significant numerical differences and thus provides a powerful new tool for drug discovery applications.

  2. An improved affine projection algorithm for active noise cancellation

    Science.gov (United States)

    Zhang, Congyan; Wang, Mingjiang; Han, Yufei; Sun, Yunzhuo

    2017-08-01

    Affine projection algorithm is a signal reuse algorithm, and it has a good convergence rate compared to other traditional adaptive filtering algorithm. There are two factors that affect the performance of the algorithm, which are step factor and the projection length. In the paper, we propose a new variable step size affine projection algorithm (VSS-APA). It dynamically changes the step size according to certain rules, so that it can get smaller steady-state error and faster convergence speed. Simulation results can prove that its performance is superior to the traditional affine projection algorithm and in the active noise control (ANC) applications, the new algorithm can get very good results.

  3. Phosphopeptide enrichment by immobilized metal affinity chromatography

    DEFF Research Database (Denmark)

    Thingholm, Tine E.; Larsen, Martin R.

    2016-01-01

    Immobilized metal affinity chromatography (IMAC) has been the method of choice for phosphopeptide enrichment prior to mass spectrometric analysis for many years and it is still used extensively in many laboratories. Using the affinity of negatively charged phosphate groups towards positively...... charged metal ions such as Fe3+, Ga3+, Al3+, Zr4+, and Ti4+ has made it possible to enrich phosphorylated peptides from peptide samples. However, the selectivity of most of the metal ions is limited, when working with highly complex samples, e.g., whole-cell extracts, resulting in contamination from...

  4. Satake diagrams of affine Kac-Moody algebras

    Energy Technology Data Exchange (ETDEWEB)

    Tripathy, L K [S B R Government Womens' College, Berhampur, Orissa 760 001 (India); Pati, K C [Department of Physics, Khallikote College, Berhampur, Orissa 760 001 (India)

    2006-02-10

    Satake diagrams of affine Kac-Moody algebras (untwisted and twisted) are obtained from their Dynkin diagrams. These diagrams give a classification of restricted root systems associated with these algebras. In the case of simple Lie algebras, these root systems and Satake diagrams correspond to symmetric spaces which have recently found many physical applications in quantum integrable systems, quantum transport problems, random matrix theories etc. We hope these types of root systems may have similar applications in theoretical physics in future and may correspond to symmetric spaces analogue of affine Kac-Moody algebras if they exist.

  5. Benchmark study of ionization potentials and electron affinities of armchair single-walled carbon nanotubes using density functional theory

    Science.gov (United States)

    Zhou, Bin; Hu, Zhubin; Jiang, Yanrong; He, Xiao; Sun, Zhenrong; Sun, Haitao

    2018-05-01

    The intrinsic parameters of carbon nanotubes (CNTs) such as ionization potential (IP) and electron affinity (EA) are closely related to their unique properties and associated applications. In this work, we demonstrated the success of optimal tuning method based on range-separated (RS) density functionals for both accurate and efficient prediction of vertical IPs and electron affinities (EAs) of a series of armchair single-walled carbon nanotubes C20n H20 (n  =  2–6) compared to the high-level IP/EA equation-of-motion coupled-cluster method with single and double substitutions (IP/EA-EOM-CCSD). Notably, the resulting frontier orbital energies (–ε HOMO and –ε LUMO) from the tuning method exhibit an excellent approximation to the corresponding IPs and EAs, that significantly outperform other conventional density functionals. In addition, it is suggested that the RS density functionals that possess both a fixed amount of exact exchange in the short-range and a correct long-range asymptotic behavior are suitable for calculating electronic structures of finite-sized CNTs. Next the performance of density functionals for description of various molecular properties such as chemical potential, hardness and electrophilicity are assessed as a function of tube length. Thanks to the efficiency and accuracy of this tuning method, the related behaviors of much longer armchair single-walled CNTs until C200H20 were studied. Lastly, the present work is proved to provide an efficient theoretical tool for future materials design and reliable characterization of other interesting properties of CNT-based systems.

  6. A new scintillation proximity assay-based approach for the detection of KRAS mutations

    Energy Technology Data Exchange (ETDEWEB)

    Lee, So-Young; Lim, Jae-Cheong; Cho, Eun-Ha; Jung, Sung-Hee [Korea Atomic Energy Research Institute (KAERI), Daejeon (Korea, Republic of). Radioisotope Research Div.

    2016-04-01

    KRAS is very commonly mutated resulting in a constitutively activated protein, which is independent of epidermal growth factor receptor (EGFR) ligand binding and resistant to anti-EGFR therapy. Although KRAS is frequently studied, there is still no uniform standard for detecting of KRAS mutations. In this report, a new scintillation proximity assay-based approach is described that determines the relative affinities of wild-type and mutated KRAS to the anti-KRAS antibody. We performed in vitro experiments using normal human colonic cells (CCD18Co), KRAS wild type (Caco-2) and KRAS mutant (HCT 116) cell lines to determine the relative affinities of wild type or mutated KRAS toward an anti-KRAS monoclonal antibody. The process consists of two primary steps: immunoprecipitation from cell lysate to enrich the KRAS protein and the scintillation proximity assay of the immunoprecipitant to determine the relative affinity against the antibody. A fixed concentration of cell lysates was purified by the immunoprecipitation method. The expressions of the KRAS protein in all cell lines was quantitatively confirmed by western blot analysis. For the scintillation proximity assay, the KRAS standard protein was radiolabeled with {sup 125}I by a simple mixing process in the iodogen tube immediately at room temperature immediately before use. The obtained CPM (count per minute) values of were used to calculate the KRAS concentration using purified KRAS as the standard. The calculated relative affinities of 7 μg of Caco-2 and HCT 116 immunoprecipitants for the anti-KRAS antibody were 77 and 0%, respectively. The newly developed scintillation proximity assay-based strategy determines the relative affinities of wild-type or mutated KRAS towards the anti-KRAS monoclonal antibody. This determination can help distinguish mutated KRAS from the wild type protein. The new SPA based approach for detecting KRAS mutations is applicable to many other cancer-related mutations.

  7. A new scintillation proximity assay-based approach for the detection of KRAS mutations

    International Nuclear Information System (INIS)

    Lee, So-Young; Lim, Jae-Cheong; Cho, Eun-Ha; Jung, Sung-Hee

    2016-01-01

    KRAS is very commonly mutated resulting in a constitutively activated protein, which is independent of epidermal growth factor receptor (EGFR) ligand binding and resistant to anti-EGFR therapy. Although KRAS is frequently studied, there is still no uniform standard for detecting of KRAS mutations. In this report, a new scintillation proximity assay-based approach is described that determines the relative affinities of wild-type and mutated KRAS to the anti-KRAS antibody. We performed in vitro experiments using normal human colonic cells (CCD18Co), KRAS wild type (Caco-2) and KRAS mutant (HCT 116) cell lines to determine the relative affinities of wild type or mutated KRAS toward an anti-KRAS monoclonal antibody. The process consists of two primary steps: immunoprecipitation from cell lysate to enrich the KRAS protein and the scintillation proximity assay of the immunoprecipitant to determine the relative affinity against the antibody. A fixed concentration of cell lysates was purified by the immunoprecipitation method. The expressions of the KRAS protein in all cell lines was quantitatively confirmed by western blot analysis. For the scintillation proximity assay, the KRAS standard protein was radiolabeled with 125 I by a simple mixing process in the iodogen tube immediately at room temperature immediately before use. The obtained CPM (count per minute) values of were used to calculate the KRAS concentration using purified KRAS as the standard. The calculated relative affinities of 7 μg of Caco-2 and HCT 116 immunoprecipitants for the anti-KRAS antibody were 77 and 0%, respectively. The newly developed scintillation proximity assay-based strategy determines the relative affinities of wild-type or mutated KRAS towards the anti-KRAS monoclonal antibody. This determination can help distinguish mutated KRAS from the wild type protein. The new SPA based approach for detecting KRAS mutations is applicable to many other cancer-related mutations.

  8. Determining the ice-binding planes of antifreeze proteins by fluorescence-based ice plane affinity.

    Science.gov (United States)

    Basu, Koli; Garnham, Christopher P; Nishimiya, Yoshiyuki; Tsuda, Sakae; Braslavsky, Ido; Davies, Peter

    2014-01-15

    Antifreeze proteins (AFPs) are expressed in a variety of cold-hardy organisms to prevent or slow internal ice growth. AFPs bind to specific planes of ice through their ice-binding surfaces. Fluorescence-based ice plane affinity (FIPA) analysis is a modified technique used to determine the ice planes to which the AFPs bind. FIPA is based on the original ice-etching method for determining AFP-bound ice-planes. It produces clearer images in a shortened experimental time. In FIPA analysis, AFPs are fluorescently labeled with a chimeric tag or a covalent dye then slowly incorporated into a macroscopic single ice crystal, which has been preformed into a hemisphere and oriented to determine the a- and c-axes. The AFP-bound ice hemisphere is imaged under UV light to visualize AFP-bound planes using filters to block out nonspecific light. Fluorescent labeling of the AFPs allows real-time monitoring of AFP adsorption into ice. The labels have been found not to influence the planes to which AFPs bind. FIPA analysis also introduces the option to bind more than one differently tagged AFP on the same single ice crystal to help differentiate their binding planes. These applications of FIPA are helping to advance our understanding of how AFPs bind to ice to halt its growth and why many AFP-producing organisms express multiple AFP isoforms.

  9. Growth and mortality of larval Myctophum affine (Myctophidae, Teleostei).

    Science.gov (United States)

    Namiki, C; Katsuragawa, M; Zani-Teixeira, M L

    2015-04-01

    The growth and mortality rates of Myctophum affine larvae were analysed based on samples collected during the austral summer and winter of 2002 from south-eastern Brazilian waters. The larvae ranged in size from 2·75 to 14·00 mm standard length (L(S)). Daily increment counts from 82 sagittal otoliths showed that the age of M. affine ranged from 2 to 28 days. Three models were applied to estimate the growth rate: linear regression, exponential model and Laird-Gompertz model. The exponential model best fitted the data, and L(0) values from exponential and Laird-Gompertz models were close to the smallest larva reported in the literature (c. 2·5 mm L(S)). The average growth rate (0·33 mm day(-1)) was intermediate among lanternfishes. The mortality rate (12%) during the larval period was below average compared with other marine fish species but similar to some epipelagic fishes that occur in the area. © 2015 The Fisheries Society of the British Isles.

  10. Critical biological parameters modulate affinity as a determinant of function in T-cell receptor gene-modified T-cells.

    Science.gov (United States)

    Spear, Timothy T; Wang, Yuan; Foley, Kendra C; Murray, David C; Scurti, Gina M; Simms, Patricia E; Garrett-Mayer, Elizabeth; Hellman, Lance M; Baker, Brian M; Nishimura, Michael I

    2017-11-01

    T-cell receptor (TCR)-pMHC affinity has been generally accepted to be the most important factor dictating antigen recognition in gene-modified T-cells. As such, there is great interest in optimizing TCR-based immunotherapies by enhancing TCR affinity to augment the therapeutic benefit of TCR gene-modified T-cells in cancer patients. However, recent clinical trials using affinity-enhanced TCRs in adoptive cell transfer (ACT) have observed unintended and serious adverse events, including death, attributed to unpredicted off-tumor or off-target cross-reactivity. It is critical to re-evaluate the importance of other biophysical, structural, or cellular factors that drive the reactivity of TCR gene-modified T-cells. Using a model for altered antigen recognition, we determined how TCR-pMHC affinity influenced the reactivity of hepatitis C virus (HCV) TCR gene-modified T-cells against a panel of naturally occurring HCV peptides and HCV-expressing tumor targets. The impact of other factors, such as TCR-pMHC stabilization and signaling contributions by the CD8 co-receptor, as well as antigen and TCR density were also evaluated. We found that changes in TCR-pMHC affinity did not always predict or dictate IFNγ release or degranulation by TCR gene-modified T-cells, suggesting that less emphasis might need to be placed on TCR-pMHC affinity as a means of predicting or augmenting the therapeutic potential of TCR gene-modified T-cells used in ACT. A more complete understanding of antigen recognition by gene-modified T-cells and a more rational approach to improve the design and implementation of novel TCR-based immunotherapies is necessary to enhance efficacy and maximize safety in patients.

  11. Heparin-binding peptide as a novel affinity tag for purification of recombinant proteins.

    Science.gov (United States)

    Morris, Jacqueline; Jayanthi, Srinivas; Langston, Rebekah; Daily, Anna; Kight, Alicia; McNabb, David S; Henry, Ralph; Kumar, Thallapuranam Krishnaswamy Suresh

    2016-10-01

    Purification of recombinant proteins constitutes a significant part of the downstream processing in biopharmaceutical industries. Major costs involved in the production of bio-therapeutics mainly depend on the number of purification steps used during the downstream process. Affinity chromatography is a widely used method for the purification of recombinant proteins expressed in different expression host platforms. Recombinant protein purification is achieved by fusing appropriate affinity tags to either N- or C- terminus of the target recombinant proteins. Currently available protein/peptide affinity tags have proved quite useful in the purification of recombinant proteins. However, these affinity tags suffer from specific limitations in their use under different conditions of purification. In this study, we have designed a novel 34-amino acid heparin-binding affinity tag (HB-tag) for the purification of recombinant proteins expressed in Escherichia coli (E. coli) cells. HB-tag fused recombinant proteins were overexpressed in E. coli in high yields. A one-step heparin-Sepharose-based affinity chromatography protocol was developed to purify HB-fused recombinant proteins to homogeneity using a simple sodium chloride step gradient elution. The HB-tag has also been shown to facilitate the purification of target recombinant proteins from their 8 M urea denatured state(s). The HB-tag has been demonstrated to be successfully released from the fusion protein by an appropriate protease treatment to obtain the recombinant target protein(s) in high yields. Results of the two-dimensional NMR spectroscopy experiments indicate that the purified recombinant target protein(s) exist in the native conformation. Polyclonal antibodies raised against the HB-peptide sequence, exhibited high binding specificity and sensitivity to the HB-fused recombinant proteins (∼10 ng) in different crude cell extracts obtained from diverse expression hosts. In our opinion, the HB-tag provides a

  12. Direct electrochemical sensing of glucose using glucose oxidase immobilized on functionalized carbon nanotubes via a novel metal chelate-based affinity method

    International Nuclear Information System (INIS)

    Tu, X.; Zhao, Y.; Luo, S.; Luo, X.; Feng, L.

    2012-01-01

    We report on a novel amperometric glassy carbon biosensing electrode for glucose. It is based on the immobilization of a highly sensitive glucose oxidase (GOx) by affinity interaction on carbon nanotubes (CNTs) functionalized with iminodiacetic acid and metal chelates. The new technique for immobilization is exploiting the affinity of Co(II) ions to the histidine and cysteine moieties on the surface of GOx. The direct electrochemistry of immobilized GOx revealed that the functionalized CNTs greatly improve the direct electron transfer between GOx and the surface of the electrode to give a pair of well-defined and almost reversible redox peaks and undergoes fast heterogeneous electron transfer with a rate constant (k s) of 0. 59 s -1 . The GOx immobilized in this way fully retained its activity for the oxidation of glucose. The resulting biosensor is capable of detecting glucose at levels as low as 0.01 mM, and has excellent operational stability (with no decrease in the activity of enzyme over a 10 days period). The method of immobilizing GOx is easy and also provides a model technique for potential use with other redox enzymes and proteins. (author)

  13. ODE/IM correspondence and Bethe ansatz for affine Toda field equations

    Directory of Open Access Journals (Sweden)

    Katsushi Ito

    2015-07-01

    Full Text Available We study the linear problem associated with modified affine Toda field equation for the Langlands dual gˆ∨, where gˆ is an untwisted affine Lie algebra. The connection coefficients for the asymptotic solutions of the linear problem are found to correspond to the Q-functions for g-type quantum integrable models. The ψ-system for the solutions associated with the fundamental representations of g leads to Bethe ansatz equations associated with the affine Lie algebra gˆ. We also study the A2r(2 affine Toda field equation in massless limit in detail and find its Bethe ansatz equations as well as T–Q relations.

  14. Methods for Fault Diagnosability Analysis of a Class of Affine Nonlinear Systems

    Directory of Open Access Journals (Sweden)

    Xiafu Peng

    2015-01-01

    Full Text Available The fault diagnosability analysis for a given model, before developing a diagnosis algorithm, can be used to answer questions like “can the fault fi be detected by observed states?” and “can it separate fault fi from fault fj by observed states?” If not, we should redesign the sensor placement. This paper deals with the problem of the evaluation of detectability and separability for the diagnosability analysis of affine nonlinear system. First, we used differential geometry theory to analyze the nonlinear system and proposed new detectability criterion and separability criterion. Second, the related matrix between the faults and outputs of the system and the fault separable matrix are designed for quantitative fault diagnosability calculation and fault separability calculation, respectively. Finally, we illustrate our approach to exemplify how to analyze diagnosability by a certain nonlinear system example, and the experiment results indicate the effectiveness of the fault evaluation methods.

  15. Tracking control of air-breathing hypersonic vehicles with non-affine dynamics via improved neural back-stepping design.

    Science.gov (United States)

    Bu, Xiangwei; He, Guangjun; Wang, Ke

    2018-04-01

    This study considers the design of a new back-stepping control approach for air-breathing hypersonic vehicle (AHV) non-affine models via neural approximation. The AHV's non-affine dynamics is decomposed into velocity subsystem and altitude subsystem to be controlled separately, and robust adaptive tracking control laws are developed using improved back-stepping designs. Neural networks are applied to estimate the unknown non-affine dynamics, which guarantees the addressed controllers with satisfactory robustness against uncertainties. In comparison with the existing control methodologies, the special contributions are that the non-affine issue is handled by constructing two low-pass filters based on model transformations, and virtual controllers are treated as intermediate variables such that they aren't needed for back-stepping designs any more. Lyapunov techniques are employed to show the uniformly ultimately boundedness of all closed-loop signals. Finally, simulation results are presented to verify the tracking performance and superiorities of the investigated control strategy. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

  16. Mutational analysis of affinity and selectivity of kringle-tetranectin interaction. Grafting novel kringle affinity ontp the trtranectin lectin scaffold

    DEFF Research Database (Denmark)

    Graversen, Jonas Heilskov; Jacobsen, C; Sigurskjold, B W

    2000-01-01

    -type lectin-like domain of tetranectin, involving Lys-148, Glu-150, and Asp-165, which mediates calcium-sensitive binding to plasminogen kringle 4. Here, we investigate the effect of conservative substitutions of these and a neighboring amino acid residue. Substitution of Thr-149 in tetranectin...... with a tyrosine residue considerably increases the affinity for plasminogen kringle 4, and, in addition, confers affinity for plasminogen kringle 2. As shown by isothermal titration calorimetry analysis, this new interaction is stronger than the binding of wild-type tetranectin to plasminogen kringle 4...

  17. Simple and Efficient Purification of Recombinant Proteins Using the Heparin-Binding Affinity Tag.

    Science.gov (United States)

    Jayanthi, Srinivas; Gundampati, Ravi Kumar; Kumar, Thallapuranam Krishnaswamy Suresh

    2017-11-01

    Heparin, a member of the glycosaminoglycan family, is known to interact with more than 400 different types of proteins. For the past few decades, significant progress has been made to understand the molecular details involved in heparin-protein interactions. Based on the structural knowledge available from the FGF1-heparin interaction studies, we have designed a novel heparin-binding peptide (HBP) affinity tag that can be used for the simple, efficient, and cost-effective purification of recombinant proteins of interest. HBP-tagged fusion proteins can be purified by heparin Sepharose affinity chromatography using a simple sodium chloride gradient to elute the bound fusion protein. In addition, owing to the high density of positive charges on the HBP tag, recombinant target proteins are preferably expressed in their soluble forms. The purification of HBP-fusion proteins can also be achieved in the presence of chemical denaturants, including urea. Additionally, polyclonal antibodies raised against the affinity tag can be used to detect HBP-fused target proteins with high sensitivity. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  18. Partial filling affinity capillary electrophoresis as a useful tool for fragment-based drug discovery: A proof of concept on thrombin.

    Science.gov (United States)

    Farcaş, E; Bouckaert, C; Servais, A-C; Hanson, J; Pochet, L; Fillet, M

    2017-09-01

    With the emergence of more challenging targets, a relatively new approach, fragment-based drug discovery (FBDD), proved its efficacy and gained increasing importance in the pharmaceutical industry. FBDD identifies low molecular-weight (MW) ligands (fragments) that bind to biologically important macromolecules, then a structure-guided fragment growing or merging approach is performed, contributing to the quality of the lead. However, to select the appropriate fragment to be evolved, sensitive analytical screening methods must be used to measure the affinity in the μM or even mM range. In this particular context, we developed a robust and selective partial filling affinity CE (ACE) method for the direct binding screening of a small fragment library in order to identify new thrombin inhibitors. To demonstrate the accuracy of our assay, the complex dissociation constants of three known thrombin inhibitors, namely benzamidine, p-aminobenzamidine and nafamostat were determined and found to be in good concordance with the previously reported values. Finally, the screening of a small library was performed and demonstrated the high discriminatory power of our method towards weak binders compared to classical spectrophotometric activity assay, proving the interest of our method in the context of FBDD. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. A DFT and semiempirical model-based study of opioid receptor affinity and selectivity in a group of molecules with a morphine structural core.

    Science.gov (United States)

    Bruna-Larenas, Tamara; Gómez-Jeria, Juan S

    2012-01-01

    We report the results of a search for model-based relationships between mu, delta, and kappa opioid receptor binding affinity and molecular structure for a group of molecules having in common a morphine structural core. The wave functions and local reactivity indices were obtained at the ZINDO/1 and B3LYP/6-31G(∗∗) levels of theory for comparison. New developments in the expression for the drug-receptor interaction energy expression allowed several local atomic reactivity indices to be included, such as local electronic chemical potential, local hardness, and local electrophilicity. These indices, together with a new proposal for the ordering of the independent variables, were incorporated in the statistical study. We found and discussed several statistically significant relationships for mu, delta, and kappa opioid receptor binding affinity at both levels of theory. Some of the new local reactivity indices incorporated in the theory appear in several equations for the first time in the history of model-based equations. Interaction pharmacophores were generated for mu, delta, and kappa receptors. We discuss possible differences regulating binding and selectivity in opioid receptor subtypes. This study, contrarily to the statistically backed ones, is able to provide a microscopic insight of the mechanisms involved in the binding process.

  20. A DFT and Semiempirical Model-Based Study of Opioid Receptor Affinity and Selectivity in a Group of Molecules with a Morphine Structural Core

    Directory of Open Access Journals (Sweden)

    Tamara Bruna-Larenas

    2012-01-01

    Full Text Available We report the results of a search for model-based relationships between mu, delta, and kappa opioid receptor binding affinity and molecular structure for a group of molecules having in common a morphine structural core. The wave functions and local reactivity indices were obtained at the ZINDO/1 and B3LYP/6-31 levels of theory for comparison. New developments in the expression for the drug-receptor interaction energy expression allowed several local atomic reactivity indices to be included, such as local electronic chemical potential, local hardness, and local electrophilicity. These indices, together with a new proposal for the ordering of the independent variables, were incorporated in the statistical study. We found and discussed several statistically significant relationships for mu, delta, and kappa opioid receptor binding affinity at both levels of theory. Some of the new local reactivity indices incorporated in the theory appear in several equations for the first time in the history of model-based equations. Interaction pharmacophores were generated for mu, delta, and kappa receptors. We discuss possible differences regulating binding and selectivity in opioid receptor subtypes. This study, contrarily to the statistically backed ones, is able to provide a microscopic insight of the mechanisms involved in the binding process.

  1. 2D Affine and Projective Shape Analysis.

    Science.gov (United States)

    Bryner, Darshan; Klassen, Eric; Huiling Le; Srivastava, Anuj

    2014-05-01

    Current techniques for shape analysis tend to seek invariance to similarity transformations (rotation, translation, and scale), but certain imaging situations require invariance to larger groups, such as affine or projective groups. Here we present a general Riemannian framework for shape analysis of planar objects where metrics and related quantities are invariant to affine and projective groups. Highlighting two possibilities for representing object boundaries-ordered points (or landmarks) and parameterized curves-we study different combinations of these representations (points and curves) and transformations (affine and projective). Specifically, we provide solutions to three out of four situations and develop algorithms for computing geodesics and intrinsic sample statistics, leading up to Gaussian-type statistical models, and classifying test shapes using such models learned from training data. In the case of parameterized curves, we also achieve the desired goal of invariance to re-parameterizations. The geodesics are constructed by particularizing the path-straightening algorithm to geometries of current manifolds and are used, in turn, to compute shape statistics and Gaussian-type shape models. We demonstrate these ideas using a number of examples from shape and activity recognition.

  2. Alkali Metal Cation Affinities of Anionic Main Group-Element Hydrides Across the Periodic Table

    NARCIS (Netherlands)

    Boughlala, Zakaria; Fonseca Guerra, Célia; Bickelhaupt, F. Matthias

    2017-01-01

    We have carried out an extensive exploration of gas-phase alkali metal cation affinities (AMCA) of archetypal anionic bases across the periodic system using relativistic density functional theory at ZORA-BP86/QZ4P//ZORA-BP86/TZ2P. AMCA values of all bases were computed for the lithium, sodium,

  3. Local uncontrollability for affine control systems with jumps

    Science.gov (United States)

    Treanţă, Savin

    2017-09-01

    This paper investigates affine control systems with jumps for which the ideal If(g1, …, gm) generated by the drift vector field f in the Lie algebra L(f, g1, …, gm) can be imbedded as a kernel of a linear first-order partial differential equation. It will lead us to uncontrollable affine control systems with jumps for which the corresponding reachable sets are included in explicitly described differentiable manifolds.

  4. Rapid Diagnostic Assay for Intact Influenza Virus Using a High Affinity Hemagglutinin Binding Protein.

    Science.gov (United States)

    Anderson, Caitlin E; Holstein, Carly A; Strauch, Eva-Maria; Bennett, Steven; Chevalier, Aaron; Nelson, Jorgen; Fu, Elain; Baker, David; Yager, Paul

    2017-06-20

    Influenza is a ubiquitous and recurring infection that results in approximately 500 000 deaths globally each year. Commercially available rapid diagnostic tests are based upon detection of the influenza nucleoprotein, which are limited in that they are unable to differentiate by species and require an additional viral lysis step. Sample preprocessing can be minimized or eliminated by targeting the intact influenza virus, thereby reducing assay complexity and leveraging the large number of hemagglutinin proteins on the surface of each virus. Here, we report the development of a paper-based influenza assay that targets the hemagglutinin protein; the assay employs a combination of antibodies and novel computationally designed, recombinant affinity proteins as the capture and detection agents. This system leverages the customizability of recombinant protein design to target the conserved receptor-binding pocket of the hemagglutinin protein and to match the trimeric nature of hemagglutinin for improved avidity. Using this assay, we demonstrate the first instance of intact influenza virus detection using a combination of antibody and affinity proteins within a porous network. The recombinant head region binder based assays yield superior analytical sensitivity as compared to the antibody based assay, with lower limits of detection of 3.54 × 10 7 and 1.34 × 10 7 CEID 50 /mL for the mixed and all binder stacks, respectively. Not only does this work describe the development of a novel influenza assay, it also demonstrates the power of recombinant affinity proteins for use in rapid diagnostic assays.

  5. An {Mathematical expression} iteration bound primal-dual cone affine scaling algorithm for linear programmingiteration bound primal-dual cone affine scaling algorithm for linear programming

    NARCIS (Netherlands)

    J.F. Sturm; J. Zhang (Shuzhong)

    1996-01-01

    textabstractIn this paper we introduce a primal-dual affine scaling method. The method uses a search-direction obtained by minimizing the duality gap over a linearly transformed conic section. This direction neither coincides with known primal-dual affine scaling directions (Jansen et al., 1993;

  6. Relative Binding Free Energy Calculations in Drug Discovery: Recent Advances and Practical Considerations.

    Science.gov (United States)

    Cournia, Zoe; Allen, Bryce; Sherman, Woody

    2017-12-26

    Accurate in silico prediction of protein-ligand binding affinities has been a primary objective of structure-based drug design for decades due to the putative value it would bring to the drug discovery process. However, computational methods have historically failed to deliver value in real-world drug discovery applications due to a variety of scientific, technical, and practical challenges. Recently, a family of approaches commonly referred to as relative binding free energy (RBFE) calculations, which rely on physics-based molecular simulations and statistical mechanics, have shown promise in reliably generating accurate predictions in the context of drug discovery projects. This advance arises from accumulating developments in the underlying scientific methods (decades of research on force fields and sampling algorithms) coupled with vast increases in computational resources (graphics processing units and cloud infrastructures). Mounting evidence from retrospective validation studies, blind challenge predictions, and prospective applications suggests that RBFE simulations can now predict the affinity differences for congeneric ligands with sufficient accuracy and throughput to deliver considerable value in hit-to-lead and lead optimization efforts. Here, we present an overview of current RBFE implementations, highlighting recent advances and remaining challenges, along with examples that emphasize practical considerations for obtaining reliable RBFE results. We focus specifically on relative binding free energies because the calculations are less computationally intensive than absolute binding free energy (ABFE) calculations and map directly onto the hit-to-lead and lead optimization processes, where the prediction of relative binding energies between a reference molecule and new ideas (virtual molecules) can be used to prioritize molecules for synthesis. We describe the critical aspects of running RBFE calculations, from both theoretical and applied perspectives

  7. The topological entropy of iterated piecewise affine maps is uncomputable

    Directory of Open Access Journals (Sweden)

    Pascal Koiran

    2001-12-01

    Full Text Available We show that it is impossible to compute (or even to approximate the topological entropy of a continuous piecewise affine function in dimension four. The same result holds for saturated linear functions in unbounded dimension. We ask whether the topological entropy of a piecewise affine function is always a computable real number, and conversely whether every non-negative computable real number can be obtained as the topological entropy of a piecewise affine function. It seems that these two questions are also open for cellular automata.

  8. Low affinity uniporter carrier proteins can increase net substrate uptake rate by reducing efflux

    NARCIS (Netherlands)

    Bosdriesz, Evert; Wortel, Meike T.; Haanstra, Jurgen R.; Wagner, Marijke J.; De La Torre Cortés, Pilar; Teusink, Bas

    2018-01-01

    Many organisms have several similar transporters with different affinities for the same substrate. Typically, high-affinity transporters are expressed when substrate is scarce and low-affinity ones when it is abundant. The benefit of using low instead of high-affinity transporters remains unclear,

  9. Low affinity uniporter carrier proteins can increase net substrate uptake rate by reducing efflux

    NARCIS (Netherlands)

    Bosdriesz, Evert; Wortel, M.T.; Haanstra, Jurgen R.; Wagner, Marijke J.; De La Torre, P.; Teusink, Bas

    2018-01-01

    Many organisms have several similar transporters with different affinities for the same substrate. Typically, high-affinity transporters are expressed when substrate is scarce and low-affinity ones when it is abundant. The benefit of using low instead of high-affinity transporters remains

  10. Antibody affinity maturation

    DEFF Research Database (Denmark)

    Skjødt, Mette Louise

    Yeast surface display is an effective tool for antibody affinity maturation because yeast can be used as an all-in-one workhorse to assemble, display and screen diversified antibody libraries. By employing the natural ability of yeast Saccharomyces cerevisiae to efficiently recombine multiple DNA...... laboratory conditions. A particular emphasis was put on using molecular techniques in conjunction with microenvironmental measurements (O2, pH, irradiance), a combination that is rarely found but provides a much more detailed understanding of “cause and effect” in complex natural systems...

  11. The competitor-introduced Ggamma recruitment system, a new approach for screening affinity-enhanced proteins.

    Science.gov (United States)

    Fukuda, Nobuo; Ishii, Jun; Tanaka, Tsutomu; Kondo, Akihiko

    2010-04-01

    We have developed a new approach based on the Ggamma recruitment system to screen affinity-enhanced proteins by expressing a binding competitor. The previously established Ggamma recruitment system is a yeast two-hybrid (Y2H) system that utilizes G-protein signaling, and is based on the fact that membrane localization of the G-protein gamma subunit (Ggamma) is essential for signal transduction in yeast. In the original Y2H system, an engineered Ggamma that lacks membrane localization upon deletion of the lipid modification site (Ggamma(cyto)) is produced, and a candidate protein with an artificial lipidation site and its counterpart fused with Ggamma(cyto) are expressed. As protein-protein interactions bring Ggamma(cyto) towards the plasma membrane, G-protein signaling can be activated, and the interaction is detected by various cellular responses as the readout. In the current study, we expressed a third cytosolic protein that competes with the candidate protein to specifically isolate affinity-enhanced mutants from a mutation library of the candidate protein. Enhancing the affinity of the protein candidate guides the counterpart-Ggamma(cyto) fusion protein towards the plasma membrane and activates signaling. Using mutants of the Z domain derived from Staphylococcus aureus protein A as candidate proteins or competitors, and the Fc portion of human immunoglobulin G (IgG) as the counterpart, we demonstrate that affinity-enhanced proteins can be effectively screened from a library containing a 10 000-fold excess of non-enhanced proteins. This new approach, called the competitor-introduced Ggamma recruitment system, will be useful for efficient discovery of rare valuable candidates hidden among excess ordinary ones.

  12. Affinity biosensors: techniques and protocols

    National Research Council Canada - National Science Library

    Rogers, Kim R; Mulchandani, Ashok

    1998-01-01

    ..., and government to begin or expand their biosensors research. This volume, Methods in Biotechnology vol. 7: Affinity Biosensors: Techniques and Protocols, describes a variety of classical and emerging transduction technologies that have been interfaced to bioaffinity elements (e.g., antibodies and receptors). Some of the reas...

  13. A Lyapunov method for stability analysis of piecewise-affine systems over non-invariant domains

    Science.gov (United States)

    Rubagotti, Matteo; Zaccarian, Luca; Bemporad, Alberto

    2016-05-01

    This paper analyses stability of discrete-time piecewise-affine systems, defined on possibly non-invariant domains, taking into account the possible presence of multiple dynamics in each of the polytopic regions of the system. An algorithm based on linear programming is proposed, in order to prove exponential stability of the origin and to find a positively invariant estimate of its region of attraction. The results are based on the definition of a piecewise-affine Lyapunov function, which is in general discontinuous on the boundaries of the regions. The proposed method is proven to lead to feasible solutions in a broader range of cases as compared to a previously proposed approach. Two numerical examples are shown, among which a case where the proposed method is applied to a closed-loop system, to which model predictive control was applied without a-priori guarantee of stability.

  14. The affine quantum gravity programme

    CERN Document Server

    Klauder, J R

    2002-01-01

    The central principle of affine quantum gravity is securing and maintaining the strict positivity of the matrix left brace g-hat sub a sub b (x)right brace composed of the spatial components of the local metric operator. On spectral grounds, canonical commutation relations are incompatible with this principle, and they must be replaced by noncanonical, affine commutation relations. Due to the partial second-class nature of the quantum gravitational constraints, it is advantageous to use the recently developed projection operator method, which treats all quantum constraints on an equal footing. Using this method, enforcement of regularized versions of the gravitational operator constraints is formulated quite naturally by means of a novel and relatively well-defined functional integral involving only the same set of variables that appears in the usual classical formulation. It is anticipated that skills and insight to study this formulation can be developed by studying special, reduced-variable models that sti...

  15. Calculating Program for Decommissioning Work Productivity based on Decommissioning Activity Experience Data

    Energy Technology Data Exchange (ETDEWEB)

    Song, Chan-Ho; Park, Seung-Kook; Park, Hee-Seong; Moon, Jei-kwon [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-10-15

    KAERI is performing research to calculate a coefficient for decommissioning work unit productivity to calculate the estimated time decommissioning work and estimated cost based on decommissioning activity experience data for KRR-2. KAERI used to calculate the decommissioning cost and manage decommissioning activity experience data through systems such as the decommissioning information management system (DECOMMIS), Decommissioning Facility Characterization DB System (DEFACS), decommissioning work-unit productivity calculation system (DEWOCS). In particular, KAERI used to based data for calculating the decommissioning cost with the form of a code work breakdown structure (WBS) based on decommissioning activity experience data for KRR-2.. Defined WBS code used to each system for calculate decommissioning cost. In this paper, we developed a program that can calculate the decommissioning cost using the decommissioning experience of KRR-2, UCP, and other countries through the mapping of a similar target facility between NPP and KRR-2. This paper is organized as follows. Chapter 2 discusses the decommissioning work productivity calculation method, and the mapping method of the decommissioning target facility will be described in the calculating program for decommissioning work productivity. At KAERI, research on various decommissioning methodologies of domestic NPPs will be conducted in the near future. In particular, It is difficult to determine the cost of decommissioning because such as NPP facility have the number of variables, such as the material of the target facility decommissioning, size, radiographic conditions exist.

  16. Calculating Program for Decommissioning Work Productivity based on Decommissioning Activity Experience Data

    International Nuclear Information System (INIS)

    Song, Chan-Ho; Park, Seung-Kook; Park, Hee-Seong; Moon, Jei-kwon

    2014-01-01

    KAERI is performing research to calculate a coefficient for decommissioning work unit productivity to calculate the estimated time decommissioning work and estimated cost based on decommissioning activity experience data for KRR-2. KAERI used to calculate the decommissioning cost and manage decommissioning activity experience data through systems such as the decommissioning information management system (DECOMMIS), Decommissioning Facility Characterization DB System (DEFACS), decommissioning work-unit productivity calculation system (DEWOCS). In particular, KAERI used to based data for calculating the decommissioning cost with the form of a code work breakdown structure (WBS) based on decommissioning activity experience data for KRR-2.. Defined WBS code used to each system for calculate decommissioning cost. In this paper, we developed a program that can calculate the decommissioning cost using the decommissioning experience of KRR-2, UCP, and other countries through the mapping of a similar target facility between NPP and KRR-2. This paper is organized as follows. Chapter 2 discusses the decommissioning work productivity calculation method, and the mapping method of the decommissioning target facility will be described in the calculating program for decommissioning work productivity. At KAERI, research on various decommissioning methodologies of domestic NPPs will be conducted in the near future. In particular, It is difficult to determine the cost of decommissioning because such as NPP facility have the number of variables, such as the material of the target facility decommissioning, size, radiographic conditions exist

  17. Affinity resins as new tools for identifying target proteins of ascorbic acid.

    Science.gov (United States)

    Iwaoka, Yuji; Nishino, Kohei; Ishikawa, Takahiro; Ito, Hideyuki; Sawa, Yoshihiro; Tai, Akihiro

    2018-02-12

    l-Ascorbic acid (AA) has diverse physiological functions, but little is known about the functional mechanisms of AA. In this study, we synthesized two types of affinity resin on which AA is immobilized in a stable form to identify new AA-targeted proteins, which can provide important clues for elucidating unknown functional mechanisms of AA. To our knowledge, an affinity resin on which AA as a ligand is immobilized has not been prepared, because AA is very unstable and rapidly degraded in an aqueous solution. By using the affinity resins, cytochrome c (cyt c) was identified as an AA-targeted protein, and we showed that oxidized cyt c exhibits specific affinity for AA. These results suggest that two kinds of AA-affinity resin can be powerful tools to identify new target proteins of AA.

  18. Analysis of Weyl-affine theories of gravity in terms of the gravitational frequency shift effect

    International Nuclear Information System (INIS)

    Coley, A.A.; Sarmiento, G.A.

    1986-01-01

    A subclass of nonmetric theories of gravity, called Weyl-affine theories of gravity (WATGs), is analyzed by calculating their predictions for the gravitational frequency shift undergone by a wave signal in a planned solar probe. The analysis is carried out using a formalism in a spherically symmetric and static gravitational field. One of the advantages of the formalism is that any possible ''nonmetricity'' is contained in an arbitrary function, λ, of the Newtonian gravitational potential, U. The numerical results are calculated for a situation modeling a future experiment in the solar system. In the calculations, the metric components and the function, λ, are expanded up to third order in U. Within the limits of the gravitational redshift experiments performed to date, it is found that WATGs must coincide with their metric counterparts (i.e., λ is unity). It is hoped that the planned solar probe will test the nature of the theories under investigation to a higher degree of accuracy

  19. Modeling DNA affinity landscape through two-round support vector regression with weighted degree kernels

    KAUST Repository

    Wang, Xiaolei; Kuwahara, Hiroyuki; Gao, Xin

    2014-01-01

    high-quality estimates of such complex affinity landscapes is, thus, essential to the control of gene expression and the advance of synthetic biology. Results: Here, we propose a two-round prediction method that is based on support vector regression

  20. Homogeneous competitive assay of ligand affinities based on quenching fluorescence of tyrosine/tryptophan residues in a protein via Főrster-resonance-energy-transfer

    Science.gov (United States)

    Xie, Yanling; Yang, Xiaolan; Pu, Jun; Zhao, Yunsheng; Zhang, Ying; Xie, Guoming; Zheng, Jun; Yuan, Huidong; Liao, Fei

    2010-11-01

    A new homogeneous competitive assay of ligand affinities was proposed based on quenching the fluorescence of tryptophan/tyrosine residues in a protein via Főrster-resonance-energy-transfer using a fluorescent reference ligand as the acceptor. Under excitation around 280 nm, the fluorescence of a protein or a bound acceptor was monitored upon competitive binding against a nonfluorescent candidate ligand. Chemometrics for deriving the binding ratio of the acceptor with either fluorescence signal was discussed; the dissociation constant ( Kd) of a nonfluorescent candidate ligand was calculated from its concentration to displace 50% binding of the acceptor. N-biotinyl-N'-(1-naphthyl)-ethylenediamine (BNEDA) and N-biotinyl-N'-dansyl-ethylenediamine (BDEDA) were used as the reference ligands and acceptors to streptavidin to test this new homogeneous competitive assay. Upon binding of an acceptor to streptavidin, there were the quench of streptavidin fluorescence at 340 nm and the characteristic fluorescence at 430 nm for BNEDA or at 525 nm for BDEDA. Kd of BNEDA and BDEDA was obtained via competitive binding against biotin. By quantifying BNEDA fluorescence, Kd of each tested nonfluorescent biotin derivative was consistent with that by quantifying streptavidin fluorescence using BNEDA or BDEDA as the acceptor. The overall coefficients of variation were about 10%. Therefore, this homogeneous competitive assay was effective and promising to high-throughput-screening.

  1. Affinity for Poetry and Aesthetic Appreciation of Joyful and Sad Poems.

    Science.gov (United States)

    Kraxenberger, Maria; Menninghaus, Winfried

    2016-01-01

    Artworks with sad and affectively negative content have repeatedly been reported to elicit positive aesthetic appreciation. This topic has received much attention both in the history of poetics and aesthetics as well as in recent studies on sad films and sad music. However, poetry and aesthetic evaluations of joyful and sad poetry have received only little attention in empirical studies to date. We collected beauty and liking ratings for 24 sad and 24 joyful poems from 128 participants. Following previous studies, we computed an integrated measure for overall aesthetic appreciation based on the beauty and liking ratings to test for differences in appreciation between joyful and sad poems. Further, we tested whether readers' judgments are related to their affinity for poetry. Results show that sad poems are rated significantly higher for aesthetic appreciation than joyful poems, and that aesthetic appreciation is influenced by the participants' affinity for poetry.

  2. Dental affinities of the C-group inhabitants of Hierakonpolis, Egypt: Nubian, Egyptian, or both?

    Science.gov (United States)

    Irish, J D; Friedman, R

    2010-04-01

    By c. 2050 BC a small community of C-Group Nubians was present deep within Egyptian territory at the city of Hierakonpolis. Their descendants stayed for the next 400 years. Today, the site of Hierakonpolis, 113 km north of Aswan, is known for its Egyptian deposits; however, it also contains a C-Group cemetery, which documents the northernmost occurrence of this culture. Sixty skeletons were excavated. Tombs feature Nubian architecture and goods, including leather garments, although the use of Egyptian mortuary practices and artifacts increased through time. Dates range from the early 11th Dynasty into the Second Intermediate period. During this time the Egyptian empire occupied Lower Nubia, and their state ideology vilified Nubians. Yet, at least in death, the C-Group inhabitants of Hierakonpolis proudly displayed their cultural heritage. Beyond discerning the reason(s) for their presence at the site (e.g., mercenaries, leather-workers, entertainers?), the focus of this report is to estimate their biological affinity. Were they akin to other Nubians, Egyptians, or both? And, was increasing 'Egyptianization' evident in the mortuary ritual accompanied by concomitant genetic influence? To address these queries, up to 36 dental morphological traits in the recovered individuals were compared to those in 26 regional comparative samples. The most influential traits were identified and phenetic affinities were calculated using the mean measure of divergence and other multivariate analyses. Assuming phenetic similarity provides an estimate of genetic relatedness, these affinities suggest the individuals comprising the C-Group sample were, and remained Nubian during their tenure at Hierakonpolis. Copyright 2010 Elsevier GmbH. All rights reserved.

  3. Production and Identification of High Affinity Monoclonal Antibodies Against Pesticide Carbofuran

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    To produce high-affinity monoclonal antibodies against pesticide carbofuran, and the develop immunochemical assays for people's health and environmental protection, the hapten 4-[[(2,3-dihydro-2,2-dimethyl-7-benzofuranyloxy) carbonyl]-amino]-butanoic acid (BFNB) of carbofuran was synthesized and Balb/c mice were immunized by the hapten-carrier (BFNB-bovine serum albumin, BFNB-BSA) conjugates. The splenocytes of immunized mice were fused with Sp2/0 cells and the cultural supernatants of hybridoma cells were screened by the indirect enzyme-linked immunoabsorbent assay (ELISA), based on BFNB-ovoalbumin conjugates (BFNB-OVA). Purified monoclonal antibody (McAb) was obtained from fluids of ascites, deposited by octanoic acid and ammonium sulfate. The affinity and the specificity of McAb were characterized by ELISA or indirect competitive ELISA. A hybridoma cell line (5D3) secreting anti-carbofuran McAb had been established. The titer of culture medium and ascites was up to 1:2.048 × 103 and 1:1.024 × 106, respectively, and the subtype of the McAb was IgG1. The affinity constant of the McAb was about 2.54 × 109 L mol-1, with an IC50 value of 1.18 ng mL-1 and a detection limit of 0.01 ng mL-1. Cross-reactivity studies showed that the McAb was quiet specific for carbofuran, as among the four analogous compounds, they were all hardly recognized (4.59 × 10-4% for 2,3-dihydro-2,2-dimethyl-7-benzofuranol and less than 3.0 × 10-4% for others). The prepared McAb had a very high affinity and specificity,and it could be used to develop ELISA for rapid determination of carbofuran.

  4. Online identification of continuous bimodal and trimodal piecewise affine systems

    NARCIS (Netherlands)

    Le, Q.T.; van den Boom, A.J.J.; Baldi, S.; Rantzer, Anders; Bagterp Jørgensen, John; Stoustrup, Jakob

    2016-01-01

    This paper investigates the identification of continuous piecewise affine systems in state space form with jointly unknown partition and subsystem matrices. The partition of the system is generated by the so-called centers. By representing continuous piecewise affine systems in the max-form and

  5. Nonempirical electron-correlation calculations on ALik and Alik+1+ clusters formed with elements from the second and third periods

    International Nuclear Information System (INIS)

    Mebel', A.M.; Klimenko, N.M.; Charkin, O.P.

    1988-01-01

    Several basic sets have been used (from 3-21 G A * to DZHD + P A ) with electron correlation in the Meller-Plesset MP3 approximation in nonempirical calculations on ALi k+1 + and ALi K+1 + lithium clusters (CLi 2 , CLi 3 + , NLi 3 , NLi 4 + , OLi 2 , OLi 3 + , etc.) formed with elements from the second and third periods in the lowest singlet states. A study has been made on the effects of the approximation on the results. Several reference systems are used to show that the SCF/3-21G A * approximation describes the lithide geometry satisfactorily, while MP3/DZHD + P A gives a satisfactory description of the affinity of Ali k for Li + . These approximations have been taken as optimal for calculations on the other compounds. The Li + affinities are highest for NLi 3 and PLi 3 (90 and 84 kcal correspondingly) and decrease as A varies along the subgroups from the second to the third and the lower sp periods, as well as when A varies in each period from the middle to the start or end. The affinities of the analogous compounds for Na + are less by 5-10 kcal than those for Li + . The values are compared with the proton affinities for the related hydrides AK k

  6. Affinity of Iresine herbstii and Brugmansia arborea extracts on different cerebral receptors.

    Science.gov (United States)

    Nencini, Cristina; Cavallo, Federica; Bruni, Giancarlo; Capasso, Anna; De Feo, Vincenzo; De Martino, Laura; Giorgi, Giorgio; Micheli, Lucia

    2006-05-24

    Iresine herbstii Hook. (Amaranthaceae) and Brugmansia arborea (L.) Lagerheim (Solanaceae) are used in the northern Peruvian Andes for magic-therapeutical purposes. The traditional healers use Iresine herbstii with the ritual aim to expel bad spirits from the body. Furthermore, Iresine herbstii was used in association with other plants, such as Trichocereus pachanoi Britt. et Rose, for divination, to diagnose diseases, and to take possession of another identity. Also, species of Brugmansia have been reported to be used during ritual practices for magical and curative purposes. Given the above evidence, the aim of the present study is to evaluate if the central effects of Iresine herbstii and Brugmansia arborea could be associated with interaction with SNC receptors. Two Iresine herbstii extracts (methanolic and aqueous) and one Brugmansia arborea aqueous extract were tested for in vitro affinity on 5-HT(1A), 5-HT(2A), 5-HT(2C), D1, D2, alpha(1), and alpha(2) receptors by radioligand binding assays. The biological materials for binding assay (cerebral cortex) were taken from male Sprague-Dawley rats. The extracts affinity for receptors is definite as inhibition percentage of radioligand/receptor binding and measured as the radioactivity of remaining complex radioligand/receptor. The data obtained for Iresine extracts have shown a low affinity for the 5-HT(1A) receptor and no affinity for 5-HT(2A) receptor. Otherwise the methanolic extract showed affinity for 5-HT(2C) receptor (IC(50): 34.78 microg/ml) and for D1 receptor (IC(50): 19.63 microg/ml), instead the Iresine aqueous extract displayed a lower affinity for D1 (48.3% at the maximum concentration tested) and a higher value of affinity for D2 receptors (IC(50): 32.08 microg/ml). The Brugmansia aqueous extract displayed affinity for D1 receptors (IC(50): 17.68 microg/ml), D2 receptors (IC(50): 15.95 microg/ml) and weak affinity for the serotoninergic receptors. None of the three extracts showed relevant affinity

  7. Biochemical method for fast affinity diagnosis in grape-vine transplantation

    International Nuclear Information System (INIS)

    Lilov, D.

    1977-01-01

    Long term experiments have proved the affinity of cv. Mavroud in transplantations on various root stocks. Best affinity was observed in the combination cv. Mavroud X Riparia tomanteau, followed, in a descending order, by the combinations Mavroud X Mavroud (autotransplantation), Mavroud X Berlandieri X Riparia Kobber SBB and Mavroud X Riparia 33 EM. In view to establish indices for predicting the transplantation affinity a great number of physiological-biochemical and morphological-anatomical studies were carried out. The results obtained showed that a most clearly expressed positive, statistically significant correlation exists between the amount of 15 N transported from the root stock to the scions, shoots and leaves. As a result, a biochemical method for fast affinity diagnosis in grape-vine transplantation has been developed. The reliability of the method has been checked up also with other cultivars. Up to the present no such method was known in grape-vine science and practice. (author)

  8. Methods for quantifying T cell receptor binding affinities and thermodynamics

    Science.gov (United States)

    Piepenbrink, Kurt H.; Gloor, Brian E.; Armstrong, Kathryn M.; Baker, Brian M.

    2013-01-01

    αβ T cell receptors (TCRs) recognize peptide antigens bound and presented by class I or class II major histocompatibility complex (MHC) proteins. Recognition of a peptide/MHC complex is required for initiation and propagation of a cellular immune response, as well as the development and maintenance of the T cell repertoire. Here we discuss methods to quantify the affinities and thermodynamics of interactions between soluble ectodomains of TCRs and their peptide/MHC ligands, focusing on titration calorimetry, surface plasmon resonance, and fluorescence anisotropy. As TCRs typically bind ligand with weak-to-moderate affinities, we focus the discussion on means to enhance the accuracy and precision of low affinity measurements. In addition to further elucidating the biology of the T cell mediated immune response, more reliable low affinity measurements will aid with more probing studies with mutants or altered peptides that can help illuminate the physical underpinnings of how TCRs achieve their remarkable recognition properties. PMID:21609868

  9. Affinity purification using recombinant PXR as a tool to characterize environmental ligands.

    Science.gov (United States)

    Dagnino, Sonia; Bellet, Virginie; Grimaldi, Marina; Riu, Anne; Aït-Aïssa, Sélim; Cavaillès, Vincent; Fenet, Hélène; Balaguer, Patrick

    2014-02-01

    Many environmental endocrine disrupting compounds act as ligands for nuclear receptors. The human pregnane X receptor (hPXR), for instance, is activated by a variety of environmental ligands such as steroids, pharmaceutical drugs, pesticides, alkylphenols, polychlorinated biphenyls and polybromo diethylethers. Some of us have previously reported the occurrence of hPXR ligands in environmental samples but failed to identify them. The aim of this study was to test whether a PXR-affinity column, in which recombinant hPXR was immobilized on solid support, could help the purification of these chemicals. Using PXR ligands of different affinity (10 nM < EC50 < 10 μM), we demonstrated that the PXR-affinity preferentially column captured ligands with medium to high affinities (EC50 < 1 μM). Furthermore, by using the PXR-affinity column to analyze an environmental sample containing ERα, AhR, AR, and PXR activities, we show that (i) half of the PXR activity of the sample was due to compounds with medium to high affinity for PXR and (ii) PXR shared ligands with ERα, AR, and AhR. These findings demonstrate that the newly developed PXR-affinity column coupled to reporter cell lines represents a valuable tool for the characterization of the nature of PXR active compounds and should therefore guide and facilitate their further analysis. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

  10. Visual and Plasmon Resonance Absorption Sensor for Adenosine Triphosphate Based on the High Affinity between Phosphate and Zr(IV).

    Science.gov (United States)

    Qi, Wenjing; Liu, Zhongyuan; Zhang, Wei; Halawa, Mohamed Ibrahim; Xu, Guobao

    2016-10-12

    Zr(IV) can form phosphate and Zr(IV) (-PO₃ 2- -Zr 4+ -) complex owing to the high affinity between Zr(IV) with phosphate. Zr(IV) can induce the aggregation of gold nanoparticles (AuNPs), while adenosine triphosphate(ATP) can prevent Zr(IV)-induced aggregation of AuNPs. Herein, a visual and plasmon resonance absorption (PRA)sensor for ATP have been developed using AuNPs based on the high affinity between Zr(IV)with ATP. AuNPs get aggregated in the presence of certain concentrations of Zr(IV). After the addition of ATP, ATP reacts with Zr(IV) and prevents AuNPs from aggregation, enabling the detection of ATP. Because of the fast interaction of ATP with Zr(IV), ATP can be detected with a detection limit of 0.5 μM within 2 min by the naked eye. Moreover, ATP can be detected by the PRA technique with higher sensitivity. The A 520nm / A 650nm values in PRA spectra increase linearly with the concentrations of ATP from 0.1 μM to 15 μM (r = 0.9945) with a detection limit of 28 nM. The proposed visual and PRA sensor exhibit good selectivity against adenosine, adenosine monophosphate, guanosine triphosphate, cytidine triphosphate and uridine triphosphate. The recoveries for the analysis of ATP in synthetic samples range from 95.3% to 102.0%. Therefore, the proposed novel sensor for ATP is promising for real-time or on-site detection of ATP.

  11. Hierarchy and Assortativity as New Tools for Binding-Affinity Investigation: The Case of the TBA Aptamer-Ligand Complex.

    Science.gov (United States)

    Cataldo, Rosella; Alfinito, Eleonora; Reggiani, Lino

    2017-12-01

    Aptamers are single stranded DNA, RNA, or peptide sequences having the ability to bind several specific targets (proteins, molecules as well as ions). Therefore, aptamer production and selection for therapeutic and diagnostic applications is very challenging. Usually, they are generated in vitro, although computational approaches have been recently developed for the in silico production. Despite these efforts, the mechanism of aptamer-ligand formation is not completely clear, and producing high-affinity aptamers is still quite difficult. This paper aims to develop a computational model able to describe aptamer-ligand affinity. Topological tools, such as the conventional degree distribution, the rank-degree distribution (hierarchy), and the node assortativity are employed. In doing so, the macromolecules tertiary-structures are mapped into appropriate graphs. These graphs reproduce the main topological features of the macromolecules, by preserving the distances between amino acids (nucleotides). Calculations are applied to the thrombin binding aptamer (TBA), and the TBA-thrombin complex produced in the presence of Na + or K + . The topological analysis is able to detect several differences between complexes obtained in the presence of the two cations, as expected by previous investigations. These results support graph analysis as a novel computational tool for testing affinity. Otherwise, starting from the graphs, an electrical network can be obtained by using the specific electrical properties of amino acids and nucleobases. Therefore, a further analysis concerns with the electrical response, revealing that the resistance is sensitively affected by the presence of sodium or potassium, thus suggesting resistance as a useful physical parameter for testing binding affinity.

  12. Interactions of model biomolecules. Benchmark CC calculations within MOLCAS

    Energy Technology Data Exchange (ETDEWEB)

    Urban, Miroslav [Slovak University of Technology in Bratislava, Faculty of Materials Science and Technology in Trnava, Institute of Materials Science, Bottova 25, SK-917 24 Trnava, Slovakia and Department of Physical and Theoretical Chemistry, Faculty of Natural Scie (Slovakia); Pitoňák, Michal; Neogrády, Pavel; Dedíková, Pavlína [Department of Physical and Theoretical Chemistry, Faculty of Natural Sciences, Comenius University, Mlynská dolina, SK-842 15 Bratislava (Slovakia); Hobza, Pavel [Institute of Organic Chemistry and Biochemistry and Center for Complex Molecular Systems and biomolecules, Academy of Sciences of the Czech Republic, Prague (Czech Republic)

    2015-01-22

    We present results using the OVOS approach (Optimized Virtual Orbitals Space) aimed at enhancing the effectiveness of the Coupled Cluster calculations. This approach allows to reduce the total computer time required for large-scale CCSD(T) calculations about ten times when the original full virtual space is reduced to about 50% of its original size without affecting the accuracy. The method is implemented in the MOLCAS computer program. When combined with the Cholesky decomposition of the two-electron integrals and suitable parallelization it allows calculations which were formerly prohibitively too demanding. We focused ourselves to accurate calculations of the hydrogen bonded and the stacking interactions of the model biomolecules. Interaction energies of the formaldehyde, formamide, benzene, and uracil dimers and the three-body contributions in the cytosine – guanine tetramer are presented. Other applications, as the electron affinity of the uracil affected by solvation are also shortly mentioned.

  13. Titanium dioxide as chemo-affinity chromatographic sorbent of biomolecular compounds - Applications in acidic modification-specific proteomics

    DEFF Research Database (Denmark)

    Engholm-Keller, Kasper; Larsen, Martin R

    2011-01-01

    biomolecules due to its unique ion and ligand exchange properties and high stability towards pH and temperature. Recently, titanium dioxide chromatography was introduced in proteomics as a highly specific method for enriching phosphorylated peptides - a method, which has been widely adapted by the field...... matrices for further characterization is affinity chromatography, which relies on the specific interaction between an analyte in solution and a solid adsorbent. Titanium dioxide-based affinity chromatography has proven to be a versatile tool in enrichment of various compounds such as phosphorylated....... The development of TiO(2)-based chromatographic strategies for separation of various biomolecules from its introduction for small molecules more than 20years ago until recent proteomics applications today will be reviewed here....

  14. Decrease in the red cell cofactor 2,3-diphosphoglycerate increases hemoglobin oxygen affinity in the hibernating brown bear Ursus arctos.

    Science.gov (United States)

    Revsbech, Inge G; Malte, Hans; Fröbert, Ole; Evans, Alina; Blanc, Stéphane; Josefsson, Johan; Fago, Angela

    2013-01-01

    During winter hibernation, brown bears (Ursus arctos) reduce basal O(2) consumption rate to ∼25% compared with the active state, while body temperature decreases moderately (to ∼30°C), suggesting a temperature-independent component in their metabolic depression. To establish whether changes in O(2) consumption during hibernation correlate with changes in blood O(2) affinity, we took blood samples from the same six individuals of hibernating and nonhibernating free-ranging brown bears during winter and summer, respectively. A single hemoglobin (Hb) component was detected in all samples, indicating no switch in Hb synthesis. O(2) binding curves measured on red blood cell lysates at 30°C and 37°C showed a less temperature-sensitive O(2) affinity than in other vertebrates. Furthermore, hemolysates from hibernating bears consistently showed lower cooperativity and higher O(2) affinity than their summer counterparts, regardless of the temperature. We found that this increase in O(2) affinity was associated with a significant decrease in the red cell Hb-cofactor 2,3-diphosphoglycerate (DPG) during hibernation to approximately half of the summer value. Experiments performed on purified Hb, to which DPG had been added to match summer and winter levels, confirmed that the low DPG content was the cause of the left shift in the Hb-O(2) equilibrium curve during hibernation. Levels of plasma lactate indicated that glycolysis is not upregulated during hibernation and that metabolism is essentially aerobic. Calculations show that the increase in Hb-O(2) affinity and decrease in cooperativity resulting from decreased red cell DPG may be crucial in maintaining a fairly constant tissue oxygen tension during hibernation in vivo.

  15. Proton affinities of maingroup-element hydrides and noble gases: trends across the periodic table, structural effects, and DFT validation.

    Science.gov (United States)

    Swart, Marcel; Rösler, Ernst; Bickelhaupt, F Matthias

    2006-10-01

    We have carried out an extensive exploration of the gas-phase basicity of archetypal neutral bases across the periodic system using the generalized gradient approximation (GGA) of the density functional theory (DFT) at BP86/QZ4P//BP86/TZ2P. First, we validate DFT as a reliable tool for computing proton affinities and related thermochemical quantities: BP86/QZ4P//BP86/TZ2P is shown to yield a mean absolute deviation of 2.0 kcal/mol for the proton affinity at 298 K with respect to experiment, and 1.2 kcal/mol with high-level ab initio benchmark data. The main purpose of this work is to provide the proton affinities (and corresponding entropies) at 298 K of the neutral bases constituted by all maingroup-element hydrides of groups 15-17 and the noble gases, that is, group 18, and periods 1-6. We have also studied the effect of step-wise methylation of the protophilic center of the second- and third-period bases. Copyright 2006 Wiley Periodicals, Inc.

  16. APPLICATION OF IMMUNOGLOBULIN-BINDING PROTEINS A, G, L IN THE AFFINITY CHROMATOGRAPHY

    Directory of Open Access Journals (Sweden)

    О. V. Sviatenko

    2014-04-01

    Full Text Available Proteins A, G and L are native or recombinant proteins of microbial origin that bind to mammalian immunoglobulins. Preferably recombinant variants of proteins A, G, L are used in biotechnology for affinity sorbents production. Сomparative characteristics of proteins A, G, L and affinity sorbents on the basis of them, advantages and disadvantages of these proteins application as ligands in the affinity chromatography are done. Analysis of proteins A, G, L properties is presented. Binding specificities and affinities of these proteins differ between species and antibody subclass. Protein А has high affinity to human IgG1, IgG2, IgG4, mouse IgG2a, IgG2b, IgG3, goat and sheep IgG2, dog, cat, guinea pig, rabbit IgG. Protein G binds strongly to human, mouse, cow, goat, sheep and rabbit IgG. Protein L has ability of strong binding to immunoglobulin kappa-chains of human, mouse, rat and pig. Expediency of application of affinity chromatography with usage of sorbents on the basis of immobilized proteins A, G, L are shown for isolation and purification of antibodies different classes. Previously mentioned method is used as an alternative to conventional methods of protein purification, such as ion-exchange, hydrophobic interactions, metal affinity chromatography, ethanol precipitation due to simplicity in usage, possibility of one-step purification process, obtaining of proteins high level purity, multiuse at maintenance of proper storage and usage conditions. Affinity sorbents on the basis of immobilized proteins A, G, L are used not only for antibodies purification, but also for extraction of different antibodies fractions from blood serum.

  17. The O-H Bond Dissociation Energies of Substituted Phenols and Proton Affinities of Substituted Phenoxide Ions: A DFT Study

    Directory of Open Access Journals (Sweden)

    Tadafumi Uchimaru

    2002-04-01

    Full Text Available Abstract: The accurate O-H bond dissociation enthalpies for a series of meta and para substituted phenols (X-C6H4-OH, X=H, F, Cl, CH3, OCH3, OH, NH2, CF3, CN, and NO2 have been calculated by using the (ROB3LYP procedure with 6-311G(d,p and 6-311++G(2df,2p basis sets. The proton affinities of the corresponding phenoxide ions (XC6H4-O- have also been computed at the same level of theory. The effect of change of substituent position on the energetics of substituted phenols has been analyzed. The correlations of Hammett’s substituent constants with the bond dissociation enthalpies of the O-H bonds of phenols and proton affinities of phenoxide ions have been explored.

  18. 3D atlas-based registration can calculate malalignment of femoral shaft fractures in six degrees of freedom.

    Science.gov (United States)

    Crookshank, Meghan C; Beek, Maarten; Hardisty, Michael R; Schemitsch, Emil H; Whyne, Cari M

    2014-01-01

    This study presents and evaluates a semi-automated algorithm for quantifying malalignment in complex femoral shaft fractures from a single intraoperative cone-beam CT (CBCT) image of the fractured limb. CBCT images were acquired of complex comminuted diaphyseal fractures created in 9 cadaveric femora (27 cases). Scans were segmented using intensity-based thresholding, yielding image stacks of the proximal, distal and comminuted bone. Semi-deformable and rigid affine registrations to an intact femur atlas (synthetic or cadaveric-based) were performed to transform the distal fragment to its neutral alignment. Leg length was calculated from the volume of bone within the comminution fragment. The transformations were compared to the physical input malalignments. Using the synthetic atlas, translations were within 1.71 ± 1.08 mm (medial/lateral) and 2.24 ± 2.11 mm (anterior/posterior). The varus/valgus, flexion/extension and periaxial rotation errors were 3.45 ± 2.6°, 1.86 ± 1.5° and 3.4 ± 2.0°, respectively. The cadaveric-based atlas yielded similar results in medial/lateral and anterior/posterior translation (1.73 ± 1.28 mm and 2.15 ± 2.13 mm, respectively). Varus/valgus, flexion/extension and periaxial rotation errors were 2.3 ± 1.3°, 2.0 ± 1.6° and 3.4 ± 2.0°, respectively. Leg length errors were 1.41 ± 1.01 mm (synthetic) and 1.26 ± 0.94 mm (cadaveric). The cadaveric model demonstrated a small improvement in flexion/extension and the synthetic atlas performed slightly faster (6 min 24 s ± 50 s versus 8 min 42 s ± 2 min 25 s). This atlas-based algorithm quantified malalignment in complex femoral shaft fractures within clinical tolerances from a single CBCT image of the fractured limb.

  19. Failure Probability Calculation Method Using Kriging Metamodel-based Importance Sampling Method

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seunggyu [Korea Aerospace Research Institue, Daejeon (Korea, Republic of); Kim, Jae Hoon [Chungnam Nat’l Univ., Daejeon (Korea, Republic of)

    2017-05-15

    The kernel density was determined based on sampling points obtained in a Markov chain simulation and was assumed to be an important sampling function. A Kriging metamodel was constructed in more detail in the vicinity of a limit state. The failure probability was calculated based on importance sampling, which was performed for the Kriging metamodel. A pre-existing method was modified to obtain more sampling points for a kernel density in the vicinity of a limit state. A stable numerical method was proposed to find a parameter of the kernel density. To assess the completeness of the Kriging metamodel, the possibility of changes in the calculated failure probability due to the uncertainty of the Kriging metamodel was calculated.

  20. Occupation of low-affinity cholecystokinin (CCK) receptors by CCK activates signal transduction and stimulates amylase secretion in pancreatic acinar cells.

    Science.gov (United States)

    Vinayek, R; Patto, R J; Menozzi, D; Gregory, J; Mrozinski, J E; Jensen, R T; Gardner, J D

    1993-03-10

    Based on the effects of monensin on binding of 125I-CCK-8 and its lack of effect on CCK-8-stimulated amylase secretion we previously proposed that pancreatic acinar cells possess three classes of CCK receptors: high-affinity receptors, low-affinity receptors and very low-affinity receptors [1]. In the present study we treated pancreatic acini with carbachol to induce a complete loss of high-affinity CCK receptors and then examined the action of CCK-8 on inositol trisphosphate IP3(1,4,5), cytosolic calcium and amylase secretion in an effort to confirm and extend our previous hypothesis. We found that first incubating pancreatic acini with 10 mM carbachol decreased binding of 125I-CCK-8 measured during a second incubation by causing a complete loss of high-affinity CCK receptors with no change in the low-affinity CCK receptors. Carbachol treatment of acini, however, did not alter the action of CCK-8 on IP3(1,4,5), cytosolic calcium or amylase secretion or the action of CCK-JMV-180 on amylase secretion or on the supramaximal inhibition of amylase secretion caused by CCK-8. The present findings support our previous hypothesis that pancreatic acinar cells possess three classes of CCK receptors and suggest that high-affinity CCK receptors do not mediate the action of CCK-8 on enzyme secretion, that low-affinity CCK receptors may mediate the action of CCK on cytosolic calcium that does not involve IP3(1,4,5) and produce the upstroke of the dose-response curve for CCK-8-stimulated amylase secretion and that very low-affinity CCK receptors mediate the actions of CCK on IP3(1,4,5) and cytosolic calcium and produce the downstroke of the dose-response curve for CCK-8-stimulated amylase secretion. Moreover, CCK-JMV-180 is a full agonist for stimulating amylase secretion by acting at low-affinity CCK receptors and is an antagonist at very low-affinity CCK receptors.

  1. Simulation and analysis of main steam control system based on heat transfer calculation

    Science.gov (United States)

    Huang, Zhenqun; Li, Ruyan; Feng, Zhongbao; Wang, Songhan; Li, Wenbo; Cheng, Jiwei; Jin, Yingai

    2018-05-01

    In this paper, after thermal power plant 300MW boiler was studied, mat lab was used to write calculation program about heat transfer process between the main steam and boiler flue gas and amount of water was calculated to ensure the main steam temperature keeping in target temperature. Then heat transfer calculation program was introduced into Simulink simulation platform based on control system multiple models switching and heat transfer calculation. The results show that multiple models switching control system based on heat transfer calculation not only overcome the large inertia of main stream temperature, a large hysteresis characteristic of main stream temperature, but also adapted to the boiler load changing.

  2. Effect of 2,3-diphosphoglycerate on oxygen affinity of blood in sickle cell anemia

    Science.gov (United States)

    Charache, Samuel; Grisolia, Santiago; Fiedler, Adam J.; Hellegers, Andre E.

    1970-01-01

    Blood of patients with sickle cell anemia (SS) exhibits decreased affinity for oxygen, although the oxygen affinity of hemoglobin S is the same as that of hemoglobin A. SS red cells contain more 2,3-diphosphoglycerate (DPG) than normal erythrocytes. The oxygen affinity of hemolyzed red cells is decreased by added DPG, and hemolysates prepared from SS red cells do not differ from normal hemolysates in this regard. Reduction of oxygen affinity to the levels found in intact SS red cells required DPG concentrations in excess of those found in most SS patients. The same was true of oxygen affinity of patients with pyruvate kinase deficiency. Other organic phosphates, as well as inorganic ions, are known to alter the oxygen affinity of dilute solutions of hemoglobin. These substances, the state of aggregation of hemoglobin molecules, and cytoarchitectural factors probably play roles in determining oxygen affinity of both normal and SS red cells. PMID:5443181

  3. On the Lp affine isoperimetric inequalities

    Indian Academy of Sciences (India)

    surface area measure on convex bodies. We also establish the reverse version of -Petty projection inequality and an affine isoperimetric inequality of − p K . Author Affiliations. Wuyang Yu1 Gangsong Leng2. Institute of Management Decision ...

  4. Specificity and affinity quantification of flexible recognition from underlying energy landscape topography.

    Directory of Open Access Journals (Sweden)

    Xiakun Chu

    2014-08-01

    Full Text Available Flexibility in biomolecular recognition is essential and critical for many cellular activities. Flexible recognition often leads to moderate affinity but high specificity, in contradiction with the conventional wisdom that high affinity and high specificity are coupled. Furthermore, quantitative understanding of the role of flexibility in biomolecular recognition is still challenging. Here, we meet the challenge by quantifying the intrinsic biomolecular recognition energy landscapes with and without flexibility through the underlying density of states. We quantified the thermodynamic intrinsic specificity by the topography of the intrinsic binding energy landscape and the kinetic specificity by association rate. We found that the thermodynamic and kinetic specificity are strongly correlated. Furthermore, we found that flexibility decreases binding affinity on one hand, but increases binding specificity on the other hand, and the decreasing or increasing proportion of affinity and specificity are strongly correlated with the degree of flexibility. This shows more (less flexibility leads to weaker (stronger coupling between affinity and specificity. Our work provides a theoretical foundation and quantitative explanation of the previous qualitative studies on the relationship among flexibility, affinity and specificity. In addition, we found that the folding energy landscapes are more funneled with binding, indicating that binding helps folding during the recognition. Finally, we demonstrated that the whole binding-folding energy landscapes can be integrated by the rigid binding and isolated folding energy landscapes under weak flexibility. Our results provide a novel way to quantify the affinity and specificity in flexible biomolecular recognition.

  5. Differential affinity of mammalian histone H1 somatic subtypes for DNA and chromatin

    Directory of Open Access Journals (Sweden)

    Mora Xavier

    2007-05-01

    Full Text Available Abstract Background Histone H1 is involved in the formation and maintenance of chromatin higher order structure. H1 has multiple isoforms; the subtypes differ in timing of expression, extent of phosphorylation and turnover rate. In vertebrates, the amino acid substitution rates differ among subtypes by almost one order of magnitude, suggesting that each subtype might have acquired a unique function. We have devised a competitive assay to estimate the relative binding affinities of histone H1 mammalian somatic subtypes H1a-e and H1° for long chromatin fragments (30–35 nucleosomes in physiological salt (0.14 M NaCl at constant stoichiometry. Results The H1 complement of native chromatin was perturbed by adding an additional amount of one of the subtypes. A certain amount of SAR (scaffold-associated region DNA was present in the mixture to avoid precipitation of chromatin by excess H1. SAR DNA also provided a set of reference relative affinities, which were needed to estimate the relative affinities of the subtypes for chromatin from the distribution of the subtypes between the SAR and the chromatin. The amounts of chromatin, SAR and additional H1 were adjusted so as to keep the stoichiometry of perturbed chromatin similar to that of native chromatin. H1 molecules freely exchanged between the chromatin and SAR binding sites. In conditions of free exchange, H1a was the subtype of lowest affinity, H1b and H1c had intermediate affinities and H1d, H1e and H1° the highest affinities. Subtype affinities for chromatin differed by up to 19-fold. The relative affinities of the subtypes for chromatin were equivalent to those estimated for a SAR DNA fragment and a pUC19 fragment of similar length. Avian H5 had an affinity ~12-fold higher than H1e for both DNA and chromatin. Conclusion H1 subtypes freely exchange in vitro between chromatin binding sites in physiological salt (0.14 M NaCl. The large differences in relative affinity of the H1 subtypes for

  6. Binding affinity and adhesion force of organophosphate hydrolase enzyme with soil particles related to the isoelectric point of the enzyme.

    Science.gov (United States)

    Islam, Shah Md Asraful; Yeasmin, Shabina; Islam, Md Saiful; Islam, Md Shariful

    2017-07-01

    The binding affinity of organophosphate hydrolase enzyme (OphB) with soil particles in relation to the isoelectric point (pI) was studied. Immobilization of OphB with soil particles was observed by confocal microscopy, Fourier transform infrared spectroscopy (FT-IR), and Atomic force microscopy (AFM). The calculated pI of OphB enzyme was increased from 8.69 to 8.89, 9.04 and 9.16 by the single, double and triple mutant of OphB enzyme, respectively through the replacement of negatively charged aspartate with positively charged histidine. Practically, the binding affinity was increased to 5.30%, 11.50%, and 16.80% for single, double and triple mutants, respectively. In contrast, enzyme activity of OphB did not change by the mutation of the enzyme. On the other hand, adhesion forces were gradually increased for wild type OphB enzyme (90 pN) to 96, 100 and 104 pN for single, double and triple mutants of OphB enzyme, respectively. There was an increasing trend of binding affinity and adhesion force by the increase of isoelectric point (pI) of OphB enzyme. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. INFORMATION BEHAVIOR AND TECHNOLOGY AFFINITY AMONG HIGHER INSTITUTION LEARNERS IN BORNEO

    OpenAIRE

    Johari, Nurul Muizzah

    2016-01-01

    This study aims to provide an understanding of information behavior with technology based on gender. It also to investigate the relationship between information behavior and degree of technology affinity. This research has been conducted quantitatively and using survey to gain data from participants.  Participant are selected randomly across Universiti Malaysia Sarawak, Sarawak. The instrument are adopted from Mills, Knezek, and Wakefield (2013) which taking interest into information behavior...

  8. Deviation equation in spaces with affine connection. Pts. 3 and 4

    International Nuclear Information System (INIS)

    Iliev, B.Z.

    1987-01-01

    The concept of a parallel transport is used to define a class of displacement vectors in spaces with affine connection. The nonlocal deviation equation in such spaces is introduced using a definition of the deviation vector based on the displacement vector. It turns out to be a special of the generalized deviation equation, but having an appropriate physical interpretation. The equation of geodesic deviation is presented as an example

  9. Spectral response variation of a negative-electron-affinity photocathode in the preparation process

    International Nuclear Information System (INIS)

    Liu Lei; Du Yujie; Chang Benkang; Yunsheng Qian

    2006-01-01

    In order to research the spectral response variation of a negative electron affinity (NEA) photocathode in the preparation process, we have done two experiments on a transmission-type GaAs photocathode.First, an automatic spectral response recording system is described, which is used to take spectral response curves during the activation procedure of the photocathode. By this system, the spectral response curves of a GaAs:Cs-Ophotocathode measured in situ are presented. Then, after the cathode is sealed with a microchannel plate and a fluorescence screen into the image tube, we measure the spectral response of the tube by another measurement instrument. By way of comparing and analyzing these curves, we can find the typical variation in spectral-responses.The reasons for the variation are discussed. Based on these curves, spectral matching factors of a GaAs cathode for green vegetation and rough concrete are calculated. The visual ranges of night-vision goggles under specific circumstances are estimated. The results show that the spectral response of the NEA photocathode degraded in the sealing process, especially at long wavelengths. The variation has also influenced the whole performance of the intensifier tube

  10. Alkali Metal Cation versus Proton and Methyl Cation Affinities: Structure and Bonding Mechanism

    NARCIS (Netherlands)

    Boughlala, Z.; Guerra, C.F.; Bickelhaupt, F.M.

    2016-01-01

    We have analyzed the structure and bonding of gas-phase Cl X and [HCl X](+) complexes for X+ = H+, CH3+, Li+, and Na+, using relativistic density functional theory (DFT). We wish to establish a quantitative trend in affinities of the anionic and neutral Lewis bases Cl- and HCl for the various

  11. Independent Monte-Carlo dose calculation for MLC based CyberKnife radiotherapy

    Science.gov (United States)

    Mackeprang, P.-H.; Vuong, D.; Volken, W.; Henzen, D.; Schmidhalter, D.; Malthaner, M.; Mueller, S.; Frei, D.; Stampanoni, M. F. M.; Dal Pra, A.; Aebersold, D. M.; Fix, M. K.; Manser, P.

    2018-01-01

    This work aims to develop, implement and validate a Monte Carlo (MC)-based independent dose calculation (IDC) framework to perform patient-specific quality assurance (QA) for multi-leaf collimator (MLC)-based CyberKnife® (Accuray Inc., Sunnyvale, CA) treatment plans. The IDC framework uses an XML-format treatment plan as exported from the treatment planning system (TPS) and DICOM format patient CT data, an MC beam model using phase spaces, CyberKnife MLC beam modifier transport using the EGS++ class library, a beam sampling and coordinate transformation engine and dose scoring using DOSXYZnrc. The framework is validated against dose profiles and depth dose curves of single beams with varying field sizes in a water tank in units of cGy/Monitor Unit and against a 2D dose distribution of a full prostate treatment plan measured with Gafchromic EBT3 (Ashland Advanced Materials, Bridgewater, NJ) film in a homogeneous water-equivalent slab phantom. The film measurement is compared to IDC results by gamma analysis using 2% (global)/2 mm criteria. Further, the dose distribution of the clinical treatment plan in the patient CT is compared to TPS calculation by gamma analysis using the same criteria. Dose profiles from IDC calculation in a homogeneous water phantom agree within 2.3% of the global max dose or 1 mm distance to agreement to measurements for all except the smallest field size. Comparing the film measurement to calculated dose, 99.9% of all voxels pass gamma analysis, comparing dose calculated by the IDC framework to TPS calculated dose for the clinical prostate plan shows 99.0% passing rate. IDC calculated dose is found to be up to 5.6% lower than dose calculated by the TPS in this case near metal fiducial markers. An MC-based modular IDC framework was successfully developed, implemented and validated against measurements and is now available to perform patient-specific QA by IDC.

  12. Error Propagation dynamics: from PIV-based pressure reconstruction to vorticity field calculation

    Science.gov (United States)

    Pan, Zhao; Whitehead, Jared; Richards, Geordie; Truscott, Tadd; USU Team; BYU Team

    2017-11-01

    Noninvasive data from velocimetry experiments (e.g., PIV) have been used to calculate vorticity and pressure fields. However, the noise, error, or uncertainties in the PIV measurements would eventually propagate to the calculated pressure or vorticity field through reconstruction schemes. Despite the vast applications of pressure and/or vorticity field calculated from PIV measurements, studies on the error propagation from the velocity field to the reconstructed fields (PIV-pressure and PIV-vorticity are few. In the current study, we break down the inherent connections between PIV-based pressure reconstruction and PIV-based vorticity calculation. The similar error propagation dynamics, which involve competition between physical properties of the flow and numerical errors from reconstruction schemes, are found in both PIV-pressure and PIV-vorticity reconstructions.

  13. Synthetic Polymer Affinity Ligand for Bacillus thuringiensis ( Bt) Cry1Ab/Ac Protein: The Use of Biomimicry Based on the Bt Protein-Insect Receptor Binding Mechanism.

    Science.gov (United States)

    Liu, Mingming; Huang, Rong; Weisman, Adam; Yu, Xiaoyang; Lee, Shih-Hui; Chen, Yalu; Huang, Chao; Hu, Senhua; Chen, Xiuhua; Tan, Wenfeng; Liu, Fan; Chen, Hao; Shea, Kenneth J

    2018-05-24

    We report a novel strategy for creating abiotic Bacillus thuringiensis ( Bt) protein affinity ligands by biomimicry of the recognition process that takes place between Bt Cry1Ab/Ac proteins and insect receptor cadherin-like Bt-R 1 proteins. Guided by this strategy, a library of synthetic polymer nanoparticles (NPs) was prepared and screened for binding to three epitopes 280 FRGSAQGIEGS 290 , 368 RRPFNIGINNQQ 379 and 436 FRSGFSNSSVSIIR 449 located in loop α8, loop 2 and loop 3 of domain II of Bt Cry1Ab/Ac proteins. A negatively charged and hydrophilic nanoparticle (NP12) was found to have high affinity to one of the epitopes, 368 RRPFNIGINNQQ 379 . This same NP also had specific binding ability to both Bt Cry1Ab and Bt Cry1Ac, proteins that share the same epitope, but very low affinity to Bt Cry2A, Bt Cry1C and Bt Cry1F closely related proteins that lack epitope homology. To locate possible NP- Bt Cry1Ab/Ac interaction sites, NP12 was used as a competitive inhibitor to block the binding of 865 NITIHITDTNNK 876 , a specific recognition site in insect receptor Bt-R 1 , to 368 RRPFNIGINNQQ 379 . The inhibition by NP12 reached as high as 84%, indicating that NP12 binds to Bt Cry1Ab/Ac proteins mainly via 368 RRPFNIGINNQQ 379 . This epitope region was then utilized as a "target" or "bait" for the separation and concentration of Bt Cry1Ac protein from the extract of transgenic Bt cotton leaves by NP12. This strategy, based on the antigen-receptor recognition mechanism, can be extended to other biotoxins and pathogen proteins when designing biomimic alternatives to natural protein affinity ligands.

  14. Dual Affinity Heparin-Based Hydrogels Achieve Pro-Regenerative Immunomodulation and Microvascular Remodeling.

    Science.gov (United States)

    Ogle, Molly E; Krieger, Jack R; Tellier, Liane E; McFaline-Figueroa, Jennifer; Temenoff, Johnna S; Botchwey, Edward A

    2018-04-09

    The immune response to biomaterial implants critically regulates functional outcomes such as vascularization, transplant integration/survival, and fibrosis. To create "immunologically smart" materials, the host-material response may be engineered to optimize the recruitment of pro-regenerative leukocyte subsets which mature into corresponding wound-healing macrophages. We have recently identified a unique feature of pro-regenerative Ly6C low monocytes that is a higher expression of both the bioactive lipid receptor sphingosine-1-phosphate receptor 3 (S1PR3) and the stromal derived factor-1α (SDF-1α) receptor CXCR4. Therefore, we designed a bifunctional hydrogel to harnesses a mechanistic synergy between these signaling axes to enhance the recruitment of endogenous pro-regenerative monocytes. To overcome the challenge of codelivering two physiochemically distinct molecules-a large hydrophilic protein and hydrophobic small molecule-we engineered a dual affinity hydrogel that exploits the growth factor affinity of a heparin derivative (Hep -N ) and lipid chaperone activity of albumin. The sphingosine analog FTY720 and SDF-1α are successfully loaded and coreleased from the Hep -N -functionalized PEG-DA hydrogels while maintaining bioactivity. Placement of these hydrogels into a murine partial thickness skin wound demonstrates that corelease of FTY720 and SDF-1α yields superior recruitment of myeloid cells to the implant interface compared to either factor alone. Although in vivo delivery of FTY720 or SDF-1α individually promotes the enhanced recruitment of Ly-6C low anti-inflammatory monocytes, codelivery enhances the early accumulation and persistence of the differentiated wound healing CD206 + macrophages in the tissue surrounding the gel. Co-delivery similarly promoted the synergistic expansion of vasculature adjacent to the implant, a key step in tissue healing. Taken together, these findings suggest that the combination of chemotactic molecules may provide

  15. Deployment Strategy for Car-Sharing Depots by Clustering Urban Traffic Big Data Based on Affinity Propagation

    Directory of Open Access Journals (Sweden)

    Zhihan Liu

    2018-01-01

    Full Text Available Car sharing is a type of car rental service, by which consumers rent cars for short periods of time, often charged by hours. The analysis of urban traffic big data is full of importance and significance to determine locations of depots for car-sharing system. Taxi OD (Origin-Destination is a typical dataset of urban traffic. The volume of the data is extremely large so that traditional data processing applications do not work well. In this paper, an optimization method to determine the depot locations by clustering taxi OD points with AP (Affinity Propagation clustering algorithm has been presented. By analyzing the characteristics of AP clustering algorithm, AP clustering has been optimized hierarchically based on administrative region segmentation. Considering sparse similarity matrix of taxi OD points, the input parameters of AP clustering have been adapted. In the case study, we choose the OD pairs information from Beijing’s taxi GPS trajectory data. The number and locations of depots are determined by clustering the OD points based on the optimization AP clustering. We describe experimental results of our approach and compare it with standard K-means method using quantitative and stationarity index. Experiments on the real datasets show that the proposed method for determining car-sharing depots has a superior performance.

  16. On $L_p$ Affine Surface Area and Curvature Measures

    OpenAIRE

    Zhao, Yiming

    2015-01-01

    The relationship between $L_p$ affine surface area and curvature measures is investigated. As a result, a new representation of the existing notion of $L_p$ affine surface area depending only on curvature measures is derived. Direct proofs of the equivalence between this new representation and those previously known are provided. The proofs show that the new representation is, in a sense, "polar" to that of Lutwak's and "dual" to that of Sch\\"utt & Werner's.

  17. Accurate density functional prediction of molecular electron affinity with the scaling corrected Kohn–Sham frontier orbital energies

    Science.gov (United States)

    Zhang, DaDi; Yang, Xiaolong; Zheng, Xiao; Yang, Weitao

    2018-04-01

    Electron affinity (EA) is the energy released when an additional electron is attached to an atom or a molecule. EA is a fundamental thermochemical property, and it is closely pertinent to other important properties such as electronegativity and hardness. However, accurate prediction of EA is difficult with density functional theory methods. The somewhat large error of the calculated EAs originates mainly from the intrinsic delocalisation error associated with the approximate exchange-correlation functional. In this work, we employ a previously developed non-empirical global scaling correction approach, which explicitly imposes the Perdew-Parr-Levy-Balduz condition to the approximate functional, and achieve a substantially improved accuracy for the calculated EAs. In our approach, the EA is given by the scaling corrected Kohn-Sham lowest unoccupied molecular orbital energy of the neutral molecule, without the need to carry out the self-consistent-field calculation for the anion.

  18. [An examination of the determinants of social withdrawal and affinity for social withdrawal].

    Science.gov (United States)

    Watanabe, Asami; Matsui, Yutaka; Takatsuka, Yusuke

    2010-12-01

    This study examined the determinants of social withdrawal using data from a survey by the Tokyo Metropolitan Government Office for Youth Affairs and Public Safety (2008). In addition, this study identified young people who showed an affinity for social withdrawal although they were not in a state of withdrawal, and examined the determinants of an affinity for social withdrawal. The results of stepwise discriminant analysis showed that factors such as social phobia, depression, violence, and emotional bonds with family differentiated between the general youth group and the social withdrawal group and the "affinity group". Social phobia, violence, and refusal to be interfered in self-decision making differentiated between the social withdrawal group and the "affinity group". This study shows that an "affinity group" should be cared as well as an actual withdrawal group.

  19. Effect of different hapten-carrier conjugation ratios and molecular orientations on antibody affinity against a peptide antigen

    DEFF Research Database (Denmark)

    Pedersen, M. K.; Sørensen, Nanna Skall; Heegaard, Peter M. H.

    2006-01-01

    -based assay systems and in deciding whether a vaccine-induced antibody response will be protective. With ovalbumin as a carrier protein and a peptide (7.2NY) representing a 19 ammo acid sequence from the E. coli-derived Verotoxin 2e as a model hapten we investigated whether it was possible to influence...... ten dines at two-weeks intervals with low doses of the eight conjugates, Blood samples collected between each immunisation were analysed by ELISA for specific antibody titres and relative affinities. With both types of conjugations, the anti-peptide antibody titres increased in response to increasing...... for terminal conjugation. Thus, it appears that the molar ratio of a peptide and its carrier may affect the resulting antibody affinities, and that a conjugation ratio between a terminally Conjugated peptide and its carrier approaching one will result in relatively high antibody affinities. Furthermore...

  20. Feasibility of CBCT-based dose calculation: Comparative analysis of HU adjustment techniques

    International Nuclear Information System (INIS)

    Fotina, Irina; Hopfgartner, Johannes; Stock, Markus; Steininger, Thomas; Lütgendorf-Caucig, Carola; Georg, Dietmar

    2012-01-01

    Background and purpose: The aim of this work was to compare the accuracy of different HU adjustments for CBCT-based dose calculation. Methods and materials: Dose calculation was performed on CBCT images of 30 patients. In the first two approaches phantom-based (Pha-CC) and population-based (Pop-CC) conversion curves were used. The third method (WAB) represents override of the structures with standard densities for water, air and bone. In ROI mapping approach all structures were overridden with average HUs from planning CT. All techniques were benchmarked to the Pop-CC and CT-based plans by DVH comparison and γ-index analysis. Results: For prostate plans, WAB and ROI mapping compared to Pop-CC showed differences in PTV D median below 2%. The WAB and Pha-CC methods underestimated the bladder dose in IMRT plans. In lung cases PTV coverage was underestimated by Pha-CC method by 2.3% and slightly overestimated by the WAB and ROI techniques. The use of the Pha-CC method for head–neck IMRT plans resulted in difference in PTV coverage up to 5%. Dose calculation with WAB and ROI techniques showed better agreement with pCT than conversion curve-based approaches. Conclusions: Density override techniques provide an accurate alternative to the conversion curve-based methods for dose calculation on CBCT images.

  1. Affinity chromatography: A versatile technique for antibody purification.

    Science.gov (United States)

    Arora, Sushrut; Saxena, Vikas; Ayyar, B Vijayalakshmi

    2017-03-01

    Antibodies continue to be extremely utilized entities in myriad applications including basic research, imaging, targeted delivery, chromatography, diagnostics, and therapeutics. At production stage, antibodies are generally present in complex matrices and most of their intended applications necessitate purification. Antibody purification has always been a major bottleneck in downstream processing of antibodies, due to the need of high quality products and associated high costs. Over the years, extensive research has focused on finding better purification methodologies to overcome this holdup. Among a plethora of different techniques, affinity chromatography is one of the most selective, rapid and easy method for antibody purification. This review aims to provide a detailed overview on affinity chromatography and the components involved in purification. An array of support matrices along with various classes of affinity ligands detailing their underlying working principles, together with the advantages and limitations of each system in purifying different types of antibodies, accompanying recent developments and important practical methodological considerations to optimize purification procedure are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Evaluation of RSG-GAS Core Management Based on Burnup Calculation

    International Nuclear Information System (INIS)

    Lily Suparlina; Jati Susilo

    2009-01-01

    Evaluation of RSG-GAS Core Management Based on Burnup Calculation. Presently, U 3 Si 2 -Al dispersion fuel is used in RSG-GAS core and had passed the 60 th core. At the beginning of each cycle the 5/1 fuel reshuffling pattern is used. Since 52 nd core, operators did not use the core fuel management computer code provided by vendor for this activity. They use the manually calculation using excel software as the solving. To know the accuracy of the calculation, core calculation was carried out using two kinds of 2 dimension diffusion codes Batan-2DIFF and SRAC. The beginning of cycle burn-up fraction data were calculated start from 51 st to 60 th using Batan-EQUIL and SRAC COREBN. The analysis results showed that there is a disparity in reactivity values of the two calculation method. The 60 th core critical position resulted from Batan-2DIFF calculation provide the reduction of positive reactivity 1.84 % Δk/k, while the manually calculation results give the increase of positive reactivity 2.19 % Δk/k. The minimum shutdown margin for stuck rod condition for manual and Batan-3DIFF calculation are -3.35 % Δk/k dan -1.13 % Δk/k respectively, it means that both values met the safety criteria, i.e <-0.5 % Δk/k. Excel program can be used for burn-up calculation, but it is needed to provide core management code to reach higher accuracy. (author)

  3. Comparison of Binding Affinities of Water-Soluble Calixarenes with the Organophosphorus Nerve Agent Soman (GD and Commonly-Used Nerve Agent Simulants

    Directory of Open Access Journals (Sweden)

    Jayne A. Ede

    2018-01-01

    Full Text Available The formation of inclusion complexes of the water-soluble p-sulfonatocalix[n]arenes, where n = 4 or 6, with the Chemical Warfare Agent (CWA GD, or Soman, and commonly used dialkyl methylphosphonate simulants has been studied by experimental solution NMR methods and by Molecular Mechanics (MMFF and semi-empirical (PM6 calculations. Complex formation in non-buffered and buffered solutions is driven by the hydrophobic effect, and complex stoichiometry determined as 1:1 for all host:guest pairs. Low affinity complexes (Kassoc < 100 M−1 are observed for all guests, attributed to poor host–guest complementarity and the role of buffer cation species accounts for the low affinity of the complexes. Comparison of CWA and simulant behavior adds to understanding of CWA–simulant correlations and the challenges of simulant selection.

  4. Visual and Plasmon Resonance Absorption Sensor for Adenosine Triphosphate Based on the High Affinity between Phosphate and Zr(IV

    Directory of Open Access Journals (Sweden)

    Wenjing Qi

    2016-10-01

    Full Text Available Zr(IV can form phosphate and Zr(IV (–PO32−–Zr4+– complex owing to the high affinity between Zr(IV with phosphate. Zr(IV can induce the aggregation of gold nanoparticles (AuNPs, while adenosine triphosphate(ATP can prevent Zr(IV-induced aggregation of AuNPs. Herein, a visual and plasmon resonance absorption (PRAsensor for ATP have been developed using AuNPs based on the high affinity between Zr(IVwith ATP. AuNPs get aggregated in the presence of certain concentrations of Zr(IV. After the addition of ATP, ATP reacts with Zr(IV and prevents AuNPs from aggregation, enabling the detection of ATP. Because of the fast interaction of ATP with Zr(IV, ATP can be detected with a detection limit of 0.5 μM within 2 min by the naked eye. Moreover, ATP can be detected by the PRA technique with higher sensitivity. The A520nm/A650nm values in PRA spectra increase linearly with the concentrations of ATP from 0.1 μM to 15 μM (r = 0.9945 with a detection limit of 28 nM. The proposed visual and PRA sensor exhibit good selectivity against adenosine, adenosine monophosphate, guanosine triphosphate, cytidine triphosphate and uridine triphosphate. The recoveries for the analysis of ATP in synthetic samples range from 95.3% to 102.0%. Therefore, the proposed novel sensor for ATP is promising for real-time or on-site detection of ATP.

  5. Density-conserving affine continuous cellular automata solving the relaxed density classification problem

    International Nuclear Information System (INIS)

    Wolnik, Barbara; Dembowski, Marcin; Bołt, Witold; Baetens, Jan M; De Baets, Bernard

    2017-01-01

    The focus of this paper is on the density classification problem in the context of affine continuous cellular automata. Although such cellular automata cannot solve this problem in the classical sense, most density-conserving affine continuous cellular automata with a unit neighborhood radius are valid solutions of a slightly relaxed version of this problem. This result follows from a detailed study of the dynamics of the density-conserving affine continuous cellular automata that we introduce. (paper)

  6. Calculating the Fee-Based Services of Library Institutions: Theoretical Foundations and Practical Challenges

    Directory of Open Access Journals (Sweden)

    Sysіuk Svitlana V.

    2017-05-01

    Full Text Available The article is aimed at highlighting features of the provision of the fee-based services by library institutions, identifying problems related to the legal and regulatory framework for their calculation, and the methods to implement this. The objective of the study is to develop recommendations to improve the calculation of the fee-based library services. The theoretical foundations have been systematized, the need to develop a Provision for the procedure of the fee-based services by library institutions has been substantiated. Such a Provision would protect library institution from errors in fixing the fee for a paid service and would be an informational source of its explicability. The appropriateness of applying the market pricing law based on demand and supply has been substantiated. The development and improvement of accounting and calculation, taking into consideration both industry-specific and market-based conditions, would optimize the costs and revenues generated by the provision of the fee-based services. In addition, the complex combination of calculation leverages with development of the system of internal accounting together with use of its methodology – provides another equally efficient way of improving the efficiency of library institutions’ activity.

  7. Data base for terrestrial food pathways dose commitment calculations

    International Nuclear Information System (INIS)

    Bailey, C.E.

    1979-01-01

    A computer program is under development to allow calculation of the dose-to-man in Georgia and South Carolina from ingestion of radionuclides in terrestrial foods resulting from deposition of airborne radionuclides. This program is based on models described in Regulatory Guide 1.109 (USNRC, 1977). The data base describes the movement of radionuclides through the terrestrial food chain, growth and consumption factors for a variety of radionuclides

  8. Relativistic calculations of the fine-structure intervals of the ns2np2P terms and the ionization energies of the Ca-, Sr-and Ba- ions

    International Nuclear Information System (INIS)

    Wijesundera, W.P.; Vosko, S.H.; Parpia, F.A.

    1996-01-01

    We report new calculations of the energy differences between the ns 1/2 2 np 1/2 and ns 1/2 2 np 3/2 levels of the Ca - , Sr - and Ba - ions; here n 4, 5 and 6 for Ca - , Sr - and Ba - , respectively. The electron affinities of Ca, Ba and Sr have also been calculated. All estimates were obtained by performing a series of multiconfiguration Dirac-Fock calculations for the neutral atoms and their anions. Correlations among valence electrons in both the ground and excited states were included in these calculations. Our estimate of the fine structure of the ground state of Sr - is in good agreement with recent measurements. Our estimates of the electron affinities of Ca, Sr and Ba are in reasonable agreement with experiment. (author)

  9. Quark confinement and the short-range component of general affine gauge gravity

    International Nuclear Information System (INIS)

    Sijacki, D.

    1982-01-01

    Within the framework of a gauge field theory based on the general affine space-time symmetry, we propose a certain purely quadratic gauge field lagrangian. In the large-scale region it yields an Einstein-Cartan-like gravity with Newton's constand generated spontaneously, while in the particle domain it yields a renormalizable theory with a confining potential applying to quarks and not to leptons. (orig.)

  10. Na+,K+-ATPase Na+ affinity in rat skeletal muscle fiber types

    DEFF Research Database (Denmark)

    Kristensen, Michael; Juel, Carsten

    2010-01-01

    Previous studies in expression systems have found different ion activation of the Na(+)/K(+)-ATPase isozymes, which suggest that different muscles have different ion affinities. The rate of ATP hydrolysis was used to quantify Na(+),K(+)-ATPase activity, and the Na(+) affinity of Na(+),K(+)-ATPase...

  11. THEXSYST - a knowledge based system for the control and analysis of technical simulation calculations

    International Nuclear Information System (INIS)

    Burger, B.

    1991-07-01

    This system (THEXSYST) will be used for control, analysis and presentation of thermal hydraulic simulation calculations of light water reactors. THEXSYST is a modular system consisting of an expert shell with user interface, a data base, and a simulation program and uses techniques available in RSYST. A knowledge base, which was created to control the simulational calculation of pressurized water reactors, includes both the steady state calculation and the transient calculation in the domain of the depressurization, as a result of a small break loss of coolant accident. The methods developed are tested using a simulational calculation with RELAP5/Mod2. It will be seen that the application of knowledge base techniques may be a helpful tool to support existing solutions especially in graphical analysis. (orig./HP) [de

  12. Ab initio Calculations of Electronic Fingerprints of DNA bases on Graphene

    Science.gov (United States)

    Ahmed, Towfiq; Rehr, John J.; Kilina, Svetlana; Das, Tanmoy; Haraldsen, Jason T.; Balatsky, Alexander V.

    2012-02-01

    We have carried out first principles DFT calculations of the electronic local density of states (LDOS) of DNA nucleotide bases (A,C,G,T) adsorbed on graphene using LDA with ultra-soft pseudo-potentials. We have also calculated the longitudinal transmission currents T(E) through graphene nano-pores as an individual DNA base passes through it, using a non-equilibrium Green's function (NEGF) formalism. We observe several dominant base-dependent features in the LDOS and T(E) in an energy range within a few eV of the Fermi level. These features can serve as electronic fingerprints for the identification of individual bases from dI/dV measurements in scanning tunneling spectroscopy (STS) and nano-pore experiments. Thus these electronic signatures can provide an alternative approach to DNA sequencing.

  13. Two distinct affinity binding sites for IL-1 on human cell lines

    International Nuclear Information System (INIS)

    Bensimon, C.; Wakasugi, N.; Tagaya, Y.; Takakura, K.; Yodoi, J.; Tursz, T.; Wakasugi, H.

    1989-01-01

    We used two human cell lines, NK-like YT-C3 and an EBV-containing B cell line, 3B6, as models to study the receptor(s) for IL-1. Two distinct types of saturable binding sites were found on both cell lines at 37 degrees C. Between 1 pM and 100 pM of 125I-IL-1-alpha concentration, saturable binding sites were detected on the YT-C3 cells with a K of 4 x 10(-11) M. The K found for the IL-1-alpha binding sites on 3B6 cells was 7.5 x 10(-11) M. An additional binding curve was detected above 100 pM on YT-C3 cells with a K of 7 x 10(-9) M and on 3B6 cells with a K of 5 x 10(-9) M. Scatchard plot analysis revealed 600 sites/cell with high affinity binding and 7000 sites/cell with low affinity for YT-C3 cells and 300 sites/cell with high affinity binding and 6000 sites/cell with low affinity for 3B6 cells. At 37 degrees C, the internalization of 125I-labeled IL-1 occurred via both high and low affinity IL-1R on both YT-C3 and 3B6 cells, whereas the rates of internalization for high affinity binding sites on YT-C3 cells were predominant in comparison to that of low affinity binding sites. In chemical cross-linking studies of 125 I-IL-1-alpha to 3B6 and YT-C3 cells, two protein bands were immunoprecipitated with Mr around 85 to 90 kDa leading to an estimation of the Mr of the IL-1R around 68 to 72 kDa. In similar experiments, the Mr found for the IL-1R expressed on the murine T cell line EL4 was slightly higher (around 80 kDa). Whether these distinct affinity binding sites are shared by a single molecule or by various chains remains to be elucidated

  14. Structural analysis of dihydrofolate reductases enables rationalization of antifolate binding affinities and suggests repurposing possibilities.

    Science.gov (United States)

    Bhosle, Amrisha; Chandra, Nagasuma

    2016-03-01

    Antifolates are competitive inhibitors of dihydrofolate reductase (DHFR), a conserved enzyme that is central to metabolism and widely targeted in pathogenic diseases, cancer and autoimmune disorders. Although most clinically used antifolates are known to be target specific, some display a fair degree of cross-reactivity with DHFRs from other species. A method that enables identification of determinants of affinity and specificity in target DHFRs from different species and provides guidelines for the design of antifolates is currently lacking. To address this, we first captured the potential druggable space of a DHFR in a substructure called the 'supersite' and classified supersites of DHFRs from 56 species into 16 'site-types' based on pairwise structural similarity. Analysis of supersites across these site-types revealed that DHFRs exhibit varying extents of dissimilarity at structurally equivalent positions in and around the binding site. We were able to explain the pattern of affinities towards chemically diverse antifolates exhibited by DHFRs of different site-types based on these structural differences. We then generated an antifolate-DHFR network by mapping known high-affinity antifolates to their respective supersites and used this to identify antifolates that can be repurposed based on similarity between supersites or antifolates. Thus, we identified 177 human-specific and 458 pathogen-specific antifolates, a large number of which are supported by available experimental data. Thus, in the light of the clinical importance of DHFR, we present a novel approach to identifying differences in the druggable space of DHFRs that can be utilized for rational design of antifolates. © 2016 Federation of European Biochemical Societies.

  15. Characterization of edible emulsified films with low affinity to water based on kefiran and oleic acid.

    Science.gov (United States)

    Ghasemlou, Mehran; Khodaiyan, Faramarz; Oromiehie, Abdulrasoul; Yarmand, Mohammad Saeid

    2011-10-01

    New edible composite films based on kefiran and oleic acid (OA) at the ratio of 15, 25, and 35% (w/w) were prepared using emulsification with the aim of improving their water vapour barrier and mechanical properties. Film-forming solutions were characterized in terms of rheological properties and particle-size distribution. The impact of the incorporation of OA into the film matrix was studied by investigating the physical, mechanical, and thermal properties of the films. The water vapour permeability (WVP) of the emulsified films was reduced by approximately 33% by adding OA. The mechanical properties of kefiran films were also affected by adding OA: tensile strength was diminished, and elongation increased considerably. Differential scanning calorimetry showed that the glass transition temperature (T(g)) of the kefiran film was -16°C and was not considerably affected by adding OA. Therefore, OA could be incorporated into these films for some food-technology applications that need a low affinity toward water. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Detection of Hepatitis C core antibody by dual-affinity yeast chimera and smartphone-based electrochemical sensing.

    Science.gov (United States)

    Aronoff-Spencer, Eliah; Venkatesh, A G; Sun, Alex; Brickner, Howard; Looney, David; Hall, Drew A

    2016-12-15

    Yeast cell lines were genetically engineered to display Hepatitis C virus (HCV) core antigen linked to gold binding peptide (GBP) as a dual-affinity biobrick chimera. These multifunctional yeast cells adhere to the gold sensor surface while simultaneously acting as a "renewable" capture reagent for anti-HCV core antibody. This streamlined functionalization and detection strategy removes the need for traditional purification and immobilization techniques. With this biobrick construct, both optical and electrochemical immunoassays were developed. The optical immunoassays demonstrated detection of anti-HCV core antibody down to 12.3pM concentrations while the electrochemical assay demonstrated higher binding constants and dynamic range. The electrochemical format and a custom, low-cost smartphone-based potentiostat ($20 USD) yielded comparable results to assays performed on a state-of-the-art electrochemical workstation. We propose this combination of synthetic biology and scalable, point-of-care sensing has potential to provide low-cost, cutting edge diagnostic capability for many pathogens in a variety of settings. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Accurate and sensitive quantification of protein-DNA binding affinity.

    Science.gov (United States)

    Rastogi, Chaitanya; Rube, H Tomas; Kribelbauer, Judith F; Crocker, Justin; Loker, Ryan E; Martini, Gabriella D; Laptenko, Oleg; Freed-Pastor, William A; Prives, Carol; Stern, David L; Mann, Richard S; Bussemaker, Harmen J

    2018-04-17

    Transcription factors (TFs) control gene expression by binding to genomic DNA in a sequence-specific manner. Mutations in TF binding sites are increasingly found to be associated with human disease, yet we currently lack robust methods to predict these sites. Here, we developed a versatile maximum likelihood framework named No Read Left Behind (NRLB) that infers a biophysical model of protein-DNA recognition across the full affinity range from a library of in vitro selected DNA binding sites. NRLB predicts human Max homodimer binding in near-perfect agreement with existing low-throughput measurements. It can capture the specificity of the p53 tetramer and distinguish multiple binding modes within a single sample. Additionally, we confirm that newly identified low-affinity enhancer binding sites are functional in vivo, and that their contribution to gene expression matches their predicted affinity. Our results establish a powerful paradigm for identifying protein binding sites and interpreting gene regulatory sequences in eukaryotic genomes. Copyright © 2018 the Author(s). Published by PNAS.

  18. Effect of isotopic substitution upon the gas phase and solution electron affinities of nitrobenzene

    International Nuclear Information System (INIS)

    Stevenson, G.R.; Reiter, R.C.; Espe, M.E.; Bartmess, J.E.

    1987-01-01

    Ion cyclotron resonance and electron spin resonance have been utilized to determine the equilibrium constant for the electron transfer from the nitrobenzene anion radical to 15 N labeled nitrobenzene (Ph 14 NO 2 - + Ph 15 NO 2 ↔ Ph 14 NO 2 + Ph 15 NO 2 9 . It was found that the equilibrium constant is within experimental error of unity at 305 K. Molecular orbital calculations indicate that this might be accounted for by the shortening of the C-N bond and a counterbalancing lengthening of the N-O bonds upon electron attachment to nitrobenzene. An equilibrium constant that is much larger than unity can be observed in liquid ammonia at 208 K when K + serves as the gegenion (K/sub eq/ = 2.1). However, when Na + serves as the gegenion, the solution electron affinity of Ph 14 NO 2 is greater than that of Ph 15 NO 2 (K/sub eq/ = 0.4). These results are explained in terms of ion association. When the hydrogen atoms are replaced with deuteriums, the gas phase electron affinity is decreased. A similar decrease is observed in liquid ammonia. In the gas phase this is attributed to the slight lengthening of all the C-H bonds upon electron attachment

  19. Lapa vermelha IV Hominid 1: morphological affinities of the earliest known American

    Directory of Open Access Journals (Sweden)

    Neves Walter A.

    1999-01-01

    Full Text Available Several studies concerning the extra-continental morphological affinities of Paleo-Indian skeletons, carried out independently in South and North America, have indicated that the Americas were first occupied by non-Mongoloids that made their way to the New World through the Bering Strait in ancient times. The first South Americans show a clear resemblance to modern South Pacific and African populations, while the first North Americans seem to be at an unresolved morphological position between modern South Pacific and Europeans. In none of these analyses the first Americans show any resemblance to either northeast Asians or modern native Americans. So far, these studies have included affirmed and putative early skeletons thought to date between 8,000 and 10,000 years B.P. In this work the extra-continental morphological affinities of a Paleo-Indian skeleton well dated between 11,000 and 11,500 years B.P. (Lapa Vermelha IV Hominid 1, or "Luzia" is investigated, using as comparative samples Howells' (1989 world-wide modern series and Habgood's (1985 Old World Late Pleistocene fossil hominids. The comparison between Lapa Vermelha IV Hominid 1 and Howells' series was based on canonical variate analysis, including 45 size-corrected craniometric variables, while the comparison with fossil hominids was based on principal component analysis, including 16 size-corrected variables. In the first case, Lapa Vermelha IV Hominid 1 exhibited an undisputed morphological affinity firstly with Africans and secondly with South Pacific populations. In the second comparison, the earliest known American skeleton had its closest similarities with early Australians, Zhoukoudian Upper Cave 103, and Taforalt 18. The results obtained clearly confirm the idea that the Americas were first colonized by a generalized Homo sapiens population which inhabited East Asia in the Late Pleistocene, before the definition of the classic Mongoloid morphology.

  20. Oxoanion Recognition by Benzene-based Tripodal Pyrrolic Receptors

    Energy Technology Data Exchange (ETDEWEB)

    Bill, Nathan [University of Texas at Austin; Kim, Dae-Sik [University of Texas at Austin; Kim, Sung Kuk [University of Texas at Austin; Park, Jung Su [University of Texas at Austin; Lynch, Vincent M. [University of Texas at Austin; Young, Neil J [ORNL; Hay, Benjamin [ORNL; Yang, Youjun [University of Texas at Austin; Anslyn, Eric [University of Texas at Austin; Sessler, Jonathan L. [University of Texas

    2012-01-01

    Two new tripodal receptors based on pyrrole- and dipyrromethane-functionalised derivatives of a sterically geared precursor, 1,3,5-tris(aminomethyl)-2,4,6-triethylbenzene, are reported; these systems, compounds 1 and 2, display high affinity and selectivity for tetrahedral anionic guests, in particular dihydrogen phosphate, pyrophosphate and hydrogen sulphate, in acetonitrile as inferred from isothermal titration calorimetry measurements. Support for the anion-binding ability of these systems comes from theoretical calculations and a single-crystal X-ray diffraction structure of the 2:2 (host:guest) dihydrogen phosphate complex is obtained in the case of the pyrrole-based receptor system, 1. Keywords anion receptors, dihydrogen phosphate, hydrogen sulphate, X-ray structure, theoretical calculations.

  1. Computational modeling and molecular imprinting for the development of acrylic polymers with high affinity for bile salts.

    Science.gov (United States)

    Yañez, Fernando; Chianella, Iva; Piletsky, Sergey A; Concheiro, Angel; Alvarez-Lorenzo, Carmen

    2010-02-05

    This work has focused on the rational development of polymers capable of acting as traps of bile salts. Computational modeling was combined with molecular imprinting technology to obtain networks with high affinity for cholate salts in aqueous medium. The screening of a virtual library of 18 monomers, which are commonly used for imprinted networks, identified N-(3-aminopropyl)-methacrylate hydrochloride (APMA.HCl), N,N-diethylamino ethyl methacrylate (DEAEM) and ethyleneglycol methacrylate phosphate (EGMP) as suitable functional monomers with medium-to-high affinity for cholic acid. The polymers were prepared with a fix cholic acid:functional monomer mole ratio of 1:4, but with various cross-linking densities. Compared to polymers prepared without functional monomer, both imprinted and non-imprinted microparticles showed a high capability to remove sodium cholate from aqueous medium. High affinity APMA-based particles even resembled the performance of commercially available cholesterol-lowering granules. The imprinting effect was evident in most of the networks prepared, showing that computational modeling and molecular imprinting can act synergistically to improve the performance of certain polymers. Nevertheless, both the imprinted and non-imprinted networks prepared with the best monomer (APMA.HCl) identified by the modeling demonstrated such high affinity for the template that the imprinting effect was less important. The fitting of adsorption isotherms to the Freundlich model indicated that, in general, imprinting increases the population of high affinity binding sites, except when the affinity of the functional monomer for the target molecule is already very high. The cross-linking density was confirmed as a key parameter that determines the accessibility of the binding points to sodium cholate. Materials prepared with 9% mol APMA and 91% mol cross-linker showed enough affinity to achieve binding levels of up to 0.4 mmol g(-1) (i.e., 170 mg g(-1)) under flow

  2. A density functional theory (DFT) calculation

    Indian Academy of Sciences (India)

    Acid-base properties of drugs are important in understanding the behaviour of these compounds under physiological condition. In order to understand such behaviour the proton affinities of acridine 4-carboxamides with substitution (R) at the 9-position are theoretically studied, and considered for the basic sites of both the ...

  3. Enhanced starch hydrolysis using α-amylase immobilized on cellulose ultrafiltration affinity membrane.

    Science.gov (United States)

    Konovalova, Viktoriia; Guzikevich, Kateryna; Burban, Anatoliy; Kujawski, Wojciech; Jarzynka, Karolina; Kujawa, Joanna

    2016-11-05

    In order to prepare ultrafiltration membranes possessing biocatalytic properties, α-amylase has been immobilized on cellulose membranes. Enzyme immobilization was based on a covalent bonding between chitosan and a surface of cellulose membrane, followed by an attachment of Cibacron Blue F3G-A dye as affinity ligand. Various factors affecting the immobilization process, such as enzyme concentration, pH of modifying solution, zeta-potential of membrane surface, and stability of immobilized enzyme were studied. The applicability of immobilized α-amylase has been investigated in ultrafiltration processes. The immobilization of α-amylase on membrane surface allows to increase the value of mass transfer coefficient and to decrease the concentration polarization effect during ultrafiltration of starch solutions. The enzyme layer on the membrane surface prevents a rapid increase of starch concentration due to the amylase hydrolysis of starch in the boundary layer. The presented affinity immobilization technique allows also for the regeneration of membranes from inactivated enzyme. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Constraints on the affinity term for modeling long-term glass dissolution rates

    International Nuclear Information System (INIS)

    Bourcier, W.L.; Carroll, S.A.; Phillips, B.L.

    1993-11-01

    Predictions of long-term glass dissolution rates are highly dependent on the form of the affinity term in the rate expression. Analysis of the quantitative effect of saturation state on glass dissolution rate for CSG glass (a simple analog of SRL-165 glass), shows that a simple (1-Q/K) affinity term does not match experimental results. Our data at 100 degree C show that the data is better fit by an affinity term having the form (1 - (Q/K) 1 /σ) where σ = 10

  5. Affinity purification of recombinant human plasminogen activator ...

    African Journals Online (AJOL)

    Affinity purification of recombinant human plasminogen activator from ... Screening antibody was performed using rhPA milk in an ELISA-elution assay. ... useful for purifying other tPA mutants or other novel recombinant milkderived proteins.

  6. Evaluation Codes from an Affine Veriety Code Perspective

    DEFF Research Database (Denmark)

    Geil, Hans Olav

    2008-01-01

    Evaluation codes (also called order domain codes) are traditionally introduced as generalized one-point geometric Goppa codes. In the present paper we will give a new point of view on evaluation codes by introducing them instead as particular nice examples of affine variety codes. Our study...... includes a reformulation of the usual methods to estimate the minimum distances of evaluation codes into the setting of affine variety codes. Finally we describe the connection to the theory of one-pointgeometric Goppa codes. Contents 4.1 Introduction...... . . . . . . . . . . . . . . . . . . . . . . . 171 4.9 Codes form order domains . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173 4.10 One-point geometric Goppa codes . . . . . . . . . . . . . . . . . . . . . . . . 176 4.11 Bibliographical Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178 References...

  7. New approaches for the reliable in vitro assessment of binding affinity based on high-resolution real-time data acquisition of radioligand-receptor binding kinetics.

    Science.gov (United States)

    Zeilinger, Markus; Pichler, Florian; Nics, Lukas; Wadsak, Wolfgang; Spreitzer, Helmut; Hacker, Marcus; Mitterhauser, Markus

    2017-12-01

    Resolving the kinetic mechanisms of biomolecular interactions have become increasingly important in early-phase drug development. Since traditional in vitro methods belong to dose-dependent assessments, binding kinetics is usually overlooked. The present study aimed at the establishment of two novel experimental approaches for the assessment of binding affinity of both, radiolabelled and non-labelled compounds targeting the A 3 R, based on high-resolution real-time data acquisition of radioligand-receptor binding kinetics. A novel time-resolved competition assay was developed and applied to determine the K i of eight different A 3 R antagonists, using CHO-K1 cells stably expressing the hA 3 R. In addition, a new kinetic real-time cell-binding approach was established to quantify the rate constants k on and k off , as well as the dedicated K d of the A 3 R agonist [ 125 I]-AB-MECA. Furthermore, lipophilicity measurements were conducted to control influences due to physicochemical properties of the used compounds. Two novel real-time cell-binding approaches were successfully developed and established. Both experimental procedures were found to visualize the kinetic binding characteristics with high spatial and temporal resolution, resulting in reliable affinity values, which are in good agreement with values previously reported with traditional methods. Taking into account the lipophilicity of the A 3 R antagonists, no influences on the experimental performance and the resulting affinity were investigated. Both kinetic binding approaches comprise tracer administration and subsequent binding to living cells, expressing the dedicated target protein. Therefore, the experiments resemble better the true in vivo physiological conditions and provide important markers of cellular feedback and biological response.

  8. The Purification of a Blood Group A Glycoprotein: An Affinity Chromatography Experiment.

    Science.gov (United States)

    Estelrich, J.; Pouplana, R.

    1988-01-01

    Describes a purification process through affinity chromatography necessary to obtain specific blood group glycoproteins from erythrocytic membranes. Discusses the preparation of erythrocytic membranes, extraction of glycoprotein from membranes, affinity chromatography purification, determination of glycoproteins, and results. (CW)

  9. Applications of thermodynamic calculations to Mg alloy design: Mg-Sn based alloy development

    International Nuclear Information System (INIS)

    Jung, In-Ho; Park, Woo-Jin; Ahn, Sang Ho; Kang, Dae Hoon; Kim, Nack J.

    2007-01-01

    Recently an Mg-Sn based alloy system has been investigated actively in order to develop new magnesium alloys which have a stable structure and good mechanical properties at high temperatures. Thermodynamic modeling of the Mg-Al-Mn-Sb-Si-Sn-Zn system was performed based on available thermodynamic, phase equilibria and phase diagram data. Using the optimized database, the phase relationships of the Mg-Sn-Al-Zn alloys with additions of Si and Sb were calculated and compared with their experimental microstructures. It is shown that the calculated results are in good agreement with experimental microstructures, which proves the applicability of thermodynamic calculations for new Mg alloy design. All calculations were performed using FactSage thermochemical software. (orig.)

  10. Exact form factors for the scaling ZN-Ising and the affine AN-1-Toda quantum field theories

    International Nuclear Information System (INIS)

    Babujian, H.; Karowski, M.

    2003-01-01

    Previous results on form factors for the scaling Ising and the sinh-Gordon models are extended to general Z N -Ising and affine A N-1 -Toda quantum field theories. In particular result for order, disorder parameters and para-Fermi fields σ Q (x), μ Q-tilde (x) and ψ Q (x) are presented for the Z N -model. For the A N-1 -Toda model form factors for exponentials of the Toda fields are proposed. The quantum field equation of motion is proved and the mass and wave function renormalization are calculated exactly

  11. Proton affinities in water of maingroup-element Hydrides - Effects of hydration and methyl substitution

    NARCIS (Netherlands)

    Swart, M.; Rosler, E.; Bickelhaupt, F.M.

    2007-01-01

    We have computed the proton affinities in water of archetypal anionic and neutral bases across the periodic table using the generalized gradient approximation (GGA) of density functional theory (DFT) at BP86/QZ4P//BP86/TZ2P. The main purpose of this work is to provide an intrinsically consistent set

  12. Quantum deformation of the affine transformation algebra

    International Nuclear Information System (INIS)

    Aizawa, N.; Sato, Haru-Tada

    1994-01-01

    We discuss a quantum deformation of the affine transformation algebra in one-dimensional space. It is shown that the quantum algebra has a non-cocommutative Hopf algebra structure, simple realizations and quantum tensor operators. (orig.)

  13. Amphiphilic Bio-molecules/ZnO Interface: Enhancement of Bio-affinity and Dispersibility

    International Nuclear Information System (INIS)

    Meng Xiu-Qing; Fang Yun-Zhang; Wu Feng-Min

    2012-01-01

    The dispersibility of bio-molecules such as lecithins on the surface of ZnO nanowires are investigated for biosensor applications. Lecithins can be absorbed on an as-synthesized ZnO nanowire surface in the form of sub-micro sized clusters, while scattering well on those annealed under oxygen atmosphere. Wettability analysis reveals that the as-synthesized ZnO nanowires bear a super-hydrophobic surface, which convents to superhydrophilic after oxygen annealing. First-principles calculations indicate that the adsorption energy of ZnO with water is about 0.2 eV at a distance of 2 Å when it is superhydrophilic, suggesting that lecithin can be absorbed on the hydrophilic surface stably at this distance and the bio-affinity can be enhanced under this condition. (condensed matter: structure, mechanical and thermal properties)

  14. Cyclization strategies of meditopes: affinity and diffraction studies of meditope–Fab complexes

    International Nuclear Information System (INIS)

    Bzymek, Krzysztof P.; Ma, Yuelong; Avery, Kendra A.; Horne, David A.; Williams, John C.

    2016-01-01

    An overview of cyclization strategies of a Fab-binding peptide to maximize affinity. Recently, a unique binding site for a cyclic 12-residue peptide was discovered within a cavity formed by the light and heavy chains of the cetuximab Fab domain. In order to better understand the interactions that drive this unique complex, a number of variants including the residues within the meditope peptide and the antibody, as well as the cyclization region of the meditope peptide, were created. Here, multiple crystal structures of meditope peptides incorporating different cyclization strategies bound to the central cavity of the cetuximab Fab domain are presented. The affinity of each cyclic derivative for the Fab was determined by surface plasmon resonance and correlated to structural differences. Overall, it was observed that the disulfide bond used to cyclize the peptide favorably packs against a hydrophobic ‘pocket’ and that amidation and acetylation of the original disulfide meditope increased the overall affinity ∼2.3-fold. Conversely, replacing the terminal cysteines with serines and thus creating a linear peptide reduced the affinity over 50-fold, with much of this difference being reflected in a decrease in the on-rate. Other cyclization methods, including the formation of a lactam, reduced the affinity but not to the extent of the linear peptide. Collectively, the structural and kinetic data presented here indicate that small perturbations introduced by different cyclization strategies can significantly affect the affinity of the meditope–Fab complex

  15. Cyclization strategies of meditopes: affinity and diffraction studies of meditope–Fab complexes

    Energy Technology Data Exchange (ETDEWEB)

    Bzymek, Krzysztof P.; Ma, Yuelong; Avery, Kendra A.; Horne, David A.; Williams, John C., E-mail: jcwilliams@coh.org [Beckman Research Institute of City of Hope, 1710 Flower Street, Duarte, CA 91010 (United States)

    2016-05-23

    An overview of cyclization strategies of a Fab-binding peptide to maximize affinity. Recently, a unique binding site for a cyclic 12-residue peptide was discovered within a cavity formed by the light and heavy chains of the cetuximab Fab domain. In order to better understand the interactions that drive this unique complex, a number of variants including the residues within the meditope peptide and the antibody, as well as the cyclization region of the meditope peptide, were created. Here, multiple crystal structures of meditope peptides incorporating different cyclization strategies bound to the central cavity of the cetuximab Fab domain are presented. The affinity of each cyclic derivative for the Fab was determined by surface plasmon resonance and correlated to structural differences. Overall, it was observed that the disulfide bond used to cyclize the peptide favorably packs against a hydrophobic ‘pocket’ and that amidation and acetylation of the original disulfide meditope increased the overall affinity ∼2.3-fold. Conversely, replacing the terminal cysteines with serines and thus creating a linear peptide reduced the affinity over 50-fold, with much of this difference being reflected in a decrease in the on-rate. Other cyclization methods, including the formation of a lactam, reduced the affinity but not to the extent of the linear peptide. Collectively, the structural and kinetic data presented here indicate that small perturbations introduced by different cyclization strategies can significantly affect the affinity of the meditope–Fab complex.

  16. IA-2 autoantibody affinity in children at risk for type 1 diabetes.

    Science.gov (United States)

    Krause, Stephanie; Chmiel, Ruth; Bonifacio, Ezio; Scholz, Marlon; Powell, Michael; Furmaniak, Jadwiga; Rees Smith, Bernard; Ziegler, Anette-G; Achenbach, Peter

    2012-12-01

    Autoantibodies to insulinoma-associated protein 2 (IA-2A) are associated with increased risk for type 1 diabetes. Here we examined IA-2A affinity and epitope specificity to assess heterogeneity in response intensity in relation to pathogenesis and diabetes risk in 50 children who were prospectively followed from birth. At first IA-2A appearance, affinity ranged from 10(7) to 10(11)L/mol and was high (>1.0×10(9)L/mol) in 41 (82%) children. IA-2A affinity was not associated with epitope specificity or HLA class II haplotype. On follow-up, affinity increased or remained high, and IA-2A were commonly against epitopes within the protein tyrosine phosphatase-like IA-2 domain and the homologue protein IA-2β. IA-2A were preceded or accompanied by other islet autoantibodies in 49 (98%) children, of which 34 progressed to diabetes. IA-2A affinity did not stratify diabetes risk. In conclusion, the IA-2A response in children is intense with rapid maturation against immunogenic epitopes and a strong association with diabetes development. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Many-body calculations with deuteron based single-particle bases and their associated natural orbits

    Science.gov (United States)

    Puddu, G.

    2018-06-01

    We use the recently introduced single-particle states obtained from localized deuteron wave-functions as a basis for nuclear many-body calculations. We show that energies can be substantially lowered if the natural orbits (NOs) obtained from this basis are used. We use this modified basis for {}10{{B}}, {}16{{O}} and {}24{{Mg}} employing the bare NNLOopt nucleon–nucleon interaction. The lowering of the energies increases with the mass. Although in principle NOs require a full scale preliminary many-body calculation, we found that an approximate preliminary many-body calculation, with a marginal increase in the computational cost, is sufficient. The use of natural orbits based on an harmonic oscillator basis leads to a much smaller lowering of the energies for a comparable computational cost.

  18. Affinity extraction of emerging contaminants from water based on bovine serum albumin as a binding agent.

    Science.gov (United States)

    Papastavros, Efthimia; Remmers, Rachael A; Snow, Daniel D; Cassada, David A; Hage, David S

    2018-03-01

    Affinity sorbents using bovine serum albumin as a binding agent were developed and tested for the extraction of environmental contaminants from water. Computer simulations based on a countercurrent distribution model were also used to study the behavior of these sorbents. Several model drugs, pesticides, and hormones of interest as emerging contaminants were considered in this work, with carbamazepine being used as a representative analyte when coupling the albumin column on-line with liquid chromatography and tandem mass spectrometry. The albumin column was found to be capable of extracting carbamazepine from aqueous solutions that contained trace levels of this analyte. Further studies of the bovine serum albumin sorbent indicated that it had higher retention under aqueous conditions than a traditional C 18 support for most of the tested emerging contaminants. Potential advantages of using these protein-based sorbents included the low cost of bovine serum albumin and its ability to bind to a relatively wide range of drugs and related compounds. It was also shown how simulations could be used to describe the elution behavior of the model compounds on the bovine serum albumin sorbents as an aid in optimizing the retention and selectivity of these supports for use with liquid chromatography or methods such as liquid chromatography with tandem mass spectrometry. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Application of Ni(II-assisted peptide bond hydrolysis to non-enzymatic affinity tag removal.

    Directory of Open Access Journals (Sweden)

    Edyta Kopera

    Full Text Available In this study, we demonstrate a non-enzymatic method for hydrolytic peptide bond cleavage, applied to the removal of an affinity tag from a recombinant fusion protein, SPI2-SRHWAP-His(6. This method is based on a highly specific Ni(II reaction with (S/TXHZ peptide sequences. It can be applied for the protein attached to an affinity column or to the unbound protein in solution. We studied the effect of pH, temperature and Ni(II concentration on the efficacy of cleavage and developed an analytical protocol, which provides active protein with a 90% yield and ∼100% purity. The method works well in the presence of non-ionic detergents, DTT and GuHCl, therefore providing a viable alternative for currently used techniques.

  20. A disturbance attenuation approach for a class of continuous piecewise affine systems : control design and experiments

    NARCIS (Netherlands)

    Doris, A.; Wouw, van de N.; Heemels, W.P.M.H.; Nijmeijer, H.

    2010-01-01

    We consider the disturbance attenuation problem for a class of continuous piecewise affine systems. Hereto, observer-based output-feedback controllers are proposed that render the closed-loop system uniformly convergent. The convergence property ensures, first, stability and, second, the existence

  1. Influence of bone affinity on the skeletal distribution of fluorescently labeled bisphosphonates in vivo.

    Science.gov (United States)

    Roelofs, Anke J; Stewart, Charlotte A; Sun, Shuting; Błażewska, Katarzyna M; Kashemirov, Boris A; McKenna, Charles E; Russell, R Graham G; Rogers, Michael J; Lundy, Mark W; Ebetino, Frank H; Coxon, Fraser P

    2012-04-01

    Bisphosphonates are widely used antiresorptive drugs that bind to calcium. It has become evident that these drugs have differing affinities for bone mineral; however, it is unclear whether such differences affect their distribution on mineral surfaces. In this study, fluorescent conjugates of risedronate, and its lower-affinity analogues deoxy-risedronate and 3-PEHPC, were used to compare the localization of compounds with differing mineral affinities in vivo. Binding to dentine in vitro confirmed differences in mineral binding between compounds, which was influenced predominantly by the characteristics of the parent compound but also by the choice of fluorescent tag. In growing rats, all compounds preferentially bound to forming endocortical as opposed to resorbing periosteal surfaces in cortical bone, 1 day after administration. At resorbing surfaces, lower-affinity compounds showed preferential binding to resorption lacunae, whereas the highest-affinity compound showed more uniform labeling. At forming surfaces, penetration into the mineralizing osteoid was found to inversely correlate with mineral affinity. These differences in distribution at resorbing and forming surfaces were not observed at quiescent surfaces. Lower-affinity compounds also showed a relatively higher degree of labeling of osteocyte lacunar walls and labeled lacunae deeper within cortical bone, indicating increased penetration of the osteocyte canalicular network. Similar differences in mineralizing surface and osteocyte network penetration between high- and low-affinity compounds were evident 7 days after administration, with fluorescent conjugates at forming surfaces buried under a new layer of bone. Fluorescent compounds were incorporated into these areas of newly formed bone, indicating that "recycling" had occurred, albeit at very low levels. Taken together, these findings indicate that the bone mineral affinity of bisphosphonates is likely to influence their distribution within the

  2. On dynamic equations for interaction of the affinor field with affine connection

    International Nuclear Information System (INIS)

    Pestov, A.B.

    1987-01-01

    The Lagrangian of interaction of an affinor field with an affine connection is constructed and the equations of motion and conservation laws are derived. It is shown that there exists a symmetric conserved tensor of the affine-connection energy-momentum

  3. Affinity for Quantitative Tools: Undergraduate Marketing Students Moving beyond Quantitative Anxiety

    Science.gov (United States)

    Tarasi, Crina O.; Wilson, J. Holton; Puri, Cheenu; Divine, Richard L.

    2013-01-01

    Marketing students are known as less likely to have an affinity for the quantitative aspects of the marketing discipline. In this article, we study the reasons why this might be true and develop a parsimonious 20-item scale for measuring quantitative affinity in undergraduate marketing students. The scale was administered to a sample of business…

  4. Modifiers of hemoglobin/oxygen affinity as sensitizers of tumors to radiation

    International Nuclear Information System (INIS)

    Hirst, D.G.; Wood, P.J.

    1987-01-01

    A powerful mechanism in the control of oxygen delivery to tissues is the allosteric modification of hemoglobin. Increased or decreased release of oxygen can be achieved by altering the affinity of hemoglobin for oxygen. Several studies have shown that tumor radiosensitivity is dependent on this relationship. The authors studied affinity changes produced in two distinctly different ways. Tumor bearing mice were given isovolemic exchange blood transfusions with the blood from donor mice which had been exposed to abnormal oxygen tensions, leading to increased or slightly decreased levels of 2,3-diphosphoglycerate (2,3 DPG) in their blood. When the recipient mice were irradiated, those receiving the blood with higher 2,3 DPG levels showed greater tumor sensitivity to radiation. An alternative strategy is the use of drugs which directly alter hemoglobin/oxygen affinity. The authors studied three antihyperlipoproteinemia drugs, all of which have produced markedly reduced affinities in vivo. Preliminary data indicate that the radiosensitization produced by at least one of these compounds is less than would have been expected from the 2,3 DPG experiments

  5. Solitons and the energy-momentum tensor for affine Toda theory

    Science.gov (United States)

    Olive, D. I.; Turok, N.; Underwood, J. W. R.

    1993-07-01

    Following Leznov and Saveliev, we present the general solution to Toda field theories of conformal, affine or conformal affine type, associated with a simple Lie algebra g. These depend on a free massless field and on a group element. By putting the former to zero, soliton solutions to the affine Toda theories with imaginary coupling constant result with the soliton data encoded in the group element. As this requires a reformulation of the affine Kac-Moody algebra closely related to that already used to formulate the physical properties of the particle excitations, including their scattering matrices, a unified treatment of particles and solitons emerges. The physical energy—momentum tensor for a general solution is broken into a total derivative plus a part dependent only on the derivatives of the free field. Despite the non-linearity of the field equations and their complex nature the energy and momentum of the N-soliton solution is shown to be real, equalling the sum of contributions from the individual solitons. There are rank-g species of soliton, with masses given by a generalisation of a formula due to Hollowood, being proportional to the components of the left Perron-Frobenius eigenvector of the Cartan matrix of g.

  6. Solitons and the energy-momentum tensor for affine Toda theory

    International Nuclear Information System (INIS)

    Olive, D.I.; Turok, N.; Underwood, J.W.R.

    1993-01-01

    Following Leznov and Saveliev, we present the general solution to Toda field theories of conformal, affine or conformal affine type, associated with a simple Lie algebra g. These depend on a free massless field and on a group element. By putting the former to zero, soliton solutions to the affine Toda theories with imaginary coupling constant result with the soliton data encoded in the group element. As this requires a reformulation of the affine Kac-Moodyy algebra closely related to that already used to formulate the physical properties of the particle excitations, including their scattering matrices, a unified treatment of particles and solitons emerges. The physical energy-momentum tensor for a general solution is broken into a total derivative plus a part dependent only on the derivatives of the free field. Despite the non-linearity of the field equations and their complex nature the energy and momentum of the N-soliton solution is shown to be real, equalling the sum of contributions from the individual solitons. There are rank-g species of soliton, with masses given by a generalisation of a formula due to Hollowood, being proportional to the components of the left Perron-Frobenius eigenvector of the Cartan matrix of g. (orig.)

  7. Prediction of trypsin/molecular fragment binding affinities by free energy decomposition and empirical scores

    Science.gov (United States)

    Benson, Mark L.; Faver, John C.; Ucisik, Melek N.; Dashti, Danial S.; Zheng, Zheng; Merz, Kenneth M.

    2012-05-01

    Two families of binding affinity estimation methodologies are described which were utilized in the SAMPL3 trypsin/fragment binding affinity challenge. The first is a free energy decomposition scheme based on a thermodynamic cycle, which included separate contributions from enthalpy and entropy of binding as well as a solvent contribution. Enthalpic contributions were estimated with PM6-DH2 semiempirical quantum mechanical interaction energies, which were modified with a statistical error correction procedure. Entropic contributions were estimated with the rigid-rotor harmonic approximation, and solvent contributions to the free energy were estimated with several different methods. The second general methodology is the empirical score LISA, which contains several physics-based terms trained with the large PDBBind database of protein/ligand complexes. Here we also introduce LISA+, an updated version of LISA which, prior to scoring, classifies systems into one of four classes based on a ligand's hydrophobicity and molecular weight. Each version of the two methodologies (a total of 11 methods) was trained against a compiled set of known trypsin binders available in the Protein Data Bank to yield scaling parameters for linear regression models. Both raw and scaled scores were submitted to SAMPL3. Variants of LISA showed relatively low absolute errors but also low correlation with experiment, while the free energy decomposition methods had modest success when scaling factors were included. Nonetheless, re-scaled LISA yielded the best predictions in the challenge in terms of RMS error, and six of these models placed in the top ten best predictions by RMS error. This work highlights some of the difficulties of predicting binding affinities of small molecular fragments to protein receptors as well as the benefit of using training data.

  8. Affine invariants of convex polygons.

    Science.gov (United States)

    Flusser, Jan

    2002-01-01

    In this correspondence, we prove that the affine invariants, for image registration and object recognition, proposed recently by Yang and Cohen (see ibid., vol.8, no.7, p.934-46, July 1999) are algebraically dependent. We show how to select an independent and complete set of the invariants. The use of this new set leads to a significant reduction of the computing complexity without decreasing the discrimination power.

  9. 19 CFR 351.405 - Calculation of normal value based on constructed value.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Calculation of normal value based on constructed value. 351.405 Section 351.405 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Calculation of Export Price, Constructed Export Price, Fair Value, and...

  10. Use of Intrinsic Viscosity for evaluation of polymer-solvent affinity

    DEFF Research Database (Denmark)

    Marani, Debora; Hjelm, Johan; Wandel, Marie

    2013-01-01

    The objective of the current paper was to define a rheological method for the study of the solvent/binder affinity. The adopted strategy involves the study of the intrinsic viscosity [η] of polymer solutions. [η] was estimated via an extrapolation procedure using the Huggins and Kramer equations....... The intrinsic viscosity and the Mark-Houwink shape parameter were estimated for the three polymers and used as criteria for estimating the polymer/solvent affinity....

  11. Integrated Power Flow and Short Circuit Calculation Method for Distribution Network with Inverter Based Distributed Generation

    Directory of Open Access Journals (Sweden)

    Shan Yang

    2016-01-01

    Full Text Available Power flow calculation and short circuit calculation are the basis of theoretical research for distribution network with inverter based distributed generation. The similarity of equivalent model for inverter based distributed generation during normal and fault conditions of distribution network and the differences between power flow and short circuit calculation are analyzed in this paper. Then an integrated power flow and short circuit calculation method for distribution network with inverter based distributed generation is proposed. The proposed method let the inverter based distributed generation be equivalent to Iθ bus, which makes it suitable to calculate the power flow of distribution network with a current limited inverter based distributed generation. And the low voltage ride through capability of inverter based distributed generation can be considered as well in this paper. Finally, some tests of power flow and short circuit current calculation are performed on a 33-bus distribution network. The calculated results from the proposed method in this paper are contrasted with those by the traditional method and the simulation method, whose results have verified the effectiveness of the integrated method suggested in this paper.

  12. Affinity enhancement of nanobody binding to EGFR: in silico site-directed mutagenesis and molecular dynamics simulation approaches.

    Science.gov (United States)

    Farasat, Alireza; Rahbarizadeh, Fatemeh; Hosseinzadeh, Ghader; Sajjadi, Sharareh; Kamali, Mehdi; Keihan, Amir Homayoun

    2017-06-01

    Epidermal growth factor receptor (EGFR), a transmembrane glycoprotein, is overexpressed in many cancers such as head-neck, breast, prostate, and skin cancers for this reason it is a good target in cancer therapy and diagnosis. In nanobody-based cancer diagnosis and treatment, nanobodies with high affinity toward receptor (e.g. EGFR) results in effective treatment or diagnosis of cancer. In this regard, the main aim of this study is to develop a method based on molecular dynamic (MD) simulations for designing of 7D12 based nanobody with high affinity compared with wild-type nanobody. By surveying electrostatic and desolvation interactions between different residues of 7D12 and EGFR, the critical residues of 7D12 that play the main role in the binding of 7D12 to EGFR were elucidated and based on these residues, five logical variants were designed. Following the 50 ns MD simulations, pull and umbrella sampling simulation were performed for 7D12 and all its variants in complex with EGFR. Binding free energy of 7D12 (and all its variants) with EGFR was obtained by weighted histogram analysis method. According to binding free energy results, GLY101 to GLU mutation showed the highest binding affinity but this variant is unstable after 50 ns MD simulations. ALA100 to GLU mutation shows suitable binding enhancement with acceptable structural stability. Suitable position and orientation of GLU in residue 100 of 7D12 against related amino acids of EGFR formed some extra hydrogen and electrostatic interactions which resulted in binding enhancement.

  13. A solid-on-solid invasion percolation model for self-affine interfaces

    International Nuclear Information System (INIS)

    Arizmendi, C.M.; Martin, H.O.; Sanchez, J.R.

    1993-08-01

    The scaling properties of the interface of a new growth model are studied. The model is based on the standard invasion percolation without trapping in which the solid-on-solid condition is imposed. The local correlation between points of the interface can be controlled through a parameter. The self-affine properties of the interface show strong dependence on the existence of the local correlation. The dependence of the relevant exponents of the interface with the correlation is analysed. (author). 8 refs, 4 figs

  14. Affinity of nat/68Ga-Labelled Curcumin and Curcuminoid Complexes for β-Amyloid Plaques: Towards the Development of New Metal-Curcumin Based Radiotracers

    Directory of Open Access Journals (Sweden)

    Sara Rubagotti

    2016-09-01

    Full Text Available Curcumin derivatives labelled with fluorine-18 or technetium-99m have recently shown their potential as diagnostic tools for Alzheimer’s disease. Nevertheless, no study by exploiting the labelling with gallium-68 has been performed so far, in spite of its suitable properties (positron emitter, generator produced radionuclide. Herein, an evaluation of the affinity for synthetic β-amyloid fibrils and for amyloid plaques of three nat/68Ga-labelled curcumin analogues, namely curcumin curcumin (CUR, bis-dehydroxy-curcumin (bDHC and diacetyl-curcumin (DAC, was performed. Affinity and specificity were tested in vitro on amyloid synthetic fibrils by using gallium-68 labelled compounds. Post-mortem brain cryosections from Tg2576 mice were used for the ex vivo visualization of amyloid plaques. The affinity of 68Ga(CUR2+, 68Ga(DAC2+, and 68Ga(bDHC2+ for synthetic β-amyloid fibrils was moderate and their uptake could be observed in vitro. On the other hand, amyloid plaques could not be visualized on brain sections of Tg2576 mice after injection, probably due to the low stability of the complexes in vivo and of a hampered passage through the blood–brain barrier. Like curcumin, all nat/68Ga-curcuminoid complexes maintain a high affinity for β-amyloid plaques. However, structural modifications are still needed to improve their applicability as radiotracers in vivo.

  15. CT-3DRA registration for radiosurgery treatments: a comparison among rigid, affine and non rigid approaches

    International Nuclear Information System (INIS)

    Stancanello, J.; Loeckx, D.; Francescon, P.; Calvedon, C.; Avanzo, M.; Cora, S.; Scalchi, P.; Cerveri, P.; Ferrigno, G.

    2004-01-01

    This work aims at comparing rigid, affine and Local Non Rigid (LNR) CT-3D Rotational Angiography (CT-3DRA) registrations based on mutual information. 10 cranial and 1 spinal cases have been registered by rigid and affine transformations; while LNR has been applied to the cases where residual deformation must be corrected. An example of CT-3DRA registration without regularization term and an example of LNR using the similarity criterion and the regularization term as well as 3D superposition of the 3DRA before and after the registration without the regularization term are presented. All the registrations performed by rigid transformation converged to an acceptable solution. The results about the robustness test in axial direction are reported. Conclusions: For cranial cases, affine transformation endowed with threshold-segmentation pre-processing can be considered the most favourable solution for almost all registrations; for some cases, LNR provides more accurate results. For the spinal case rigid transformation is the most suitable when immobilizing patient during examinations; in this case the increase of accuracy by using LNR registrations seems to be not significant

  16. Einstein’s gravity from a polynomial affine model

    Science.gov (United States)

    Castillo-Felisola, Oscar; Skirzewski, Aureliano

    2018-03-01

    We show that the effective field equations for a recently formulated polynomial affine model of gravity, in the sector of a torsion-free connection, accept general Einstein manifolds—with or without cosmological constant—as solutions. Moreover, the effective field equations are partially those obtained from a gravitational Yang–Mills theory known as Stephenson–Kilmister–Yang theory. Additionally, we find a generalization of a minimally coupled massless scalar field in General Relativity within a ‘minimally’ coupled scalar field in this affine model. Finally, we present a brief (perturbative) analysis of the propagators of the gravitational theory, and count the degrees of freedom. For completeness, we prove that a Birkhoff-like theorem is valid for the analyzed sector.

  17. Development of Calculation Module for Intake Retention Functions based on Occupational Intakes of Radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Noh, Siwan; Kwon, Tae-Eun; Lee, Jai-Ki [Hanyang Univ., Seoul (Korea, Republic of); Lee, Jong-Il; Kim, Jang-Lyul [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-10-15

    In internal dosimetry, intake retention and excretion functions are essential to estimate intake activity using bioassay sample such as whole body counter, lung counter, and urine sample. Even though ICRP (International Commission on Radiological Protection)provides the functions in some ICRP publications, it is needed to calculate the functions because the functions from the publications are provided for very limited time. Thus, some computer program are generally used to calculate intake retention and excretion functions and estimate intake activity. OIR (Occupational Intakes of Radionuclides) will be published soon by ICRP, which totally replaces existing internal dosimetry models and relevant data including intake retention and excretion functions. Thus, the calculation tool for the functions is needed based on OIR. In this study, we developed calculation module for intake retention and excretion functions based on OIR using C++ programming language with Intel Math Kernel Library. In this study, we developed the intake retention and excretion function calculation module based on OIR using C++ programing language.

  18. Development of Calculation Module for Intake Retention Functions based on Occupational Intakes of Radionuclides

    International Nuclear Information System (INIS)

    Noh, Siwan; Kwon, Tae-Eun; Lee, Jai-Ki; Lee, Jong-Il; Kim, Jang-Lyul

    2014-01-01

    In internal dosimetry, intake retention and excretion functions are essential to estimate intake activity using bioassay sample such as whole body counter, lung counter, and urine sample. Even though ICRP (International Commission on Radiological Protection)provides the functions in some ICRP publications, it is needed to calculate the functions because the functions from the publications are provided for very limited time. Thus, some computer program are generally used to calculate intake retention and excretion functions and estimate intake activity. OIR (Occupational Intakes of Radionuclides) will be published soon by ICRP, which totally replaces existing internal dosimetry models and relevant data including intake retention and excretion functions. Thus, the calculation tool for the functions is needed based on OIR. In this study, we developed calculation module for intake retention and excretion functions based on OIR using C++ programming language with Intel Math Kernel Library. In this study, we developed the intake retention and excretion function calculation module based on OIR using C++ programing language

  19. Analysis of Biological Interactions by Affinity Chromatography: Clinical and Pharmaceutical Applications.

    Science.gov (United States)

    Hage, David S

    2017-06-01

    The interactions between biochemical and chemical agents in the body are important in many clinical processes. Affinity chromatography and high-performance affinity chromatography (HPAC), in which a column contains an immobilized biologically related binding agent, are 2 methods that can be used to study these interactions. This review presents various approaches that can be used in affinity chromatography and HPAC to characterize the strength or rate of a biological interaction, the number and types of sites that are involved in this process, and the interactions between multiple solutes for the same binding agent. A number of applications for these methods are examined, with an emphasis on recent developments and high-performance affinity methods. These applications include the use of these techniques for fundamental studies of biological interactions, high-throughput screening of drugs, work with modified proteins, tools for personalized medicine, and studies of drug-drug competition for a common binding agent. The wide range of formats and detection methods that can be used with affinity chromatography and HPAC for examining biological interactions makes these tools attractive for various clinical and pharmaceutical applications. Future directions in the development of small-scale columns and the coupling of these methods with other techniques, such as mass spectrometry or other separation methods, should continue to increase the flexibility and ease with which these approaches can be used in work involving clinical or pharmaceutical samples. © 2016 American Association for Clinical Chemistry.

  20. The affine quantum gravity programme

    International Nuclear Information System (INIS)

    Klauder, John R

    2002-01-01

    The central principle of affine quantum gravity is securing and maintaining the strict positivity of the matrix { g-hat ab (x)} composed of the spatial components of the local metric operator. On spectral grounds, canonical commutation relations are incompatible with this principle, and they must be replaced by noncanonical, affine commutation relations. Due to the partial second-class nature of the quantum gravitational constraints, it is advantageous to use the recently developed projection operator method, which treats all quantum constraints on an equal footing. Using this method, enforcement of regularized versions of the gravitational operator constraints is formulated quite naturally by means of a novel and relatively well-defined functional integral involving only the same set of variables that appears in the usual classical formulation. It is anticipated that skills and insight to study this formulation can be developed by studying special, reduced-variable models that still retain some basic characteristics of gravity, specifically a partial second-class constraint operator structure. Although perturbatively nonrenormalizable, gravity may possibly be understood nonperturbatively from a hard-core perspective that has proved valuable for specialized models. Finally, developing a procedure to pass to the genuine physical Hilbert space involves several interconnected steps that require careful coordination

  1. Sugawara construction for affine SL(N,1)

    International Nuclear Information System (INIS)

    Henningson, M.

    1990-01-01

    We investigate the sl(N,1) superalgebras, their affine extensions and their representations. This is used to perform a Sugawara construction of the Virasoro algebra. The allowed values of the conformal anomaly and the conformal dimension are computed. (orig.)

  2. Prediction of fission mass-yield distributions based on cross section calculations

    International Nuclear Information System (INIS)

    Hambsch, F.-J.; G.Vladuca; Tudora, Anabella; Oberstedt, S.; Ruskov, I.

    2005-01-01

    For the first time, fission mass-yield distributions have been predicted based on an extended statistical model for fission cross section calculations. In this model, the concept of the multi-modality of the fission process has been incorporated. The three most dominant fission modes, the two asymmetric standard I (S1) and standard II (S2) modes and the symmetric superlong (SL) mode are taken into account. De-convoluted fission cross sections for S1, S2 and SL modes for 235,238 U(n, f) and 237 Np(n, f), based on experimental branching ratios, were calculated for the first time in the incident neutron energy range from 0.01 to 5.5 MeV providing good agreement with the experimental fission cross section data. The branching ratios obtained from the modal fission cross section calculations have been used to deduce the corresponding fission yield distributions, including mean values also for incident neutron energies hitherto not accessible to experiment

  3. Use of thermodynamic coupling between antibody-antigen binding and phospholipid acyl chain phase transition energetics to predict immunoliposome targeting affinity.

    Science.gov (United States)

    Klegerman, Melvin E; Zou, Yuejiao; Golunski, Eva; Peng, Tao; Huang, Shao-Ling; McPherson, David D

    2014-09-01

    Thermodynamic analysis of ligand-target binding has been a useful tool for dissecting the nature of the binding mechanism and, therefore, potentially can provide valuable information regarding the utility of targeted formulations. Based on a consistent coupling of antibody-antigen binding and gel-liquid crystal transition energetics observed for antibody-phosphatidylethanolamine (Ab-PE) conjugates, we hypothesized that the thermodynamic parameters and the affinity for antigen of the Ab-PE conjugates could be effectively predicted once the corresponding information for the unconjugated antibody is determined. This hypothesis has now been tested in nine different antibody-targeted echogenic liposome (ELIP) preparations, where antibody is conjugated to dipalmitoylphosphatidylethanolamine (DPPE) head groups through a thioether linkage. Predictions were satisfactory (affinity not significantly different from the population of values found) in five cases (55.6%), but the affinity of the unconjugated antibody was not significantly different from the population of values found in six cases (66.7%), indicating that the affinities of the conjugated antibody tended not to deviate appreciably from those of the free antibody. While knowledge of the affinities of free antibodies may be sufficient to judge their suitability as targeting agents, thermodynamic analysis may still provide valuable information regarding their usefulness for specific applications.

  4. Inverse scattering and solitons in An-1 affine Toda field theories

    International Nuclear Information System (INIS)

    Beggs, E.J.; Johnson, P.R.

    1997-01-01

    We implement the inverse scattering method in the case of the A n affine Toda field theories, by studying the space-time evolution of simple poles in the underlying loop group. We find the known single-soliton solutions, as well as additional solutions with non-linear modes of oscillation around the standard solution, by studying the particularly simple case where the residue at the pole is a rank-one projection. We show that these solutions with extra modes have the same mass and topological charges as the standard solutions, so we do not shed any light on the missing topological charge problem in these models. From the monodromy matrix it is shown that these solutions have the same higher conserved charges as the standard solutions. We also show that the integrated energy-momentum density can be calculated from the central extension of the loop group. (orig.)

  5. Gaussian and Affine Approximation of Stochastic Diffusion Models for Interest and Mortality Rates

    Directory of Open Access Journals (Sweden)

    Marcus C. Christiansen

    2013-10-01

    Full Text Available In the actuarial literature, it has become common practice to model future capital returns and mortality rates stochastically in order to capture market risk and forecasting risk. Although interest rates often should and mortality rates always have to be non-negative, many authors use stochastic diffusion models with an affine drift term and additive noise. As a result, the diffusion process is Gaussian and, thus, analytically tractable, but negative values occur with positive probability. The argument is that the class of Gaussian diffusions would be a good approximation of the real future development. We challenge that reasoning and study the asymptotics of diffusion processes with affine drift and a general noise term with corresponding diffusion processes with an affine drift term and an affine noise term or additive noise. Our study helps to quantify the error that is made by approximating diffusive interest and mortality rate models with Gaussian diffusions and affine diffusions. In particular, we discuss forward interest and forward mortality rates and the error that approximations cause on the valuation of life insurance claims.

  6. Affinity chromatography with pseudobiospecific ligands on high-performance supports for purification of proteins of biotechnological interest

    Directory of Open Access Journals (Sweden)

    N.B. Iannucci

    2003-03-01

    Full Text Available High-performance affinity matrices were obtained by attaching pseudobiospecific ligands to hollow-fibre membranes. The neutral protease contained in FlavourzymeTM was purified to homogeneity with Yellow 4R-HE affinity hollow-fibre membranes. Immobilisation of Red HE-3B allowed purification of a milk-clotting enzyme obtained by solid-state culture of Mucor bacilliformis. Copper immobilisation through iminodiacetic acid allowed fractionation of Biocon Bioconcentrated PlusTM to separate the pectinesterase-containing fraction. The productivity of the developed processes - 1900, 94 and 750 U/ml.min, respectively - was 10- to 15-fold higher than that achieved with the same ligands immobilised on agarose-based soft gels, mainly due to the shortening of the purification processes.

  7. Positron-attachment to small molecules: Vibrational enhancement of positron affinities with configuration interaction level of multi-component molecular orbital approach

    Energy Technology Data Exchange (ETDEWEB)

    Tachikawa, Masanori [Quantum Chemistry Division, Graduate School of NanoBioScience, Yokohama City University, 22-2 Seto, Kanazawa, Yokohama 236-0027 (Japan)

    2015-12-31

    To theoretically demonstrate the binding of a positron to small polarized molecules, we have calculated the vibrational averaged positron affinity (PA) values along the local vibrational contribution with the configuration interaction level of multi-component molecular orbital method. This method can take the electron-positron correlation contribution into account through single electronic - single positronic excitation configurations. The PA values are enhanced by including the local vibrational contribution from vertical PA values due to the anharmonicity of the potential.

  8. Uniform Orientation of Biotinylated Nanobody as an Affinity Binder for Detection of Bacillus thuringiensis (Bt) Cry1Ac Toxin

    Science.gov (United States)

    Li, Min; Zhu, Min; Zhang, Cunzheng; Liu, Xianjin; Wan, Yakun

    2014-01-01

    Nanobodies are the smallest natural fragments with useful properties such as high affinity, distinct paratope and high stability, which make them an ideal tool for detecting target antigens. In this study, we generated and characterized nanobodies against the Cry1Ac toxin and applied them in a biotin-streptavidin based double antibodies (nanobodies) sandwich-ELISA (DAS-ELISA) assay. After immunizing a camel with soluble Cry1Ac toxin, a phage displayed library was constructed to generate Nbs against the Cry1Ac toxin. Through successive rounds of affinity bio-panning, four nanobodies with greatest diversity in CDR3 sequences were obtained. After affinity determination and conjugating to HRP, two nanobodies with high affinity which can recognize different epitopes of the same antigen (Cry1Ac) were selected as capture antibody (Nb61) and detection antibody (Nb44). The capture antibody (Nb61) was biotinylated in vivo for directional immobilization on wells coated with streptavidin matrix. Both results of specificity analysis and thermal stability determination add support for reliability of the following DAS-ELISA with a minimum detection limit of 0.005 μg·mL−1 and a working range 0.010–1.0 μg·mL−1. The linear curve displayed an acceptable correlation coefficient of 0.9976. These results indicated promising applications of nanobodies for detection of Cry1Ac toxin with biotin-streptavidin based DAS-ELISA system. PMID:25474492

  9. Uniform Orientation of Biotinylated Nanobody as an Affinity Binder for Detection of Bacillus thuringiensis (Bt Cry1Ac Toxin

    Directory of Open Access Journals (Sweden)

    Min Li

    2014-12-01

    Full Text Available Nanobodies are the smallest natural fragments with useful properties such as high affinity, distinct paratope and high stability, which make them an ideal tool for detecting target antigens. In this study, we generated and characterized nanobodies against the Cry1Ac toxin and applied them in a biotin-streptavidin based double antibodies (nanobodies sandwich-ELISA (DAS-ELISA assay. After immunizing a camel with soluble Cry1Ac toxin, a phage displayed library was constructed to generate Nbs against the Cry1Ac toxin. Through successive rounds of affinity bio-panning, four nanobodies with greatest diversity in CDR3 sequences were obtained. After affinity determination and conjugating to HRP, two nanobodies with high affinity which can recognize different epitopes of the same antigen (Cry1Ac were selected as capture antibody (Nb61 and detection antibody (Nb44. The capture antibody (Nb61 was biotinylated in vivo for directional immobilization on wells coated with streptavidin matrix. Both results of specificity analysis and thermal stability determination add support for reliability of the following DAS-ELISA with a minimum detection limit of 0.005 μg·mL−1 and a working range 0.010–1.0 μg·mL−1. The linear curve displayed an acceptable correlation coefficient of 0.9976. These results indicated promising applications of nanobodies for detection of Cry1Ac toxin with biotin-streptavidin based DAS-ELISA system.

  10. Application of γ field theory based calculation method to the monitoring of mine nuclear radiation environment

    International Nuclear Information System (INIS)

    Du Yanjun; Liu Qingcheng; Liu Hongzhang; Qin Guoxiu

    2009-01-01

    In order to find the feasibility of calculating mine radiation dose based on γ field theory, this paper calculates the γ radiation dose of a mine by means of γ field theory based calculation method. The results show that the calculated radiation dose is of small error and can be used to monitor mine environment of nuclear radiation. (authors)

  11. Medication calculation: the potential role of digital game-based learning in nurse education.

    Science.gov (United States)

    Foss, Brynjar; Mordt Ba, Petter; Oftedal, Bjørg F; Løkken, Atle

    2013-12-01

    Medication dose calculation is one of several medication-related activities that are conducted by nurses daily. However, medication calculation skills appear to be an area of global concern, possibly because of low numeracy skills, test anxiety, low self-confidence, and low self-efficacy among student nurses. Various didactic strategies have been developed for student nurses who still lack basic mathematical competence. However, we suggest that the critical nature of these skills demands the investigation of alternative and/or supplementary didactic approaches to improve medication calculation skills and to reduce failure rates. Digital game-based learning is a possible solution because of the following reasons. First, mathematical drills may improve medication calculation skills. Second, games are known to be useful during nursing education. Finally, mathematical drill games appear to improve the attitudes of students toward mathematics. The aim of this article was to discuss common challenges of medication calculation skills in nurse education, and we highlight the potential role of digital game-based learning in this area.

  12. The MiAge Calculator: a DNA methylation-based mitotic age calculator of human tissue types.

    Science.gov (United States)

    Youn, Ahrim; Wang, Shuang

    2018-01-01

    Cell division is important in human aging and cancer. The estimation of the number of cell divisions (mitotic age) of a given tissue type in individuals is of great interest as it allows not only the study of biological aging (using a new molecular aging target) but also the stratification of prospective cancer risk. Here, we introduce the MiAge Calculator, a mitotic age calculator based on a novel statistical framework, the MiAge model. MiAge is designed to quantitatively estimate mitotic age (total number of lifetime cell divisions) of a tissue using the stochastic replication errors accumulated in the epigenetic inheritance process during cell divisions. With the MiAge model, the MiAge Calculator was built using the training data of DNA methylation measures of 4,020 tumor and adjacent normal tissue samples from eight TCGA cancer types and was tested using the testing data of DNA methylation measures of 2,221 tumor and adjacent normal tissue samples of five other TCGA cancer types. We showed that within each of the thirteen cancer types studied, the estimated mitotic age is universally accelerated in tumor tissues compared to adjacent normal tissues. Across the thirteen cancer types, we showed that worse cancer survivals are associated with more accelerated mitotic age in tumor tissues. Importantly, we demonstrated the utility of mitotic age by showing that the integration of mitotic age and clinical information leads to improved survival prediction in six out of the thirteen cancer types studied. The MiAge Calculator is available at http://www.columbia.edu/∼sw2206/softwares.htm .

  13. Haemoglobin Pierre-Benite--a high affinity variant associated with relative polycythaemia.

    Science.gov (United States)

    Beard, M E; Potter, H C; Spearing, R L; Brennan, S O

    2001-12-01

    This is the second reported example of Hb Pierre--Benite (beta90 Glu-->Asp). This mutation is associated with increased oxygen affinity and polycythaemia. No instability was found and there was no charge shift detected by cellulose acetate electrophoresis at pH 8.3. The mutation was however, clearly indicated by electrospray ionization mass spectrometry (ESI MS), which showed an abnormal beta chain with a 14 Da decrease in mass. Blood volume studies documented a relative rather than a true polycythaemia and this finding has been reported in at least two other high affinity haemoglobin variants--Hb Heathrow and Hb Rahere. This finding led to delay in diagnosis because high oxygen affinity variants are conventionally considered to cause a true polycythaemia.

  14. Myoglobin oxygen affinity in aquatic and terrestrial birds and mammals.

    Science.gov (United States)

    Wright, Traver J; Davis, Randall W

    2015-07-01

    Myoglobin (Mb) is an oxygen binding protein found in vertebrate skeletal muscle, where it facilitates intracellular transport and storage of oxygen. This protein has evolved to suit unique physiological needs in the muscle of diving vertebrates that express Mb at much greater concentrations than their terrestrial counterparts. In this study, we characterized Mb oxygen affinity (P50) from 25 species of aquatic and terrestrial birds and mammals. Among diving species, we tested for correlations between Mb P50 and routine dive duration. Across all species examined, Mb P50 ranged from 2.40 to 4.85 mmHg. The mean P50 of Mb from terrestrial ungulates was 3.72±0.15 mmHg (range 3.70-3.74 mmHg). The P50 of cetaceans was similar to terrestrial ungulates ranging from 3.54 to 3.82 mmHg, with the exception of the melon-headed whale, which had a significantly higher P50 of 4.85 mmHg. Among pinnipeds, the P50 ranged from 3.23 to 3.81 mmHg and showed a trend for higher oxygen affinity in species with longer dive durations. Among diving birds, the P50 ranged from 2.40 to 3.36 mmHg and also showed a trend of higher affinities in species with longer dive durations. In pinnipeds and birds, low Mb P50 was associated with species whose muscles are metabolically active under hypoxic conditions associated with aerobic dives. Given the broad range of potential globin oxygen affinities, Mb P50 from diverse vertebrate species appears constrained within a relatively narrow range. High Mb oxygen affinity within this range may be adaptive for some vertebrates that make prolonged dives. © 2015. Published by The Company of Biologists Ltd.

  15. Proadifen-sensitive high affinity binding of 3H-alaproclate to liver membranes

    International Nuclear Information System (INIS)

    Ross, S.B.

    1987-01-01

    3 H-alaproclate, a selective 5 h ydroxytryptamine uptake inhibitor, was found to bind to microsomal membranes from the rat liver with high affinity (K D -=3 nM) and large capacity (B max about 2 nmol/g liver). This binding was stereoselective since S-( - )-alaproclate was 30 times more potent than the R-( + )-enantiomer to displace the 3 H-labelled racemate. Proadifen (SKF 525A), an inhibitor of cytochrome P-450, displaced the 3 H-alaproclate binding with the same, high affinity (K i =3 nM) as alaproclate itself. Repeated treatment with phenobarbital sodium (5x75 mg/kg intraperitoneally) increased the number of alaproclate binding sites 7-8 times without changing the affinity. However, most of the phenobarbital induced 3 H-alaproclate binding was not displaceable by proadifen, showing the presence of at least two different high affinity binding sites. The possible involvement of cytochrome P-450 in the alaproclate binding is discussed. (author)

  16. Plasma density calculation based on the HCN waveform data

    International Nuclear Information System (INIS)

    Chen Liaoyuan; Pan Li; Luo Cuiwen; Zhou Yan; Deng Zhongchao

    2004-01-01

    A method to improve the plasma density calculation is introduced using the base voltage and the phase zero points obtained from the HCN interference waveform data. The method includes making the signal quality higher by putting the signal control device and the analog-to-digit converters in the same location and charging them by the same power, and excluding the noise's effect according to the possible changing rate of the signal's phase, and to make the base voltage more accurate by dynamical data processing. (authors)

  17. Ferromagnetic Levan Composite: An Affinity Matrix to Purify Lectin

    Directory of Open Access Journals (Sweden)

    Renata Angeli

    2009-01-01

    Full Text Available A simple and inexpensive procedure used magnetite and levan to synthesize a composite recovered by a magnetic field. Lectins from Canavalia ensiformis (Con A and Cratylia mollis (Cramoll 1 and Cramoll 1,4 did bind specifically to composite. The magnetic property of derivative favored washing out contaminating proteins and recovery of pure lectins with glucose elution. Cramoll 1 was purified by this affinity binding procedure in two steps instead of a previous three-step protocol with ammonium sulfate fractionation, affinity chromatography on Sephadex G-75, and ion exchange chromatography through a CM-cellulose column.

  18. It's the peptide-MHC affinity, stupid.

    Science.gov (United States)

    Kammertoens, Thomas; Blankenstein, Thomas

    2013-04-15

    Adoptively transferred T cells can reject large established tumors, but recurrence due to escape variants frequently occurs. In this issue of Cancer Cell, Engels et al. demonstrate that the affinity of the target peptide to the MHC molecule determines whether large tumors will relapse following adoptive T cell therapy. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. WE-DE-201-06: Impact of Temporal Image Coregistration Methods On 3D Internal Dose Calculations in Targeted Radionuclide Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Besemer, A; Marsh, I; Bednarz, B [University of Wisconsin, Madison, WI (United States)

    2016-06-15

    Purpose: The calculation of 3D internal dose calculations in targeted radionuclide therapy requires the acquisition and temporal coregistration of a serial PET/CT or SPECT/CT images. This work investigates the dosimetric impact of different temporal coregistration methods commonly used for 3D internal dosimetry. Methods: PET/CT images of four mice were acquired at 1, 24, 48, 72, 96, 144 hrs post-injection of {sup 124}I-CLR1404. The therapeutic {sup 131}I-CLR1404 absorbed dose rate (ADR) was calculated at each time point using a Geant4-based MC dosimetry platform using three temporal image coregistration Methods: (1) no coregistration (NC), whole body sequential CT-CT affine coregistration (WBAC), and individual sequential ROI-ROI affine coregistration (IRAC). For NC, only the ROI mean ADR was integrated to obtain ROI mean doses. For WBAC, the CT at each time point was coregistered to a single reference CT. The CT transformations were applied to the corresponding ADR images and the dose was calculated on a voxel-basis within the whole CT volume. For IRAC, each individual ROI was isolated and sequentially coregistered to a single reference ROI. The ROI transformations were applied to the corresponding ADR images and the dose was calculated on a voxel-basis within the ROI volumes. Results: The percent differences in the ROI mean doses were as large as 109%, 88%, and 32%, comparing the WBAC vs. IRAC, NC vs. IRAC, and NC vs. WBAC methods, respectively. The CoV in the mean dose between the all three methods ranged from 2–36%. The pronounced curvature of the spinal cord was not adequately coregistered using WBAC which resulted in large difference between the WBAC and IRAC. Conclusion: The method used for temporal image coregistration can result in large differences in 3D internal dosimetry calculations. Care must be taken to choose the most appropriate method depending on the imaging conditions, clinical site, and specific application. This work is partially funded by

  20. Interactions between alkaline earth cations and oxo ligands. DFT study of the affinity of the Mg²+ cation for phosphoryl ligands.

    Science.gov (United States)

    da Costa, Leonardo Moreira; de Mesquita Carneiro, José Walkimar; Paes, Lilian Weitzel Coelho

    2011-08-01

    DFT (B3LYP/6-31+G(d)) calculations of Mg(2+) affinities for a set of phosphoryl ligands were performed. Two types of ligands were studied: a set of trivalent [O = P(R)] and a set of pentavalent phosphoryl ligands [O = P(R)(3)] (R = H, F, Cl, Br, OH, OCH(3), CH(3), CN, NH(2) and NO(2)), with R either bound directly to the phosphorus atom or to the para position of a phenyl ring. The affinity of the Mg(2+) cation for the ligands was quantified by means of the enthalpy for the substitution of one water molecule in the [Mg(H(2)O)(6)](2+) complex for a ligand. The enthalpy of substitution was correlated with electronic and geometric parameters. Electron-donor groups increase the interaction between the cation and the ligand, while electron-acceptor groups decrease the interaction enthalpy.

  1. Removal of PCR error products and unincorporated primers by metal-chelate affinity chromatography.

    Directory of Open Access Journals (Sweden)

    Indhu Kanakaraj

    Full Text Available Immobilized Metal Affinity Chromatography (IMAC has been used for decades to purify proteins on the basis of amino acid content, especially surface-exposed histidines and "histidine tags" genetically added to recombinant proteins. We and others have extended the use of IMAC to purification of nucleic acids via interactions with the nucleotide bases, especially purines, of single-stranded RNA and DNA. We also have demonstrated the purification of plasmid DNA from contaminating genomic DNA by IMAC capture of selectively-denatured genomic DNA. Here we describe an efficient method of purifying PCR products by specifically removing error products, excess primers, and unincorporated dNTPs from PCR product mixtures using flow-through metal-chelate affinity adsorption. By flowing a PCR product mixture through a Cu(2+-iminodiacetic acid (IDA agarose spin column, 94-99% of the dNTPs and nearly all the primers can be removed. Many of the error products commonly formed by Taq polymerase also are removed. Sequencing of the IMAC-processed PCR product gave base-calling accuracy comparable to that obtained with a commercial PCR product purification method. The results show that IMAC matrices (specifically Cu(2+-IDA agarose can be used for the purification of PCR products. Due to the generality of the base-specific mechanism of adsorption, IMAC matrices may also be used in the purification of oligonucleotides, cDNA, mRNA and micro RNAs.

  2. Recent improvements to Binding MOAD: a resource for protein–ligand binding affinities and structures

    Science.gov (United States)

    Ahmed, Aqeel; Smith, Richard D.; Clark, Jordan J.; Dunbar, James B.; Carlson, Heather A.

    2015-01-01

    For over 10 years, Binding MOAD (Mother of All Databases; http://www.BindingMOAD.org) has been one of the largest resources for high-quality protein–ligand complexes and associated binding affinity data. Binding MOAD has grown at the rate of 1994 complexes per year, on average. Currently, it contains 23 269 complexes and 8156 binding affinities. Our annual updates curate the data using a semi-automated literature search of the references cited within the PDB file, and we have recently upgraded our website and added new features and functionalities to better serve Binding MOAD users. In order to eliminate the legacy application server of the old platform and to accommodate new changes, the website has been completely rewritten in the LAMP (Linux, Apache, MySQL and PHP) environment. The improved user interface incorporates current third-party plugins for better visualization of protein and ligand molecules, and it provides features like sorting, filtering and filtered downloads. In addition to the field-based searching, Binding MOAD now can be searched by structural queries based on the ligand. In order to remove redundancy, Binding MOAD records are clustered in different families based on 90% sequence identity. The new Binding MOAD, with the upgraded platform, features and functionalities, is now equipped to better serve its users. PMID:25378330

  3. Modeling and Calculation of Dent Based on Pipeline Bending Strain

    Directory of Open Access Journals (Sweden)

    Qingshan Feng

    2016-01-01

    Full Text Available The bending strain of long-distance oil and gas pipelines can be calculated by the in-line inspection tool which used inertial measurement unit (IMU. The bending strain is used to evaluate the strain and displacement of the pipeline. During the bending strain inspection, the dent existing in the pipeline can affect the bending strain data as well. This paper presents a novel method to model and calculate the pipeline dent based on the bending strain. The technique takes inertial mapping data from in-line inspection and calculates depth of dent in the pipeline using Bayesian statistical theory and neural network. To verify accuracy of the proposed method, an in-line inspection tool is used to inspect pipeline to gather data. The calculation of dent shows the method is accurate for the dent, and the mean relative error is 2.44%. The new method provides not only strain of the pipeline dent but also the depth of dent. It is more benefit for integrity management of pipeline for the safety of the pipeline.

  4. Expedient and click synthesis, spectroscopic characterizations and DFT calculations of novel 1,5-bis(N-substituted 1,2,3‒triazole) benzodiazepinedione scaffolds

    Science.gov (United States)

    Paghandeh, Hossein; Saeidian, Hamid

    2018-04-01

    A practically reliable procedure for synthesis of new 1,5-bis(N-substituted 1,2,3‒triazole) benzodiazepinedione derivatives was reported by sequential amidation, propargylation and a click azide‒alkyne [3 + 2] cycloaddition reaction in a one pot fashion. The desired products were characterized by CHN analysis, 1H and 13C NMR and ESI-MS spectroscopy. Short reaction time, good yields (55-91%), mild reaction conditions and easily available and less expensive starting materials are advantages of this protocol. Natural bond orbital charge distribution and HOMO-LUMO analysis of the characterized structure of 4e have been also calculated by density functional theory (DFT) calculations. The Li+ and Na+ ion affinities of 4e have been also investigated by DFT studies to find the applicability of these products as ligand in coordination chemistry. Sodium ion affinity of 4e was determined as 60 kJ mol-1 is less than its lithium ion affinity, indicating that the lithiation of 4e is more exothermic than the sodiation.

  5. CT-based dose calculations and in vivo dosimetry for lung cancer treatment

    International Nuclear Information System (INIS)

    Essers, M.; Lanson, J.H.; Leunens, G.; Schnabel, T.; Mijnheer, B.J.

    1995-01-01

    Reliable CT-based dose calculations and dosimetric quality control are essential for the introduction of new conformal techniques for the treatment of lung cancer. The first aim of this study was therefore to check the accuracy of dose calculations based on CT-densities, using a simple inhomogeneity correction model, for lung cancer patients irradiated with an AP-PA treatment technique. Second, the use of diodes for absolute exit dose measurements and an Electronic Portal Imaging Device (EPID) for relative transmission dose verification was investigated for 22 and 12 patients, respectively. The measured dose values were compared with calculations performed using our 3-dimensional treatment planning system, using CT-densities or assuming the patient to be water-equivalent. Using water-equivalent calculations, the actual exit dose value under lung was, on average, underestimated by 30%, with an overall spread of 10% (1 SD). Using inhomogeneity corrections, the exit dose was, on average, overestimated by 4%, with an overall spread of 6% (1 SD). Only 2% of the average deviation was due to the inhomogeneity correction model. An uncertainty in exit dose calculation of 2.5% (1 SD) could be explained by organ motion, resulting from the ventilatory or cardiac cycle. The most important reason for the large overall spread was, however, the uncertainty involved in performing point measurements: about 4% (1 SD). This difference resulted from the systematic and random deviation in patient set-up and therefore in diode position with respect to patient anatomy. Transmission and exit dose values agreed with an average difference of 1.1%. Transmission dose profiles also showed good agreement with calculated exit dose profiles. Our study shows that, for this treatment technique, the dose in the thorax region is quite accurately predicted using CT-based dose calculations, even if a simple inhomogeneity correction model is used. Point detectors such as diodes are not suitable for exit

  6. Calculating the knowledge-based similarity of functional groups using crystallographic data

    Science.gov (United States)

    Watson, Paul; Willett, Peter; Gillet, Valerie J.; Verdonk, Marcel L.

    2001-09-01

    A knowledge-based method for calculating the similarity of functional groups is described and validated. The method is based on experimental information derived from small molecule crystal structures. These data are used in the form of scatterplots that show the likelihood of a non-bonded interaction being formed between functional group A (the `central group') and functional group B (the `contact group' or `probe'). The scatterplots are converted into three-dimensional maps that show the propensity of the probe at different positions around the central group. Here we describe how to calculate the similarity of a pair of central groups based on these maps. The similarity method is validated using bioisosteric functional group pairs identified in the Bioster database and Relibase. The Bioster database is a critical compilation of thousands of bioisosteric molecule pairs, including drugs, enzyme inhibitors and agrochemicals. Relibase is an object-oriented database containing structural data about protein-ligand interactions. The distributions of the similarities of the bioisosteric functional group pairs are compared with similarities for all the possible pairs in IsoStar, and are found to be significantly different. Enrichment factors are also calculated showing the similarity method is statistically significantly better than random in predicting bioisosteric functional group pairs.

  7. Genetic affinities of Helicobacter pylori isolates from ethnic Arabs in Kuwait

    Directory of Open Access Journals (Sweden)

    Albert M John

    2010-07-01

    Full Text Available Abstract Helicobacter pylori is one of the most genetically diverse of bacterial species, and since the 5'-end of cagA gene and the middle allele of vacA gene of H. pylori from different populations exhibit considerable polymorphisms, these sequence diversities were used to gain insights into the genetic affinities of this gastric pathogen from different populations. Because the genetic affinity of Arab strains from the Arabian Gulf is not known, we carried out genetic analysis based on sequence diversities of the cagA and the vacA genes of H. pylori from 9 ethnic Arabs in Kuwait. The analysis showed that the Kuwaiti isolates are closely related to the Indo-European group of strains, although some strains have a tendency to form a separate cluster close to the Indo- European group, but clearly distinct from East Asian strains. However, these results need to be confirmed by analyses of neutral markers (house-keeping genes in a multi-locus sequence typing [MLST] platform. The profiling of virulence-associated genes may have resulted from ecologically distinct populations due to human migration and geographical separation over long periods of time.

  8. Code accuracy evaluation of ISP 35 calculations based on NUPEC M-7-1 test

    International Nuclear Information System (INIS)

    Auria, F.D.; Oriolo, F.; Leonardi, M.; Paci, S.

    1995-01-01

    Quantitative evaluation of code uncertainties is a necessary step in the code assessment process, above all if best-estimate codes are utilised for licensing purposes. Aiming at quantifying the code accuracy, an integral methodology based on the Fast Fourier Transform (FFT) has been developed at the University of Pisa (DCMN) and has been already applied to several calculations related to primary system test analyses. This paper deals with the first application of the FFT based methodology to containment code calculations based on a hydrogen mixing and distribution test performed in the NUPEC (Nuclear Power Engineering Corporation) facility. It is referred to pre-test and post-test calculations submitted for the International Standard Problem (ISP) n. 35. This is a blind exercise, simulating the effects of steam injection and spray behaviour on gas distribution and mixing. The result of the application of this methodology to nineteen selected variables calculated by ten participants are here summarized, and the comparison (where possible) of the accuracy evaluated for the pre-test and for the post-test calculations of a same user is also presented. (author)

  9. Microfluidics in the selection of affinity reagents for the detection of cancer: paving a way towards future diagnostics.

    Science.gov (United States)

    Hung, Lien-Yu; Wang, Chih-Hung; Fu, Chien-Yu; Gopinathan, Priya; Lee, Gwo-Bin

    2016-08-07

    Microfluidic technologies have miniaturized a variety of biomedical applications, and these chip-based systems have several significant advantages over their large-scale counterparts. Recently, this technology has been used for automating labor-intensive and time-consuming screening processes, whereby affinity reagents, including aptamers, peptides, antibodies, polysaccharides, glycoproteins, and a variety of small molecules, are used to probe for molecular biomarkers. When compared to conventional methods, the microfluidic approaches are faster, more compact, require considerably smaller quantities of samples and reagents, and can be automated. Furthermore, they allow for more precise control of reaction conditions (e.g., pH, temperature, and shearing forces) such that more efficient screening can be performed. A variety of affinity reagents for targeting cancer cells or cancer biomarkers are now available and will likely replace conventional antibodies. In this review article, the selection of affinity reagents for cancer cells or cancer biomarkers on microfluidic platforms is reviewed with the aim of highlighting the utility of such approaches in cancer diagnostics.

  10. Affine Kac-Moody algebras and their representations

    International Nuclear Information System (INIS)

    Slansky, R.

    1988-01-01

    Highest weight representation theory of finite dimensional and affine Kac-Moody algebras is summarized from a unified point of view. Lattices of discrete additive quantum numbers and the presentation of Lie algebras on Cartan matrices are the central points of departure for the analysis. (author)

  11. Affinity monolith chromatography: A review of general principles and applications.

    Science.gov (United States)

    Li, Zhao; Rodriguez, Elliott; Azaria, Shiden; Pekarek, Allegra; Hage, David S

    2017-11-01

    Affinity monolith chromatography, or AMC, is a liquid chromatographic method in which the support is a monolith and the stationary phase is a biological-binding agent or related mimic. AMC has become popular for the isolation of biochemicals, for the measurement of various analytes, and for studying biological interactions. This review will examine the principles and applications of AMC. The materials that have been used to prepare AMC columns will be discussed, which have included various organic polymers, silica, agarose, and cryogels. Immobilization schemes that have been used in AMC will also be considered. Various binding agents and applications that have been reported for AMC will then be described. These applications will include the use of AMC for bioaffinity chromatography, immunoaffinity chromatography, dye-ligand affinity chromatography, and immobilized metal-ion affinity chromatography. The use of AMC with chiral stationary phases and as a tool to characterize biological interactions will also be examined. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. MR Imaging-derived Oxygen-Hemoglobin Dissociation Curves and Fetal-Placental Oxygen-Hemoglobin Affinities.

    Science.gov (United States)

    Avni, Reut; Golani, Ofra; Akselrod-Ballin, Ayelet; Cohen, Yonni; Biton, Inbal; Garbow, Joel R; Neeman, Michal

    2016-07-01

    Purpose To generate magnetic resonance (MR) imaging-derived, oxygen-hemoglobin dissociation curves and to map fetal-placental oxygen-hemoglobin affinity in pregnant mice noninvasively by combining blood oxygen level-dependent (BOLD) T2* and oxygen-weighted T1 contrast mechanisms under different respiration challenges. Materials and Methods All procedures were approved by the Weizmann Institutional Animal Care and Use Committee. Pregnant mice were analyzed with MR imaging at 9.4 T on embryonic days 14.5 (eight dams and 58 fetuses; imprinting control region ICR strain) and 17.5 (21 dams and 158 fetuses) under respiration challenges ranging from hyperoxia to hypoxia (10 levels of oxygenation, 100%-10%; total imaging time, 100 minutes). A shorter protocol with normoxia to hyperoxia was also performed (five levels of oxygenation, 20%-100%; total imaging time, 60 minutes). Fast spin-echo anatomic images were obtained, followed by sequential acquisition of three-dimensional gradient-echo T2*- and T1-weighted images. Automated registration was applied to align regions of interest of the entire placenta, fetal liver, and maternal liver. Results were compared by using a two-tailed unpaired Student t test. R1 and R2* values were derived for each tissue. MR imaging-based oxygen-hemoglobin dissociation curves were constructed by nonlinear least square fitting of 1 minus the change in R2*divided by R2*at baseline as a function of R1 to a sigmoid-shaped curve. The apparent P50 (oxygen tension at which hemoglobin is 50% saturated) value was derived from the curves, calculated as the R1 scaled value (x) at which the change in R2* divided by R2*at baseline scaled (y) equals 0.5. Results The apparent P50 values were significantly lower in fetal liver than in maternal liver for both gestation stages (day 14.5: 21% ± 5 [P = .04] and day 17.5: 41% ± 7 [P hemoglobin dissociation curves with a shorter protocol that excluded the hypoxic periods was demonstrated. Conclusion MR imaging-based

  13. Engineering an antibody with picomolar affinity to DOTA chelates of multiple radionuclides for pretargeted radioimmunotherapy and imaging

    Energy Technology Data Exchange (ETDEWEB)

    Orcutt, Kelly Davis; Slusarczyk, Adrian L. [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Cieslewicz, Maryelise [Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Ruiz-Yi, Benjamin [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Bhushan, Kumar R. [Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Frangioni, John V. [Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Wittrup, K. Dane, E-mail: wittrup@mit.ed [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States)

    2011-02-15

    Introduction: In pretargeted radioimmunotherapy (PRIT), a bifunctional antibody is administered and allowed to pre-localize to tumor cells. Subsequently, a chelated radionuclide is administered and captured by cell-bound antibody while unbound hapten clears rapidly from the body. We aim to engineer high-affinity binders to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelates for use in PRIT applications. Methods: We mathematically modeled antibody and hapten pharmacokinetics to analyze hapten tumor retention as a function of hapten binding affinity. Motivated by model predictions, we used directed evolution and yeast surface display to affinity mature the 2D12.5 antibody to DOTA, reformatted as a single chain variable fragment (scFv). Results: Modeling predicts that for high antigen density and saturating bsAb dose, a hapten-binding affinity of 100 pM is needed for near-maximal hapten retention. We affinity matured 2D12.5 with an initial binding constant of about 10 nM to DOTA-yttrium chelates. Affinity maturation resulted in a 1000-fold affinity improvement to biotinylated DOTA-yttrium, yielding an 8.2{+-}1.9 picomolar binder. The high-affinity scFv binds DOTA complexes of lutetium and gadolinium with similar picomolar affinity and indium chelates with low nanomolar affinity. When engineered into a bispecific antibody construct targeting carcinoembryonic antigen, pretargeted high-affinity scFv results in significantly higher tumor retention of a {sup 111}In-DOTA hapten compared to pretargeted wild-type scFv in a xenograft mouse model. Conclusions: We have engineered a versatile, high-affinity, DOTA-chelate-binding scFv. We anticipate it will prove useful in developing pretargeted imaging and therapy protocols to exploit the potential of a variety of radiometals.

  14. Role of the T cell receptor ligand affinity in T cell activation by bacterial superantigens

    DEFF Research Database (Denmark)

    Andersen, P S; Geisler, C; Buus, S

    2001-01-01

    Similar to native peptide/MHC ligands, bacterial superantigens have been found to bind with low affinity to the T cell receptor (TCR). It has been hypothesized that low ligand affinity is required to allow optimal TCR signaling. To test this, we generated variants of Staphylococcus enterotoxin C3...... (SEC3) with up to a 150-fold increase in TCR affinity. By stimulating T cells with SEC3 molecules immobilized onto plastic surfaces, we demonstrate that increasing the affinity of the SEC3/TCR interaction caused a proportional increase in the ability of SEC3 to activate T cells. Thus, the potency...... correlation between ligand affinity and ligand potency indicating that it is the density of receptor-ligand complexes in the T cell contact area that determines TCR signaling strength....

  15. Development of an affinity-matured humanized anti-epidermal growth factor receptor antibody for cancer immunotherapy.

    Science.gov (United States)

    Nakanishi, Takeshi; Maru, Takamitsu; Tahara, Kazuhiro; Sanada, Hideaki; Umetsu, Mitsuo; Asano, Ryutaro; Kumagai, Izumi

    2013-02-01

    We showed previously that humanization of 528, a murine anti-epidermal growth factor receptor (EGFR) antibody, causes reduced affinity for its target. Here, to improve the affinity of the humanized antibody for use in cancer immunotherapy, we constructed phage display libraries focused on the complementarity-determining regions (CDRs) of the antibody and carried out affinity selection. Two-step selections using libraries constructed in a stepwise manner enabled a 32-fold affinity enhancement of humanized 528 (h528). Thermodynamic analysis of the interactions between the variable domain fragment of h528 (h528Fv) mutants and the soluble extracellular domain of EGFR indicated that the h528Fv mutants obtained from the first selection showed a large increase in negative enthalpy change due to binding, resulting in affinity enhancement. Furthermore, mutants from the second selection showed a decrease in entropy loss, which led to further affinity maturation. These results suggest that a single mutation in the heavy chain variable domain (i.e. Tyr(52) to Trp) enthalpically contributed for overcoming the energetic barrier to the antigen-antibody interaction, which was a major hurdle for the in vitro affinity maturation of h528. We reported previously that the humanized bispecific diabody hEx3 Db, which targets EGFR and CD3, shows strong anti-tumor activity. hEx3 Db mutants, in which the variable domains of h528 were replaced with those of the affinity-enhanced mutants, were prepared and characterized. In a growth inhibition assay of tumor cells, the hEx3 Db mutants showed stronger anti-tumor activity than that of hEx3 Db, suggesting that affinity enhancement of h528Fv enhances the anti-tumor activity of the bispecific diabody.

  16. High affinity calmodulin target sequence in the signalling molecule PI 3-kinase

    DEFF Research Database (Denmark)

    Fischer, R; Julsgart, J; Berchtold, M W

    1998-01-01

    M-binding peptide derived from the p110gamma isoform interacts with CaM in a calcium-dependent way. Using gel shift analysis and fluorescence spectrophotometry we discovered that the peptide forms a high affinity complex with CaM. Titration experiments using dansylated CaM gave an affinity constant of 5 n...

  17. 3D QSAR models built on structure-based alignments of Abl tyrosine kinase inhibitors.

    Science.gov (United States)

    Falchi, Federico; Manetti, Fabrizio; Carraro, Fabio; Naldini, Antonella; Maga, Giovanni; Crespan, Emmanuele; Schenone, Silvia; Bruno, Olga; Brullo, Chiara; Botta, Maurizio

    2009-06-01

    Quality QSAR: A combination of docking calculations and a statistical approach toward Abl inhibitors resulted in a 3D QSAR model, the analysis of which led to the identification of ligand portions important for affinity. New compounds designed on the basis of the model were found to have very good affinity for the target, providing further validation of the model itself.The X-ray crystallographic coordinates of the Abl tyrosine kinase domain in its active, inactive, and Src-like inactive conformations were used as targets to simulate the binding mode of a large series of pyrazolo[3,4-d]pyrimidines (known Abl inhibitors) by means of GOLD software. Receptor-based alignments provided by molecular docking calculations were submitted to a GRID-GOLPE protocol to generate 3D QSAR models. Analysis of the results showed that the models based on the inactive and Src-like inactive conformations had very poor statistical parameters, whereas the sole model based on the active conformation of Abl was characterized by significant internal and external predictive ability. Subsequent analysis of GOLPE PLS pseudo-coefficient contour plots of this model gave us a better understanding of the relationships between structure and affinity, providing suggestions for the next optimization process. On the basis of these results, new compounds were designed according to the hydrophobic and hydrogen bond donor and acceptor contours, and were found to have improved enzymatic and cellular activity with respect to parent compounds. Additional biological assays confirmed the important role of the selected compounds as inhibitors of cell proliferation in leukemia cells.

  18. Theoretical calculations of positron annihilation characteristics in inorganic solids -- Recent advances and problems

    Science.gov (United States)

    Sob, M.; Sormann, H.; Kuriplach, J.

    Principles and applications of positron annihilation spectroscopy to electronic structure and defect studies are briefly reviewed and some recent advances and pending problems are illustrated by specific examples. In particular, it turns out that the sensitivity of calculated momentum densities of electron-positron annihilation pairs (MDAP) to the choice of electron crystal potential is higher or comparable to its sensitivity with respect to the choice of description of the electron-positron interaction. As a result, it is very hard to distinguish between various electron-positron interaction theories on the basis of the comparison of theoretical and experimental MDAPs. Furthermore, the positron affinity is determined theorttically for several systems having a band gap (semiconductors, insulators). It appears that the calculated positron affinities are significantly underestimated when compared to experimental data and, apparently, electron-positron interactions in such systems are not described satisfactorily by contemporary theoretical approaches. The above examples are related rather to electronic structure studies, but positrons are often used to investigate various open-volume defects in solids, which is dealt with in the last illustration. A non-selfconsistent computational technique suitable for the theoretical examination of configurations having large number (thousands) of non-equivalent atoms has been updated recently to treat non-periodic solids. It is based on the superposition of atomic densities in order to approximate the electronic density of the system studied. Though the charge redistribution due to selfconsistency effects is neglected, positron annihilation characteristics are determined quite reasonably. This allows for studying properties of extended defects like grain boundaries (and other interfaces), dislocations, precipitates, etc., which is very helpful when interpreting experimental positron annihilation data. Our technique is

  19. Integrated Power Flow and Short Circuit Calculation Method for Distribution Network with Inverter Based Distributed Generation

    OpenAIRE

    Yang, Shan; Tong, Xiangqian

    2016-01-01

    Power flow calculation and short circuit calculation are the basis of theoretical research for distribution network with inverter based distributed generation. The similarity of equivalent model for inverter based distributed generation during normal and fault conditions of distribution network and the differences between power flow and short circuit calculation are analyzed in this paper. Then an integrated power flow and short circuit calculation method for distribution network with inverte...

  20. Tryptophan tags and de novo designed complementary affinity ligands for the expression and purification of recombinant proteins.

    Science.gov (United States)

    Pina, Ana Sofia; Carvalho, Sara; Dias, Ana Margarida G C; Guilherme, Márcia; Pereira, Alice S; Caraça, Luciana T; Coroadinha, Ana Sofia; Lowe, Christopher R; Roque, A Cecília A

    2016-11-11

    A common strategy for the production and purification of recombinant proteins is to fuse a tag to the protein terminal residues and employ a "tag-specific" ligand for fusion protein capture and purification. In this work, we explored the effect of two tryptophan-based tags, NWNWNW and WFWFWF, on the expression and purification of Green Fluorescence Protein (GFP) used as a model fusion protein. The titers obtained with the expression of these fusion proteins in soluble form were 0.11mgml -1 and 0.48mgml -1 for WFWFWF and NWNWNW, respectively. A combinatorial library comprising 64 ligands based on the Ugi reaction was prepared and screened for binding GFP-tagged and non-tagged proteins. Complementary ligands A2C2 and A3C1 were selected for the effective capture of NWNWNW and WFWFWF tagged proteins, respectively, in soluble forms. These affinity pairs displayed 10 6 M -1 affinity constants and Qmax values of 19.11±2.60ugg -1 and 79.39ugg -1 for the systems WFWFWF AND NWNWNW, respectively. GFP fused to the WFWFWF affinity tag was also produced as inclusion bodies, and a refolding-on column strategy was explored using the ligand A4C8, selected from the combinatorial library of ligands but in presence of denaturant agents. Copyright © 2016 Elsevier B.V. All rights reserved.