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Sample records for affinity constant km

  1. Automatic gesture analysis using constant affine velocity.

    PubMed

    Cifuentes, Jenny; Boulanger, Pierre; Pham, Minh Tu; Moreau, Richard; Prieto, Flavio

    2014-01-01

    Hand human gesture recognition has been an important research topic widely studied around the world, as this field offers the ability to identify, recognize, and analyze human gestures in order to control devices or to interact with computer interfaces. In particular, in medical training, this approach is an important tool that can be used to obtain an objective evaluation of a procedure performance. In this paper, some obstetrical gestures, acquired by a forceps, were studied with the hypothesis that, as the scribbling and drawing movements, they obey the one-sixth power law, an empirical relationship which connects path curvature, torsion, and euclidean velocity. Our results show that obstetrical gestures have a constant affine velocity, which is different for each type of gesture and based on this idea this quantity is proposed as an appropriate classification feature in the hand human gesture recognition field.

  2. Direct measurement of equilibrium constants for high-affinity hemoglobins.

    PubMed

    Kundu, Suman; Premer, Scott A; Hoy, Julie A; Trent, James T; Hargrove, Mark S

    2003-06-01

    The biological functions of heme proteins are linked to their rate and affinity constants for ligand binding. Kinetic experiments are commonly used to measure equilibrium constants for traditional hemoglobins comprised of pentacoordinate ligand binding sites and simple bimolecular reaction schemes. However, kinetic methods do not always yield reliable equilibrium constants with more complex hemoglobins for which reaction mechanisms are not clearly understood. Furthermore, even where reaction mechanisms are clearly understood, it is very difficult to directly measure equilibrium constants for oxygen and carbon monoxide binding to high-affinity (K(D) < 1 micro M) hemoglobins. This work presents a method for direct measurement of equilibrium constants for high-affinity hemoglobins that utilizes a competition for ligands between the "target" protein and an array of "scavenger" hemoglobins with known affinities. This method is described for oxygen and carbon monoxide binding to two hexacoordinate hemoglobins: rice nonsymbiotic hemoglobin and Synechocystis hemoglobin. Our results demonstrate that although these proteins have different mechanisms for ligand binding, their affinities for oxygen and carbon monoxide are similar. Their large affinity constants for oxygen, 285 and approximately 100 micro M(-1) respectively, indicate that they are not capable of facilitating oxygen transport.

  3. Affinity constants for small molecules from SPR competition experiments.

    PubMed

    de Mol, Nico J

    2010-01-01

    Direct assay of small molecules by SPR in general is troublesome and at least tedious procedures have to be applied. Competition experiments offer an attractive alternative. A small ligand known to bind to the analyte is immobilized on an SPR sensor surface, and the binding of the larger analyte in the presence of compounds under investigation in a concentration range is assayed. The resulting inhibition curves of the equilibrium SPR signal as function of the compound concentration can be analyzed to yield thermodynamic binding constants for the interaction in solution between analyte and the compounds under investigation. An additional advantage of this method is that series of compounds can be analyzed using the same sensor surface, so there is no immobilization needed for each compound. An adaptation of the method to analyze interactions with bivalent analytes (e.g., antibodies) is also included. Some observed different affinities in solution compared to that on the SPR surface are discussed.

  4. The Case for a Hubble Constant of 30 km s-1 Mpc-1.

    PubMed

    Bartlett, J G; Blanchard, A; Silk, J; Turner, M S

    1995-02-17

    Although recent determinations of the distance to the Virgo cluster based on Cepheid variable stars represent an important step in pinning down the Hubble constant, after 65 years a definitive determination of the Hubble constant still eludes cosmologists. At present, most of the observational determinations place the Hubble constant between 40 and 90 kilometers per second per megaparsec (km s(-1) Mpc(-1)). The case is made here for a Hubble constant that is even smaller than the lower bound of the accepted range on the basis of the great advantages, all theoretical in nature, of a Hubble constant of around 30 kilometers per second per megaparsec. Such a value for the Hubble cures all of the ills of the current theoretical orthodoxy, that is, a spatially flat universe composed predominantly of cold dark matter.

  5. Determination of rate constants and equilibrium constants for solution-phase drug-protein interactions by ultrafast affinity extraction.

    PubMed

    Zheng, Xiwei; Li, Zhao; Podariu, Maria I; Hage, David S

    2014-07-01

    A method was created on the basis of ultrafast affinity extraction to determine both the dissociation rate constants and equilibrium constants for drug-protein interactions in solution. Human serum albumin (HSA), an important binding agent for many drugs in blood, was used as both a model soluble protein and as an immobilized binding agent in affinity microcolumns for the analysis of free drug fractions. Several drugs were examined that are known to bind to HSA. Various conditions to optimize in the use of ultrafast affinity extraction for equilibrium and kinetic studies were considered, and several approaches for these measurements were examined. The dissociation rate constants obtained for soluble HSA with each drug gave good agreement with previous rate constants reported for the same drugs or other solutes with comparable affinities for HSA. The equilibrium constants that were determined also showed good agreement with the literature. The results demonstrated that ultrafast affinity extraction could be used as a rapid approach to provide information on both the kinetics and thermodynamics of a drug-protein interaction in solution. This approach could be extended to other systems and should be valuable for high-throughput drug screening or biointeraction studies.

  6. Determination of Rate Constants and Equilibrium Constants for Solution-Phase Drug–Protein Interactions by Ultrafast Affinity Extraction

    PubMed Central

    2015-01-01

    A method was created on the basis of ultrafast affinity extraction to determine both the dissociation rate constants and equilibrium constants for drug–protein interactions in solution. Human serum albumin (HSA), an important binding agent for many drugs in blood, was used as both a model soluble protein and as an immobilized binding agent in affinity microcolumns for the analysis of free drug fractions. Several drugs were examined that are known to bind to HSA. Various conditions to optimize in the use of ultrafast affinity extraction for equilibrium and kinetic studies were considered, and several approaches for these measurements were examined. The dissociation rate constants obtained for soluble HSA with each drug gave good agreement with previous rate constants reported for the same drugs or other solutes with comparable affinities for HSA. The equilibrium constants that were determined also showed good agreement with the literature. The results demonstrated that ultrafast affinity extraction could be used as a rapid approach to provide information on both the kinetics and thermodynamics of a drug–protein interaction in solution. This approach could be extended to other systems and should be valuable for high-throughput drug screening or biointeraction studies. PMID:24911267

  7. Complex unconstrained three-dimensional hand movement and constant equi-affine speed.

    PubMed

    Maoz, Uri; Berthoz, Alain; Flash, Tamar

    2009-02-01

    One long-established simplifying principle behind the large repertoire and high versatility of human hand movements is the two-thirds power law-an empirical law stating a relationship between local geometry and kinematics of human hand trajectories during planar curved movements. It was further generalized not only to various types of human movements, but also to motion perception and prediction, although it was unsuccessful in explaining unconstrained three-dimensional (3D) movements. Recently, movement obeying the power law was proved to be equivalent to moving with constant planar equi-affine speed. Generalizing such motion to 3D space-i.e., to movement at constant spatial equi-affine speed-predicts the emergence of a new power law, whose utility for describing spatial scribbling movements we have previously demonstrated. In this empirical investigation of the new power law, subjects repetitively traced six different 3D geometrical shapes with their hand. We show that the 3D power law explains the data consistently better than both the two-thirds power law and an additional power law that was previously suggested for spatial hand movements. We also found small yet systematic modifications of the power-law's exponents across the various shapes, which further scrutiny suggested to be correlated with global geometric factors of the traced shape. Nevertheless, averaging over all subjects and shapes, the power-law exponents are generally in accordance with constant spatial equi-affine speed. Taken together, our findings provide evidence for the potential role of non-Euclidean geometry in motion planning and control. Moreover, these results seem to imply a relationship between geometry and kinematics that is more complex than the simple local one stipulated by the two-thirds power law and similar models.

  8. Determination of equilibrium dissociation constants for recombinant antibodies by high-throughput affinity electrophoresis.

    PubMed

    Pan, Yuchen; Sackmann, Eric K; Wypisniak, Karolina; Hornsby, Michael; Datwani, Sammy S; Herr, Amy E

    2016-12-23

    High-quality immunoreagents enhance the performance and reproducibility of immunoassays and, in turn, the quality of both biological and clinical measurements. High quality recombinant immunoreagents are generated using antibody-phage display. One metric of antibody quality - the binding affinity - is quantified through the dissociation constant (KD) of each recombinant antibody and the target antigen. To characterize the KD of recombinant antibodies and target antigen, we introduce affinity electrophoretic mobility shift assays (EMSAs) in a high-throughput format suitable for small volume samples. A microfluidic card comprised of free-standing polyacrylamide gel (fsPAG) separation lanes supports 384 concurrent EMSAs in 30 s using a single power source. Sample is dispensed onto the microfluidic EMSA card by acoustic droplet ejection (ADE), which reduces EMSA variability compared to sample dispensing using manual or pin tools. The KD for each of a six-member fragment antigen-binding fragment library is reported using ~25-fold less sample mass and ~5-fold less time than conventional heterogeneous assays. Given the form factor and performance of this micro- and mesofluidic workflow, we have developed a sample-sparing, high-throughput, solution-phase alternative for biomolecular affinity characterization.

  9. Determination of equilibrium dissociation constants for recombinant antibodies by high-throughput affinity electrophoresis

    PubMed Central

    Pan, Yuchen; Sackmann, Eric K.; Wypisniak, Karolina; Hornsby, Michael; Datwani, Sammy S.; Herr, Amy E.

    2016-01-01

    High-quality immunoreagents enhance the performance and reproducibility of immunoassays and, in turn, the quality of both biological and clinical measurements. High quality recombinant immunoreagents are generated using antibody-phage display. One metric of antibody quality – the binding affinity – is quantified through the dissociation constant (KD) of each recombinant antibody and the target antigen. To characterize the KD of recombinant antibodies and target antigen, we introduce affinity electrophoretic mobility shift assays (EMSAs) in a high-throughput format suitable for small volume samples. A microfluidic card comprised of free-standing polyacrylamide gel (fsPAG) separation lanes supports 384 concurrent EMSAs in 30 s using a single power source. Sample is dispensed onto the microfluidic EMSA card by acoustic droplet ejection (ADE), which reduces EMSA variability compared to sample dispensing using manual or pin tools. The KD for each of a six-member fragment antigen-binding fragment library is reported using ~25-fold less sample mass and ~5-fold less time than conventional heterogeneous assays. Given the form factor and performance of this micro- and mesofluidic workflow, we have developed a sample-sparing, high-throughput, solution-phase alternative for biomolecular affinity characterization. PMID:28008969

  10. Bayesian Estimation of the Active Concentration and Affinity Constants Using Surface Plasmon Resonance Technology.

    PubMed

    Feng, Feng; Kepler, Thomas B

    2015-01-01

    Surface plasmon resonance (SPR) has previously been employed to measure the active concentration of analyte in addition to the kinetic rate constants in molecular binding reactions. Those approaches, however, have a few restrictions. In this work, a Bayesian approach is developed to determine both active concentration and affinity constants using SPR technology. With the appropriate prior probabilities on the parameters and a derived likelihood function, a Markov Chain Monte Carlo (MCMC) algorithm is applied to compute the posterior probability densities of both the active concentration and kinetic rate constants based on the collected SPR data. Compared with previous approaches, ours exploits information from the duration of the process in its entirety, including both association and dissociation phases, under partial mass transport conditions; do not depend on calibration data; multiple injections of analyte at varying flow rates are not necessary. Finally the method is validated by analyzing both simulated and experimental datasets. A software package implementing our approach is developed with a user-friendly interface and made freely available.

  11. Experimental-like affinity constants and enantioselectivity estimates from flexible docking.

    PubMed

    Gumede, N J; Singh, P; Sabela, M I; Bisetty, K; Escuder-Gilabert, L; Medina-Hernández, M J; Sagrado, S

    2012-10-22

    Experimental-like affinity constants and enantioselectivity estimates, not predicted so far computationally, were obtained using a novel flexible modeling/docking combined strategy. The S- and R-warfarin-human serum albumin (HSA, site I) complexes were used as an interaction model. The process for a verified estimation includes the following: (i) ionized open chain forming at physiological pH (a recent focus); (ii) conformational search (molecular mechanics and Monte Carlo methods); (iii) rigid protein-flexible ligand docking (GlideXP) generating low energy paired S- and R-poses; (iv) graphical comparison against the X-ray crystal structure (unsatisfactory verification step); (v) quantum polarized ligand docking (insufficient verification step); (vi) induced fit docking (one pose satisfying the verification criterion; selection step); (vii) converting docking scores to affinity and enantioselectivity estimates (log K(S) = 5.43, log K(R) = 5.34, ES = K(S)/K(R) = 1.23) and numerical comparison against equivalent literature data from bioanalytical techniques (validation step); (viii) intermolecular forces explaining ES (hydrogen bonding and π-π interactions).

  12. The universal statistical distributions of the affinity, equilibrium constants, kinetics and specificity in biomolecular recognition.

    PubMed

    Zheng, Xiliang; Wang, Jin

    2015-04-01

    We uncovered the universal statistical laws for the biomolecular recognition/binding process. We quantified the statistical energy landscapes for binding, from which we can characterize the distributions of the binding free energy (affinity), the equilibrium constants, the kinetics and the specificity by exploring the different ligands binding with a particular receptor. The results of the analytical studies are confirmed by the microscopic flexible docking simulations. The distribution of binding affinity is Gaussian around the mean and becomes exponential near the tail. The equilibrium constants of the binding follow a log-normal distribution around the mean and a power law distribution in the tail. The intrinsic specificity for biomolecular recognition measures the degree of discrimination of native versus non-native binding and the optimization of which becomes the maximization of the ratio of the free energy gap between the native state and the average of non-native states versus the roughness measured by the variance of the free energy landscape around its mean. The intrinsic specificity obeys a Gaussian distribution near the mean and an exponential distribution near the tail. Furthermore, the kinetics of binding follows a log-normal distribution near the mean and a power law distribution at the tail. Our study provides new insights into the statistical nature of thermodynamics, kinetics and function from different ligands binding with a specific receptor or equivalently specific ligand binding with different receptors. The elucidation of distributions of the kinetics and free energy has guiding roles in studying biomolecular recognition and function through small-molecule evolution and chemical genetics.

  13. Determination of the kinetic rate constant of cyclodextrin supramolecular systems by high performance affinity chromatography.

    PubMed

    Li, Haiyan; Ge, Jingwen; Guo, Tao; Yang, Shuo; He, Zhonggui; York, Peter; Sun, Lixin; Xu, Xu; Zhang, Jiwen

    2013-08-30

    It is challenging and extremely difficult to measure the kinetics of supramolecular systems with extensive, weak binding (Ka<10(5)M(-1)), and fast dissociation, such as those composed of cyclodextrins and drugs. In this study, a modified peak profiling method based on high performance affinity chromatography (HPAC) was established to determine the dissociation rate constant of cyclodextrin supramolecular systems. The interactions of β-cyclodextrin with acetaminophen and sertraline were used to exemplify the method. The retention times, variances and the plate heights of the peaks for acetaminophen or sertraline, conventional non-retained substance (H2O) on the β-cyclodextrin bonded column and a control column were determined at four flow rates under linear elution conditions. Then, plate heights for the theoretical non-retained substance were estimated by the modified HPAC method, in consideration of the diffusion and stagnant mobile phase mass transfer. As a result, apparent dissociation rate constants of 1.82 (±0.01)s(-1) and 3.55 (±0.37)s(-1) were estimated for acetaminophen and sertraline respectively at pH 6.8 and 25°C with multiple flow rates. Following subtraction of the non-specific binding with the support, dissociation rate constants were estimated as 1.78 (±0.00) and 1.91 (±0.02)s(-1) for acetaminophen and sertraline, respectively. These results for acetaminophen and sertraline were in good agreement with the magnitude of the rate constants for other drugs determined by capillary electrophoresis reported in the literature and the peak fitting method we performed. The method described in this work is thought to be suitable for other supramolecules, with relatively weak, fast and extensive interactions.

  14. Measuring affinity constants of 1450 monoclonal antibodies to peptide targets with a microarray-based label-free assay platform.

    PubMed

    Landry, J P; Ke, Yaohuang; Yu, Guo-Liang; Zhu, X D

    2015-02-01

    Monoclonal antibodies (mAbs) are major reagents for research and clinical diagnosis. For their inherently high specificities to intended antigen targets and thus low toxicity in general, they are pursued as one of the major classes of new drugs. Yet binding properties of most monoclonal antibodies are not well characterized in terms of affinity constants and how they vary with presentations and/or conformational isomers of antigens, buffer compositions, and temperature. We here report a microarray-based label-free assay platform for high-throughput measurements of monoclonal antibody affinity constants to antigens immobilized on solid surfaces. Using this platform we measured affinity constants of over 1410 rabbit monoclonal antibodies and 46 mouse monoclonal antibodies to peptide targets that are immobilized through a terminal cysteine residue to a glass surface. The experimentally measured affinity constants vary from 10 pM to 200 pM with the median value at 66 pM. We compare the results obtained from the microarray-based platform with those from a benchmarking surface-plasmon-resonance-based (SPR) sensor (Biacore 3000).

  15. The role of human cytochrome P450 enzymes in the formation of 2-hydroxymetronidazole: CYP2A6 is the high affinity (low Km) catalyst.

    PubMed

    Pearce, Robin E; Cohen-Wolkowiez, Michael; Sampson, Mario R; Kearns, Gregory L

    2013-09-01

    Despite metronidazole's widespread clinical use since the 1960s, the specific enzymes involved in its biotransformation have not been previously identified. Hence, in vitro studies were conducted to identify and characterize the cytochrome P450 enzymes involved in the formation of the major metabolite, 2-hydroxymetronidazole. Formation of 2-hydroxymetronidazole in human liver microsomes was consistent with biphasic, Michaelis-Menten kinetics. Although several cDNA-expressed P450 enzymes catalyzed 2-hydroxymetronidazole formation at a supratherapeutic concentration of metronidazole (2000 μM), at a "therapeutic concentration" of 100 μM only CYPs 2A6, 3A4, 3A5, and 3A7 catalyzed metronidazole 2-hydroxylation at rates substantially greater than control vector, and CYP2A6 catalyzed 2-hydroxymetronidazole formation at rates 6-fold higher than the next most active enzyme. Kinetic studies with these recombinant enzymes revealed that CYP2A6 has a Km = 289 μM which is comparable to the Km for the high-affinity (low-Km) enzyme in human liver microsomes, whereas the Km values for the CYP3A enzymes corresponded with the low-affinity (high-Km) component. The sample-to-sample variation in 2-hydroxymetronidazole formation correlated significantly with CYP2A6 activity (r ≥ 0.970, P < 0.001) at substrate concentrations of 100 and 300 μM. Selective chemical inhibitors of CYP2A6 inhibited metronidazole 2-hydroxylation in a concentration-dependent manner and inhibitory antibodies against CYP2A6 virtually eliminated metronidazole 2-hydroxylation (>99%). Chemical and antibody inhibitors of other P450 enzymes had little or no effect on metronidazole 2-hydroxylation. These results suggest that CYP2A6 is the primary catalyst responsible for the 2-hydroxylation of metronidazole, a reaction that may function as a marker of CYP2A6 activity both in vitro and in vivo.

  16. Pinealectomy increases ouabain high-affinity binding sites and dissociation constant in rat cerebral cortex.

    PubMed

    Acuña Castroviejo, D; del Aguila, C M; Fernández, B; Gomar, M D; Castillo, J L

    1991-06-24

    The effect of the pineal gland on the ouabain high-affinity binding sites (Kd = 3.1 +/- 0.4 nM, Bmax = 246.4 +/- 18.4 fmol/mg protein) in rat cerebral cortex was studied. Pinealectomy increased Bmax (940.7 +/- 42.8 fmol/mg protein) and Kd (7.6 +/- 1.5 nM) while melatonin injection (100 micrograms/kg b.wt.) counteracted these effects, restoring kinetic parameters (Kd = 1.9 +/- 0.05 nM; Bmax = 262.2 +/- 29.6 fmol/mg prot) to control values. Melatonin activity on ouabain binding in vitro did not depend upon a direct effect on the binding sites themselves. However, in competition experiments, melatonin increased binding affinity of ouabain as shown by the decreased IC50 values.

  17. Revision of the affinity constant for perchlorate binding to the sodium-iodide symporter based on in vitro and human in vivo data.

    PubMed

    Schlosser, Paul M

    2016-12-01

    A series of previously published physiologically based pharmacokinetic (PBPK) models describe the effect of perchlorate on iodide uptake by the thyroid, with the mechanism being competitive inhibition of iodide transport by the sodium-iodide symporter (NIS). Hence a key parameter of these models is the affinity of perchlorate for the NIS, characterized as the Michaelis-Menten kinetic constant, Km . However, when model predictions were compared to published results of a human study measuring radio-iodide uptake (RAIU) inhibition after controlled perchlorate exposures, it was found to only fit the lowest exposure level and underpredicted RAIU inhibition at higher levels. Published in vitro data, in which perchlorate-induced inhibition of iodide uptake via the NIS was measured, were re-analyzed. Km for binding of perchlorate to the NIS originally derived from these data, 1.5 μm, had been obtained using Lineweaver-Burk plots, which allow for linear regression but invert the signal-noise of the data. Re-fitting these data by non-linear regression of the non-inverted data yielded a 60% lower value for the Km , 0.59 μm. Substituting this value into the PBPK model for an average adult human significantly improved model agreement with the human RAIU data for exposures <100 μg kg(-1)  day(-1) . Thus, this lower Km value both fits the in vitro NIS kinetics and provides better predictions of human in vivo RAIU data. This change in Km increases the predicted sensitivity of humans to perchlorate over twofold for low-level exposures. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  18. Photodetachment of an electron from selenide ion - The electron affinity and spin-orbit coupling constant for SeH.

    NASA Technical Reports Server (NTRS)

    Smyth, K. C.; Brauman, J. I.

    1972-01-01

    The relative cross section for the gas phase photodetachment of an electron from SeH(-) was determined in the wavelength region 428 to 578 nm. An ion cyclotron resonance spectrometer was used to generate, trap, and detect the negative ions, and a 1000-W xenon arc lamp with a grating monochromator was employed as the light source. The cross section exhibited two sharp thresholds, whose positions remained unchanged for the photodetachment of SeD(-). As a result of these thresholds, the electron affinity and the spin-orbit coupling constant were evaluated.

  19. Improved accuracy of low affinity protein-ligand equilibrium dissociation constants directly determined by electrospray ionization mass spectrometry.

    PubMed

    Jaquillard, Lucie; Saab, Fabienne; Schoentgen, Françoise; Cadene, Martine

    2012-05-01

    There is continued interest in the determination by ESI-MS of equilibrium dissociation constants (K(D)) that accurately reflect the affinity of a protein-ligand complex in solution. Issues in the measurement of K(D) are compounded in the case of low affinity complexes. Here we present a K(D) measurement method and corresponding mathematical model dealing with both gas-phase dissociation (GPD) and aggregation. To this end, a rational mathematical correction of GPD (f(sat)) is combined with the development of an experimental protocol to deal with gas-phase aggregation. A guide to apply the method to noncovalent protein-ligand systems according to their kinetic behavior is provided. The approach is validated by comparing the K(D) values determined by this method with in-solution K(D) literature values. The influence of the type of molecular interactions and instrumental setup on f(sat) is examined as a first step towards a fine dissection of factors affecting GPD. The method can be reliably applied to a wide array of low affinity systems without the need for a reference ligand or protein.

  20. Interaction between DNA and Drugs Having Protonable Basic Groups: Characterization through Affinity Constants, Drug Release Kinetics, and Conformational Changes.

    PubMed

    Alarcón, Liliana P; Baena, Yolima; Manzo, Rubén H

    2017-01-04

    This paper reports the in vitro characterization of the interaction between the phosphate groups of DNA and the protonated species of drugs with basic groups through the determination of the affinity constants, the reversibility of the interaction, and the effect on the secondary structure of the macromolecule. Affinity constants of the counterionic condensation DNA-drug were in the order of 10⁶. The negative electrokinetic potential of DNA decreased with the increase of the proportion of loading drugs. The drugs were slowly released from the DNA-drug complexes and had release kinetics consistent with the high degree of counterionic condensation. The circular dichroism profile of DNA was not modified by complexation with atenolol, lidocaine, or timolol, but was significantly altered by the more lipophilic drugs benzydamine and propranolol, revealing modifications in the secondary structure of the DNA. The in vitro characterization of such interactions provides a physicochemical basis that would contribute to identify the effects of this kind of drugs in cellular cultures, as well as side effects observed under their clinical use. Moreover, this methodology could also be projected to the fields of intracellular DNA transfection and the use of DNA as a carrier of active drugs.

  1. SNAP-Tag Technology: A Useful Tool To Determine Affinity Constants and Other Functional Parameters of Novel Antibody Fragments.

    PubMed

    Niesen, Judith; Sack, Markus; Seidel, Melanie; Fendel, Rolf; Barth, Stefan; Fischer, Rainer; Stein, Christoph

    2016-08-17

    Antibody derivatives, such as the single chain fragment variable (scFv), can be developed as diagnostic and therapeutic tools in cancer research, especially in the form of fusion proteins. Such derivatives are easier to produce and modify than monoclonal antibodies (mAbs) and achieve better tissue/tumor penetration. The genetic modification of scFvs is also much more straightforward than the challenging chemical modification of mAbs. Therefore, we constructed two scFvs derived from the approved monoclonal antibodies cetuximab (scFv2112) and panitumumab (scFv1711), both of which are specific for the epidermal growth factor receptor (EGFR), a well-characterized solid tumor antigen. Both scFvs were genetically fused to the SNAP-tag, an engineered version of the human DNA repair enzyme O(6)-alkylguanine DNA alkyltransferase that allows the covalent coupling of benzylguanine (BG)-modified substrates such as fluorescent dyes. The SNAP-tag achieves controllable and irreversible protein modification and is an important tool for experimental studies in vitro and in vivo. The affinity constant of a scFv is a key functional parameter, especially in the context of a fusion protein. Therefore, we developed a method to define the affinity constants of scFv-SNAP fusion proteins by surface plasmon resonance (SPR) spectroscopy. We could confirm that both scFvs retained their functionality after fusion to the SNAP-tag in a variety of procedures and assays, including ELISA, flow cytometry, and confocal microscopy. The experimental procedures described herein, and the new protocol for affinity determination by SPR spectroscopy, are suitable for the preclinical evaluation of diverse antibody formats and derivatives.

  2. Estimation of apparent binding constant of complexes of selected acyclic nucleoside phosphonates with β-cyclodextrin by affinity capillary electrophoresis.

    PubMed

    Šolínová, Veronika; Mikysková, Hana; Kaiser, Martin Maxmilián; Janeba, Zlatko; Holý, Antonín; Kašička, Václav

    2016-01-01

    Affinity capillary electrophoresis (ACE) has been applied to estimation of apparent binding constant of complexes of (R,S)-enantiomers of selected acyclic nucleoside phosphonates (ANPs) with chiral selector β-cyclodextrin (βCD) in aqueous alkaline medium. The noncovalent interactions of five pairs of (R,S)-enantiomers of ANPs-based antiviral drugs and their derivatives with βCD were investigated in the background electrolyte (BGE) composed of 35 or 50 mM sodium tetraborate, pH 10.0, and containing variable concentration (0-25 mM) of βCD. The apparent binding constants of the complexes of (R,S)-enantiomers of ANPs with βCD were estimated from the dependence of effective electrophoretic mobilities of (R,S)-enantiomers of ANPs (measured simultaneously by ACE at constant reference temperature 25°C inside the capillary) on the concentration of βCD in the BGE using different nonlinear and linear calculation methodologies. Nonlinear regression analysis provided more precise and accurate values of the binding constants and a higher correlation coefficient as compared to the regression analysis of the three linearized plots of the effective mobility dependence on βCD concentration in the BGE. The complexes of (R,S)-enantiomers of ANPs with βCD have been found to be relatively weak - their apparent binding constants determined by the nonlinear regression analysis were in the range 13.3-46.4 L/mol whereas the values from the linearized plots spanned the interval 12.3-55.2 L/mol.

  3. Determination of drug-polymer binding constants by affinity capillary electrophoresis for aryl propionic acid derivatives and related compounds.

    PubMed

    Jia, Zhongjiang; Choi, Duk Soon; Chokshi, Hitesh

    2013-03-01

    The binding constants (K(b)s) of 17 aryl propionic acid derivatives (APADs) and related compounds with polyvinylpyrrolidone (PVP K30) and vinylpyrrolidone-vinyl acetate copolymer (Kollidon VA64) in aqueous media were determined by affinity capillary electrophoreses (ACE). The K(b)s of APAD to polymers increase with octanol-water partition coefficients of the compounds. Kollidon VA64 is a stronger binder than PVP K30 to APAD compounds. The K(b)s are greater at pH 4 than at pH 9. Both hydrophobic interaction and hydrogen bonding may be involved. However, hydrophobic interaction appears to be dominant. The ACE method is simple and fast, which could be used to study drug-polymer interaction in aqueous media.

  4. Determining the binding mode and binding affinity constant of tyrosine kinase inhibitor PD153035 to DNA using optical tweezers

    SciTech Connect

    Cheng, Chih-Ming; Lee, Yuarn-Jang; Wang, Wei-Ting; Hsu, Chien-Ting; Tsai, Jing-Shin; Wu, Chien-Ming; Ou, Keng-Liang; and others

    2011-01-07

    Research highlights: {yields} PD153035 is a DNA intercalator and intercalation occurs only under very low salt concentration. {yields} The minimum distance between adjacent bound PD153035 {approx} 11 bp. {yields} Binding affinity constant for PD153035 is 1.18({+-}0.09) x 10{sup 4} (1/M). {yields} The change of binding free energy of PD153035-DNA interaction is -5.49 kcal mol{sup -1} at 23 {+-} 0.5 {sup o}C. -- Abstract: Accurately predicting binding affinity constant (K{sub A}) is highly required to determine the binding energetics of the driving forces in drug-DNA interactions. Recently, PD153035, brominated anilinoquinazoline, has been reported to be not only a highly selective inhibitor of epidermal growth factor receptor but also a DNA intercalator. Here, we use a dual-trap optical tweezers to determining K{sub A} for PD153035, where K{sub A} is determined from the changes in B-form contour length (L) of PD153035-DNA complex. Here, L is fitted using a modified wormlike chain model. We found that a noticeable increment in L in 1 mM sodium cacodylate was exhibited. Furthermore, our results showed that K{sub A} = 1.18({+-}0.09) x 10{sup 4} (1/M) at 23 {+-} 0.5 {sup o}C and the minimum distance between adjacent bound PD153035 {approx} 11 bp. We anticipate that by using this approach we can determine the complete thermodynamic profiles due to the presence of DNA intercalators.

  5. Asymmetry in inward- and outward-affinity constant of transport explain unidirectional lysine flux in Saccharomyces cerevisiae

    PubMed Central

    Bianchi, Frans; Klooster, Joury S. van ‘t; Ruiz, Stephanie J.; Luck, Katja; Pols, Tjeerd; Urbatsch, Ina L.; Poolman, Bert

    2016-01-01

    The import of basic amino acids in Saccharomyces cerevisiae has been reported to be unidirectional, which is not typical of how secondary transporters work. Since studies of energy coupling and transport kinetics are complicated in vivo, we purified the major lysine transporter (Lyp1) of yeast and reconstituted the protein into lipid vesicles. We show that the Michaelis constant (KM) of transport from out-to-in is well in the millimolar range and at least 3 to 4-orders of magnitude higher than that of transport in the opposite direction, disfavoring the efflux of solute via Lyp1. We also find that at low values of the proton motive force, the transport by Lyp1 is comparatively slow. We benchmarked the properties of eukaryotic Lyp1 to that of the prokaryotic homologue LysP and find that LysP has a similar KM for transport from in-to-out and out-to-in, consistent with rapid influx and efflux. We thus explain the previously described unidirectional nature of lysine transport in S. cerevisiae by the extraordinary kinetics of Lyp1 and provide a mechanism and rationale for previous observations. The high asymmetry in transport together with secondary storage in the vacuole allow the cell to accumulate basic amino acids to very high levels. PMID:27550794

  6. Mapping of the high affinity Fc epsilon receptor binding site to the third constant region domain of IgE.

    PubMed Central

    Nissim, A; Jouvin, M H; Eshhar, Z

    1991-01-01

    Identification of the precise region(s) on the IgE molecule that take part in the binding of IgE to its high affinity receptor (Fc epsilon RI) may lead to the design of IgE analogues able to block the allergic response. To localize the Fc epsilon RI-binding domain of mouse IgE, we attempted to confer on human IgE, which normally does not bind to the rodent receptor, the ability to bind to the rat Fc epsilon RI. Employing exon shuffling, we have expressed chimeric epsilon-heavy chain genes composed of a mouse (4-hydroxy-3-nitrophenyl)acetic acid (NP)-binding VH domain, and human C epsilon in which various domains were replaced by their murine counterparts. This has enabled us to test the Fc epsilon RI-binding of each mouse IgE domain while maintaining the overall conformation of the molecule. All of the chimeric IgE molecules which contain the murine C epsilon 3, bound equally to both the rodent and human receptor, as well as to monoclonal antibodies recognizing a site on IgE which is identical or very close to the Fc epsilon RI binding site. Deletion of the second constant region domain did not impair either the binding capacity of the mutated IgE or its ability to mediate mast cell degradation. These results assign the third epsilon domain of IgE as the principal region involved in the interaction with the Fc epsilon RI. Images PMID:1824934

  7. Lattice-constant and electron-affinity effects on negative-ion conversion in atom-ionic-crystal-surface grazing scattering

    NASA Astrophysics Data System (ADS)

    Zhou, Wang; Zhou, Hu; Zhang, Meixiao; Zhou, Lihua; Li, Yuan; Li, Bowen; Chen, Ximeng

    2016-11-01

    The effects of the lattice constant and electron affinity on the negative-ion conversion of a neutral atom undergoing grazing scattering on an ionic-crystal surface over the complete velocity range were investigated. Here, a comparison of negative-ion conversion of neutral O0-KCl (100 ) , F0-KCl (100 ) , and O0-KI (100 ) surface systems shows that the pronounced difference in the efficiency of negative-ion formation between F0-KCl (100 ) and O0-KCl (100 ) is caused by the large difference in their projectile electron affinities, whereas the difference between O0-KI (100 ) and O0-KCl (100 ) is caused by the difference in their lattice constants.

  8. Estimation of the receptor-state affinity constants of ligands in functional studies using wild type and constitutively active mutant receptors: Implications for estimation of agonist bias.

    PubMed

    Ehlert, Frederick J; Stein, Richard S L

    We describe a method for estimating the affinities of ligands for active and inactive states of a G protein-coupled receptor (GPCR). Our protocol involves measuring agonist-induced signaling responses of a wild type GPCR and a constitutively active mutant of it under control conditions and after partial receptor inactivation or reduced receptor expression. Our subsequent analysis is based on the assumption that the activating mutation increases receptor isomerization into the active state without affecting the affinities of ligands for receptor states. A means of confirming this assumption is provided. Global nonlinear regression analysis yields estimates of 1) the active (Kact) and inactive (Kinact) receptor-state affinity constants, 2) the isomerization constant of the unoccupied receptor (Kq-obs), and 3) the sensitivity constant of the signaling pathway (KE-obs). The latter two parameters define the output response of the receptor, and hence, their ratio (Kq-obs/KE) is a useful measure of system bias. If the cellular system is reasonably stable and the Kq-obs and KE-obs values of the signaling pathway are known, the Kact and Kinact values of additional agonists can be estimated in subsequent experiments on cells expressing the wild type receptor. We validated our method through computer simulation, an analytical proof, and analysis of previously published data. Our approach provides 1) a more meaningful analysis of structure-activity relationships, 2) a means of validating in silico docking experiments on active and inactive receptor structures and 3) an absolute, in contrast to relative, measure of agonist bias.

  9. Evaluation of three neutral capillary coatings for the determination of analyte-cyclodextrin binding constants by affinity capillary electrophoresis. Application to N,N'-disubstituted piperazine derivatives.

    PubMed

    Danel, Cécile; Melnyk, Patricia; Azaroual, Nathalie; Larchanché, Paul-Emmanuel; Goossens, Jean-François; Vaccher, Claude

    2016-07-15

    The performances of three neutral static coatings (hydroxypropyl cellulose, polyethylene oxide and poly(N,N-dimethylacrylamide) have been evaluated in order to determine the binding constants of the complexes formed between four polycationic compounds (piperazine derivatives) and four cyclodextrins of pharmaceutical interest (β-CD, HP-β-CD, Me-β-CD and sulfobutyl ether-β-CD) by affinity capillary electrophoresis. The physically-adsorbed poly(N,N-dimethylacrylamide) coating proves to be the more efficient to mask the silanol groups of the capillary wall since the lowest electroosmotic flow was measured for this coating. Moreover, it drastically reduces the adsorption of the compounds since it allows a correct repeatability of their migration time, higher efficiencies of the peaks and no baseline shift. Then, it was verified for four complexes that this coating allows a correct determination of the binding constants avoiding the CD adsorption which is responsible of an undervaluation of binding constants. The highest binding constants are obtained using the anionic sulfobutyl ether-β-CD (SBE-β-CD). The structure of the complex formed between the tacrine derivative and the SBE-β-CD was further investigated through 2D ROESY NMR experiments and structure-binding constant relationships. Results suggest that the inclusion in the SBE-β-CD cavity occurs through the aliphatic ring portion of the tacrine moiety.

  10. Fermion Interactions, Cosmological Constant and Space-Time Dimensionality in a Unified Approach Based on Affine Geometry

    NASA Astrophysics Data System (ADS)

    Capozziello, Salvatore; Cirilo-Lombardo, Diego Julio; Dorokhov, Alexander E.

    2014-11-01

    One of the main features of unified models, based on affine geometries, is that all possible interactions and fields naturally arise under the same standard. Here, we consider, from the effective Lagrangian of the theory, the torsion induced 4-fermion interaction. In particular, how this interaction affects the cosmological term, supposing that a condensation occurs for quark fields during the quark-gluon/hadron phase transition in the early universe. We explicitly show that there is no parity-violating pseudo-scalar density, dual to the curvature tensor (Holst term) and the spinor-bilinear scalar density has no mixed couplings of A-V form. On the other hand, the space-time dimensionality cannot be constrained from multidimensional phenomenological models admitting torsion.

  11. Analysis of agonism and inverse agonism in functional assays with constitutive activity: estimation of orthosteric ligand affinity constants for active and inactive receptor states.

    PubMed

    Ehlert, Frederick J; Suga, Hinako; Griffin, Michael T

    2011-08-01

    We describe a modification of receptor theory for the estimation of observed affinities (K(obs)) and relative efficacies of orthosteric ligands in functional assays that exhibit constitutive activity. Our theory includes parameters for the fractions of the occupied receptor population in the active (intrinsic efficacy, ε) and inactive (ε(i)) states and analogous parameters for the fractions of the free receptor population in the active (ε(sys)) and inactive (ε(i-sys)) states. The total stimulus represents the summation of the active states of the free and occupied receptor populations. A modified operational model is developed that expresses the response as a logistic function of the total stimulus. This function includes the standard parameters related to affinity and efficacy (K(obs) and τ) as well as a parameter proportional to the activity of the free receptor complex, τ(sys). Two related parameters are proportional to the fraction of the free (τ(i-sys)) and occupied (τ(i)) receptor populations in the inactive state. We show that the estimates of the affinity constants of orthosteric ligands for the active (K(b)) and inactive (K(a)) states of the receptor are equivalent to τK(obs)/τ(sys) and τ(i)K(obs)/τ(i-sys), respectively. We verify our method with computer simulation techniques and apply it to the analysis of M(2) and M(3) muscarinic receptors. Our method is applicable in the analysis of ligand bias in drug discovery programs.

  12. Km as an Apparent Dissociation Constant.

    ERIC Educational Resources Information Center

    Cohlberg, Jeffrey A.

    1979-01-01

    An approach to enzyme kinetics which emphasizes similarities between equilibrium binding and steady state kinetics is outlined. It is intended for use in teaching biochemistry to beginning students. (Author/SA)

  13. A Small, Dilute-Cytoplasm, High-Affinity, Novel Bacterium Isolated by Extinction Culture and Having Kinetic Constants Compatible with Growth at Ambient Concentrations of Dissolved Nutrients in Seawater

    PubMed Central

    Button, D. K.; Robertson, Betsy R.; Lepp, Paul W.; Schmidt, Thomas M.

    1998-01-01

    Dilutions of raw seawater produced a bacterial isolate capable of extended growth in unamended seawater. Its 2.9-Mb genome size and 40-fg dry mass were similar to values for many naturally occurring aquatic organotrophs, but water and DNA comprised a large portion of this small chemoheterotroph, as compared to Escherichia coli. The isolate used only a few aromatic hydrocarbons and acetate, and glucose and amino acid incorporation were entirely absent, although many membrane and cytoplasmic proteins were inducible; it was named Cycloclasticus oligotrophus. A general rate equation that incorporates saturation phenomena into specific affinity theory is derived. It is used to relate the kinetic constants for substrate uptake by the isolate to its cellular proteins. The affinity constant KA for toluene was low at 1.3 μg/liter under optimal conditions, similar to those measured in seawater, and the low value was ascribed to an unknown slow step such as limitation by a cytoplasmic enzyme; KA increased with increasing specific affinities. Specific affinities, a°s, were protocol sensitive, but under optimal conditions were 47.4 liters/mg of cells/h, the highest reported in the literature and a value sufficient for growth in seawater at concentrations sometimes found. Few rRNA operons, few cytoplasmic proteins, a small genome size, and a small cell size, coupled with a high a°s and a low solids content and the ability to grow without intentionally added substrate, are consistent with the isolation of a marine bacterium with properties typical of the bulk of those present. PMID:9797308

  14. A novel strategy of profiling the mechanism of herbal medicines by combining network pharmacology with plasma concentration determination and affinity constant measurement.

    PubMed

    Chen, Langdong; Lv, Diya; Wang, Dongyao; Chen, Xiaofei; Zhu, Zhenyu; Cao, Yan; Chai, Yifeng

    2016-10-18

    Herbal medicines have long been widely used in the treatment of various complex diseases in China. However, the active constituents and therapeutic mechanisms of many herbal medicines remain undefined. Therefore, the identification of the active components and target proteins in these herbal medicines is a formidable task in herbal medicine research. In this study, we proposed a strategy, which integrates network pharmacology with biomedical analysis and surface plasmon resonance (SPR) to predict the active ingredients and potential targets of herbal medicine Sophora flavescens or Kushen in Chinese, and evaluate its anti-fibrosis activity. First, we applied a virtual HTDocking platform to predict the potential targets of Kushen related to liver fibrosis by selecting five crucial protein targets based on network parameters and text mining. Then, we identified nine components in mice plasma after oral administration of Kushen extract and determined the plasma concentration of each compound. Binding affinities between the nine potential active compounds and five target proteins were detected by SPR assays. Finally, we constructed a multi-parameter network model on the basis of three important parameters to tentatively explain the anti-fibrosis mechanism of Kushen. The results not only provide evidence for the therapeutic mechanism of Kushen but also shed new light on the activity-based analysis of other Chinese herbal medicines.

  15. The Measurements of Affinity Constants of Osmptrophs For P and Release Rates of P From Microbial Food Web From Late Summer To Early Winter In The Bay of Villefranche, The NW Mediterranean

    NASA Astrophysics Data System (ADS)

    Tanaka, T.; Rassoulzadegan, F.; Thingstad, T. F.

    Orthophosphate uptake by bacteria and phytoplankton was measured with 32P for wa- ter from the Bay of Villefranche (NW Mediterranean) from September to December 2001. The 32P release rate was measured for waters with different size of micro- bial community. During this period, the thermocline was gradually declined and the vertical mixing started, showing the transition from nutrient depleted to replete pe- riods. Before the vertical mixing started, orthophosphate turnover time ranged from 1 to 5 h. The fraction of orthophosphate uptake was dominated (mean 70%) by the 0.6-2 µm fraction where cyanobacteria biomass was dominant. Based on the theo- retical considerations proposed by Thingstad and Rassoulzadegan (1999), the affinity constants were estimated for bacteria, cyanobacteria and autotrophic nanoflagellates, respectively. They ranged from 0.001 to 0.028 L/nM-P/h for bacteria, from 0.047 to 0.103 L/nM-P/h for cyanobacteria and from 0.002 to 0.032 L/nM-P/h for autotrophic nanoflagellates when 32P turnover time was relatively shorter (<5 h). This may sup- port the previous report in which cyanobacteria were dominant in the primary pro- duction in autumn at the study site. The 32P release rates after the addition of cold chase were always less than 0.5%/h. This release appeared to be from the 0.2-0.6 or 0.6-2 µm fractions. The increase of 32P in the >2 µm fraction suggests P transfer by predation. Virus appeared to not contribute to 32P release from bacteria during the study period. These results indicate long P turnover times within particulate fraction and thus less contribution of P release from microbial food web.

  16. Calorimetric investigation of proton linkage by monitoring both the enthalpy and association constant of binding: application to the interaction of the Src SH2 domain with a high-affinity tyrosyl phosphopeptide.

    PubMed

    Bradshaw, J M; Waksman, G

    1998-11-03

    The binding of Src homology 2 (SH2) domains to tyrosyl phosphopeptides depends on electrostatic interactions between the phosphotyrosine and its binding site. To probe the role of these interactions, we have used isothermal titration calorimetry to study the pH dependence of the binding of the SH2 domain of the Src kinase to a high-affinity tyrosyl phosphopeptide. Two independent approaches were employed. In a first series of experiments that focused on determining the peptide's association constant between pH 5.0 and 9.0, two ionizable groups were characterized. One group, with free and bound pKas of 6.2 and 4.4, respectively, could be identified as the phosphate in the phosphotyrosine while the other group, with free and bound pKas of 8.2 and 8.5, respectively, could be only tentatively assigned to a cysteine in the phosphotyrosine binding pocket. Further information on the linkage between peptide binding and protonation of the phosphotyrosine was obtained from a second series of experiments, which focused on determining the peptide binding enthalpy at low values of pH in several buffers with different ionization enthalpies. These data provided free and bound pKa values for the phosphotyrosine identical to those derived from the first series of experiments, and hence demonstrated for the first time that the two approaches provide identical information regarding proton linkage. In addition, the second series of experiments also determined the intrinsic enthalpy of binding of both the protonated and deprotonated phosphate forms of the peptide. These two sets of experiments provided a complete energetic profile of the linkage between phosphate ionization and peptide binding. From this profile, it was determined that the PO32- form of the peptide binds 2.3 kcal mol-1 more favorably than the PO3H1- form due entirely to a more favorable entropy of binding.

  17. 40Km Into Lebanon,

    DTIC Science & Technology

    1987-07-01

    answer to the difficulties in Palestine, London organized a study of the problem under Lord Peel , a for- mer Secretary of State for India, who in 1937...issued the report of the Commission bearing his name. As Peel saw it, the only solution was to partition Palestine between the two communities. The...minority suggestions. The majority 22 40Km into Lebanon report recommended partition with an economic union, much as Peel had proposed in 1937. A

  18. High affinity choline uptake: an early index of cholinergic innervation in rat brain.

    PubMed

    Sorimachi, M; Kataoka, K

    1975-08-29

    The uptake of [3H]choline was investigated in nuclei-free homogenates or crude synaptosomal fractions (P2) from rat brain under various stages of development. A comparable sensitivity of uptake to treatment by hyposmotic shock suggested the involvement of synaptosomal populations in choline uptake in immature as well as in adult brains. However, significant changes in the "apparent" Km for the high affinity transport system and quantitative differences in the Na ion requirement for maximal uptake at 0.43 muM choline concentration were found during development; facts which suggested a greater contribution of the low affinity system in the more immature brains. Assuming that the uptake with high and low sensitivity to Na+ reduction reflected that via the high and low affinity system reslectively, we have attempted to obtain real Km values for the high affinity system. These Km values changed less than those measured directly, suggesting that the affinity constant for the high affinity system does not change during development. On these assumptions, the developmental changes of cholinergic synaptogenesis were examined in 5 distinct regions of the brain. It was found that the synaptogenesis begins several days earlier than the increase of choline acetyltransferase (ChAc) level in the frontal cortex, the hippocampus, the superior colliculus and the cerebellum. These regions may be included among the terminal-rich regions according to available evidence related to cholinergic systems. On the other hand, synaptogenesis accompanied the concomitant ChAc increase in the striatum, where the cholinergic interneurons are present. It is concluded that the increase of ChAc in the terminal-rich regions is delayed by the axoplasmic flow; therefore, the earlier index of cholinergic synaptogenesis in these regions is the high affinity uptake activity rather than the enzyme activity.

  19. The Hubble Constant.

    PubMed

    Jackson, Neal

    2015-01-01

    I review the current state of determinations of the Hubble constant, which gives the length scale of the Universe by relating the expansion velocity of objects to their distance. There are two broad categories of measurements. The first uses individual astrophysical objects which have some property that allows their intrinsic luminosity or size to be determined, or allows the determination of their distance by geometric means. The second category comprises the use of all-sky cosmic microwave background, or correlations between large samples of galaxies, to determine information about the geometry of the Universe and hence the Hubble constant, typically in a combination with other cosmological parameters. Many, but not all, object-based measurements give H0 values of around 72-74 km s(-1) Mpc(-1), with typical errors of 2-3 km s(-1) Mpc(-1). This is in mild discrepancy with CMB-based measurements, in particular those from the Planck satellite, which give values of 67-68 km s(-1) Mpc(-1) and typical errors of 1-2 km s(-1) Mpc(-1). The size of the remaining systematics indicate that accuracy rather than precision is the remaining problem in a good determination of the Hubble constant. Whether a discrepancy exists, and whether new physics is needed to resolve it, depends on details of the systematics of the object-based methods, and also on the assumptions about other cosmological parameters and which datasets are combined in the case of the all-sky methods.

  20. Radiotracers for Cardiac Sympathetic Innervation: Transport Kinetics and Binding Affinities for the Human Norepinephrine Transporter

    PubMed Central

    Raffel, David M.; Chen, Wei; Jung, Yong-Woon; Jang, Keun Sam; Gu, Guie; Cozzi, Nicholas V.

    2013-01-01

    Introduction Most radiotracers for imaging of cardiac sympathetic innervation are substrates of the norepinephrine transporter (NET). The goal of this study was to characterize the NET transport kinetics and binding affinities of several sympathetic nerve radiotracers, including [11C]-(−)-meta-hydroxyephedrine, [11C]-(−)-epinephrine, and a series of [11C]-labeled phenethylguanidines under development in our laboratory. For comparison, the NET transport kinetics and binding affinities of some [3H]-labeled biogenic amines were also determined. Methods Transport kinetics studies were performed using rat C6 glioma cells stably transfected with the human norepinephrine transporter (C6-hNET cells). For each radiolabeled NET substrate, saturation transport assays with C6-hNET cells measured the Michaelis-Menten transport constants Km and Vmax for NET transport. Competitive inhibition binding assays with homogenized C6-hNET cells and [3H]mazindol provided estimates of binding affinities (KI) for NET. Results Km, Vmax and KI values were determined for each NET substrate with a high degree of reproducibility. Interestingly, C6-hNET transport rates for ‘tracer concentrations’ of substrate, given by the ratio Vmax/Km, were found to be highly correlated with neuronal transport rates measured previously in isolated rat hearts (r2 = 0.96). This suggests that the transport constants Km and Vmax measured using the C6-hNET cells accurately reflect in vivo transport kinetics. Conclusion The results of these studies show how structural changes in NET substrates influence NET binding and transport constants, providing valuable insights that can be used in the design of new tracers with more optimal kinetics for quantifying regional sympathetic nerve density. PMID:23306137

  1. Are Fundamental Constants Really Constant?

    ERIC Educational Resources Information Center

    Swetman, T. P.

    1972-01-01

    Dirac's classical conclusions, that the values of e2, M and m are constants and the quantity of G decreases with time. Evoked considerable interest among researchers and traces historical development by which further experimental evidence points out that both e and G are constant values. (PS)

  2. Determination of the constants of affinity of FeCl3, CuCl2, and ZnCl2 for a nitrogen-containing organosilane bonded on Al2O3-cellulose acetate hybrid material surface from ethanol solution.

    PubMed

    Lazarin, Angélica M; Landers, Richard; Kholin, Yuriy V; Gushikem, Yoshitaka

    2002-10-01

    This work describes the preparation and characterization of a cellulose acetate fiber coated with Al(2)O(3), resulting in the organic-inorganic hybrid Cel/Al(2)O(3). Furthermore, the hybrid was modified by attaching organofunctional groups by reaction with the precursor reagents (RO)(3)Si(CH(2))(3)L (L=NH(2), NH(CH(2))(2)NH(2), NH(CH(2))(2)NH(CH(2))(2)NH(2), and N(2)C(3)H(3) (imidazole)), resulting in Cel/Al(2)O(3)/Si(CH(2))(3)NH(2) (1), Cel/Al(2)O(3)/Si(CH(2))(3)NH(CH(2))(2)NH(2) (2), Cel/Al(2)O(3)/Si(CH(2))(3)NH(CH(2))(2)NH(CH(2))(2)NH(2) (3), and Cel/Al(2)O(3)/Si(CH(2))(3)N(2)C(3)H(3) (4). The amounts of attached organofunctional groups were (in mmol per gram of the material) 1=1.90, 2=1.89, 3=1.66, and 4=1.35. The isotherms of adsorption of FeCl(3), CuCl(2), and ZnCl(2) by Cel/Al(2)O(3)/Si(CH(2))(3)L from ethanol solutions were obtained at 298 K. Accurate estimates of the specific sorption capacities and the heteregeneous stability constants of the immobilized metal complexes were determined with the aid of several computational procedures. It is shown that the sorptional capacities are much less than the concentrations of the attached organofunctional groups. As all sorption isotherms are fitted properly with the Langmuir isotherm equation, the effects of the energetic heterogeneity and the lateral interactions do not affect the chemisorption equilibria. The heterogeneous stability constants of the immobilized complexes are fairly high, which provides efficient removal of the metal ions from solutions by the hybrid materials.

  3. KM3NeT

    SciTech Connect

    Jong, M. de; Collaboration: KM3NeT Collaboration

    2015-07-15

    KM3NeT is a large research infrastructure, that will consist of a network of deep-sea neutrino telescopes in the Mediterranean Sea. The main objective of KM3NeT is the discovery and subsequent observation of high-energy neutrino sources in the Universe. A further physics perspective is the measurement of the mass hierarchy of neutrinos. A corresponding study, ORCA, is ongoing within KM3NeT. A cost effective technology for (very) large water Cherenkov detectors has been developed based on a new generation of low price 3-inch photo-multiplier tubes. Following the successful deployment and operation of two prototypes, the construction of the KM3NeT research infrastructure has started. The prospects of the different phases of the implementation of KM3NeT are summarised.

  4. Deriving the therapeutic concentrations for clozapine and haloperidol: the apparent dissociation constant of a neuroleptic at the dopamine D2 or D4 receptor varies with the affinity of the competing radioligand.

    PubMed

    Seeman, P; Van Tol, H H

    1995-10-15

    The apparent dissociation constant, Ki, for a neuroleptic at the dopamine D2 or D4 receptor was consistently higher when competed against [3H]nemonapride than against [3H]spiperone which was in turn higher than that against [3H]raclopride. This finding obtained for all four types of dopamine receptors studied, including the native dopamine D2 receptor in the anterior pituitary tissue, the human D2long receptor, the human D2short receptor and the human D4.4 receptor. Some neuroleptics revealed a difference of over 10-fold between the Ki using [3H]nemonapride and the Ki using [3H]raclopride. The KD values of the three 3H-ligands and the neuroleptic Ki values were lower when using a much lower concentration of tissue, indicating that depletion of ligand presumably accounted for the phenomenon. The Ki values of each neuroleptic were related to the the tissue/buffer partition coefficients of the three 3H-ligands. Extrapolating the neuroleptic Ki value down to a tissue/buffer partition coefficient of unity or zero led to a Ki value for competition versus a water-soluble ligand such as dopamine. Clozapine extrapolated to a Ki value of 1.3 nM. Direct measurement gave a Ki value of 1.6 nM for [3H]clozapine at the dopamine D4 receptor. When competing versus endogenous dopamine, this clozapine value of 1.6 nM would rise to 20 nM for the blockade of 75% of dopamine D4 receptors, matching the observed therapeutic concentration of 18 nM. These data also explain why clozapine occupies 48% of the D2 receptors in patients when measured with [11C]raclopride, but between 0% and 22% when measured with [18F]methylspiperone or [18F]fluoroethylspiperone.

  5. Knob manager (KM) operators guide

    SciTech Connect

    1993-10-08

    KM, Knob Manager, is a tool which enables the user to use the SUNDIALS knob box to adjust the settings of the control system. The followings are some features of KM: dynamic knob assignments with the user friendly interface; user-defined gain for individual knob; graphical displays for operating range and status of each process variable is assigned; backup and restore one or multiple process variable; save current settings to a file and recall the settings from that file in future.

  6. Conformational kinetics reveals affinities of protein conformational states.

    PubMed

    Daniels, Kyle G; Suo, Yang; Oas, Terrence G

    2015-07-28

    Most biological reactions rely on interplay between binding and changes in both macromolecular structure and dynamics. Practical understanding of this interplay requires detection of critical intermediates and determination of their binding and conformational characteristics. However, many of these species are only transiently present and they have often been overlooked in mechanistic studies of reactions that couple binding to conformational change. We monitored the kinetics of ligand-induced conformational changes in a small protein using six different ligands. We analyzed the kinetic data to simultaneously determine both binding affinities for the conformational states and the rate constants of conformational change. The approach we used is sufficiently robust to determine the affinities of three conformational states and detect even modest differences in the protein's affinities for relatively similar ligands. Ligand binding favors higher-affinity conformational states by increasing forward conformational rate constants and/or decreasing reverse conformational rate constants. The amounts by which forward rate constants increase and reverse rate constants decrease are proportional to the ratio of affinities of the conformational states. We also show that both the affinity ratio and another parameter, which quantifies the changes in conformational rate constants upon ligand binding, are strong determinants of the mechanism (conformational selection and/or induced fit) of molecular recognition. Our results highlight the utility of analyzing the kinetics of conformational changes to determine affinities that cannot be determined from equilibrium experiments. Most importantly, they demonstrate an inextricable link between conformational dynamics and the binding affinities of conformational states.

  7. The Hubble Constant.

    PubMed

    Jackson, Neal

    2007-01-01

    I review the current state of determinations of the Hubble constant, which gives the length scale of the Universe by relating the expansion velocity of objects to their distance. In the last 20 years, much progress has been made and estimates now range between 60 and 75 km s(-1) Mpc(-1), with most now between 70 and 75 km s(-1) Mpc(-1), a huge improvement over the factor-of-2 uncertainty which used to prevail. Further improvements which gave a generally agreed margin of error of a few percent rather than the current 10% would be vital input to much other interesting cosmology. There are several programmes which are likely to lead us to this point in the next 10 years.

  8. Applying WebMining on KM system

    NASA Astrophysics Data System (ADS)

    Shimazu, Keiko; Ozaki, Tomonobu; Furukawa, Koichi

    KM (Knowledge Management) systems have recently been adopted within the realm of enterprise management. On the other hand, data mining technology is widely acknowledged within Information systems' R&D Divisions. Specially, acquisition of meaningful information from Web usage data has become one of the most exciting eras. In this paper, we employ a Web based KM system and propose a framework for applying Web Usage Mining technology to KM data. As it turns out, task duration varies according to different user operations such as referencing a table-of-contents page, down-loading a target file, and writing to a bulletin board. This in turn makes it possible to easily predict the purpose of the user's task. By taking these observations into account, we segmented access log data manually. These results were compared with results abstained by applying the constant interval method. Next, we obtained a segmentation rule of Web access logs by applying a machine-learning algorithm to manually segmented access logs as training data. Then, the newly obtained segmentation rule was compared with other known methods including the time interval method by evaluating their segmentation results in terms of recall and precision rates and it was shown that our rule attained the best results in both measures. Furthermore, the segmented data were fed to an association rule miner and the obtained association rules were utilized to modify the Web structure.

  9. The Cutting Edge of Affinity Electrophoresis Technology

    PubMed Central

    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

  10. Stability of flavin semiquinones in the gas phase: the electron affinity, proton affinity, and hydrogen atom affinity of lumiflavin.

    PubMed

    Zhang, Tianlan; Papson, Kaitlin; Ochran, Richard; Ridge, Douglas P

    2013-11-07

    Examination of electron transfer and proton transfer reactions of lumiflavin and proton transfer reactions of the lumiflavin radical anion by Fourier transform ion cyclotron resonance mass spectrometry is described. From the equilibrium constant determined for electron transfer between 1,4-naphthoquinone and lumiflavin the electron affinity of lumiflavin is deduced to be 1.86 ± 0.1 eV. Measurements of the rate constants and efficiencies for proton transfer reactions indicate that the proton affinity of the lumiflavin radical anion is between that of difluoroacetate (331.0 kcal/mol) and p-formyl-phenoxide (333.0 kcal/mol). Combining the electron affinity of lumiflavin with the proton affinity of the lumiflavin radical anion gives a lumiflavin hydrogen atom affinity of 59.7 ± 2.2 kcal/mol. The ΔG298 deduced from these results for adding an H atom to gas phase lumiflavin, 52.1 ± 2.2 kcal/mol, is in good agreement with ΔG298 for adding an H atom to aqueous lumiflavin from electrochemical measurements in the literature, 51.0 kcal/mol, and that from M06-L density functional calculations in the literature, 51.2 kcal/mol, suggesting little, if any, solvent effect on the H atom addition. The proton affinity of lumiflavin deduced from the equilibrium constant for the proton transfer reaction between lumiflavin and 2-picoline is 227.3 ± 2.0 kcal mol(-1). Density functional theory calculations on isomers of protonated lumiflavin provide a basis for assigning the most probable site of protonation as position 1 on the isoalloxazine ring and for estimating the ionization potentials of lumiflavin neutral radicals.

  11. A dielectric affinity microbiosensor

    NASA Astrophysics Data System (ADS)

    Huang, Xian; Li, Siqi; Schultz, Jerome S.; Wang, Qian; Lin, Qiao

    2010-01-01

    We present an affinity biosensing approach that exploits changes in dielectric properties of a polymer due to its specific, reversible binding with an analyte. The approach is demonstrated using a microsensor comprising a pair of thin-film capacitive electrodes sandwiching a solution of poly(acrylamide-ran-3-acrylamidophenylboronic acid), a synthetic polymer with specific affinity to glucose. Binding with glucose induces changes in the permittivity of the polymer, which can be measured capacitively for specific glucose detection, as confirmed by experimental results at physiologically relevant concentrations. The dielectric affinity biosensing approach holds the potential for practical applications such as long-term continuous glucose monitoring.

  12. Affinity in electrophoresis.

    PubMed

    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.

  13. Affine dynamics with torsion

    NASA Astrophysics Data System (ADS)

    Gültekin, Kemal

    2016-03-01

    In this study, we give a thorough analysis of a general affine gravity with torsion. After a brief exposition of the affine gravities considered by Eddington and Schrödinger, we construct and analyze different affine gravities based on the determinants of the Ricci tensor, the torsion tensor, the Riemann tensor, and their combinations. In each case we reduce equations of motion to their simplest forms and give a detailed analysis of their solutions. Our analyses lead to the construction of the affine connection in terms of the curvature and torsion tensors. Our solutions of the dynamical equations show that the curvature tensors at different points are correlated via non-local, exponential rescaling factors determined by the torsion tensor.

  14. Lectin affinity electrophoresis.

    PubMed

    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.

  15. The Hubble constant.

    PubMed Central

    Tully, R B

    1993-01-01

    Five methods of estimating distances have demonstrated internal reproducibility at the level of 5-20% rms accuracy. The best of these are the cepheid (and RR Lyrae), planetary nebulae, and surface-brightness fluctuation techniques. Luminosity-line width and Dn-sigma methods are less accurate for an individual case but can be applied to large numbers of galaxies. The agreement is excellent between these five procedures. It is determined that Hubble constant H0 = 90 +/- 10 km.s-1.Mpc-1 [1 parsec (pc) = 3.09 x 10(16) m]. It is difficult to reconcile this value with the preferred world model even in the low-density case. The standard model with Omega = 1 may be excluded unless there is something totally misunderstood about the foundation of the distance scale or the ages of stars. PMID:11607391

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

    SciTech Connect

    Chou, Ching-Yi; Ita, Eyo; Soo, Chopin

    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.

  17. Extraction of haemoglobin from human blood by affinity precipitation using a haptoglobin-based stimuli-responsive affinity macroligand.

    PubMed

    Stocker-Majd, Gisela; Hilbrig, Frank; Freitag, Ruth

    2008-06-13

    Affinity precipitation was compared to affinity chromatography and batch adsorption as the final purification step in a protocol for the isolation of haemoglobin from human blood. Haptoglobin was the affinity ligand. The first steps on the process were realized by traditional methods (lyses of red blood cells followed by ammonium sulphate precipitation). For affinity chromatography (and batch adsorption) the ligand was linked to Sepharose, for affinity precipitation to a thermoresponsive polymer, namely poly(N-isopropylacrylamide). Five haptoglobin-poly(N-isopropylacrylamide) bioconjugates (affinity macroligands) were constructed with different polymer: haptoglobin-coupling ratios. Conjugation of haptoglobin to the soluble poly(N-isopropylacrylamide) apparently does not change the interaction thermodynamics with haemoglobin, as the haemoglobin binding constants calculated by a Scatchard analysis for the affinity macroligand were of the same order of magnitude as those described in the literature for the haemoglobin-haptoglobin complex in solution. Two elution protocols were used for haemoglobin release from the various affinity materials, one at pH 2, the other with 5 M urea at pH 11. Both affinity chromatography and affinity precipitation yielded a pure haemoglobin of high quality. Compared to the affinity chromatography, affinity precipitation showed a significantly higher ligand efficiency (ratio of the experimental capacity to the theoretical one). The method thus makes better use of the expensive affinity ligands. As affinity precipitation only requires small temperature changes to bring about precipitation/redissolution of the affinity complexes and a centrifugation step for recovery of the precipitate, the method in addition has advantages in term of scalability and simplicity.

  18. Affine Sphere Relativity

    NASA Astrophysics Data System (ADS)

    Minguzzi, E.

    2017-03-01

    We investigate spacetimes whose light cones could be anisotropic. We prove the equivalence of the structures: (a) Lorentz-Finsler manifold for which the mean Cartan torsion vanishes, (b) Lorentz-Finsler manifold for which the indicatrix (observer space) at each point is a convex hyperbolic affine sphere centered on the zero section, and (c) pair given by a spacetime volume and a sharp convex cone distribution. The equivalence suggests to describe (affine sphere) spacetimes with this structure, so that no algebraic-metrical concept enters the definition. As a result, this work shows how the metric features of spacetime emerge from elementary concepts such as measure and order. Non-relativistic spacetimes are obtained replacing proper spheres with improper spheres, so the distinction does not call for group theoretical elements. In physical terms, in affine sphere spacetimes the light cone distribution and the spacetime measure determine the motion of massive and massless particles (hence the dispersion relation). Furthermore, it is shown that, more generally, for Lorentz-Finsler theories non-differentiable at the cone, the lightlike geodesics and the transport of the particle momentum over them are well defined, though the curve parametrization could be undefined. Causality theory is also well behaved. Several results for affine sphere spacetimes are presented. Some results in Finsler geometry, for instance in the characterization of Randers spaces, are also included.

  19. Experimental and theoretical bases of specific affinity, a cytoarchitecture-based formulation of nutrient collection proposed to supercede the Michaelis-Menten paradigm of microbial kinetics.

    PubMed

    Button, D K; Robertson, Betsy; Gustafson, Elizabeth; Zhao, Xiaoming

    2004-09-01

    A theory for solute uptake by whole cells was derived with a focus on the ability of oligobacteria to sequester nutrients. It provided a general relationship that was used to obtain the kinetic constants for in situ marine populations in the presence of naturally occurring substrates. In situ affinities of 0.9 to 400 liters g of cells(-1) h(-1) found were up to 10(3) times smaller than those from a "Marinobacter arcticus " isolate, but springtime values were greatly increased by warming. Affinities of the isolate for usual polar substrates but not for hydrocarbons were diminished by ionophores. A kinetic curve or Monod plot was constructed from the best available data for cytoarchitectural components of the isolate by using the theory together with concepts and calculations from first principles. The order of effect of these components on specific affinity was membrane potential > cytoplasmic enzyme concentration > cytoplasmic enzyme affinity > permease concentration > area of the permease site > translation coefficient > porin concentration. Component balance was influential as well; a small increase in cytoplasmic enzyme concentration gave a large increase in the effect of permease concentration. The effect of permease concentration on specific affinity was large, while the effect on K(m) was small. These results are in contrast to the Michaelis-Menten theory as applied by Monod that has uptake kinetics dependent on the quality of the permease molecules, with K(m) as an independent measure of affinity. Calculations demonstrated that most oligobacteria in the environment must use multiple substrates simultaneously to attain sufficient energy and material for growth, a requirement consistent with communities largely comprising few species.

  20. Analysis of sex differences in open-water ultra-distance swimming performances in the FINA World Cup races in 5 km, 10 km and 25 km from 2000 to 2012

    PubMed Central

    2014-01-01

    Background The present study investigated the changes in swimming speeds and sex differences for elite male and female swimmers competing in 5 km, 10 km and 25 km open-water FINA World Cup races held between 2000 and 2012. Methods The changes in swimming speeds and sex differences across years were analysed using linear, non-linear, and multi-level regression analyses for the annual fastest and the annual ten fastest competitors. Results For the annual fastest, swimming speed remained stable for men and women in 5 km (5.50 ± 0.21 and 5.08 ± 0.19 km/h, respectively), in 10 km (5.38 ± 0.21 and 5.05 ± 0.26 km/h, respectively) and in 25 km (5.03 ± 0.32 and 4.58 ± 0.27 km/h, respectively). In the annual ten fastest, swimming speed remained constant in 5 km in women (5.02 ± 0.19 km/h) but decreased significantly and linearly in men from 5.42 ± 0.03 km/h to 5.39 ± 0.02 km/h. In 10 km, swimming speed increased significantly and linearly in women from 4.75 ± 0.01 km/h to 5.74 ± 0.01 km/h but remained stable in men at 5.36 ± 0.21 km/h. In 25 km, swimming speed decreased significantly and linearly in women from 4.60 ± 0.06 km/h to 4.44 ± 0.08 km/h but remained unchanged at 4.93 ± 0.34 km/h in men. For the annual fastest, the sex difference in swimming speed remained unchanged in 5 km (7.6 ± 3.0%), 10 km (6.1 ± 2.5%) and 25 km (9.0 ± 3.7%). For the annual ten fastest, the sex difference remained stable in 5 km at 7.6 ± 0.6%, decreased significantly and linearly in 10 km from 7.7 ± 0.7% to 1.2 ± 0.3% and increased significantly and linearly from 4.7 ± 1.4% to 9.6 ± 1.5% in 25 km. Conclusions To summarize, elite female open-water ultra-distance swimmers improved in 10 km but impaired in 25 km leading to a linear decrease in sex difference in 10 km and a linear increase in sex difference in 25 km. The linear changes in sex differences

  1. Cloning and functional characterization of the high-affinity K+ transporter HAK1 of pepper.

    PubMed

    Martínez-Cordero, M Angeles; Martínez, Vicente; Rubio, Francisco

    2004-10-01

    High-affinity K+ uptake in plants plays a crucial role in K+ nutrition and different systems have been postulated to contribute to the high-affinity K+ uptake. The results presented here with pepper (Capsicum annum) demonstrate that a HAK1-type transporter greatly contributes to the high-affinity K+ uptake observed in roots. Pepper plants starved of K+ for 3 d showed high-affinity K+ uptake (Km of 6 microM K+) that was very sensitive to NH and their roots expressed a high-affinity K+ transporter, CaHAK1, which clusters in group I of the KT/HAK/KUP family of transporters. When expressed in yeast ( Saccharomyces cerevisiae ), CaHAK1 mediated high-affinity K+ and Rb+ uptake with Km values of 3.3 and 1.9 microM, respectively. Rb+ uptake was competitively inhibited by micromolar concentrations of NH and Cs+, and by millimolar concentrations of Na+.

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

    PubMed Central

    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

  3. Kernel Affine Projection Algorithms

    NASA Astrophysics Data System (ADS)

    Liu, Weifeng; Príncipe, José C.

    2008-12-01

    The combination of the famed kernel trick and affine projection algorithms (APAs) yields powerful nonlinear extensions, named collectively here, KAPA. This paper is a follow-up study of the recently introduced kernel least-mean-square algorithm (KLMS). KAPA inherits the simplicity and online nature of KLMS while reducing its gradient noise, boosting performance. More interestingly, it provides a unifying model for several neural network techniques, including kernel least-mean-square algorithms, kernel adaline, sliding-window kernel recursive-least squares (KRLS), and regularization networks. Therefore, many insights can be gained into the basic relations among them and the tradeoff between computation complexity and performance. Several simulations illustrate its wide applicability.

  4. Adjoint affine fusion and tadpoles

    NASA Astrophysics Data System (ADS)

    Urichuk, Andrew; Walton, Mark A.

    2016-06-01

    We study affine fusion with the adjoint representation. For simple Lie algebras, elementary and universal formulas determine the decomposition of a tensor product of an integrable highest-weight representation with the adjoint representation. Using the (refined) affine depth rule, we prove that equally striking results apply to adjoint affine fusion. For diagonal fusion, a coefficient equals the number of nonzero Dynkin labels of the relevant affine highest weight, minus 1. A nice lattice-polytope interpretation follows and allows the straightforward calculation of the genus-1 1-point adjoint Verlinde dimension, the adjoint affine fusion tadpole. Explicit formulas, (piecewise) polynomial in the level, are written for the adjoint tadpoles of all classical Lie algebras. We show that off-diagonal adjoint affine fusion is obtained from the corresponding tensor product by simply dropping non-dominant representations.

  5. Cosmological constant, fine structure constant and beyond

    NASA Astrophysics Data System (ADS)

    Wei, Hao; Zou, Xiao-Bo; Li, Hong-Yu; Xue, Dong-Ze

    2017-01-01

    In the present work, we consider the cosmological constant model Λ ∝ α ^{-6}, which is well motivated from three independent approaches. As is well known, the hint of varying fine structure constant α was found in 1998. If Λ ∝ α ^{-6} is right, it means that the cosmological constant Λ should also be varying. Here, we try to develop a suitable framework to model this varying cosmological constant Λ ∝ α ^{-6}, in which we view it from an interacting vacuum energy perspective. Then we consider the observational constraints on these models by using the 293 Δ α /α data from the absorption systems in the spectra of distant quasars. We find that the model parameters can be tightly constrained to the very narrow ranges of O(10^{-5}) typically. On the other hand, we can also view the varying cosmological constant model Λ ∝ α ^{-6} from another perspective, namely it can be equivalent to a model containing "dark energy" and "warm dark matter", but there is no interaction between them. We find that this is also fully consistent with the observational constraints on warm dark matter.

  6. Running economy during a simulated 60-km trial.

    PubMed

    Schena, Federico; Pellegrini, Barbara; Tarperi, Cantor; Calabria, Elisa; Salvagno, Gian Luca; Capelli, Carlo

    2014-07-01

    The effect of a prolonged running trial on the energy cost of running (C(r)) during a 60-km ultramarathon simulation at the pace of a 100-km competition was investigated in 13 men (40.8 ± 5.6 y, 70.7 ± 5.5 kg, 177.5 ± 4.5 cm) and 5 women (40.4 ± 2.3 y, 53.7 ± 4.4 kg, 162.4 ± 4.8 cm) who participated in a 60-km trial consisting of 3 consecutive 20-km laps. Oxygen uptake (VO(2)) at steady state was determined at constant speed before the test and at the end of each lap; stride length (SL) and frequency and contact time were measured at the same time points; serum creatine kinase (S-CPK) was measured before and at the end of the test. C(r) in J · kg(-1) · m(-1), as calculated from VO(2ss) and respiratory-exchange ratio, did not increase with distance. SL significantly decreased with distance. The net increase in S-CPK was linearly related with the percentage increase of C(r) observed during the trial. It is concluded that, in spite of increased S-CPK, this effort was not able to elicit any peripheral or central fatigue or biomechanical adaptation leading to any modification of C(r).

  7. Neutral Wind Observations below 200 km altitudes

    NASA Astrophysics Data System (ADS)

    Watanabe, S.; Abe, T.; Habu, H.; Kakinami, Y.; Larsen, M. F.; Pfaff, R. F., Jr.; Yamamoto, M.

    2015-12-01

    Neutral Wind Observations below 200 km altitudesS. Watanabe1, T. Abe2, H. Habu2, Y. Kakinami3, M. Larsen4, R. Pfaff5, M. Yamamoto6, M-Y. Yamamoto31Hokkaido University/Hokkaido Information University, 2JAXA/ISAS, 3Kochi University of Technology, 4Clemson University, 5NASA/Goddard Space Flight Center, 6Kyoto University, Neutral wind in the thermosphere is one of the key parameters to understand the ionosphere-thermosphere coupling process. JAXA/ISAS successfully launched sounding rockets from Uchinoura Space Center (USC) on September 2, 2007, January 12, 2012, and July 20, 2013, and NASA launched sounding rockets from Kwajalein on May 7, 2013 and from Wallops on July 4, 2013. The rockets installed Lithium and/or TMA canisters as well as instruments for plasma and electric and magnetic fields. The atomic Lithium gases were released at altitudes between 150 km and 300 km in the evening on September 2, 2007, at altitude of ~100 km in the morning on January 12, 2012, at altitude of ~120km in the midnight on July 20, 2013, at altitude between 150 km and 300 km in the evening on May 7, 2013 and at altitude of ~150 km in the noon on July 4, 2013. The Lithium atoms were scattering sunlight by resonance scattering with wavelength of 670nm. However, the Lithium atoms scattered moon light on July 20, 2013. The moon light scattering is the first time to use for thermospheric wind measurement in the midnight. The Lithium clouds/trails and TMA trails showed clearly the neutral wind shears and atmospheric waves at ~150 km altitude in the lower thermosphere for all local time.

  8. News from KM3NeT

    SciTech Connect

    Katz, Ulrich F.; Collaboration: KM3NeT Collaboration

    2014-11-18

    KM3NeT is a future research infrastructure in the Mediterranean Sea, hosting a multi-cubic-kilometre neutrino telescope and nodes for Earth and Sea sciences. In this report we shortly summarise the genesis of the KM3NeT project and present key elements of its technical design. The physics objectives of the KM3NeT neutrino telescope and some selected sensitivity estimates are discussed. Finally, some first results from prototype operations and the next steps towards implementation – in particular the first construction phase in 2014/15 – are described.

  9. Fact Sheet for KM200 Front-end Electronics

    SciTech Connect

    Ianakiev, Kiril Dimitrov; Iliev, Metodi; Swinhoe, Martyn Thomas

    2015-07-08

    The KM200 device is a versatile, configurable front-end electronics boards that can be used as a functional replacement for Canberra’s JAB-01 boards based on the Amptek A-111 hybrid chip, which continues to be the preferred choice of electronics for large number of the boards in junction boxes of multiplicity counters that process the signal from an array of 3He detectors. Unlike the A-111 chip’s fixed time constants and sensitivity range, the shaping time and sensitivity of the new KM200 can be optimized for demanding applications such as spent fuel, and thus could improve the safeguards measurements of existing systems where the A-111 or PDT electronics does not perform well.

  10. A new affinity method for purification of bovine testicular hyaluronidase enzyme and an investigation of the effects of some compounds on this enzyme.

    PubMed

    Kaya, Mustafa Oguzhan; Arslan, Oktay; Guler, Ozen Ozensoy

    2015-01-01

    In this study, a new affinity gel for the purification of bovine testicular hyaluronidase (BTH) was synthesized. L-Tyrosine was added as the extension arm to the Sepharose-4B activated with cyanogen bromide. m-Anisidine is a specific inhibitor of BTH enzyme. m-Anisidine was clamped to the newly formed Sepharose-4B-L-tyrosine as a ligand. As a result, an affinity gel having the chemical structure of Sepharose-4B-L-tyrosine-m-anisidine was obtained. BTH purified by ammonium sulfate precipitation and affinity chromatography was obtained with a 16.95% yield and 881.78 degree of purity. The kinetic constants K(M) and V(Max) for BTH were determined by using hyaluronic acid as a substrate. K(M) and V(Max) values obtained from the Lineweaver-Burk graph were found to be 2.23 mM and 19.85 U/mL, respectively. In vitro effects of some chemicals were determined on purified BTH enzyme. Some chemically active ingredients were 1,1-dimethyl piperidinium chloride, β-naphthoxyacetic acid and gibberellic acid. Gibberellic acid showed the best inhibition effect on BTH.

  11. Status of KM3NeT

    NASA Astrophysics Data System (ADS)

    Riccobene, G.

    2016-07-01

    The recent observation of cosmic neutrinos by IceCube has pushed the quest towards the identification of cosmic sources of high-energy particles. The KM3NeT Collaboration is now ready to launch the massive construction of detection units to be installed in deep sea to build a km-cubic size neutrino telescope. The main elements of the detector, the status of the project and the expected perfomances are briefly reported.

  12. Affine conformal vectors in space-time

    NASA Astrophysics Data System (ADS)

    Coley, A. A.; Tupper, B. O. J.

    1992-05-01

    All space-times admitting a proper affine conformal vector (ACV) are found. By using a theorem of Hall and da Costa, it is shown that such space-times either (i) admit a covariantly constant vector (timelike, spacelike, or null) and the ACV is the sum of a proper affine vector and a conformal Killing vector or (ii) the space-time is 2+2 decomposable, in which case it is shown that no ACV can exist (unless the space-time decomposes further). Furthermore, it is proved that all space-times admitting an ACV and a null covariantly constant vector (which are necessarily generalized pp-wave space-times) must have Ricci tensor of Segré type {2,(1,1)}. It follows that, among space-times admitting proper ACV, the Einstein static universe is the only perfect fluid space-time, there are no non-null Einstein-Maxwell space-times, and only the pp-wave space-times are representative of null Einstein-Maxwell solutions. Otherwise, the space-times can represent anisotropic fluids and viscous heat-conducting fluids, but only with restricted equations of state in each case.

  13. Electron Affinity Calculations for Thioethers

    NASA Technical Reports Server (NTRS)

    Sulton, Deley L.; Boothe, Michael; Ball, David W.; Morales, Wilfredo

    1997-01-01

    Previous work indicated that polyphenyl thioethers possessed chemical properties, related to their electron affinities, which could allow them to function as vapor phase lubricants (VPL). Indeed, preliminary tribological tests revealed that the thioethers could function as vapor phase lubricants but not over a wide temperature and hertzian pressure range. Increasing the electron affinity of the thioethers may improve their VPL properties over this range. Adding a substituent group to the thioether will alter its electron affinity in many cases. Molecular orbital calculations were undertaken to determine the effect of five different substituent groups on the electron affinity of polyphenyl thioethers. It was found that the NO2, F, and I groups increased the thioethers electron affinity by the greatest amount. Future work will involve the addition of these groups to the thioethers followed by tribological testing to assess their VPL properties.

  14. On the Khinchin Constant

    NASA Technical Reports Server (NTRS)

    Bailey, David H.; Borwein, Jonathan M.; Crandall, Richard E.; Craw, James M. (Technical Monitor)

    1995-01-01

    We prove known identities for the Khinchin constant and develop new identities for the more general Hoelder mean limits of continued fractions. Any of these constants can be developed as a rapidly converging series involving values of the Riemann zeta function and rational coefficients. Such identities allow for efficient numerical evaluation of the relevant constants. We present free-parameter, optimizable versions of the identities, and report numerical results.

  15. The Influence of Organizational Culture on Affinity for Knowledge Management Practices of Registered Nurses

    ERIC Educational Resources Information Center

    Allen, Gregory

    2013-01-01

    This study addressed the problems of hospitals' duplicated effort and ad hoc knowledge management (KM) practices. The purpose of this quantitative study was to examine the focus and type of organizational culture in order to describe and predict the relationship between organizational culture and the affinity for KM of nurses working in health…

  16. Fundamental Physical Constants

    National Institute of Standards and Technology Data Gateway

    SRD 121 CODATA Fundamental Physical Constants (Web, free access)   This site, developed in the Physics Laboratory at NIST, addresses three topics: fundamental physical constants, the International System of Units (SI), which is the modern metric system, and expressing the uncertainty of measurement results.

  17. Plasma cortisol and testosterone following 19-km and 42-km kayak races.

    PubMed

    Lutoslawska, G; Obminski, Z; Krogulski, A; Sendecki, W

    1991-12-01

    Plasma cortisol and testosterone levels were examined in five, elite, male kayakers before and after 19-km and 42-km kayak races. Both races resulted in significant elevation in plasma cortisol and observed increase is likely to depend on race duration, being much more pronounced after 42-km race compared to 19-km. It should be stressed that observed elevation in cortisol level after 42-km race was higher than reported previously after a marathon run. This finding is in line with reports on hormonal changes in response to arms exercise. Both contests caused a decrease in plasma testosterone level, but the difference between races was not significant. Testosterone/cortisol ratio dropped significantly immediately after the races and the observed decrease was more dominant after the 42-km distance. On the next day, 18 h after the races plasma cortisol, testosterone levels and T/C ratio returned to basal level indicating recuperation from post exercise changes.

  18. Contractions of affine spherical varieties

    SciTech Connect

    Arzhantsev, I V

    1999-08-31

    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{sub 2}-varieties are considered.

  19. Affine generalization of the Komar complex of general relativity

    NASA Astrophysics Data System (ADS)

    Mielke, Eckehard W.

    2001-02-01

    On the basis of the ``on shell'' Noether identities of the metric-affine gauge approach of gravity, an affine superpotential is derived which comprises the energy- and angular-momentum content of exact solutions. In the special case of general relativity (GR) or its teleparallel equivalent, the Komar or Freud complex, respectively, are recovered. Applying this to the spontaneously broken anti-de Sitter gauge model of McDowell and Mansouri with an induced Euler term automatically yields the correct mass and spin of the Kerr-AdS solution of GR with a (induced) cosmological constant without the factor two discrepancy of the Komar formula.

  20. "Recognizing Numerical Constants"

    NASA Technical Reports Server (NTRS)

    Bailey, David H.; Craw, James M. (Technical Monitor)

    1995-01-01

    The advent of inexpensive, high performance computer and new efficient algorithms have made possible the automatic recognition of numerically computed constants. In other words, techniques now exist for determining, within certain limits, whether a computed real or complex number can be written as a simple expression involving the classical constants of mathematics. In this presentation, some of the recently discovered techniques for constant recognition, notably integer relation detection algorithms, will be presented. As an application of these methods, the author's recent work in recognizing "Euler sums" will be described in some detail.

  1. MODIS 3 km and 10 km aerosol optical depth for China: Evaluation and comparison

    NASA Astrophysics Data System (ADS)

    He, Qingqing; Zhang, Ming; Huang, Bo; Tong, Xuelian

    2017-03-01

    The recently released Moderate Resolution Imaging Spectrometer (MODIS) Collection 6 introduced a fine scale aerosol optical depth (AOD) distribution, the 3 km product, which is expected to perform well in analyzing aerosols and identifying local air pollution, especially in the severely polluted atmosphere of China. However, few detailed evaluations of regional variations have been conducted. In this paper, we evaluate MODIS 3 km and 10 km AOD products for China against ground-based measurements and compare their performance with respect to spatial and temporal variations. The ground validations indicate that the two products are generally correlated well to ground-based observations. Spatially, the 3 km product slightly outperform the 10 km product in well-developed areas of southern China. Temporally, both products perform worse during spring and summer. Atmospheric clouds and underlying surface are two key factors that influence the accuracy and number of retrievals for both products. The comparison analysis reveals the newly introduced AOD product clearly shows good relationships with the coarse resolution retrievals in spatial and temporal variation but significant differences regarding details. The 3 km AOD product provides better aerosol gradients, more retrievals in bare areas of western China and some spikes of diurnal variation in cloudy days. Seasonal comparisons show the 3 km AOD product is higher than the 10 km product in all seasons, especially during spring and summer. Although the 3 km product for China generally performs slightly worse than the 10 km product, the added information of the MODIS 3 km AOD product shows potential for studying local aerosol characterization, and may facilitate studies of air pollution.

  2. The estimation of 550 km x 550 km mean gravity anomalies. [from free atmosphere gravimetry data

    NASA Technical Reports Server (NTRS)

    Williamson, M. R.; Gaposchkin, E. M.

    1975-01-01

    The calculation of 550 km X 550 km mean gravity anomalies from 1 degree X 1 degree mean free-air gravimetry data is discussed. The block estimate procedure developed by Kaula was used, and estimates for 1452 of the 1654 blocks were obtained.

  3. The cosmological constant problem

    SciTech Connect

    Dolgov, A.D.

    1989-05-01

    A review of the cosmological term problem is presented. Baby universe model and the compensating field model are discussed. The importance of more accurate data on the Hubble constant and the Universe age is stressed. 18 refs.

  4. Science Is Constantly Cool.

    ERIC Educational Resources Information Center

    Eichinger, John

    1996-01-01

    Presents an activity in which students attempt to keep water at a constant temperature. Helps students in grades three to six hone their skills in prediction, observation, measurement, data collection, graphing, data analysis, and communication. (JRH)

  5. Km3Net Italy - Seafloor network

    NASA Astrophysics Data System (ADS)

    Papaleo, Riccardo

    2016-04-01

    The KM3NeT European project aims to construct a large volume underwater neutrino telescope in the depths of the Mediterranean Sea. INFN and KM3NeT collaboration, thanks to a dedicated funding of 21.000.000 € (PON 2007-2013), are committed to build and deploy the Phase 1 of the telescope, composed of a network of detection units: 8 towers, equipped with single photomultiplier optical modules, and 24 strings, equipped with multi-photomultipliers optical modules. All the towers and strings are connected to the main electro optical cable by means of a network of junction boxes and electro optical interlink cables. Each junction box is an active node able to provide all the necessary power to the detection units and to guarantee the data transmission between the detector and the on-shore control station. The KM3NeT Italia project foresees the realization and the installation of the first part of the deep sea network, composed of three junction boxes, one for the towers and two for the strings. In July 2015, two junction boxes have been deployed and connected to the new cable termination frame installed during the same sea campaign. The third and last one will be installed in November 2015. The status of the deep sea network is presented together with technical details of the project.

  6. Limits for antibody affinity maturation and repertoire diversification in hypervaccinated humans.

    PubMed

    Poulsen, Tine Rugh; Jensen, Allan; Haurum, John S; Andersen, Peter S

    2011-10-15

    The immune system is known to generate a diverse panel of high-affinity Abs by adaptively improving the recognition of pathogens during ongoing immune responses. In this study, we report the biological limits for Ag-driven affinity maturation and repertoire diversification by analyzing Ab repertoires in two adult volunteers after each of three consecutive booster vaccinations with tetanus toxoid. Maturation of on-rates and off-rates occurred independently, indicating a kinetically controlled affinity maturation process. The third vaccination induced no significant changes in the distribution of somatic mutations and binding rate constants implying that the limits for affinity maturation and repertoire diversification had been reached. These fully matured Ab repertoires remained similar in size, genetically diverse, and dynamic. Somatic mutations and kinetic rate constants showed normal and log-normal distribution profiles, respectively. Mean values can therefore be considered as biological constants defining the observed boundaries. At physiological temperature, affinity maturation peaked at k(on) = 1.6 × 10(4) M(-1) s(-1) and k(off) = 1.7 × 10(-4) s(-1) leading to a maximum mean affinity of K(D) = 1.0 × 10(-9) M. At ambient temperature, the average affinity increased to K(D) = 3.4 × 10(-10) M mainly due to slower off-rates. This experimentally determined set of constants can be used as a benchmark for analysis of the maturation level of human Abs and Ab responses.

  7. Dynamic friction of self-affine surfaces

    NASA Astrophysics Data System (ADS)

    Schmittbuhl, Jean; Vilotte, Jean-Pierre; Roux, Stéphane

    1994-02-01

    We investigate the velocity dependence of the friction between two rigid blocks limited by a self-affine surface such as the one generated by a crack. The upper solid is subjected either to gravity or to an external elastic stiffness, and is driven horizontally at constant velocity, V, while the lower solid is fixed. For low velocities, the apparent friction coefficient is constant. For high velocities, the apparent friction is shown to display a velocity weakening. The weakening can be related to the variation of the mean contact time due to the occurrence of jumps during the motions. The cross-over between these two regimes corresponds to a characteristic velocity which depends on the geometry of the surfaces and on the mean normal force. In the case of simple gravity loading, the velocity dependence of the apparent friction at high velocities is proportional to 1/V^2 where V is the imposed tangential velocity. In the case of external elastic stiffness, two velocity weakening regimes can be identified, the first is identical to the gravity case with a 1/V^2 dependence, the second appears at higher velocities and is characterized by a 1/V variation. The characteristic velocity of this second cross-over depends on the roughness and the elastic stiffness. The statistical distribution of ballistic flight distances is analysed, and is shown to reveal in all cases the self-affinity of the contacting surfaces. Nous analysons la dépendence en vitesse du frottement entre deux solides limités par une surface rugueuse auto-affine comme celle d'une surface de fracture. Le solide supérieur est soumis soit à la gravité, soit à une raideur élastique externe, et est entraîné à vitesse horizontale constante V sur le solide inférieur fixe. A faible vitesse, le coefficient de friction apparent, est constant. A forte vitesse, le coefficient de friction apparent devient inversement proportionnel à la vitesse. Cette dépendance peut être reliée à la variation du temps

  8. Dielectric Constant of Suspensions

    NASA Astrophysics Data System (ADS)

    Mendelson, Kenneth S.; Ackmann, James J.

    1997-03-01

    We have used a finite element method to calculate the dielectric constant of a cubic array of spheres. Extensive calculations support preliminary conclusions reported previously (K. Mendelson and J. Ackmann, Bull. Am. Phys. Soc. 41), 657 (1996).. At frequencies below 100 kHz the real part of the dielectric constant (ɛ') shows oscillations as a function of the volume fraction of suspension. These oscillations disappear at low conductivities of the suspending fluid. Measurements of the dielectric constant (J. Ackmann, et al., Ann. Biomed. Eng. 24), 58 (1996). (H. Fricke and H. Curtis, J. Phys. Chem. 41), 729 (1937). are not sufficiently sensitive to show oscillations but appear to be consistent with the theoretical results.

  9. Elastic constants of calcite

    USGS Publications Warehouse

    Peselnick, L.; Robie, R.A.

    1962-01-01

    The recent measurements of the elastic constants of calcite by Reddy and Subrahmanyam (1960) disagree with the values obtained independently by Voigt (1910) and Bhimasenachar (1945). The present authors, using an ultrasonic pulse technique at 3 Mc and 25??C, determined the elastic constants of calcite using the exact equations governing the wave velocities in the single crystal. The results are C11=13.7, C33=8.11, C44=3.50, C12=4.82, C13=5.68, and C14=-2.00, in units of 1011 dyncm2. Independent checks of several of the elastic constants were made employing other directions and polarizations of the wave velocities. With the exception of C13, these values substantially agree with the data of Voigt and Bhimasenachar. ?? 1962 The American Institute of Physics.

  10. Twisted light transmission over 143 km

    NASA Astrophysics Data System (ADS)

    Krenn, Mario; Handsteiner, Johannes; Fink, Matthias; Fickler, Robert; Ursin, Rupert; Malik, Mehul; Zeilinger, Anton

    2016-11-01

    Spatial modes of light can potentially carry a vast amount of information, making them promising candidates for both classical and quantum communication. However, the distribution of such modes over large distances remains difficult. Intermodal coupling complicates their use with common fibers, whereas free-space transmission is thought to be strongly influenced by atmospheric turbulence. Here, we show the transmission of orbital angular momentum modes of light over a distance of 143 km between two Canary Islands, which is 50× greater than the maximum distance achieved previously. As a demonstration of the transmission quality, we use superpositions of these modes to encode a short message. At the receiver, an artificial neural network is used for distinguishing between the different twisted light superpositions. The algorithm is able to identify different mode superpositions with an accuracy of more than 80% up to the third mode order and decode the transmitted message with an error rate of 8.33%. Using our data, we estimate that the distribution of orbital angular momentum entanglement over more than 100 km of free space is feasible. Moreover, the quality of our free-space link can be further improved by the use of state-of-the-art adaptive optics systems.

  11. 45-km horizontal path optical link demonstration

    NASA Astrophysics Data System (ADS)

    Biswas, Abhijit; Wright, Malcolm W.; Sanii, Babak; Page, Norman A.

    2001-06-01

    Observations made during a mountain-top-to-mountain-top horizontal optical link demonstration are described. The optical link spans a range of 46 Km at an average altitude of 2 Km above sea level. A multibeam beacon comprised of eight laser beams emerging from four multimode fiber coupled lasers (780 nm) is launched through a 0.6 m diameter telescope located at the JPL Table Mountain Facility (TMF) in Wrightwood, California. The multibeam beacon is received at Strawberry Peak located in the San Bernardino Mountains of California. The NASA, JPL developed optical communications demonstrator (OCD) receives the beacon, senses the atmospheric turbulence induced motion and using an upgraded fine steering loop actively points a communications laser beam (852 nm, 400 Mbps on-off key modulated, PN7 pseudo random bit sequence) to TMF. The eight-beam beacon allowed a four-fold reduction in normalized irradiance or scintillation index. This in turn was sufficient to eliminate beacon fades sensed by the OCD and enable performance evaluation of the fine steering loop. The residual tracking error was determined to be +/- 1.1 to +/- 1.7 (mu) rad compared to a model prediction of +/- 3.4 (mu) rad. The best link performance observed showed average bit error rates (BER) of 1E-5 over long durations (30 seconds); however, instantaneous BERs of at least 0.8E-6 over durations of 2 ms were observed. The paper also discusses results pertaining to atmospheric effects, link analysis, and overall performance.

  12. Twisted light transmission over 143 km.

    PubMed

    Krenn, Mario; Handsteiner, Johannes; Fink, Matthias; Fickler, Robert; Ursin, Rupert; Malik, Mehul; Zeilinger, Anton

    2016-11-29

    Spatial modes of light can potentially carry a vast amount of information, making them promising candidates for both classical and quantum communication. However, the distribution of such modes over large distances remains difficult. Intermodal coupling complicates their use with common fibers, whereas free-space transmission is thought to be strongly influenced by atmospheric turbulence. Here, we show the transmission of orbital angular momentum modes of light over a distance of 143 km between two Canary Islands, which is 50× greater than the maximum distance achieved previously. As a demonstration of the transmission quality, we use superpositions of these modes to encode a short message. At the receiver, an artificial neural network is used for distinguishing between the different twisted light superpositions. The algorithm is able to identify different mode superpositions with an accuracy of more than 80% up to the third mode order and decode the transmitted message with an error rate of 8.33%. Using our data, we estimate that the distribution of orbital angular momentum entanglement over more than 100 km of free space is feasible. Moreover, the quality of our free-space link can be further improved by the use of state-of-the-art adaptive optics systems.

  13. Chemical binding affinity estimation using MSB

    NASA Astrophysics Data System (ADS)

    Weaver, John B.; Rauwerdink, Adam M.

    2011-03-01

    Binding affinity can be estimated in several ways in the laboratory but there is no viable way to estimate binding affinity in vivo without assumptions on the number of binding sites. Magnetic spectroscopy of nanoparticle Brownian motion, MSB, measures the rotational Brownian motion. The MSB signal is affected by nanoparticle binding affinity so it provides a mechanism to measure the chemical binding affinity. We present a possible mechanism to quantify the binding affinity and test that mechanism using viscous solutions.

  14. Coenzyme-like ligands for affinity isolation of cholesterol oxidase.

    PubMed

    Xin, Yu; Lu, Liushen; Wang, Qing; Zhang, Ling; Tong, Yanjun; Wang, Wu

    2016-05-15

    Two coenzyme-like chemical ligands were designed and synthesized for affinity isolation of cholesterol oxidase (COD). To simulate the structure of natural coenzyme of COD (flavin adenine dinucleotide (FAD)), on Sepharose beads, 5-aminouracil, cyanuric chloride and 1, 4-butanediamine were composed and then modified. The COD gene from Brevibacterium sp. (DQ345780) was expressed in Escherichia coli BL21 (DE3), and then the sorbents were applied to adsorption analysis with the pure enzyme. Subsequently, the captured enzyme was applied to SDS-PAGE and activity analysis. As calculated, the theoretical maximum adsorption (Qmax) of the two affinity sorbents (RL-1 and RL-2) were ∼83.5 and 46.3mg/g wet gel; and the desorption constant Kd of the two sorbents were ∼6.02×10(-4) and 1.19×10(-4)μM. The proteins after cell lysis were applied to affinity isolation, and then after one step of affinity binding on the two sorbents, the protein recoveries of RL-1 and RL-2 were 9.2% and 9.7%; the bioactivity recoveries were 92.7% and 91.3%, respectively. SDS-PAGE analysis revealed that the purities of COD isolated with the two affinity sorbents were approximately 95%.

  15. Affine Contractions on the Plane

    ERIC Educational Resources Information Center

    Celik, D.; Ozdemir, Y.; Ureyen, M.

    2007-01-01

    Contractions play a considerable role in the theory of fractals. However, it is not easy to find contractions which are not similitudes. In this study, it is shown by counter examples that an affine transformation of the plane carrying a given triangle onto another triangle may not be a contraction even if it contracts edges, heights or medians.…

  16. Affinity-aware checkpoint restart

    SciTech Connect

    Saini, Ajay; Rezaei, Arash; Mueller, Frank; Hargrove, Paul; Roman, Eric

    2014-12-08

    Current checkpointing techniques employed to overcome faults for HPC applications result in inferior application performance after restart from a checkpoint for a number of applications. This is due to a lack of page and core affinity awareness of the checkpoint/restart (C/R) mechanism, i.e., application tasks originally pinned to cores may be restarted on different cores, and in case of non-uniform memory architectures (NUMA), quite common today, memory pages associated with tasks on a NUMA node may be associated with a different NUMA node after restart. Here, this work contributes a novel design technique for C/R mechanisms to preserve task-to-core maps and NUMA node specific page affinities across restarts. Experimental results with BLCR, a C/R mechanism, enhanced with affinity awareness demonstrate significant performance benefits of 37%-73% for the NAS Parallel Benchmark codes and 6-12% for NAMD with negligible overheads instead of up to nearly four times longer an execution times without affinity-aware restarts on 16 cores.

  17. Affinity-aware checkpoint restart

    DOE PAGES

    Saini, Ajay; Rezaei, Arash; Mueller, Frank; ...

    2014-12-08

    Current checkpointing techniques employed to overcome faults for HPC applications result in inferior application performance after restart from a checkpoint for a number of applications. This is due to a lack of page and core affinity awareness of the checkpoint/restart (C/R) mechanism, i.e., application tasks originally pinned to cores may be restarted on different cores, and in case of non-uniform memory architectures (NUMA), quite common today, memory pages associated with tasks on a NUMA node may be associated with a different NUMA node after restart. Here, this work contributes a novel design technique for C/R mechanisms to preserve task-to-core mapsmore » and NUMA node specific page affinities across restarts. Experimental results with BLCR, a C/R mechanism, enhanced with affinity awareness demonstrate significant performance benefits of 37%-73% for the NAS Parallel Benchmark codes and 6-12% for NAMD with negligible overheads instead of up to nearly four times longer an execution times without affinity-aware restarts on 16 cores.« less

  18. ELECTRON AFFINITIES OF INORGANIC RADICALS.

    DTIC Science & Technology

    energy in the latter compound is 110 kcals/mole, distinctly higher than in ammonia. Cyanogen (CN)2 and hydrocyanic acid (HCN) yield values for the...ions very readily, and the electron affinity is 49 kcals/mole. A comparison with the results from thiocyanic acid (HNCS) indicates that the H-N bond

  19. Predicting km-scale shear zone formation

    NASA Astrophysics Data System (ADS)

    Gerbi, Christopher; Culshaw, Nicholas; Shulman, Deborah; Foley, Maura; Marsh, Jeffrey

    2015-04-01

    Because km-scale shear zones play a first-order role in lithospheric kinematics, accurate conceptual and numerical models of orogenic development require predicting when and where they form. Although a strain-based algorithm in the upper crust for weakening due to faulting appears to succeed (e.g., Koons et al., 2010, doi:10.1029/2009TC002463), a comparable general rule for the viscous crust remains unestablished. Here we consider two aspects of the geological argument for a similar algorithm in the viscous regime, namely (1) whether predicting km-scale shear zone development based on a single parameter (such as strain or shear heating) is reasonable; and (2) whether lithologic variability inherent in most orogenic systems precludes a simple predictive rule. A review of tectonically significant shear zones worldwide and more detailed investigations in the Central Gneiss belt of the Ontario segment of the Grenville Province reveals that most km-scale shear zones occur at lithological boundaries and involve mass transfer, but have fairly little else in common. As examples, the relatively flat-lying Twelve Mile Bay shear zone in the western Central Gneiss belt bounds the Parry Sound domain and is likely the product of both localized anatexis and later retrograde hydration with attendant metamorphism. Moderately dipping shear zones in granitoids of the Grenville Front Tectonic Zone apparently resulted from cooperation among several complementary microstructural processes, such as grain size reduction, enhanced diffusion, and a small degree of metamorphic reaction. Localization into shear zones requires the operation of some spatially restricted processes such as stress concentration, metamorphism/fluid access, textural evolution, and thermal perturbation. All of these could be due in part to strain, but not necessarily linearly related to strain. Stress concentrations, such as those that form at rheological boundaries, may be sufficient to nucleate high strain

  20. Redshift in Hubble's constant.

    NASA Astrophysics Data System (ADS)

    Temple-Raston, M.

    1997-01-01

    A topological field theory with Bogomol'nyi solitons is examined. The Bogomol'nyi solitons have much in common with the instanton in Yang-Mills theory; consequently the author called them 'topological instantons'. When periodic boundary conditions are imposed, the field theory comments indirectly on the speed of light within the theory. In this particular model the speed of light is not a universal constant. This may or may not be relevant to the current debate in astronomy and cosmology over the large values of the Hubble constant obtained by the latest generation of ground- and space-based telescopes. An experiment is proposed to detect spatial variation in the speed of light.

  1. Wall of fundamental constants

    SciTech Connect

    Olive, Keith A.; Peloso, Marco; Uzan, Jean-Philippe

    2011-02-15

    We consider the signatures of a domain wall produced in the spontaneous symmetry breaking involving a dilatonlike scalar field coupled to electromagnetism. Domains on either side of the wall exhibit slight differences in their respective values of the fine-structure constant, {alpha}. If such a wall is present within our Hubble volume, absorption spectra at large redshifts may or may not provide a variation in {alpha} relative to the terrestrial value, depending on our relative position with respect to the wall. This wall could resolve the contradiction between claims of a variation of {alpha} based on Keck/Hires data and of the constancy of {alpha} based on Very Large Telescope data. We derive the properties of the wall and the parameters of the underlying microscopic model required to reproduce the possible spatial variation of {alpha}. We discuss the constraints on the existence of the low-energy domain wall and describe its observational implications concerning the variation of the fundamental constants.

  2. Percolation with Constant Freezing

    NASA Astrophysics Data System (ADS)

    Mottram, Edward

    2014-06-01

    We introduce and study a model of percolation with constant freezing ( PCF) where edges open at constant rate , and clusters freeze at rate independently of their size. Our main result is that the infinite volume process can be constructed on any amenable vertex transitive graph. This is in sharp contrast to models of percolation with freezing previously introduced, where the limit is known not to exist. Our interest is in the study of the percolative properties of the final configuration as a function of . We also obtain more precise results in the case of trees. Surprisingly the algebraic exponent for the cluster size depends on the degree, suggesting that there is no lower critical dimension for the model. Moreover, even for , it is shown that finite clusters have algebraic tail decay, which is a signature of self organised criticality. Partial results are obtained on , and many open questions are discussed.

  3. Theoretical proton affinity and fluoride affinity of nerve agent VX.

    PubMed

    Bera, Narayan C; Maeda, Satoshi; Morokuma, Keiji; Viggiano, Al A

    2010-12-23

    Proton affinity and fluoride affinity of nerve agent VX at all of its possible sites were calculated at the RI-MP2/cc-pVTZ//B3LYP/6-31G* and RI-MP2/aug-cc-pVTZ//B3LYP/6-31+G* levels, respectively. The protonation leads to various unique structures, with H(+) attached to oxygen, nitrogen, and sulfur atoms; among which the nitrogen site possesses the highest proton affinity of -ΔE ∼ 251 kcal/mol, suggesting that this is likely to be the major product. In addition some H(2), CH(4) dissociation as well as destruction channels have been found, among which the CH(4) + [Et-O-P(═O)(Me)-S-(CH(2))(2)-N(+)(iPr)═CHMe] product and the destruction product forming Et-O-P(═O)(Me)-SMe + CH(2)═N(+)(iPr)(2) are only 9 kcal/mol less stable than the most stable N-protonated product. For fluoridization, the S-P destruction channel to give Et-O-P(═O)(Me)(F) + [S-(CH(2))(2)-N-(iPr)(2)](-) is energetically the most favorable, with a fluoride affinity of -ΔE ∼ 44 kcal. Various F(-) ion-molecule complexes are also found, with the one having F(-) interacting with two hydrogen atoms in different alkyl groups to be only 9 kcal/mol higher than the above destruction product. These results suggest VX behaves quite differently from surrogate systems.

  4. Constant-pressure Blowers

    NASA Technical Reports Server (NTRS)

    Sorensen, E

    1940-01-01

    The conventional axial blowers operate on the high-pressure principle. One drawback of this type of blower is the relatively low pressure head, which one attempts to overcome with axial blowers producing very high pressure at a given circumferential speed. The Schicht constant-pressure blower affords pressure ratios considerably higher than those of axial blowers of conventional design with approximately the same efficiency.

  5. Universe of constant

    NASA Astrophysics Data System (ADS)

    Yongquan, Han

    2016-10-01

    The ideal gas state equation is not applicable to ordinary gas, it should be applied to the Electromagnetic ``gas'' that is applied to the radiation, the radiation should be the ultimate state of matter changes or initial state, the universe is filled with radiation. That is, the ideal gas equation of state is suitable for the Singular point and the universe. Maybe someone consider that, there is no vessel can accommodate radiation, it is because the Ordinary container is too small to accommodate, if the radius of your container is the distance that Light through an hour, would you still think it can't accommodates radiation? Modern scientific determinate that the radius of the universe now is about 1027 m, assuming that the universe is a sphere whose volume is approximately: V = 4.19 × 1081 cubic meters, the temperature radiation of the universe (cosmic microwave background radiation temperature of the universe, should be the closest the average temperature of the universe) T = 3.15k, radiation pressure P = 5 × 10-6 N / m 2, according to the law of ideal gas state equation, PV / T = constant = 6 × 1075, the value of this constant is the universe, The singular point should also equal to the constant Author: hanyongquan

  6. 45 Km Horizontal Path Optical Link Experiment

    NASA Technical Reports Server (NTRS)

    Biswas, A.; Ceniceros, J.; Novak, M.; Jeganathan, M.; Portillo, A.; Erickson, D.; Depew, J.; Sanii, B.; Lesh, J. R.

    2000-01-01

    Mountain-top to mountain-top optical link experiments have been initiated at JPL, in order to perform a systems level evaluation of optical communications. Progress made so far is reported. ne NASA, JPL developed optical communications demonstrator (OCD) is used to transmit a laser signal from Strawberry Peak (SP), located in the San Bernadino mountains of California. This laser beam is received by a 0.6 m aperture telescope at JPL's Table Mountain Facility (TMF), located in Wrightwood, California. The optical link is bi-directional with the TMF telescope transmitting a continuous 4-wave (cw) 780 run beacon and the OCD sending back a 840 nm, 100 - 500 Mbps pseudo noise (PN) modulated, laser beam. The optical link path is at an average altitude of 2 km above sea level, covers a range of 46.8 km and provides an atmospheric channel equivalent to approx. 4 air masses. Average received power measured at either end fall well within the uncertainties predicted by link analysis. The reduction in normalized intensity variance (sigma(sup 2, sub I)) for the 4-beam beacon, compared to each individual beam, at SP, was from approx. 0.68 to 0.22. With some allowance for intra-beam mis-alignment, this is consistent with incoherent averaging. The sigma(sup2, sub I) measured at TMF approx. 0.43 +/- 0.22 exceeded the expected aperture averaged value of less than 0.1, probably because of beam wander. The focused spot sizes of approx. 162 +/- 6 microns at the TMF Coude and approx. 64 +/- 3 microns on the OCD compare to the predicted size range of 52 - 172 microns and 57 - 93 microns, respectively. This is consistent with 4 - 5 arcsec of atmospheric "seeing". The preliminary evaluation of OCD's fine tracking indicates that the uncompensated tracking error is approx. 3.3 micro rad compared to approx. 1.7 micro rad observed in the laboratory. Fine tracking performance was intermittent, primarily due to beacon fades on the OCD tracking sensor. The best bit error rates observed while

  7. Teleportation of entanglement over 143 km.

    PubMed

    Herbst, Thomas; Scheidl, Thomas; Fink, Matthias; Handsteiner, Johannes; Wittmann, Bernhard; Ursin, Rupert; Zeilinger, Anton

    2015-11-17

    As a direct consequence of the no-cloning theorem, the deterministic amplification as in classical communication is impossible for unknown quantum states. This calls for more advanced techniques in a future global quantum network, e.g., for cloud quantum computing. A unique solution is the teleportation of an entangled state, i.e., entanglement swapping, representing the central resource to relay entanglement between distant nodes. Together with entanglement purification and a quantum memory it constitutes a so-called quantum repeater. Since the aforementioned building blocks have been individually demonstrated in laboratory setups only, the applicability of the required technology in real-world scenarios remained to be proven. Here we present a free-space entanglement-swapping experiment between the Canary Islands of La Palma and Tenerife, verifying the presence of quantum entanglement between two previously independent photons separated by 143 km. We obtained an expectation value for the entanglement-witness operator, more than 6 SDs beyond the classical limit. By consecutive generation of the two required photon pairs and space-like separation of the relevant measurement events, we also showed the feasibility of the swapping protocol in a long-distance scenario, where the independence of the nodes is highly demanded. Because our results already allow for efficient implementation of entanglement purification, we anticipate our research to lay the ground for a fully fledged quantum repeater over a realistic high-loss and even turbulent quantum channel.

  8. Frequency-constant Q, unity and disorder

    SciTech Connect

    Hargreaves, N.D.

    1995-12-31

    In exploration geophysics we obtain information about the earth by observing its response to different types of applied force. The response can cover the full range of possible Q values (where Q, the quality factor, is a measure of energy dissipation), from close to infinity in the case of deep crustal seismic to close to 0 in the case of many electromagnetic methods. When Q is frequency-constant, however, the various types of response have a common scaling behavior and can be described as being self-affine. The wave-equation then takes on a generalised form, changing from the standard wave-equation at Q = {infinity} to the diffusion equation at Q = 0, via lossy, diffusive, propagation at intermediate Q values. Solutions of this wave-diffusion equation at any particular Q value can be converted to an equivalent set of results for any other Q value. In particular it is possible to convert from diffusive to wave propagation by a mapping from Q < {infinity} to Q = {infinity}. In the context of seismic sounding this is equivalent to applying inverse Q-filtering; in a more general context the mapping integrates different geophysical observations by referencing them to the common result at Q = {infinity}. The self-affinity of the observations for frequency-constant Q is an expression of scale invariance in the fundamental physical properties of the medium of propagation, this being the case whether the mechanism of diffusive propagation is scattering of intrinsic attenuation. Scale invariance, or fractal scaling, is a general property of disordered systems; the assumption of frequency-constant Q not only implies a unity between different geophysical observations, but also suggests that it is the disordered nature of the earth`s sub-surface that is the unifying factor.

  9. Measurement by SPR of very low dissociation rates: oxidation-mediated loss of biotin-streptavidin affinity.

    PubMed

    Rebhan, Mario A E; Brunschweiger, Andreas; Hall, Jonathan

    2013-11-04

    Long-term relationship: biotin labels on RNAs, and possibly other biomacromolecules, are easily oxidized causing a dramatic loss of affinity for streptavidin and adversely affecting the measurement of high-affinity interactions. A new SPR method has been developed for measuring the very low rate-dissociation constants of biotin- and biotin oxide-conjugated RNAs with streptavidin.

  10. The Hubble Constant

    NASA Astrophysics Data System (ADS)

    Freedman, Wendy; Madore, Barry; Mager, Violet; Persson, Eric; Rigby, Jane; Sturch, Laura

    2008-12-01

    We present a plan to measure a value of the Hubble constant having a final systematic uncertainty of only 3% by taking advantage of Spitzer's unique mid-infrared capabilities. This involves using IRAC to undertake a fundamental recalibration of the Cepheid distance scale and progressively moving it out to pure Hubble flow by an application of a revised mid-IR Tully-Fisher relation. The calibration and application, in one coherent and self-consistent program, will go continuously from distances of parsecs to several hundred megaparsecs. It will provide a first-ever mid-IR calibration of Cepheids in the Milky Way, LMC and Key Project spiral galaxies and a first-ever measurement and calibration of the TF relation at mid-infrared wavelengths, and finally a calibration of Type Ia SNe. Most importantly this program will be undertaken with a single instrument, on a single telescope, working exclusively at mid-infrared wavelengths that are far removed from the obscuring effects of dust extinction. Using Spitzer in this focused way will effectively eliminate all of the major systematics in the Cepheid and TF distance scales that have been the limiting factors in all previous applications, including the HST Key Project. By executing this program, based exclusively on Spitzer data, we will deliver a value of the Hubble constant, having a statistical precision better than 11%, with all currently known systematics quantified and constrained to a level of less than 3%. A value of Ho determined to this level of systematic accuracy is required for up-coming cosmology experiments, including Planck. A more accurate value of the Hubble constant will directly result in other contingently measured cosmological parameters (e.g., Omega_m, Omega_L, & w) having their covariant uncertainties reduced significantly now. Any further improvements using this route will have to await JWST, for which this study is designed to provide a lasting and solid foundation, and ultimately a value of Ho

  11. Change is a Constant.

    PubMed

    Lubowitz, James H; Provencher, Matthew T; Brand, Jefferson C; Rossi, Michael J; Poehling, Gary G

    2015-06-01

    In 2015, Henry P. Hackett, Managing Editor, Arthroscopy, retires, and Edward A. Goss, Executive Director, Arthroscopy Association of North America (AANA), retires. Association is a positive constant, in a time of change. With change comes a need for continuing education, research, and sharing of ideas. While the quality of education at AANA and ISAKOS is superior and most relevant, the unique reason to travel and meet is the opportunity to interact with innovative colleagues. Personal interaction best stimulates new ideas to improve patient care, research, and teaching. Through our network, we best create innovation.

  12. Cosmology with varying constants.

    PubMed

    Martins, Carlos J A P

    2002-12-15

    The idea of possible time or space variations of the 'fundamental' constants of nature, although not new, is only now beginning to be actively considered by large numbers of researchers in the particle physics, cosmology and astrophysics communities. This revival is mostly due to the claims of possible detection of such variations, in various different contexts and by several groups. I present the current theoretical motivations and expectations for such variations, review the current observational status and discuss the impact of a possible confirmation of these results in our views of cosmology and physics as a whole.

  13. Peregrine 100-km Sounding Rocket Project

    NASA Technical Reports Server (NTRS)

    Zilliac, Gregory

    2012-01-01

    The Peregrine Sounding Rocket Program is a joint basic research program of NASA Ames Research Center, NASA Wallops, Stanford University, and the Space Propulsion Group, Inc. (SPG). The goal is to determine the applicability of this technology to a small launch system. The approach is to design, build, and fly a stable, efficient liquefying fuel hybrid rocket vehicle to an altitude of 100 km. The program was kicked off in October of 2006 and has seen considerable progress in the subsequent 18 months. This research group began studying liquifying hybrid rocket fuel technology more than a decade ago. The overall goal of the research was to gain a better understanding of the fundamental physics of the liquid layer entrainment process responsible for the large increase in regression rate observed in these fuels, and to demonstrate the effect of increased regression rate on hybrid rocket motor performance. At the time of this reporting, more than 400 motor tests were conducted with a variety of oxidizers (N2O, GOx, LOx) at ever increasing scales with thrust levels from 5 to over 15,000 pounds (22 N to over 66 kN) in order to move this technology from the laboratory to practical applications. The Peregrine program is the natural next step in this development. A number of small sounding rockets with diameters of 3, 4, and 6 in. (7.6, 10.2, and 15.2 cm) have been flown, but Peregrine at a diameter of 15 in. (38.1 cm) and 14,000-lb (62.3-kN) thrust is by far the largest system ever attempted and will be one of the largest hybrids ever flown. Successful Peregrine flights will set the stage for a wide range of applications of this technology.

  14. Identification and characterization of a novel high affinity metal-binding site in the hammerhead ribozyme.

    PubMed Central

    Hansen, M R; Simorre, J P; Hanson, P; Mokler, V; Bellon, L; Beigelman, L; Pardi, A

    1999-01-01

    A novel metal-binding site has been identified in the hammerhead ribozyme by 31P NMR. The metal-binding site is associated with the A13 phosphate in the catalytic core of the hammerhead ribozyme and is distinct from any previously identified metal-binding sites. 31P NMR spectroscopy was used to measure the metal-binding affinity for this site and leads to an apparent dissociation constant of 250-570 microM at 25 degrees C for binding of a single Mg2+ ion. The NMR data also show evidence of a structural change at this site upon metal binding and these results are compared with previous data on metal-induced structural changes in the core of the hammerhead ribozyme. These NMR data were combined with the X-ray structure of the hammerhead ribozyme (Pley HW, Flaherty KM, McKay DB. 1994. Nature 372:68-74) to model RNA ligands involved in binding the metal at this A13 site. In this model, the A13 metal-binding site is structurally similar to the previously identified A(g) metal-binding site and illustrates the symmetrical nature of the tandem G x A base pairs in domain 2 of the hammerhead ribozyme. These results demonstrate that 31P NMR represents an important method for both identification and characterization of metal-binding sites in nucleic acids. PMID:10445883

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

    SciTech Connect

    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.

  16. Unitaxial constant velocity microactuator

    DOEpatents

    McIntyre, Timothy J.

    1994-01-01

    A uniaxial drive system or microactuator capable of operating in an ultra-high vacuum environment. The mechanism includes a flexible coupling having a bore therethrough, and two clamp/pusher assemblies mounted in axial ends of the coupling. The clamp/pusher assemblies are energized by voltage-operated piezoelectrics therewithin to operatively engage the shaft and coupling causing the shaft to move along its rotational axis through the bore. The microactuator is capable of repeatably positioning to sub-manometer accuracy while affording a scan range in excess of 5 centimeters. Moreover, the microactuator generates smooth, constant velocity motion profiles while producing a drive thrust of greater than 10 pounds. The system is remotely controlled and piezoelectrically driven, hence minimal thermal loading, vibrational excitation, or outgassing is introduced to the operating environment.

  17. A Constant Pressure Bomb

    NASA Technical Reports Server (NTRS)

    Stevens, F W

    1924-01-01

    This report describes a new optical method of unusual simplicity and of good accuracy suitable to study the kinetics of gaseous reactions. The device is the complement of the spherical bomb of constant volume, and extends the applicability of the relationship, pv=rt for gaseous equilibrium conditions, to the use of both factors p and v. The method substitutes for the mechanical complications of a manometer placed at some distance from the seat of reaction the possibility of allowing the radiant effects of reaction to record themselves directly upon a sensitive film. It is possible the device may be of use in the study of the photoelectric effects of radiation. The method makes possible a greater precision in the measurement of normal flame velocities than was previously possible. An approximate analysis shows that the increase of pressure and density ahead of the flame is negligible until the velocity of the flame approaches that of sound.

  18. When constants are important

    SciTech Connect

    Beiu, V.

    1997-04-01

    In this paper the authors discuss several complexity aspects pertaining to neural networks, commonly known as the curse of dimensionality. The focus will be on: (1) size complexity and depth-size tradeoffs; (2) complexity of learning; and (3) precision and limited interconnectivity. Results have been obtained for each of these problems when dealt with separately, but few things are known as to the links among them. They start by presenting known results and try to establish connections between them. These show that they are facing very difficult problems--exponential growth in either space (i.e. precision and size) and/or time (i.e., learning and depth)--when resorting to neural networks for solving general problems. The paper will present a solution for lowering some constants, by playing on the depth-size tradeoff.

  19. Unitaxial constant velocity microactuator

    DOEpatents

    McIntyre, T.J.

    1994-06-07

    A uniaxial drive system or microactuator capable of operating in an ultra-high vacuum environment is disclosed. The mechanism includes a flexible coupling having a bore therethrough, and two clamp/pusher assemblies mounted in axial ends of the coupling. The clamp/pusher assemblies are energized by voltage-operated piezoelectrics therewithin to operatively engage the shaft and coupling causing the shaft to move along its rotational axis through the bore. The microactuator is capable of repeatably positioning to sub-nanometer accuracy while affording a scan range in excess of 5 centimeters. Moreover, the microactuator generates smooth, constant velocity motion profiles while producing a drive thrust of greater than 10 pounds. The system is remotely controlled and piezoelectrically driven, hence minimal thermal loading, vibrational excitation, or outgassing is introduced to the operating environment. 10 figs.

  20. KM3NeT: towards a km 3-scale neutrino telescope in the Mediterranean Sea

    NASA Astrophysics Data System (ADS)

    Distefano, C.; KM3NeT Consortium

    2009-05-01

    The observation of high energy neutrinos ( ≳1 TeV) from astrophysical sources would substantially improve our knowledge and understanding of the non-thermal processes in these sources, and would in particular pinpoint the accelerators of cosmic rays. Theoretical predictions indicate that km 3-scale detectors are needed to detect astrophysical neutrino fluxes. That is the reason why the three Mediterranean experiments, ANTARES, NEMO and NESTOR are working together on preparing KM3NeT, a large deep-sea neutrino telescope in the Mediterranean Sea which will survey a large part of the Galactic disc, including the Galactic Centre. It will complement the IceCube telescope currently under construction at the South Pole. Furthermore, the improved optical properties of sea water, compared to Antarctic ice, will allow for a better angular resolution and hence a better background rejection. The construction of this detector will require the solution of technological problems common to many deep submarine installations, and will help paving the way for other deep-sea research facilities. In this paper the major activities and the status of KM3NeT are presented.

  1. KM3NeT: towards a km3-scale neutrino telescope in the Mediterranean Sea

    NASA Astrophysics Data System (ADS)

    Km3NeT Consortium; Distefano, C.; KM3NeT Consortium

    2009-05-01

    The observation of high energy neutrinos (≳1 TeV) from astrophysical sources would substantially improve our knowledge and understanding of the non-thermal processes in these sources, and would in particular pinpoint the accelerators of cosmic rays. Theoretical predictions indicate that km3-scale detectors are needed to detect astrophysical neutrino fluxes. That is the reason why the three Mediterranean experiments, ANTARES, NEMO and NESTOR are working together on preparing KM3NeT, a large deep-sea neutrino telescope in the Mediterranean Sea which will survey a large part of the Galactic disc, including the Galactic Centre. It will complement the IceCube telescope currently under construction at the South Pole. Furthermore, the improved optical properties of sea water, compared to Antarctic ice, will allow for a better angular resolution and hence a better background rejection. The construction of this detector will require the solution of technological problems common to many deep submarine installations, and will help paving the way for other deep-sea research facilities. In this paper the major activities and the status of KM3NeT are presented.

  2. 10 km running performance predicted by a multiple linear regression model with allometrically adjusted variables

    PubMed Central

    Abad, Cesar C. C.; Barros, Ronaldo V.; Bertuzzi, Romulo; Gagliardi, João F. L.; Lima-Silva, Adriano E.; Lambert, Mike I.

    2016-01-01

    Abstract The aim of this study was to verify the power of VO2max, peak treadmill running velocity (PTV), and running economy (RE), unadjusted or allometrically adjusted, in predicting 10 km running performance. Eighteen male endurance runners performed: 1) an incremental test to exhaustion to determine VO2max and PTV; 2) a constant submaximal run at 12 km·h−1 on an outdoor track for RE determination; and 3) a 10 km running race. Unadjusted (VO2max, PTV and RE) and adjusted variables (VO2max0.72, PTV0.72 and RE0.60) were investigated through independent multiple regression models to predict 10 km running race time. There were no significant correlations between 10 km running time and either the adjusted or unadjusted VO2max. Significant correlations (p < 0.01) were found between 10 km running time and adjusted and unadjusted RE and PTV, providing models with effect size > 0.84 and power > 0.88. The allometrically adjusted predictive model was composed of PTV0.72 and RE0.60 and explained 83% of the variance in 10 km running time with a standard error of the estimate (SEE) of 1.5 min. The unadjusted model composed of a single PVT accounted for 72% of the variance in 10 km running time (SEE of 1.9 min). Both regression models provided powerful estimates of 10 km running time; however, the unadjusted PTV may provide an uncomplicated estimation. PMID:28149382

  3. Complex high affinity interactions occur between MHCI and superantigens

    NASA Technical Reports Server (NTRS)

    Chapes, S. K.; Herpich, A. R.; Spooner, B. S. (Principal Investigator)

    1998-01-01

    Staphylococcal enterotoxins A and C1 (SEA or SEC1) bound to major histocompatibility-I (MHCI) molecules with high affinity (binding constants ranging from 1.1 microM to 79 nM). SEA and SEC1 directly bound MHCI molecules that had been captured by monoclonal antibodies specific for H-2Kk, H-2Dk, or both. In addition, MHCI-specific antibodies inhibited the binding of SEC1 to LM929 cells and SEA competitively inhibited SEC1 binding; indicating that the superantigens bound to MHCI on the cell surface. The affinity and number of superantigen binding sites differed depending on whether MHCI was expressed in the membrane of LM929 cells or whether it was captured. These data support the hypothesis that MHCI molecules can serve as superantigen receptors.

  4. Polysulfone affinity membranes for the treatment of amino acid mixtures.

    PubMed

    Rodemann, K; Staude, E

    1995-06-20

    Affinity membranes for the treatment of solutions containing amino acids were obtained via lithiating polysulfone that was subsequently converted with glycidylether. From this polymer asymmetric ultrafiltration membranes were cast. The membranes were reacted with iminodiacetic acid yielding membranes fitted out with bidentate chelates. The same reaction path was applied to commercially available symmetric microfiltration membranes. The chelate-bearing membranes were complexed with Cu, Ni, and Zn ions. For the experiments with amino acids only the Cu-complexed membranes were used. The complexation constants for histidine and tryptophan for six different membranes were determined. Because of the affinity of these two amino acids for the complexed Cu ions, they could easily be separated from solutions containing amino acids such as alanine, glycine, and valine. Also, concentrating very dilute amino acid solutions was carried out successfully.

  5. Electron attachment and detachment: Electron affinities of isomers of trifluoromethylbenzonitrile

    NASA Astrophysics Data System (ADS)

    Miller, Thomas M.; Viggiano, A. A.; Friedman, Jeffrey F.; Van Doren, Jane M.

    2004-11-01

    Rate constants for electron attachment to the three isomers of trifluoromethylbenzonitrile [(CF3)(CN)C6H4, or TFMBN] were measured over the temperature range of 303-463 K in a 133-Pa He buffer gas, using a flowing-afterglow Langmuir-probe apparatus. At 303 K, the measured attachment rate constants are 9.0×10-8 (o-TFMBN), 5.5×10-8 (m-TFMBN), and 8.9×10-8 cm3 s-1 (p-TFMBN), estimated accurate to ±25%. The attachment process formed only the parent anion in all three cases. Thermal electron detachment was observed for all three anion isomers, and rate constants for this reverse process were also measured. From the attachment and detachment results, the electron affinities of the three isomers of TFMBN were determined to be 0.70(o-TFMBN), 0.67(m-TFMBN), and 0.83 eV (p-TFMBN), all ±0.05 eV. G3(MP2) [Gaussian-3 calculations with reduced Møller-Plesset orders (MP2)] calculations were carried out for the neutrals and anions. Electron affinities derived from these calculations are in good agreement with the experimental values.

  6. Electron attachment and detachment: electron affinities of isomers of trifluoromethylbenzonitrile.

    PubMed

    Miller, Thomas M; Viggiano, A A; Friedman, Jeffrey F; Van Doren, Jane M

    2004-11-22

    Rate constants for electron attachment to the three isomers of trifluoromethylbenzonitrile [(CF(3))(CN)C(6)H(4), or TFMBN] were measured over the temperature range of 303-463 K in a 133-Pa He buffer gas, using a flowing-afterglow Langmuir-probe apparatus. At 303 K, the measured attachment rate constants are 9.0 x 10(-8) (o-TFMBN), 5.5 x 10(-8) (m-TFMBN), and 8.9 x 10(-8) cm(3) s(-1) (p-TFMBN), estimated accurate to +/-25%. The attachment process formed only the parent anion in all three cases. Thermal electron detachment was observed for all three anion isomers, and rate constants for this reverse process were also measured. From the attachment and detachment results, the electron affinities of the three isomers of TFMBN were determined to be 0.70(o-TFMBN), 0.67(m-TFMBN), and 0.83 eV (p-TFMBN), all +/-0.05 eV. G3(MP2) [Gaussian-3 calculations with reduced Møller-Plesset orders (MP2)] calculations were carried out for the neutrals and anions. Electron affinities derived from these calculations are in good agreement with the experimental values.

  7. Higher Nucleoporin-Importinβ Affinity at the Nuclear Basket Increases Nucleocytoplasmic Import

    PubMed Central

    Azimi, Mohammad; Mofrad, Mohammad R. K.

    2013-01-01

    Several in vitro studies have shown the presence of an affinity gradient in nuclear pore complex proteins for the import receptor Importinβ, at least partially contributing to nucleocytoplasmic transport, while others have historically argued against the presence of such a gradient. Nonetheless, the existence of an affinity gradient has remained an uncharacterized contributing factor. To shed light on the affinity gradient theory and better characterize how the existence of such an affinity gradient between the nuclear pore and the import receptor may influence the nucleocytoplasmic traffic, we have developed a general-purpose agent based modeling (ABM) framework that features a new method for relating rate constants to molecular binding and unbinding probabilities, and used our ABM approach to quantify the effects of a wide range of forward and reverse nucleoporin-Importinβ affinity gradients. Our results indicate that transport through the nuclear pore complex is maximized with an effective macroscopic affinity gradient of 2000 µM, 200 µM and 10 µM in the cytoplasmic, central channel and nuclear basket respectively. The transport rate at this gradient is approximately 10% higher than the transport rate for a comparable pore lacking any affinity gradient, which has a peak transport rate when all nucleoporins have an affinity of 200 µM for Importinβ. Furthermore, this optimal ratio of affinity gradients is representative of the ratio of affinities reported for the yeast nuclear pore complex – suggesting that the affinity gradient seen in vitro is highly optimized. PMID:24282617

  8. Differential Mobility Spectrometry: Preliminary Findings on Determination of Fundamental Constants

    NASA Technical Reports Server (NTRS)

    Limero, Thomas; Cheng, Patti; Boyd, John

    2007-01-01

    The electron capture detector (ECD) has been used for 40+ years (1) to derive fundamental constants such as a compound's electron affinity. Given this historical perspective, it is not surprising that differential mobility spectrometry (DMS) might be used in a like manner. This paper will present data from a gas chromatography (GC)-DMS instrument that illustrates the potential capability of this device to derive fundamental constants for electron-capturing compounds. Potential energy curves will be used to provide possible explanation of the data.

  9. MODIS 3km Aerosol Product: Algorithm and Global Perspective

    NASA Technical Reports Server (NTRS)

    Remer, L. A.; Mattoo, S.; Levy, R. C.; Munchak, L.

    2013-01-01

    After more than a decade of producing a nominal 10 km aerosol product based on the dark target method, the MODIS aerosol team will be releasing a nominal 3 km product as part of their Collection 6 release. The new product differs from the original 10 km product only in the manner in which reflectance pixels are ingested, organized and selected by the aerosol algorithm. Overall, the 3 km product closely mirrors the 10 km product. However, the finer resolution product is able to retrieve over ocean closer to islands and coastlines, and is better able to resolve fine aerosol features such as smoke plumes over both ocean and land. In some situations, it provides retrievals over entire regions that the 10 km product barely samples. In situations traditionally difficult for the dark target algorithm, such as over bright or urban surfaces the 3 km product introduces isolated spikes of artificially high aerosol optical depth (AOD) that the 10 km algorithm avoids. Over land, globally, the 3 km product appears to be 0.01 to 0.02 higher than the 10 km product, while over ocean, the 3 km algorithm is retrieving a proportionally greater number of very low aerosol loading situations. Based on collocations with ground-based observations for only six months, expected errors associated with the 3 km land product are determined to be greater than for the 10 km product: 0.05 0.25 AOD. Over ocean, the suggestion is for expected errors to be the same as the 10 km product: 0.03 0.05 AOD. The advantage of the product is on the local scale, which will require continued evaluation not addressed here. Nevertheless, the new 3 km product is expected to provide important information complementary to existing satellite-derived products and become an important tool for the aerosol community.

  10. Affinity membrane introduction mass spectrometry

    SciTech Connect

    Xu, C.; Patrick, J.S.; Cooks, R.G. )

    1995-02-15

    A new technique, affinity membrane introduction mass spectrometry, is described. In this method, a chemically modified membrane is used to selectively adsorb analytes bearing a particular functional group and concentrate them from solution. Release of the bound analyte results in its transfer across the membrane and allows it to be monitored mass spectrometrically, using, in the present case, a benchtop ion trap instrument. Alkylamine-modified cellulose membranes are used to bind substituted benzaldehydes through imine formation at high pH. Release of the bound aldehyde is achieved by acid hydrolysis of the surface-bound imine. Benzaldehyde is detected with excellent specificity at 10 ppm in a complex mixture using this method. Using the enrichment capability of the membrane, a full mass spectrum of benzaldehyde can be measured at a concentration of 10 ppb. The behavior of a variety of other aldehydes is also discussed to illustrate the capabilities of the method. 21 refs., 5 figs., 2 tabs.

  11. Antisymmetric tensor generalizations of affine vector fields

    PubMed Central

    Morisawa, Yoshiyuki; Tomoda, Kentaro

    2016-01-01

    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. PMID:26858463

  12. Conformal field theory on affine Lie groups

    SciTech Connect

    Clubok, Kenneth Sherman

    1996-04-01

    Working directly on affine Lie groups, we construct several new formulations of the WZW model, the gauged WZW model, and the generic affine-Virasoro action. In one formulation each of these conformal field theories (CFTs) is expressed as a one-dimensional mechanical system whose variables are coordinates on the affine Lie group. When written in terms of the affine group element, this formulation exhibits a two-dimensional WZW term. In another formulation each CFT is written as a two-dimensional field theory, with a three- dimensional WZW term, whose fields are coordinates on the affine group. On the basis of these equivalent formulations, we develop a translation dictionary in which the new formulations on the affine Lie group are understood as mode formulations of the conventional formulations on the Lie group. Using this dictionary, we also express each CFT as a three-dimensional field theory on the Lie group with a four-dimensional WZW term. 36 refs.

  13. Estimation of Land Surface Temperature from 1-km AVHRR data

    NASA Astrophysics Data System (ADS)

    Frey, Corinne

    2016-04-01

    In order to re-process DLRs 1km AVHRR data archive to different geophysical and descriptive parameters of the land surface and the atmosphere, a series of scientific data processors are being developed in the framework of the TIMELINE project. The archive of DLR ranges back to the 80ies. One of the data processors is SurfTemp, which processes L2 LST and emissivity datasets from AVHRR L1b data. The development of the data processor included the selection of statistical procedures suitable for time series processing, including four mono-window and six split window algorithms. For almost all of these algorithms, new constants were generated, which better account for different atmospheric and geometric acquisition situations. The selection of optimal algorithms for SurfTemp is based on a round robin approach, in which the selected mono-window and split window algorithms are tested on the basis of a large number of TOA radiance/LST pairs, which were generated using a radiative transfer model and the SeeBorV5 profile database. The original LSTs are thereby compared to the LSTs derived from the TOA radiances using the mono- and split window algorithms. The algorithm comparison includes measures of precision, as well as the sensitivity of a method to the accuracy of its input data. The results of the round robin are presented, as well as the implementation of selected algorithms into SurfTemp. Further, first cross-validation results between the AVHRR LST and MODIS LST are shown.

  14. A Novel Vertex Affinity for Community Detection

    SciTech Connect

    Yoo, Andy; Sanders, Geoffrey; Henson, Van; Vassilevski, Panayot

    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.

  15. Structural determinants of sigma receptor affinity

    SciTech Connect

    Largent, B.L.; Wikstroem, H.G.; Gundlach, A.L.; Snyder, S.H.

    1987-12-01

    The structural determinants of sigma receptor affinity have been evaluated by examining a wide range of compounds related to opioids, neuroleptics, and phenylpiperidine dopaminergic structures for affinity at sigma receptor-binding sites labeled with (+)-(/sup 3/H)3-PPP. Among opioid compounds, requirements for sigma receptor affinity differ strikingly from the determinants of affinity for conventional opiate receptors. Sigma sites display reverse stereoselectivity to classical opiate receptors. Multi-ringed opiate-related compounds such as morphine and naloxone have negligible affinity for sigma sites, with the highest sigma receptor affinity apparent for benzomorphans which lack the C ring of opioids. Highest affinity among opioids and other compounds occurs with more lipophilic N-substituents. This feature is particularly striking among the 3-PPP derivatives as well as the opioids. The butyrophenone haloperidol is the most potent drug at sigma receptors we have detected. Among the series of butyrophenones, receptor affinity is primarily associated with the 4-phenylpiperidine moiety. Conformational calculations for various compounds indicate a fairly wide range of tolerance for distances between the aromatic ring and the amine nitrogen, which may account for the potency at sigma receptors of structures of considerable diversity. Among the wide range of structures that bind to sigma receptor-binding sites, the common pharmacophore associated with high receptor affinity is a phenylpiperidine with a lipophilic N-substituent.

  16. Constant domain-regulated antibody catalysis.

    PubMed

    Sapparapu, Gopal; Planque, Stephanie; Mitsuda, Yukie; McLean, Gary; Nishiyama, Yasuhiro; Paul, Sudhir

    2012-10-19

    Some antibodies contain variable (V) domain catalytic sites. We report the superior amide and peptide bond-hydrolyzing activity of the same heavy and light chain V domains expressed in the IgM constant domain scaffold compared with the IgG scaffold. The superior catalytic activity of recombinant IgM was evident using two substrates, a small model peptide that is hydrolyzed without involvement of high affinity epitope binding, and HIV gp120, which is recognized specifically by noncovalent means prior to the hydrolytic reaction. The catalytic activity was inhibited by an electrophilic phosphonate diester, consistent with a nucleophilic catalytic mechanism. All 13 monoclonal IgMs tested displayed robust hydrolytic activities varying over a 91-fold range, consistent with expression of the catalytic functions at distinct levels by different V domains. The catalytic activity of polyclonal IgM was superior to polyclonal IgG from the same sera, indicating that on average IgMs express the catalytic function at levels greater than IgGs. The findings indicate a favorable effect of the remote IgM constant domain scaffold on the integrity of the V-domain catalytic site and provide a structural basis for conceiving antibody catalysis as a first line immune function expressed at high levels prior to development of mature IgG class antibodies.

  17. High-throughput fragment screening by affinity LC-MS.

    PubMed

    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 <4 h (corresponding to >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.

  18. Structure of classical affine and classical affine fractional W-algebras

    SciTech Connect

    Suh, Uhi Rinn

    2015-01-15

    We introduce a classical BRST complex (See Definition 3.2.) and show that one can construct a classical affine W-algebra via the complex. This definition clarifies that classical affine W-algebras can be considered as quasi-classical limits of quantum affine W-algebras. We also give a definition of a classical affine fractional W-algebra as a Poisson vertex algebra. As in the classical affine case, a classical affine fractional W-algebra has two compatible λ-brackets and is isomorphic to an algebra of differential polynomials as a differential algebra. When a classical affine fractional W-algebra is associated to a minimal nilpotent, we describe explicit forms of free generators and compute λ-brackets between them. Provided some assumptions on a classical affine fractional W-algebra, we find an infinite sequence of integrable systems related to the algebra, using the generalized Drinfel’d and Sokolov reduction.

  19. Affinity capillary electrophoresis: the theory of electromigration.

    PubMed

    Dubský, Pavel; Dvořák, Martin; Ansorge, Martin

    2016-12-01

    We focus on the state-of-the-art theory of electromigration under single and multiple complexation equilibrium. Only 1:1 complexation stoichiometry is discussed because of its unique status in the field of affinity capillary electrophoresis (ACE). First, we summarize the formulas for the effective mobility in various ACE systems as they appeared since the pioneering days in 1992 up to the most recent theories till 2015. Disturbing phenomena that do not alter the mobility of the analyte directly but cause an unexpected peak broadening have been studied only recently and are also discussed in this paper. Second, we turn our attention to the viscosity effects in ACE. Change in the background electrolyte viscosity is unavoidable in ACE but numerous observations scattered throughout the literature have not been reviewed previously. This leads to an uncritical employment of correction factors that may or may not be appropriate in practice. Finally, we consider the ionic strength effects in ACE, too. Limitations of the current theories are also discussed and the tasks identified where open problems still prevail. Graphical Abstract A weak base (A) undergoes an acidic-basic equilibria (in blue) and migrates with an electrophoretic mobility of [Formula: see text]. Simultaneously, it interacts with a selector (sel) while the analyte-selector complex migrates with an electrophoretic mobility of [Formula: see text]. The strength of the interaction (in orange) is governed by the binding constant, K A , and the concentration of the selector, c sel . This all gives the analyte an effective mobility of [Formula: see text] and moves it out of the zero position (EOF; right top insert). The interaction of the positively charged analyte with the neutral selector slows down the analyte with increasing selector concentration (right bottom insert).

  20. Is Planck's quantization constant unique?

    NASA Astrophysics Data System (ADS)

    Livadiotis, George

    2016-07-01

    A cornerstone of Quantum Mechanics is the existence of a non-zero least action, the Planck constant. However, the basic concepts and theoretical developments of Quantum Mechanics are independent of its specific numerical value. A different constant h _{*}, similar to the Planck constant h, but ˜12 orders of magnitude larger, characterizes plasmas. The study of >50 different geophysical, space, and laboratory plasmas, provided the first evidence for the universality and the quantum nature of h _{*}, revealing that it is a new quantization constant. The recent results show the diagnostics for determining whether plasmas are characterized by the Planck or the new quantization constant, compounding the challenge to reconcile both quantization constants in quantum mechanics.

  1. Delimiting affinity zones as a basis for air pollution mapping in Europe.

    PubMed

    Vienneau, Danielle; Briggs, David J

    2013-01-01

    Affinity zones are defined as areas within which air quality displays consistent behaviour over space and time. Constructed using multivariate statistical techniques and physiographic and landscape variables reflecting underlying sources and spatial patterns of air pollution, affinity zones provide a spatial structure suited to exploring the representativity of monitoring networks and as a basis for air pollution mapping and exposure assessment. The affinity zone method is demonstrated using European air pollution monitoring sites, and environmental data compiled within a 1 km GIS. Organised into three main stages, this method involves: (i) indicator selection, using principal components analysis, (ii) zonation by cluster analysis to classify areas into distinct types, and (iii) site allocation, to confirm similarity within affinity zones in terms of monitored air pollution concentrations. Ten interpretable and coherent air pollution affinity zones were constructed for Europe, including two rural zones and eight related to different types of densely populated and built up environments. Concentrations between affinity zones differed significantly for NO(2) background and traffic sites and for PM(10) traffic sites only. Not all zones, however, were found to be sufficiently represented by monitoring sites, illustrating the importance of affinity zones in identifying deficiencies in monitoring networks. Spatial modelling within affinity zones is also demonstrated, showing that simple kriging of background NO(2) concentrations within zones (compared to kriging ignoring zones) produced a ca. 22% reduction in errors and increased R(2) by 0.25 at reserved validation monitoring sites. The affinity zone method developed here is a robust, statistical approach that can be used for evaluating the representativity of routine monitoring networks often used in continental level environmental and health risk assessments.

  2. Microphysical Model of the Venus clouds between 40km and 80km

    NASA Astrophysics Data System (ADS)

    McGouldrick, Kevin

    2013-10-01

    I am continuing to adapt the Community Aerosol and Radiation Model for Atmospheres (CARMA) to successfully simulate the multi-layered clouds of Venus. The present version of the one-dimensional model now includes a simple parameterization of the photochemicial production of sulfuric acid around altitudes of 62km, and its thermochemical destruction below cloud base. Photochemical production in the model is limited by the availability of water vapor and insolation. Upper cloud particles are introduced into the model via binary homogeneous nucleation, while the lower and middle cloud particles are created via activation of involatile cloud condensation nuclei. Growth by condensation and coagulation and coalescence are also treated. Mass loadings and particle sizes compare favorably with the in situ observations by the Pioneer Venus Large Probe Particle Size Spectrometer, and mixing ratios of volatiles compare favorably with remotely sensed observations of water vapor and sulfuric acid vapor. This work was supported by the NASA Planetary Atmospheres Program, grant number NNX11AD79G.

  3. A global benchmark study using affinity-based biosensors

    PubMed Central

    Rich, Rebecca L.; Papalia, Giuseppe A.; Flynn, Peter J.; Furneisen, Jamie; Quinn, John; Klein, Joshua S.; Katsamba, Phini S.; Waddell, M. Brent; Scott, Michael; Thompson, Joshua; Berlier, Judie; Corry, Schuyler; Baltzinger, Mireille; Zeder-Lutz, Gabrielle; Schoenemann, Andreas; Clabbers, Anca; Wieckowski, Sebastien; Murphy, Mary M.; Page, Phillip; Ryan, Thomas E.; Duffner, Jay; Ganguly, Tanmoy; Corbin, John; Gautam, Satyen; Anderluh, Gregor; Bavdek, Andrej; Reichmann, Dana; Yadav, Satya P.; Hommema, Eric; Pol, Ewa; Drake, Andrew; Klakamp, Scott; Chapman, Trevor; Kernaghan, Dawn; Miller, Ken; Schuman, Jason; Lindquist, Kevin; Herlihy, Kara; Murphy, Michael B.; Bohnsack, Richard; Andrien, Bruce; Brandani, Pietro; Terwey, Danny; Millican, Rohn; Darling, Ryan J.; Wang, Liann; Carter, Quincy; Dotzlaf, Joe; Lopez-Sagaseta, Jacinto; Campbell, Islay; Torreri, Paola; Hoos, Sylviane; England, Patrick; Liu, Yang; Abdiche, Yasmina; Malashock, Daniel; Pinkerton, Alanna; Wong, Melanie; Lafer, Eileen; Hinck, Cynthia; Thompson, Kevin; Primo, Carmelo Di; Joyce, Alison; Brooks, Jonathan; Torta, Federico; Bagge Hagel, Anne Birgitte; Krarup, Janus; Pass, Jesper; Ferreira, Monica; Shikov, Sergei; Mikolajczyk, Malgorzata; Abe, Yuki; Barbato, Gaetano; Giannetti, Anthony M.; Krishnamoorthy, Ganeshram; Beusink, Bianca; Satpaev, Daulet; Tsang, Tiffany; Fang, Eric; Partridge, James; Brohawn, Stephen; Horn, James; Pritsch, Otto; Obal, Gonzalo; Nilapwar, Sanjay; Busby, Ben; Gutierrez-Sanchez, Gerardo; Gupta, Ruchira Das; Canepa, Sylvie; Witte, Krista; Nikolovska-Coleska, Zaneta; Cho, Yun Hee; D’Agata, Roberta; Schlick, Kristian; Calvert, Rosy; Munoz, Eva M.; Hernaiz, Maria Jose; Bravman, Tsafir; Dines, Monica; Yang, Min-Hsiang; Puskas, Agnes; Boni, Erica; Li, Jiejin; Wear, Martin; Grinberg, Asya; Baardsnes, Jason; Dolezal, Olan; Gainey, Melicia; Anderson, Henrik; Peng, Jinlin; Lewis, Mark; Spies, Peter; Trinh, Quyhn; Bibikov, Sergei; Raymond, Jill; Yousef, Mohammed; Chandrasekaran, Vidya; Feng, Yuguo; Emerick, Anne; Mundodo, Suparna; Guimaraes, Rejane; McGirr, Katy; Li, Yue-Ji; Hughes, Heather; Mantz, Hubert; Skrabana, Rostislav; Witmer, Mark; Ballard, Joshua; Martin, Loic; Skladal, Petr; Korza, George; Laird-Offringa, Ite; Lee, Charlene S.; Khadir, Abdelkrim; Podlaski, Frank; Neuner, Phillippe; Rothacker, Julie; Rafique, Ashique; Dankbar, Nico; Kainz, Peter; Gedig, Erk; Vuyisich, Momchilo; Boozer, Christina; Ly, Nguyen; Toews, Mark; Uren, Aykut; Kalyuzhniy, Oleksandr; Lewis, Kenneth; Chomey, Eugene; Pak, Brian J.; Myszka, David G.

    2013-01-01

    To explore the variability in biosensor studies, 150 participants from 20 countries were given the same protein samples and asked to determine kinetic rate constants for the interaction. We chose a protein system that was amenable to analysis using different biosensor platforms as well as by users of different expertise levels. The two proteins (a 50-kDa Fab and a 60-kDa glutathione S-transferase [GST] antigen) form a relatively high-affinity complex, so participants needed to optimize several experimental parameters, including ligand immobilization and regeneration conditions as well as analyte concentrations and injection/dissociation times. Although most participants collected binding responses that could be fit to yield kinetic parameters, the quality of a few data sets could have been improved by optimizing the assay design. Once these outliers were removed, the average reported affinity across the remaining panel of participants was 620 pM with a standard deviation of 980 pM. These results demonstrate that when this biosensor assay was designed and executed appropriately, the reported rate constants were consistent, and independent of which protein was immobilized and which biosensor was used. PMID:19133223

  4. Improving image segmentation by learning region affinities

    SciTech Connect

    Prasad, Lakshman; Yang, Xingwei; Latecki, Longin J

    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.

  5. Protein separation using affinity-based reversed micelles

    PubMed

    Sun; Gu; Tong; Bai; Ichikawa; Furusaki

    1999-05-01

    Reversed micellar two-phase extraction is a developing technique for protein separation. Introduction of an affinity ligand is considered to be an effective approach to increase the selectivity and capacity of reversed micelles. In this article, Cibacron Blue F3G-A (CB) as an affinity ligand was immobilized to reversed micelles composed of soybean lecithin by a two-phase reaction. The affinity partitioning of lysozyme and bovine serum albumin (BSA) to the CB-lecithin micelles was studied. Formation of mixed micelles by additionally introducing a nonionic surfactant, Tween 85, to the CB-lecithin micelles was effective to increase the solubilization of lysozyme due to the increase of W0 (water/surfactant molar ratio)/micellar size. The partitioning isotherms of lysozyme to the CB-lecithin micelles with and without Tween 85 were expressed by the Langmuir equation. The dissociation constants in the Langmuir equation decreased on addition of Tween 85, indicating the increase of the effectiveness of lysozyme binding to the immobilized CB. On addition of 20 g/L Tween 85 to 50 g/L lecithin/hexane micellar phase containing 0.1 mmol/L CB, the extraction capacity for lysozyme could be increased by 42%. Moreover, the CB-lecithin micelles with or without Tween 85 showed significant size exclusion for BSA due to its high molecular weight. Thus, lysozyme and BSA were separated from artificial solutions containing the two proteins. In addition, the affinity-based reversed micellar phase containing Tween 85 was recycled three times for lysozyme purification from crude egg-white solutions. Lysozyme purity increased by 16-18-fold, reaching 60-70% in the recycled use.

  6. Characterizing the 410 km discontinuity low-velocity layer beneath the LA RISTRA array in the North American Southwest

    NASA Astrophysics Data System (ADS)

    Jasbinsek, John J.; Dueker, Ken G.; Hansen, Steven M.

    2010-03-01

    Receiver functions recorded by the 54-station 920 km long Program for Array Seismic Studies of the Continental Lithosphere-Incorporated Research Institutions for Seismology Colorado Plateau/Rio Grande Rift Seismic Transect Experiment (LA RISTRA) line array display a pervasive negative polarity P to S conversion (Pds) arrival preceding the positive polarity 410 km discontinuity arrival. These arrivals are modeled as a low-velocity layer atop the 410 km discontinuity (410-LVL) and are inverted for a velocity profile via a grid search using a five-parameter linear gradient velocity model. Model parameter likelihood and correlations are assessed via calculation of one- and two-dimensional marginal posterior probability distributions. The maximum likelihood model parameter values found are top velocity gradient thickness of 0.0 km with a 4.6% (-0.22 km/s) shear velocity reduction, a 19.8 km constant velocity layer, and bottom gradient thickness of 25.0 km with a 3.5% (+0.17 km/s) shear velocity increase. The estimated mean thickness of the 410-LVL is 32.3 km. The top gradient of the 410-LVL is sharp within vertical resolution limits of P to S conversion (<10 km), and the diffuse 410 km velocity gradient is consistent with hydration of the olivine-wadsleyite phase transformation. The 410-LVL is interpreted as a melt layer created by the Transition Zone Water Filter model. Two secondary observations are found: (1) the 410-LVL is absent from the SE end of the array and (2) an intermittent negative polarity P525s arrival is observed. We speculate that upper mantle shear velocity anomalies above the 410 km discontinuity may manifest Rayleigh-Taylor instabilities nucleated from the 410-LVL melt layer that are being shed upward on time scales of tens of millions of years.

  7. QCD coupling constants and VDM

    SciTech Connect

    Erkol, G.; Ozpineci, A.; Zamiralov, V. S.

    2012-10-23

    QCD sum rules for coupling constants of vector mesons with baryons are constructed. The corresponding QCD sum rules for electric charges and magnetic moments are also derived and with the use of vector-meson-dominance model related to the coupling constants. The VDM role as the criterium of reciprocal validity of the sum rules is considered.

  8. Constant-Pressure Hydraulic Pump

    NASA Technical Reports Server (NTRS)

    Galloway, C. W.

    1982-01-01

    Constant output pressure in gas-driven hydraulic pump would be assured in new design for gas-to-hydraulic power converter. With a force-multiplying ring attached to gas piston, expanding gas would apply constant force on hydraulic piston even though gas pressure drops. As a result, pressure of hydraulic fluid remains steady, and power output of the pump does not vary.

  9. 7 CFR 29.1035 - Mixed color (KM).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 2 2014-01-01 2014-01-01 false Mixed color (KM). 29.1035 Section 29.1035 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Type 92) § 29.1035 Mixed color (KM). Distinctly different colors of the type mingled together....

  10. 7 CFR 29.1035 - Mixed color (KM).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 2 2013-01-01 2013-01-01 false Mixed color (KM). 29.1035 Section 29.1035 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Type 92) § 29.1035 Mixed color (KM). Distinctly different colors of the type mingled together....

  11. 7 CFR 29.1035 - Mixed color (KM).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false Mixed color (KM). 29.1035 Section 29.1035 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Type 92) § 29.1035 Mixed color (KM). Distinctly different colors of the type mingled together....

  12. 7 CFR 29.1035 - Mixed color (KM).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Mixed color (KM). 29.1035 Section 29.1035 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Type 92) § 29.1035 Mixed color (KM). Distinctly different colors of the type mingled together....

  13. 7 CFR 29.1035 - Mixed color (KM).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Mixed color (KM). 29.1035 Section 29.1035 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Type 92) § 29.1035 Mixed color (KM). Distinctly different colors of the type mingled together....

  14. Exploring KM Features of High-Performance Companies

    NASA Astrophysics Data System (ADS)

    Wu, Wei-Wen

    2007-12-01

    For reacting to an increasingly rival business environment, many companies emphasize the importance of knowledge management (KM). It is a favorable way to explore and learn KM features of high-performance companies. However, finding out the critical KM features of high-performance companies is a qualitative analysis problem. To handle this kind of problem, the rough set approach is suitable because it is based on data-mining techniques to discover knowledge without rigorous statistical assumptions. Thus, this paper explored KM features of high-performance companies by using the rough set approach. The results show that high-performance companies stress the importance on both tacit and explicit knowledge, and consider that incentives and evaluations are the essentials to implementing KM.

  15. Estimation of Anaerobic Debromination Rate Constants of PBDE Pathways Using an Anaerobic Dehalogenation Model.

    PubMed

    Karakas, Filiz; Imamoglu, Ipek

    2017-04-01

    This study aims to estimate anaerobic debromination rate constants (km) of PBDE pathways using previously reported laboratory soil data. km values of pathways are estimated by modifying a previously developed model as Anaerobic Dehalogenation Model. Debromination activities published in the literature in terms of bromine substitutions as well as specific microorganisms and their combinations are used for identification of pathways. The range of estimated km values is between 0.0003 and 0.0241 d(-1). The median and maximum of km values are found to be comparable to the few available biologically confirmed rate constants published in the literature. The estimated km values can be used as input to numerical fate and transport models for a better and more detailed investigation of the fate of individual PBDEs in contaminated sediments. Various remediation scenarios such as monitored natural attenuation or bioremediation with bioaugmentation can be handled in a more quantitative manner with the help of km estimated in this study.

  16. Thiamin-responsive maple-syrup-urine disease: decreased affinity of the mutant branched-chain alpha-keto acid dehydrogenase for alpha-ketoisovalerate and thiamin pyrophosphate.

    PubMed Central

    Chuang, D T; Ku, L S; Cox, R P

    1982-01-01

    The biochemical basis for the therapeutic effects of thiamin in thiamin-responsive maple-syrup-urine disease (MSUD) was investigated in intact and disrupted fibroblast cultures from normals and patients with various forms of MSUD. Decarboxylation of alpha-keto[1-14C]isovalerate (KIV) by intact cells from a thiamin-responsive MSUD patient was at 30-40% of the normal rate with or without thiamin in the incubation medium. Under similar conditions, intact classical MSUD fibroblasts failed to decarboxylate KIV. Branched-chain alpha-keto acid (BCKA) dehydrogenase activity measured in disrupted cells from the thiamin-responsive subject showed sigmoidal kinetics in the absence of thiamin pyrophosphate (TPP), with an increased concentration of substrate needed for half-maximal velocity (K0.5 for KIV = 7 mM vs. 0.05 mM in normal cells). When assayed with 0.2 mM TPP present, the mutant enzyme showed (i) a shift in kinetics to near Michaelis-Menten type as observed with the normal BCKA dehydrogenase and (ii) a lower K0.5 value of 4 mM for KIV, suggesting a TPP-mediated increase in the mutant enzyme's affinity for substrate. By contrast, TPP increased only the Vmax and was without effect on the apparent Km for KIV of the BCKA dehydrogenase from cells of normals and patients with classical MSUD and variant thiamin-responsive MSUD (grade 3). Measurement of the apparent Km for TPP of the BCKA dehydrogenase from thiamin-responsive mutant MSUd cells showed a 16-fold increase in the constant to 25 microM compared to enzymes from normal or classical MSUD cells. These findings demonstrate that the primary defect in the thiamin-responsive MSUD patient is a reduced affinity of the mutant BCKA dehydrogenase for TPP that results in impaired oxidative decarboxylation of BCKA. PMID:6954481

  17. Marshall Space Flight Center Propulsion Systems Department (PSD) KM Initiative

    NASA Technical Reports Server (NTRS)

    Caraccioli, Paul; Varnadoe, Tom; McCarter, Mike

    2006-01-01

    NASA Marshall Space Flight Center s Propulsion Systems Department (PSD) is four months into a fifteen month Knowledge Management (KM) initiative to support enhanced engineering decision making and analyses, faster resolution of anomalies (near-term) and effective, efficient knowledge infused engineering processes, reduced knowledge attrition, and reduced anomaly occurrences (long-term). The near-term objective of this initiative is developing a KM Pilot project, within the context of a 3-5 year KM strategy, to introduce and evaluate the use of KM within PSD. An internal NASA/MSFC PSD KM team was established early in project formulation to maintain a practitioner, user-centric focus throughout the conceptual development, planning and deployment of KM technologies and capabilities with in the PSD. The PSD internal team is supported by the University of Alabama's Aging Infrastructure Systems Center Of Excellence (AISCE), Intergraph Corporation, and The Knowledge Institute. The principle product of the initial four month effort has been strategic planning of PSD KM implementation by first determining the "as is" state of KM capabilities and developing, planning and documenting the roadmap to achieve the desired "to be" state. Activities undertaken to support the planning phase have included data gathering; cultural surveys, group work-sessions, interviews, documentation review, and independent research. Assessments and analyses have been performed including industry benchmarking, related local and Agency initiatives, specific tools and techniques used and strategies for leveraging existing resources, people and technology to achieve common KM goals. Key findings captured in the PSD KM Strategic Plan include the system vision, purpose, stakeholders, prioritized strategic objectives mapped to the top ten practitioner needs and analysis of current resource usage. Opportunities identified from research, analyses, cultural/KM surveys and practitioner interviews include

  18. Beyond Vmax and Km: How details of enzyme function influence geochemical cycles

    NASA Astrophysics Data System (ADS)

    Steen, A. D.

    2015-12-01

    Enzymes catalyze the vast majority of chemical reactions relevant to geomicrobiology. Studies of the activities of enzymes in environmental systems often report Vmax (the maximum possible rate of reaction; often proportional to the concentration of enzymes in the system) and sometimes Km (a measure of the affinity between enzymes and their substrates). However, enzyme studies - particularly those related to enzymes involved in organic carbon oxidation - are often limited to only those parameters, and a relatively limited and mixed set of enzymes. Here I will discuss some novel methods to assay and characterize the specific sets of enzymes that may be important to the carbon cycle in aquatic environments. First, kinetic experiments revealed the collective properties of the complex mixtures of extracellular peptidases that occur where microbial communities are diverse. Crystal structures combined with biochemical characterization of specific enzymes can yield more detailed information about key steps in organic carbon transformations. These new techniques have the potential to provide mechanistic grounding to geomicrobiological models.

  19. Engineering an antibody with picomolar affinity to DOTA chelates of multiple radionuclides for pretargeted radioimmunotherapy and imaging

    PubMed Central

    Orcutt, Kelly Davis; Slusarczyk, Adrian L; Cieslewicz, Maryelise; Ruiz-Yi, Benjamin; Bhushan, Kumar R; Frangioni, John V; Wittrup, K Dane

    2014-01-01

    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 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 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (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 picomolar (pM) is needed for near-maximal hapten retention. We affinity matured 2D12.5 with an initial binding constant of about 10 nanomolar (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 (CEA), pretargeted high-affinity scFv results in significantly higher tumor retention of a 111In-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. PMID:21315278

  20. Molecular oxygen measurements at 200 km from AE-D near winter solstice, 1975

    NASA Technical Reports Server (NTRS)

    Kayser, D. C.; Potter, W. E.

    1976-01-01

    Utilizing the fly-through mode, the open source neutral mass spectrometer on Atmosphere Explorer-D (AE-D) has measured O2 densities, as well as N2 densities and in situ neutral temperatures, at midmorning during winter solstice over the latitude range 90 degrees S to 90 degrees N. The expected seasonal variation in N2 was found at 200 km together with a more complex behavior in molecular oxygen than might be expected from a diffusive equilibrium model with constant lower boundary values. Under geomagnetically quiet conditions the equatorial 200 km value of O2 was about 1.7 x 10 to the 8th/cu cm. A local maximum in the 200 km O2 densities was found near 70 degrees N, where an average quiet time value was 2.5 x 10 to the 8th/cu cm, implying a 120 km density of 8.3 x 10 to the 10th/cu cm. The in situ temperature measurements confirm the presence of higher temperatures near 70 degrees N latitude, even during geomagnetically quiet conditions.

  1. Affine group representation formalism for four-dimensional, Lorentzian, quantum gravity

    NASA Astrophysics Data System (ADS)

    Chou, Ching-Yi; Ita, Eyo E.; Soo, Chopin

    2013-03-01

    Within the context of the Ashtekar variables, the Hamiltonian constraint of four-dimensional pure general relativity with cosmological constant, Λ, is re-expressed as an affine algebra with the commutator of the imaginary part of the Chern-Simons functional, Q, and the positive-definite volume element. This demonstrates that the affine algebra quantization program of Klauder can indeed be applicable to the full Lorentzian signature theory of quantum gravity with non-vanishing cosmological constant, and it facilitates the construction of solutions to all of the constraints. Unitary, irreducible representations of the affine group exhibit a natural Hilbert space structure, and coherent states and other physical states can be generated from a fiducial state. It is also intriguing that formulation of the Hamiltonian constraint or the Wheeler-DeWitt equation as an affine algebra requires a non-vanishing cosmological constant, and a fundamental uncertainty relation of the form {Δ{V}/{< {V}> }Δ {Q}≥ 2π Λ L^2_{Planck} (wherein V is the total volume) may apply to all physical states of quantum gravity.

  2. Oxygen Michaelis constants for tyrosinase.

    PubMed Central

    Rodríguez-López, J N; Ros, J R; Varón, R; García-Cánovas, F

    1993-01-01

    The Michaelis constant of tyrosinase for oxygen in the presence of monophenols and o-diphenols, which generate a cyclizable o-quinone, has been studied. This constant depends on the nature of the monophenol and o-diphenol and is always lower in the presence of the former than of the latter. From the mechanism proposed for tyrosinase and from its kinetic analysis [Rodríguez-López, J. N., Tudela, J., Varón, R., García-Carmona, F. and García-Cánovas, F. (1992) J. Biol. Chem. 267, 3801-3810] a quantitative ratio has been established between the Michaelis constants for oxygen in the presence of monophenols and their o-diphenols. This ratio is used for the determination of the Michaelis constant for oxygen with monophenols when its value cannot be calculated experimentally. PMID:8352753

  3. Avogadro's Number and Avogadro's Constant

    ERIC Educational Resources Information Center

    Davies, R. O.

    1973-01-01

    Discusses three possible methods of thinking about the implications of the definitions of the Avogadro constant and number. Indicates that there is only one way to arrive at a simple and standard conclusion. (CC)

  4. Visualizing Antibody Affinity Maturation in Germinal Centers

    PubMed Central

    Tas, Jeroen M.J.; Mesin, Luka; Pasqual, Giulia; Targ, Sasha; Jacobsen, Johanne T.; Mano, Yasuko M.; Chen, Casie S.; Weill, Jean-Claude; Reynaud, Claude-Agnès; Browne, Edward P.; Meyer-Hermann, Michael; Victora, Gabriel D.

    2016-01-01

    Antibodies somatically mutate to attain high affinity in germinal centers (GCs). There, competition between B cell clones and among somatic mutants of each clone drives an increase in average affinity across the population. The extent to which higher-affinity cells eliminating competitors restricts clonal diversity is unknown. By combining multiphoton microscopy and sequencing, we show that tens to hundreds of distinct B cell clones seed each GC, and that GCs lose clonal diversity at widely disparate rates. Furthermore, efficient affinity maturation can occur in the absence of homogenizing selection, ensuring that many clones can mature in parallel within the same GC. Our findings have implications for development of vaccines in which antibodies with non-immunodominant specificities must be elicited, as is the case for HIV-1 and influenza. PMID:26912368

  5. PRINCIPLES OF AFFINITY-BASED BIOSENSORS

    EPA Science Inventory

    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...

  6. Protein purification using PDZ affinity chromatography.

    PubMed

    Walkup, Ward G; Kennedy, Mary B

    2015-04-01

    PDZ domains function in nature as protein-binding domains within scaffold and membrane-associated proteins. They comprise approximately 90 residues and undergo specific, high-affinity interactions with complementary C-terminal peptide sequences, other PDZ domains, and/or phospholipids. We have previously shown that the specific, strong interactions of PDZ domains with their ligands make them well suited for use in affinity chromatography. This unit provides protocols for the PDZ affinity chromatography procedure that are applicable for the purification of proteins that contain PDZ domains or PDZ domain-binding ligands, either naturally or introduced by genetic engineering. We detail the preparation of affinity resins composed of PDZ domains or PDZ domain peptide ligands coupled to solid supports. These resins can be used to purify proteins containing endogenous or genetically introduced PDZ domains or ligands, eluting the proteins with free PDZ domain peptide ligands.

  7. Electron Attachment and Detachment, and the Electron Affinities of C(5)F(5)N and C(5)HF(4)N

    DTIC Science & Technology

    2005-09-19

    detachment rate at 303 K was 520 ± 180 s-1. The attachment/detachment equilibrium yielded experimental electron affinities EA(CsF 5N) = 0.70-0.05 eV and EA...are in good agreement with the present experimental results. 15. SUBJECT TERMS Electron attachment Electron affinity Electron detachment Rate constant...attachment/detachment equilibrium yielded experimental electron affinities EA(C5F5 N)=0.70±0.05 eV and EA(2,3,5,6-C5HF 4N)=0.40±0.08 eV. Electronic

  8. Affinity Electrophoresis Using Ligands Attached To Polymers

    NASA Technical Reports Server (NTRS)

    Van Alstine, James M.; Snyder, Robert S.; Harris, J. M.; Brooks, D. E.

    1990-01-01

    In new technique, reduction of electrophoretic mobilities by addition of polyethylene glycol to ligands increases electrophoretic separabilities. In immuno-affinity electrophoresis, modification of ligands extends specificity of electrophoretic separation to particles having surface electric-charge structures otherwise making them electrophoretically inseparable. Modification of antibodies by polyethylene glycol greatly reduces ability to aggregate while enhancing ability to affect electrophoretic mobilities of cells. In hydrophobic-affinity electrophoresis, addition of polyethylene glycol reduces tendency toward aggregation of cells or macromolecules.

  9. Varying Constants, Gravitation and Cosmology.

    PubMed

    Uzan, Jean-Philippe

    2011-01-01

    Fundamental constants are a cornerstone of our physical laws. Any constant varying in space and/or time would reflect the existence of an almost massless field that couples to matter. This will induce a violation of the universality of free fall. Thus, it is of utmost importance for our understanding of gravity and of the domain of validity of general relativity to test for their constancy. We detail the relations between the constants, the tests of the local position invariance and of the universality of free fall. We then review the main experimental and observational constraints that have been obtained from atomic clocks, the Oklo phenomenon, solar system observations, meteorite dating, quasar absorption spectra, stellar physics, pulsar timing, the cosmic microwave background and big bang nucleosynthesis. At each step we describe the basics of each system, its dependence with respect to the constants, the known systematic effects and the most recent constraints that have been obtained. We then describe the main theoretical frameworks in which the low-energy constants may actually be varying and we focus on the unification mechanisms and the relations between the variation of different constants. To finish, we discuss the more speculative possibility of understanding their numerical values and the apparent fine-tuning that they confront us with.

  10. Affine Equivalence of Quartic Monomial Rotation Symmetric Boolean Functions in Prime Power Dimension

    DTIC Science & Technology

    2015-01-27

    multivariate polynomial, called the algebraic normal form (ANF) f(x1, . . . , xn) = a0 + ∑ 1≤i≤n aixi + ∑ 1≤i<j≤n aijxixj + · · ·+ a12...nx1x2...xn, where the coefficients a0, aij , . . . , a12...n ∈ F2. The maximum number of variables in a monomial is called the ( algebraic ) degree, and it is...called affine functions. An affine function with constant term equal to zero is called a linear function. Define Preprint submitted to Elsevier

  11. Evaluating KM Journal Content: An Assessment of Trends (2000-2005)

    DTIC Science & Technology

    2006-03-01

    Creating a KM Systems Thinking Framework...........................................................17 What is a KM-specific Journal...loop Learning ................................................................... 27 Figure 6. Combining KM Frameworks into a KM Systems Thinking Framework...30 Figure 7. KM Systems Thinking Framework .................................................................. 31 Figure 8. Content

  12. High energy neutrino detection with KM3NeT

    NASA Astrophysics Data System (ADS)

    Migliozzi, Pasquale; KM3NeT Collaboration

    2016-05-01

    The KM3NeT Collaboration has started the construction of a next generation high-energy neutrino telescope in the Mediterranean Sea: the largest and most sensitive neutrino research infrastructure. The full KM3NeT detector will be a several cubic kilometres distributed, networked infrastructure. In Italy, off the coast of Capo Passero, and in France, off the coast of Toulon. Thanks to its location in the Northern hemisphere and to its large instrumented volume, KM3NeT will be the optimal instrument to search for neutrinos from the Southern sky and in particular from the Galactic plane, thus making it complementary to IceCube. In this work the technologically innovative component of the detector, the status of construction and the first results from prototypes of the KM3NeT detector will be described as well as its capability to discover neutrino sources are reported.

  13. Akeno 20 km (2) air shower array (Akeno Branch)

    NASA Technical Reports Server (NTRS)

    Teshima, M.; Ohoka, H.; Matsubara, Y.; Hara, T.; Hatano, Y.; Hayashida, N.; He, C. X.; Honda, M.; Ishikawa, F.; Kamata, K.

    1985-01-01

    As the first stage of the future huge array, the Akeno air shower array was expanded to about 20 sq. km. by adding 19 scintillation detectors of 2.25 sq m area outside the present 1 sq. km. Akeno array with a new data collection system. These detectors are spaced about 1km from each other and connected by two optical fiber cables. This array has been in partial operation from 8th, Sep. 1984 and full operation from 20th, Dec. 1984. 20 sq m muon stations are planned to be set with 2km separation and one of them is now under construction. The origin of the highest energy cosmic rays is studied.

  14. Low- and high-affinity transport systems for citric acid in the yeast Candida utilis.

    PubMed Central

    Cássio, F; Leáo, C

    1991-01-01

    Citric acid-grown cells of the yeast Candida utilis induced two transport systems for citric acid, presumably a proton symport and a facilitated diffusion system for the charged and the undissociated forms of the acid, respectively. Both systems could be observed simultaneously when the transport was measured at 25 degrees C with labelled citric acid at pH 3.5 with the following kinetic parameters: for the low-affinity system, Vmax, 1.14 nmol of undissociated citric acid s-1 mg (dry weight) of cells-1, and Km, 0.59 mM undissociated acid; for the high-affinity system, Vmax, 0.38 nmol of citrate s-1 mg (dry weight) of cells-1, and Km, 0.056 mM citrate. At high pH values (above 5.0), the low-affinity system was absent or not measurable. The two transport systems exhibited different substrate specificities. Isocitric acid was a competitive inhibitor of citric acid for the high-affinity system, suggesting that these tricarboxylic acids used the same transport system, while aconitic, tricarballylic, trimesic, and hemimellitic acids were not competitive inhibitors. With respect to the low-affinity system, isocitric acid, L-lactic acid, and L-malic acid were competitive inhibitors, suggesting that all of these mono-, di-, and tricarboxylic acids used the same low-affinity transport system. The two transport systems were repressed by glucose, and as a consequence diauxic growth was observed. Both systems were inducible, and not only citric acid but also lactic acid and malic acid may induce those transport systems. The induction of both systems was not dependent on the relative concentration of the anionic form(s) and of undissociated citric acid in the culture medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1664712

  15. Range Reference Atmosphere 0-70 km Altitude, Barking Sands, Hawaii

    DTIC Science & Technology

    1983-12-01

    TABLE E. LIST OF PRIMARY PHYSICAL CONSTANTS P 0 = standard atmospheric pressure at sea level = 1.013250 x 10~ Newton ~m2 = 2116.22 lb/ft2 p0 = standard...S.D. MECAN KM P8 "a DEG K DEG K 0:0 K DCG K .000 22.139 2.701 .05 301.88 1.39 .49 292.17 2.0c -.48 329. 329. .005 22.090 2.694 .05 3c0.85 1.39 .49

  16. How does music aid 5 km of running?

    PubMed

    Bigliassi, Marcelo; León-Domínguez, Umberto; Buzzachera, Cosme F; Barreto-Silva, Vinícius; Altimari, Leandro R

    2015-02-01

    This research investigated the effects of music and its time of application on a 5-km run. Fifteen well-trained male long-distance runners (24.87 ± 2.47 years; 78.87 ± 10.57 kg; 178 ± 07 cm) participated in this study. Five randomized experimental conditions during a 5-km run on an official track were tested (PM: motivational songs, applied before 5 km of running; SM: slow motivational songs, applied during 5 km of running; FM: fast and motivational songs, applied during 5 km of running; CS: calm songs, applied after 5 km of running; CO: control condition). Psychophysiological assessments were performed before (functional near-infrared spectroscopy, heart rate variability [HRV], valence, and arousal), during (performance time, heart rate, and rate of perceived exertion [RPE]), and after (mood, RPE, and HRV) tests. The chosen songs were considered pleasurable and capable of activating. Furthermore, they activated the 3 assessed prefrontal cortex (PFC) areas (medial, right dorsolateral, and left dorsolateral) similarly, generating positive emotional consequences by autonomous system analysis. The first 800 m was accomplished faster for SM and FM compared with other conditions (p ≤ 0.05); moreover, there was a high probability of improving running performance when music was applied (SM: 89%; FM: 85%; PM: 39%). Finally, music was capable of accelerating vagal tonus after 5 km of running with CS (p ≤ 0.05). In conclusion, music was able to activate the PFC area, minimize perceptions, improve performance, and accelerate recovery during 5 km of running.

  17. Constant fields and constant gradients in open ionic channels.

    PubMed Central

    Chen, D P; Barcilon, V; Eisenberg, R S

    1992-01-01

    Ions enter cells through pores in proteins that are holes in dielectrics. The energy of interaction between ion and charge induced on the dielectric is many kT, and so the dielectric properties of channel and pore are important. We describe ionic movement by (three-dimensional) Nemst-Planck equations (including flux and net charge). Potential is described by Poisson's equation in the pore and Laplace's equation in the channel wall, allowing induced but not permanent charge. Asymptotic expansions are constructed exploiting the long narrow shape of the pore and the relatively high dielectric constant of the pore's contents. The resulting one-dimensional equations can be integrated numerically; they can be analyzed when channels are short or long (compared with the Debye length). Traditional constant field equations are derived if the induced charge is small, e.g., if the channel is short or if the total concentration gradient is zero. A constant gradient of concentration is derived if the channel is long. Plots directly comparable to experiments are given of current vs voltage, reversal potential vs. concentration, and slope conductance vs. concentration. This dielectric theory can easily be tested: its parameters can be determined by traditional constant field measurements. The dielectric theory then predicts current-voltage relations quite different from constant field, usually more linear, when gradients of total concentration are imposed. Numerical analysis shows that the interaction of ion and channel can be described by a mean potential if, but only if, the induced charge is negligible, that is to say, the electric field is spatially constant. Images FIGURE 1 PMID:1376159

  18. Effective cosmological constant induced by stochastic fluctuations of Newton's constant

    NASA Astrophysics Data System (ADS)

    de Cesare, Marco; Lizzi, Fedele; Sakellariadou, Mairi

    2016-09-01

    We consider implications of the microscopic dynamics of spacetime for the evolution of cosmological models. We argue that quantum geometry effects may lead to stochastic fluctuations of the gravitational constant, which is thus considered as a macroscopic effective dynamical quantity. Consistency with Riemannian geometry entails the presence of a time-dependent dark energy term in the modified field equations, which can be expressed in terms of the dynamical gravitational constant. We suggest that the late-time accelerated expansion of the Universe may be ascribed to quantum fluctuations in the geometry of spacetime rather than the vacuum energy from the matter sector.

  19. On the estimation errors of KM and V from time-course experiments using the Michaelis-Menten equation.

    PubMed

    Stroberg, Wylie; Schnell, Santiago

    2016-12-01

    The conditions under which the Michaelis-Menten equation accurately captures the steady-state kinetics of a simple enzyme-catalyzed reaction is contrasted with the conditions under which the same equation can be used to estimate parameters, KM and V, from progress curve data. Validity of the underlying assumptions leading to the Michaelis-Menten equation are shown to be necessary, but not sufficient to guarantee accurate estimation of KM and V. Detailed error analysis and numerical "experiments" show the required experimental conditions for the independent estimation of both KM and V from progress curves. A timescale, tQ, measuring the portion of the time course over which the progress curve exhibits substantial curvature provides a novel criterion for accurate estimation of KM and V from a progress curve experiment. It is found that, if the initial substrate concentration is of the same order of magnitude as KM, the estimated values of the KM and V will correspond to their true values calculated from the microscopic rate constants of the corresponding mass-action system, only so long as the initial enzyme concentration is less than KM.

  20. Optical constants of solid methane

    NASA Technical Reports Server (NTRS)

    Khare, Bishun N.; Thompson, W. R.; Sagan, C.; Arakawa, E. T.; Bruel, C.; Judish, J. P.; Khanna, R. K.; Pollack, J. B.

    1989-01-01

    Methane is the most abundant simple organic molecule in the outer solar system bodies. In addition to being a gaseous constituent of the atmospheres of the Jovian planets and Titan, it is present in the solid form as a constituent of icy surfaces such as those of Triton and Pluto, and as cloud condensate in the atmospheres of Titan, Uranus, and Neptune. It is expected in the liquid form as a constituent of the ocean of Titan. Cometary ices also contain solid methane. The optical constants for both solid and liquid phases of CH4 for a wide temperature range are needed for radiative transfer calculations, for studies of reflection from surfaces, and for modeling of emission in the far infrared and microwave regions. The astronomically important visual to near infrared measurements of solid methane optical constants are conspicuously absent from the literature. Preliminary results are presented of the optical constants of solid methane for the 0.4 to 2.6 micron region. K is reported for both the amorphous and the crystalline (annealed) states. Using the previously measured values of the real part of the refractive index, n, of liquid methane at 110 K n is computed for solid methane using the Lorentz-Lorentz relationship. Work is in progress to extend the measurements of optical constants n and k for liquid and solid to both shorter and longer wavelengths, eventually providing a complete optical constants database for condensed CH4.

  1. Gas-phase nitronium ion affinities.

    PubMed Central

    Cacace, F; de Petris, G; Pepi, F; Angelelli, F

    1995-01-01

    Evaluation of nitronium ion-transfer equilibria, L1NO2+ + L2 = L2NO2+ + L1 (where L1 and L2 are ligands 1 and 2, respectively) by Fourier-transform ion cyclotron resonance mass spectrometry and application of the kinetic method, based on the metastable fragmentation of L1(NO2+)L2 nitronium ion-bound dimers led to a scale of relative gas-phase nitronium ion affinities. This scale, calibrated to a recent literature value for the NO2+ affinity of water, led for 18 ligands, including methanol, ammonia, representative ketones, nitriles, and nitroalkanes, to absolute NO2+ affinities, that fit a reasonably linear general correlation when plotted vs. the corresponding proton affinities (PAs). The slope of the plot depends to a certain extent on the specific nature of the ligands and, hence, the correlations between the NO2+ affinities, and the PAs of a given class of compounds display a better linearity than the general correlation and may afford a useful tool for predicting the NO2+ affinity of a molecule based on its PA. The NO2+ binding energies are considerably lower than the corresponding PAs and well below the binding energies of related polyatomic cations, such as NO+, a trend consistent with the available theoretical results on the structure and the stability of simple NO2+ complexes. The present study reports an example of extension of the kinetic method to dimers, such as L1(NO2+)L2, bound by polyatomic ions, which may considerably widen its scope. Finally, measurement of the NO2+ affinity of ammonia allowed evaluation of the otherwise inaccessible PA of the amino group of nitramide and, hence, direct experimental verification of previous theoretical estimates. PMID:11607578

  2. Local fluctuations of ozone from 16 km to 45 km deduced from in situ vertical ozone profile

    NASA Technical Reports Server (NTRS)

    Moreau, G.; Robert, C.

    1994-01-01

    A vertical ozone profile obtained by an in situ ozone sonde from 16 km to 45 km, has allowed to observe local ozone concentration variations. These variations can be observed, thanks to a fast measurement system based on a UV absorption KrF excimer laser beam in a multipass cell. Ozone standard deviation versus altitude calculated from the mean is derived. Ozone variations or fluctuations are correlated with the different dynamic zones of the stratosphere.

  3. Detection of the structure near the 410 km and 660 km discontinuities in Japan subduction zone from the waveform triplication

    NASA Astrophysics Data System (ADS)

    Cui, H.; Zhou, Y.

    2015-12-01

    Slab subduction plays an important role in the mantle material circulation [Stern, 2002], and can also affect the feature of the 410 km and 660 km seismic discontinuities (410 and 660) [Lebedev et al., 2002]. Japan subduction zone is a natural laboratory for studying the mantle composition and velocity structure associated with the deep subduction of the Pacific plate. In this study, triplicated waveforms of an intermediate-depth earthquake at the Hokkaido of Japan (2011/10/21, 08:02:37.62, 142.5315°E, 43.8729°N, Mb6.0, relocated depth: 188 km) are retrieved from the dense Chinese Digital Seismic Network (CDSN). P and S waveforms are filtered with the band of 0.05-1.0 Hz and 0.02-0.5 Hz, respectively, and then integrated into the displacement data. The relative traveltime and synthetic waveform fitting is applied to mapping the deep structure. The best fitting models are obtained through the trial and error tests. We find a 15 km uplift of the 410 and a 25 km depression of the 660, indicating the cold environment caused by the subduction slab; both the 410 and 660 show the sharp discontinuity, but a smaller velocity contrast than the IASP91 model [Kennett and Engdahl, 1991]. Atop the 410 and 660, there are high-velocity layers associated with the subduction (or stagnant) slab. We also find a low-velocity anomaly with the thickness of ~65 km below the 660, which may relate to the slab dehydration or the hot upwelling at the top of the lower mantle. The seismic velocity ratio (VP/VS) shows a lower zone at the depth of ~210-395 km, showing the consistency with the low Poisson's ratio signature of the oceanic plate; a higher zone at the depth of ~560-685 km, implying the hydrous mantle transition zone.

  4. Inconstant Planck’s constant

    NASA Astrophysics Data System (ADS)

    Mangano, Gianpiero; Lizzi, Fedele; Porzio, Alberto

    2015-12-01

    Motivated by the Dirac idea that fundamental constants are dynamical variables and by conjectures on quantum structure of space-time at small distances, we consider the possibility that Planck constant ℏ is a time depending quantity, undergoing random Gaussian fluctuations around its measured constant mean value, with variance σ2 and a typical correlation timescale Δt. We consider the case of propagation of a free particle and a one-dimensional harmonic oscillator coherent state, and show that the time evolution in both cases is different from the standard behavior. Finally, we discuss how interferometric experiments or exploiting coherent electromagnetic fields in a cavity may put effective bounds on the value of τ = σ2Δt.

  5. Optical constants of solid methane

    NASA Technical Reports Server (NTRS)

    Khare, Bishun N.; Thompson, W. R.; Sagan, C.; Arakawa, E. T.; Bruel, C.; Judish, J. P.; Khanna, R. K.; Pollack, J. B.

    1990-01-01

    Methane is the most abundant simple organic molecule in the outer solar system bodies. In addition to being a gaseous constituent of the atmospheres of the Jovian planets and Titan, it is present in the solid form as a constituent of icy surfaces such as those of Triton and Pluto, and as cloud condensate in the atmospheres of Titan, Uranus, and Neptune. It is expected in the liquid form as a constituent of the ocean of Titan. Cometary ices also contain solid methane. The optical constants for both solid and liquid phases of CH4 for a wide temperature range are needed for radiative transfer calculations, for studies of reflection from surfaces, and for modeling of emission in the far infrared and microwave regions. The astronomically important visual to near infrared measurements of solid methane optical constants are conspicuously absent from the literature. Preliminary results are presented on the optical constants of solid methane for the 0.4 to 2.6 micrometer region. Deposition onto a substrate at 10 K produces glassy (semi-amorphous) material. Annealing this material at approximately 33 K for approximately 1 hour results in a crystalline material as seen by sharper, more structured bands and negligible background extinction due to scattering. The constant k is reported for both the amorphous and the crystalline (annealed) states. Typical values (at absorption maxima) are in the .001 to .0001 range. Below lambda = 1.1 micrometers the bands are too weak to be detected by transmission through the films less than or equal to 215 micrometers in thickness, employed in the studies to date. Using previously measured values of the real part of the refractive index, n, of liquid methane at 110 K, n is computed for solid methane using the Lorentz-Lorenz relationship. Work is in progress to extend the measurements of optical constants n and k for liquid and solid to both shorter and longer wavelengths, eventually providing a complete optical constants database for

  6. Protein A affinity precipitation of human immunoglobulin G.

    PubMed

    Janoschek, Lars; Freiherr von Roman, Matthias; Berensmeier, Sonja

    2014-08-15

    The potential of protein A affinity precipitation as an alternative method for traditional antibody purification techniques was investigated. Recombinant produced protein A from Staphylococcus aureus (SpA) was covalently linked to the pH-responsive copolymer Eudragit(®) S-100 and used for purification of human immunoglobulin G (hIgG). The Eudragit-SpA conjugate had a static binding capacity of 93.9 ± 2.8 mg hIgG per g conjugate and a dissociation constant of 787 ± 67 nM at 7 ± 1°C. The antibody was adsorbed rapidly onto Eudragit-SpA and reached equilibrium within 5 min. An excess of hIgG binding sites, provided by the conjugate, as well as adjusted elution conditions resulted in an appropriate hIgG purification performance. In summary, Eudragit-SpA was successfully applied to capture hIgG from a protein mixture with 65% antibody yield in the elution step. Nearly 96% purity and a purification factor of 12.4 were achieved. The Eudragit-SpA conjugate showed a stable ligand density over several cycles, which enabled reusability for repeated precipitation of hIgG. According to this, pH induced affinity precipitation can be seen as a potential alternative for protein A chromatography in antibody purification processes.

  7. Advances in affinity ligand-functionalized nanomaterials for biomagnetic separation.

    PubMed

    Fields, Conor; Li, Peng; O'Mahony, James J; Lee, Gil U

    2016-01-01

    The downstream processing of proteins remains the most significant cost in protein production, and is largely attributed to rigorous chromatographic purification protocols, where the stringency of purity for biopharmaceutical products sometimes exceeds 99%. With an ever burgeoning biotechnology market, there is a constant demand for alternative purification methodologies, to ameliorate the dependence on chromatography, while still adhering to regulatory concerns over product purity and safety. In this article, we present an up-to-date view of bioseparation, with emphasis on magnetic separation and its potential application in the field. Additionally, we discuss the economic and performance benefits of synthetic ligands, in the form of peptides and miniaturized antibody fragments, compared to full-length antibodies. We propose that adoption of synthetic affinity ligands coupled with magnetic adsorbents, will play an important role in enabling sustainable bioprocessing in the future.

  8. Cosmological constant from quantum spacetime

    NASA Astrophysics Data System (ADS)

    Majid, Shahn; Tao, Wen-Qing

    2015-06-01

    We show that a hypothesis that spacetime is quantum with coordinate algebra [xi,t ]=λPxi , and spherical symmetry under rotations of the xi, essentially requires in the classical limit that the spacetime metric is the Bertotti-Robinson metric, i.e., a solution of Einstein's equations with a cosmological constant and a non-null electromagnetic field. Our arguments do not give the value of the cosmological constant or the Maxwell field strength, but they cannot both be zero. We also describe the quantum geometry and the full moduli space of metrics that can emerge as classical limits from this algebra.

  9. On flows having constant vorticity

    NASA Astrophysics Data System (ADS)

    Roberts, Paul H.; Wu, Cheng-Chin

    2011-10-01

    Constant vorticity flows of a uniform fluid in a rigid ellipsoidal container rotating at a variable rate are considered. These include librationally driven and precessionally driven flows. The well-known Poincaré solution for precessionally driven flow in a spheroid is generalized to an ellipsoid with unequal principal axes. The dynamic stability of these flows is investigated, and of other flows in which the angular velocity of the container is constant in time. Solutions for the Chandler wobble are discussed. The role of an invariant, called here the Helmholtzian, is examined.

  10. Vibrational force constants for acetaldehyde

    NASA Astrophysics Data System (ADS)

    Nikolova, B.

    1990-05-01

    The vibrational force field of ethanal (acetaldehyde), CH 3CHO, is refined by using procedures with differential increments for the force constants (Commun. Dep. Chem., Bulg. Acad. Sci., 21/3 (1988) 433). The characteristics general valence force constants of the high-dimensional symmetry classes of ethanal, A' of tenth and A″ of fifth order, are determined for the experimental assignment of bands. The low barrier to hindered internal rotation about the single carbon—carbon bond is quantitatively estimated on the grounds of normal vibrational analysis.

  11. Cosmologies with variable gravitational constant

    SciTech Connect

    Narkikar, J.V.

    1983-03-01

    In 1937 Dirac presented an argument, based on the socalled large dimensionless numbers, which led him to the conclusion that the Newtonian gravitational constant G changes with epoch. Towards the end of the last century Ernst Mach had given plausible arguments to link the property of inertia of matter to the large scale structure of the universe. Mach's principle also leads to cosmological models with a variable gravitational constant. Three cosmologies which predict a variable G are discussed in this paper both from theoretical and observational points of view.

  12. Gravity Waves Near 300 km Over the Polar Caps

    NASA Technical Reports Server (NTRS)

    Johnson, F. S.; Hanson, W. B.; Hodges, R. R.; Coley, W. R.; Carignan, G. R.; Spencer, N. W.

    1995-01-01

    Distinctive wave forms in the distributions of vertical velocity and temperature of both neutral particles and ions are frequently observed from Dynamics Explorer 2 at altitudes above 250 km over the polar caps. These are interpreted as being due to internal gravity waves propagating in the neutral atmosphere. The disturbances characterized by vertical velocity perturbations of the order of 100 m/s and horizontal wave lengths along the satellite path of about 500 km. They often extend across the entire polar cap. The associated temperature perturbations indicate that the horizontal phase progression is from the nightside to the dayside. Vertical displacements are inferred to be of the order of 10 km and the periods to be of the order of 10(exp 3) s. The waves must propagate in the neutral atmosphere, but they usually are most clearly recognizable in the observations of ion vertical velocity and ion temperature. By combining the neutral pressure calculated from the observed neutral concentration and temperature with the vertical component of the neutral velocity, an upward energy flux of the order of 0.04 erg/sq cm-s at 250 km has been calculated, which is about equal to the maximum total solar ultraviolet heat input above that altitude. Upward energy fluxes calculated from observations on orbital passes at altitudes from 250 to 560 km indicate relatively little attenuation with altitude.

  13. The KM3NeT Digital Optical Module

    NASA Astrophysics Data System (ADS)

    Vivolo, Daniele

    2016-04-01

    KM3NeT is a European deep-sea multidisciplinary research infrastructure in the Mediterranean Sea. It will host a km3-scale neutrino telescope and dedicated instruments for long-term and continuous measurements for Earth and Sea sciences. The KM3NeT neutrino telescope is a 3-dimensional array of Digital Optical Modules, suspended in the sea by means of vertical string structures, called Detection Units, supported by two pre-stretched Dyneema ropes, anchored to the seabed and kept taut with a system of buoys. The Digital Optical Module represents the active part of the neutrino telescope. It is composed by a 17-inch, 14 mm thick borosilicate glass (Vitrovex) spheric vessel housing 31 photomultiplier tubes with 3-inch photocathode diameter and the associated front-end and readout electronics. The technical solution adopted for the KM3NeT optical modules is characterized by an innovative design, considering that existing neutrino telescopes, Baikal, IceCube and ANTARES, all use large photomultipliers, typically with a diameter of 8″ or 10″. It offers several advantages: higher sensitive surface (1260 cm2), weaker sensitivity to Earth's magnetic field, better distinction between single-photon and multi-photon events (photon counting) and directional information with an almost isotropic field of view. In this contribution the design and the performance of the KM3NeT Digital Optical Modules are discussed, with a particular focus on enabling technologies and integration procedure.

  14. Proton Affinity Calculations with High Level Methods.

    PubMed

    Kolboe, Stein

    2014-08-12

    Proton affinities, stretching from small reference compounds, up to the methylbenzenes and naphthalene and anthracene, have been calculated with high accuracy computational methods, viz. W1BD, G4, G3B3, CBS-QB3, and M06-2X. Computed and the currently accepted reference proton affinities are generally in excellent accord, but there are deviations. The literature value for propene appears to be 6-7 kJ/mol too high. Reported proton affinities for the methylbenzenes seem 4-5 kJ/mol too high. G4 and G3 computations generally give results in good accord with the high level W1BD. Proton affinity values computed with the CBS-QB3 scheme are too low, and the error increases with increasing molecule size, reaching nearly 10 kJ/mol for the xylenes. The functional M06-2X fails markedly for some of the small reference compounds, in particular, for CO and ketene, but calculates methylbenzene proton affinities with high accuracy.

  15. Classification of neocortical interneurons using affinity propagation.

    PubMed

    Santana, Roberto; McGarry, Laura M; Bielza, Concha; Larrañaga, Pedro; Yuste, Rafael

    2013-01-01

    In spite of over a century of research on cortical circuits, it is still unknown how many classes of cortical neurons exist. In fact, neuronal classification is a difficult problem because it is unclear how to designate a neuronal cell class and what are the best characteristics to define them. Recently, unsupervised classifications using cluster analysis based on morphological, physiological, or molecular characteristics, have provided quantitative and unbiased identification of distinct neuronal subtypes, when applied to selected datasets. However, better and more robust classification methods are needed for increasingly complex and larger datasets. Here, we explored the use of affinity propagation, a recently developed unsupervised classification algorithm imported from machine learning, which gives a representative example or exemplar for each cluster. As a case study, we applied affinity propagation to a test dataset of 337 interneurons belonging to four subtypes, previously identified based on morphological and physiological characteristics. We found that affinity propagation correctly classified most of the neurons in a blind, non-supervised manner. Affinity propagation outperformed Ward's method, a current standard clustering approach, in classifying the neurons into 4 subtypes. Affinity propagation could therefore be used in future studies to validly classify neurons, as a first step to help reverse engineer neural circuits.

  16. Classification of neocortical interneurons using affinity propagation

    PubMed Central

    Santana, Roberto; McGarry, Laura M.; Bielza, Concha; Larrañaga, Pedro; Yuste, Rafael

    2013-01-01

    In spite of over a century of research on cortical circuits, it is still unknown how many classes of cortical neurons exist. In fact, neuronal classification is a difficult problem because it is unclear how to designate a neuronal cell class and what are the best characteristics to define them. Recently, unsupervised classifications using cluster analysis based on morphological, physiological, or molecular characteristics, have provided quantitative and unbiased identification of distinct neuronal subtypes, when applied to selected datasets. However, better and more robust classification methods are needed for increasingly complex and larger datasets. Here, we explored the use of affinity propagation, a recently developed unsupervised classification algorithm imported from machine learning, which gives a representative example or exemplar for each cluster. As a case study, we applied affinity propagation to a test dataset of 337 interneurons belonging to four subtypes, previously identified based on morphological and physiological characteristics. We found that affinity propagation correctly classified most of the neurons in a blind, non-supervised manner. Affinity propagation outperformed Ward's method, a current standard clustering approach, in classifying the neurons into 4 subtypes. Affinity propagation could therefore be used in future studies to validly classify neurons, as a first step to help reverse engineer neural circuits. PMID:24348339

  17. Determination of Relative Counterion Binding Constant to Cationic Micelles.

    PubMed

    Khalid, Khalisanni; Noh, Muhammad Azri Mohd; Zain, Sharifuddin Md; Khan, M Niyaz

    2017-04-01

    The efficiency of counterion affinity towards ionic micelles is often described in terms of the degree of counterion binding (β X ) to ionic micelles or the conventional ion-exchange constant ([Formula: see text]) or relative binding constant ([Formula: see text]) of X (-) and Br(-) counterions. This review describes the use of ionized phenyl salicylate ions, PSa(-), as a new probe to determine [Formula: see text] values using a semiempirical spectrophotometric method. The value of [Formula: see text] is found to be comparable to reported values obtained using different probes by the semiempirical kinetic method as well as different physical methods. Application of semiempirical methods for calculation of [Formula: see text] or [Formula: see text] values involves an inherent assumption that these values are independent of the physicochemical characteristics of the probe molecule.

  18. Influence of the galloyl moiety in tea catechins on binding affinity for human serum albumin.

    PubMed

    Minoda, Kanako; Ichikawa, Tatsuya; Katsumata, Tomoharu; Onobori, Ken-ichi; Mori, Taiki; Suzuki, Yukiko; Ishii, Takeshi; Nakayama, Tsutomu

    2010-01-01

    The major catechins of green tea extract are (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECg), and (-)-epigallocatechin gallate (EGCg). Recent research has indicated that catechins form complexes with human serum albumin (HSA) in blood, and differences in their binding affinity toward HSA are believed to modulate their bioavailability. In this study, we kinetically investigated the interaction between the catechins and HSA immobilized on a quartz-crystal microbalance (QCM). The association constants obtained from the frequency changes of QCM revealed interactions of ECg and EGCg with HSA that are 100 times stronger than those of EC and EGC. Furthermore, comparisons of these catechins by native-gel electrophoresis/blotting with redox-cycling staining revealed that, in a phosphate buffer, ECg and EGCg have a higher binding affinity toward HSA than EC and EGC. These observations indicate that catechins with a galloyl moiety have higher binding affinities toward HSA than catechins lacking a galloyl moiety.

  19. Development of prediction models for radioactive caesium distribution within the 80-km radius of the Fukushima Daiichi nuclear power plant.

    PubMed

    Kinase, Sakae; Takahashi, Tomoyuki; Sato, Satoshi; Sakamoto, Ryuichi; Saito, Kimiaki

    2014-08-01

    Preliminary prediction models have been studied for the radioactive caesium distribution within the 80-km radius of the Fukushima Daiichi nuclear power plant. The models were represented by exponential functions using ecological half-life of radioactive caesium in the environment. The ecological half-lives were derived from the changes in ambient dose equivalent rates through vehicle-borne surveys. It was found that the ecological half-lives of radioactive caesium were not constant within the 80-km radius of the Fukushima Daiichi nuclear power plant. The ecological half-life of radioactive caesium in forest areas was found to be much larger than that in urban and water areas.

  20. Identity, Affinity, Reality: Making the Case for Affinity Groups in Elementary School

    ERIC Educational Resources Information Center

    Parsons, Julie; Ridley, Kimberly

    2012-01-01

    Affinity groups are places where students build connections and process "ouch" moments from their classes. Children talk about the isolation they sometimes feel. The relationships students gain through race-based affinity groups enable them to feel less alone with their emotions and help them build a stronger sense of self. At the same…

  1. Stepparents' Affinity-Seeking and Affinity-Maintaining Strategies with Stepchildren.

    ERIC Educational Resources Information Center

    Ganong, Lawrence; Coleman, Marilyn; Fine, Mark; Martin, Patricia

    1999-01-01

    Examines the strategies that stepparents use to develop and maintain affinity with stepchildren and the effects that these strategies have on the development of stepparent-stepchildren relationships. Thirty-one affinity-seeking strategies are identified. Results show that dyadic activities worked best, but it is important that stepchildren…

  2. Reliability of 5-km Running Performance in a Competitive Environment

    ERIC Educational Resources Information Center

    Hurst, Philip; Board, Lisa

    2017-01-01

    The aim of this study was to examine the reliability of a 5-km time-trial during a competitive outdoor running event. Fifteen endurance runners (age = 29.5 ± 4.3 years, height = 1.75 ± 0.08 m, body mass = 71.0 ± 7.1 kg, 5-km lifetime personal best = 19:13 ± 1:13 minutes) completed two competitive 5-km time-trials over 2 weeks. No systematic…

  3. Energy conservation and constants variation.

    NASA Astrophysics Data System (ADS)

    Kraiselburd, L.; Miller Bertolami, M. M.; Sisterna, P.; Vucetich, H.

    If fundamental constants vary, the internal energy of macroscopic bodies should change. This should produce observable effects. It is shown that those effects can produce upper bounds on the variation of much lower than those coming from Eötvös experiments.

  4. Variations of the solar constant

    SciTech Connect

    Sofia, S.

    1981-12-01

    The variations in data received from rocket-borne and balloon-borne instruments are discussed. Indirect techniques to measure and monitor the solar constant are presented. Emphasis is placed on the correlation of data from the Solar Maximum Mission and the Nimbus 7 satellites. Abstracts of individual items from the workshop were prepared separately for the data base.

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

    PubMed

    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.

  6. Affine coherent states and Toeplitz operators

    NASA Astrophysics Data System (ADS)

    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’.

  7. Non-affine elasticity in jammed systems

    NASA Astrophysics Data System (ADS)

    Maloney, Craig

    2006-03-01

    Symmetry dictates that perfect crystals should deform homogeneously, or affinely, under external load, and computing the elastic moduli from the underlying interaction potential is then straightforward. For disordered materials no such simple procedure exists, and recent numerical works have demonstrated that non-affine corrections can dramatically reduce the naive expectation for the shear modulus in a broad class of disordered systems and may control rigidity loss in the zero pressure limit in purely repulsive systems, i.e. the unjamming transition (c.f. [O'Hern et. al. PRE 68, 011306 (2003)]). We present numerical results and an analytical framework for the study of these non-affine corrections to the elastic response of disordered packings.

  8. Biomimetic affinity ligands for protein purification.

    PubMed

    Sousa, Isabel T; Taipa, M Angela

    2014-01-01

    The development of sophisticated molecular modeling software and new bioinformatic tools, as well as the emergence of data banks containing detailed information about a huge number of proteins, enabled the de novo intelligent design of synthetic affinity ligands. Such synthetic compounds can be tailored to mimic natural biological recognition motifs or to interact with key surface-exposed residues on target proteins and are designated as "biomimetic ligands." A well-established methodology for generating biomimetic or synthetic affinity ligands integrates rational design with combinatorial solid-phase synthesis and screening, using the triazine scaffold and analogues of amino acids side chains to create molecular diversity.Triazine-based synthetic ligands are nontoxic, low-cost, highly stable compounds that can replace advantageously natural biological ligands in the purification of proteins by affinity-based methodologies.

  9. Simulation of CO2 release at 800 km altitude

    NASA Astrophysics Data System (ADS)

    Setayesh, A.

    1993-08-01

    The SOCRATES contamination-interaction code has been used to simulate the reactions of 0 + CO2 yields CO2(v) + O, O + CO2 - CO(v) + O2, and CO2 + H - CO + OH(v) at an altitude of 800 km in both ram and wake directions of the spacecraft. These simulations show that the radiation from these reactions can be measurable for the parameters which have been used in these calculations. The investigation carries out the simulations as much as 30 km from the spacecraft. The radiative intensity of CO(v) and OH(v) show the highest and lowest, respectively.

  10. Digital optical module electronics of KM3NeT

    NASA Astrophysics Data System (ADS)

    Real, D.; Calvo, D.

    2016-11-01

    The KM3NeT neutrino telescope is being built on the Mediterranean sea and, once completed, it will be composed by tens of thousands of glass spheres (nodes) including each 31 of small photocathode (3"). The readout and data acquisition system of KM3NeT has to collect, treat and send to shore, in an economic way, the enormous amount of data produced by the photomultipliers and at the same time to provide time synchronization between each node at the level of 1 ns. It is described in the present article all the electronics developed for achieving this goal.

  11. Cascade sensitivity studies for KM3NeT

    NASA Astrophysics Data System (ADS)

    Fusco, Luigi Antonio

    2016-07-01

    KM3NeT is a future research infrastructure in the deep seas of the Mediterranean housing a large scale neutrino telescope. The first phase of construction of the telescope has started. Next step is an intermediate phase realising a detector volume of about one-third of the final detector volume. We report on calculations of the sensitivity of the KM3NeT detector to showering neutrino events, the strategy to optimise the detector to a cosmic neutrino flux analogous to the one reported by the IceCube Collaboration and the results of this strategy applied to the intermediate phase detector.

  12. Neutral winds above 200Km at high latitudes

    NASA Technical Reports Server (NTRS)

    Meriwether, J. W.; Heppner, J. P.; Stolarik, J. D.; Wescott, E. M.

    1972-01-01

    Motion from multiple chemical releases between 200 and 300 km from 15 rockets launched from 4 high latitude locations are analyzed. The observations in the evening and midnight hours at magnetic altitudes or = 65 deg suggest that in these regions ion drag is the dominant force in driving neutral winds between 200 and 300 km. This conclusion is based on both the agreement between ion and neutral drift directions, and the fact that there are distinct changes in the wind associated with (a) the reversal in east-west ion drift at the Harang discontinuity, and (b) the transition from auroral belt, sunward ion drift and polar cap, anti-solar ion drift.

  13. Use of Affinity Diagrams as Instructional Tools in Inclusive Classrooms.

    ERIC Educational Resources Information Center

    Haselden, Polly G.

    2003-01-01

    This article describes how the affinity diagram, a tool for gathering information and organizing it into natural groupings, can be used in inclusive classrooms. It discusses how students can be taught to use an affinity diagram, how affinity diagrams can be used to reflect many voices, and how affinity diagrams can be used to plan class projects.…

  14. New Quasar Studies Keep Fundamental Physical Constant Constant

    NASA Astrophysics Data System (ADS)

    2004-03-01

    Very Large Telescope sets stringent limit on possible variation of the fine-structure constant over cosmological time Summary Detecting or constraining the possible time variations of fundamental physical constants is an important step toward a complete understanding of basic physics and hence the world in which we live. A step in which astrophysics proves most useful. Previous astronomical measurements of the fine structure constant - the dimensionless number that determines the strength of interactions between charged particles and electromagnetic fields - suggested that this particular constant is increasing very slightly with time. If confirmed, this would have very profound implications for our understanding of fundamental physics. New studies, conducted using the UVES spectrograph on Kueyen, one of the 8.2-m telescopes of ESO's Very Large Telescope array at Paranal (Chile), secured new data with unprecedented quality. These data, combined with a very careful analysis, have provided the strongest astronomical constraints to date on the possible variation of the fine structure constant. They show that, contrary to previous claims, no evidence exist for assuming a time variation of this fundamental constant. PR Photo 07/04: Relative Changes with Redshift of the Fine Structure Constant (VLT/UVES) A fine constant To explain the Universe and to represent it mathematically, scientists rely on so-called fundamental constants or fixed numbers. The fundamental laws of physics, as we presently understand them, depend on about 25 such constants. Well-known examples are the gravitational constant, which defines the strength of the force acting between two bodies, such as the Earth and the Moon, and the speed of light. One of these constants is the so-called "fine structure constant", alpha = 1/137.03599958, a combination of electrical charge of the electron, the Planck constant and the speed of light. The fine structure constant describes how electromagnetic forces hold

  15. Constant-bandwidth constant-temperature hot-wire anemometer.

    PubMed

    Ligeza, P

    2007-07-01

    A constant-temperature anemometer (CTA) enables the measurement of fast-changing velocity fluctuations. In the classical solution of CTA, the transmission band is a function of flow velocity. This is a minor drawback when the mean flow velocity does not significantly change, though it might lead to dynamic errors when flow velocity varies over a considerable range. A modification is outlined, whereby an adaptive controller is incorporated in the CTA system such that the anemometer's transmission band remains constant in the function of flow velocity. For that purpose, a second feedback loop is provided, and the output signal from the anemometer will regulate the controller's parameters such that the transmission bandwidth remains constant. The mathematical model of a CTA that has been developed and model testing data allow a through evaluation of the proposed solution. A modified anemometer can be used in measurements of high-frequency variable flows in a wide range of velocities. The proposed modification allows the minimization of dynamic measurement errors.

  16. Cation affinity numbers of Lewis bases.

    PubMed

    Lindner, Christoph; Tandon, Raman; Maryasin, Boris; Larionov, Evgeny; Zipse, Hendrik

    2012-01-01

    Using selected theoretical methods the affinity of a large range of Lewis bases towards model cations has been quantified. The range of model cations includes the methyl cation as the smallest carbon-centered electrophile, the benzhydryl and trityl cations as models for electrophilic substrates encountered in Lewis base-catalyzed synthetic procedures, and the acetyl cation as a substrate model for acyl-transfer reactions. Affinities towards these cationic electrophiles are complemented by data for Lewis-base addition to Michael acceptors as prototypical neutral electrophiles.

  17. New unitary affine-Virasoro constructions

    SciTech Connect

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

    1990-06-20

    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.

  18. On the electron affinity of B2

    SciTech Connect

    Glezakou, Vanda A.; Taylor, Peter

    2009-02-02

    We present the results of high-level ab initio calculations on the electron affinity of B2. Our new best estimate of 1.93±0.03 eV is in agreement with previous calculations as well as the sole existing experimental estimate of 1.8 eV, as derived from quantities with an uncertainty of 0.4 eV. The electron affinity of atomic boron, which is much smaller, is also calculated for comparison, and again found to be in good agreement with experiment. Pacific Northwest National Laboratory is operated by Battelle for the US Department of Energy.

  19. Negative Electron Affinity Mechanism for Diamond Surfaces

    NASA Technical Reports Server (NTRS)

    Krainsky, I. L.; Asnin, V. M.

    1998-01-01

    The energy distribution of the secondary electrons for chemical vacuum deposited diamond films with Negative Electron Affinity (NEA) was investigated. It was found that while for completely hydrogenated diamond surfaces the negative electron affinity peak in the energy spectrum of the secondary electrons is present for any energy of the primary electrons, for partially hydrogenated diamond surfaces there is a critical energy above which the peak is present in the spectrum. This critical energy increases sharply when hydrogen coverage of the diamond surface diminishes. This effect was explained by the change of the NEA from the true type for the completely hydrogenated surface to the effective type for the partially hydrogenated surfaces.

  20. Evidence of multi-affinity in the Japanese stock market

    NASA Astrophysics Data System (ADS)

    Katsuragi, Hiroaki

    2000-04-01

    Fluctuations of the Japanese stock market (Tokyo Stock Price Index: TOPIX) are analyzed using a multi-affine analysis method. In the research to date, only some simulated self-affine models have shown multi-affinity. In most experiments using observations of self-affine fractal profiles, multi-affinity has not been found. However, we find evidence of multi-affinity in fluctuations of the Japanese stock market (TOPIX). The qth-order Hurst exponent Hq varies with changes in q. This multi-affinity indicates that there are plural mechanisms that affect the same time scale as stock market price fluctuation dynamics.

  1. The constant region affects antigen binding of antibodies to DNA by altering secondary structure.

    PubMed

    Xia, Yumin; Janda, Alena; Eryilmaz, Ertan; Casadevall, Arturo; Putterman, Chaim

    2013-11-01

    We previously demonstrated an important role of the constant region in the pathogenicity of anti-DNA antibodies. To determine the mechanisms by which the constant region affects autoantibody binding, a panel of isotype-switch variants (IgG1, IgG2a, IgG2b) was generated from the murine PL9-11 IgG3 autoantibody. The affinity of the PL9-11 antibody panel for histone was measured by surface plasmon resonance (SPR). Tryptophan fluorescence was used to determine wavelength shifts of the antibody panel upon binding to DNA and histone. Finally, circular dichroism spectroscopy was used to measure changes in secondary structure. SPR analysis revealed significant differences in histone binding affinity between members of the PL9-11 panel. The wavelength shifts of tryptophan fluorescence emission were found to be dependent on the antibody isotype, while circular dichroism analysis determined that changes in antibody secondary structure content differed between isotypes upon antigen binding. Thus, the antigen binding affinity is dependent on the particular constant region expressed. Moreover, the effects of antibody binding to antigen were also constant region dependent. Alteration of secondary structures influenced by constant regions may explain differences in fine specificity of anti-DNA antibodies between antibodies with similar variable regions, as well as cross-reactivity of anti-DNA antibodies with non-DNA antigens.

  2. Gravity wave vertical energy flux at 95 km

    NASA Technical Reports Server (NTRS)

    Jacob, P. G.; Jacka, F.

    1985-01-01

    A three-field photometer (3FP) located at Mt. Torrens near Adelaide, is capable of monitoring different airglow emissions from three spaced fields in the sky. A wheel containing up to six different narrow bandpass interference filters can be rotated, allowing each of the filters to be sequentially placed into each of the three fields. The airglow emission of interest is the 557.7 nm line which has an intensity maximum at 95 km. Each circular field of view is located at the apexes of an equilateral triangle centered on zenith with diameters of 5 km and field separations of 13 km when projected to the 95-km level. The sampling period was 30 seconds and typical data lengths were between 7 and 8 hours. The analysis and results from the interaction of gravity waves on the 557.7 nm emission layer are derived using an atmospheric model similar to that proposed by Hines (1960) where the atmosphere is assumed isothermal and perturbations caused by gravity waves are small and adiabatic, therefore, resulting in linearized equations of motion. In the absence of waves, the atmosphere is also considered stationary. Thirteen nights of quality data from January 1983 to October 1984, covering all seasons, are used in this analysis.

  3. Body Composition Measurements of 161-km Ultramarathon Participants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study compares body composition characteristics with performance among participants in a 161-km trail ultramarathon. Height, mass, and percent body fat from bioimpedence spectroscopy were measured on 72 starters. Correlation analyses were used to compare body characteristics with finish time, ...

  4. Models of earth's atmosphere (90 to 2500 km)

    NASA Technical Reports Server (NTRS)

    1973-01-01

    This monograph replaces a monograph on the upper atmosphere which was a computerized version of Jacchia's model. The current model has a range from 90 to 2500 km. In addition to the computerized model, a quick-look prediction method is given that may be used to estimate the density for any time and spatial location without using a computer.

  5. Estimation of terrestrial carbon fluxes with 1km by 1km spatial-resolution using satellite- driven model

    NASA Astrophysics Data System (ADS)

    Sasai, T.; Nasahara, K.; Ito, A.; Saigusa, N.; Hirata, R.; Takagi, K.; Oikawa, T.

    2008-12-01

    Terrestrial carbon cycle is strongly affected by some local natural phenomena and human-induced activities, which bring change to the carbon exchanges via vegetation and soil microbe activities. In order to accurately understand a realistic spatial pattern in carbon exchanges including such an effect of local-scale events, we need to calculate carbon fluxes and storages with as detailed spatial resolution as possible. In response to this, we attempt to estimate terrestrial carbon fluxes with 1km by 1km spatial resolution using satellite-driven model. Study area of the model estimation is the Further East Asia region, which lies at 30-50 north latitude and 125-150 east longitude. The model is the Biosphere model integrating Eco-physiological And Mechanistic approaches using Satellite data (BEAMS) [Sasai et al., 2005, 2007]. Being aim at simulating terrestrial carbon exchanges under more realistic land surface condition, we applied as many as possible of satellite-observation products such as the standard MODIS, TRMM, and SRTM high-level land products as model inputs. In the model validation, we compared between model estimations and eddy covariance measurements at four flux sites. As a result, a correlation coefficient of the terrestrial carbon fluxes between estimations and measurements were high values, leading up that the model estimations are virtually reasonable. In model analysis, BEAMS was operated with 1km by 1km spatial resolution from 2001 to 2006. Spatial distributions in the annual mean NPP and NEP showed that high values were distributed over the hilly and plateau regions, and they were gradually decreasing towards the urban and high mountain areas, meaning that we could reflect an impact of the local-scale events in the carbon flux estimations. In future, we would extend study area to the East Asia region, and the carbon exchange map with 1km by 1km spatial- resolution is distributed on the website.

  6. Definition of the affinity of binding between human von Willebrand factor and coagulation factor VIII.

    PubMed

    Ganz, P R; Atkins, J S; Palmer, D S; Dudani, A K; Hashemi, S; Luison, F

    1991-10-15

    Factor VIII and von Willebrand factor are two plasma proteins essential for effective hemostasis. In vivo, they form a non-covalent complex whose association appears to be metal ion dependent. However, a precise definition of the nature of the molecular forces governing their association remains to be defined, as does their binding affinity. In this paper we have determined the dissociation constant and stoichiometry for Factor VIII binding to immobilized von Willebrand factor. The data demonstrate that these proteins interact saturably and with relatively high affinity. Computer assisted analyses of the Scatchard data favour a two site binding model. The higher affinity site was found to have a Kd of 62 (+/- 13) x 10(-12) M while that of the lower affinity site was 380 (+/- 92) x 10(-12) M. The density of Factor VIII binding sites (Bmax) present on von Willebrand factor was 31 (+/- 3) pM for the high affinity binding site and 46 (+/- 6) pM for the lower site, corresponding to a calculated Factor VIII: von Willebrand factor binding ratio of 1:33 and 1:23, respectively.

  7. On the binding affinity of macromolecular interactions: daring to ask why proteins interact

    PubMed Central

    Kastritis, Panagiotis L.; Bonvin, Alexandre M. J. J.

    2013-01-01

    Interactions between proteins are orchestrated in a precise and time-dependent manner, underlying cellular function. The binding affinity, defined as the strength of these interactions, is translated into physico-chemical terms in the dissociation constant (Kd), the latter being an experimental measure that determines whether an interaction will be formed in solution or not. Predicting binding affinity from structural models has been a matter of active research for more than 40 years because of its fundamental role in drug development. However, all available approaches are incapable of predicting the binding affinity of protein–protein complexes from coordinates alone. Here, we examine both theoretical and experimental limitations that complicate the derivation of structure–affinity relationships. Most work so far has concentrated on binary interactions. Systems of increased complexity are far from being understood. The main physico-chemical measure that relates to binding affinity is the buried surface area, but it does not hold for flexible complexes. For the latter, there must be a significant entropic contribution that will have to be approximated in the future. We foresee that any theoretical modelling of these interactions will have to follow an integrative approach considering the biology, chemistry and physics that underlie protein–protein recognition. PMID:23235262

  8. Affinity improvement by fine tuning of single-chain variable fragment against aflatoxin B1.

    PubMed

    Min, Won-Ki; Na, Kang-In; Yoon, Jung-Hyun; Heo, Yoon-Jee; Lee, Daesang; Kim, Sung-Gun; Seo, Jin-Ho

    2016-10-15

    Aflatoxin B1 (AFB1) produced in Aspergillus flavus is a major hepatocarcinogen found in foods and feed. For effective immunological detection of AFB1 at low concentrations, the development of high affinity antibody for AFB1 is required. Previously, an affinity-maturated single-chain variable fragment containing 6 mutations (scFv-M37) was isolated from an artificial mutagenic library, which showed a 9-fold higher affinity than its wild type scFv. In this study, the effect of the 6 mutated residues on the affinity improvement was characterized using surface plasmon resonance analysis, which identified a deleterious mutation (VH-A110T) located on a framework region of the scFv-M37. The back mutation of VH-A110T resulted in a 3.2-fold affinity improvement, which was attributed to decrease of dissociation rate constant (kd) in interaction between AFB1 and the back mutant scFv. The biophysical analyses using circular dichroism and gel filtration revealed that the back mutation of VH-A110T caused a subtle conformational change of the scFv toward tighter binding to AFB1.

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

    PubMed

    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.

  10. Dielectric-constant gas thermometry

    NASA Astrophysics Data System (ADS)

    Gaiser, Christof; Zandt, Thorsten; Fellmuth, Bernd

    2015-10-01

    The principles, techniques and results from dielectric-constant gas thermometry (DCGT) are reviewed. Primary DCGT with helium has been used for measuring T-T90 below the triple point of water (TPW), where T is the thermodynamic temperature and T90 is the temperature on the international temperature scale of 1990 (ITS-90), and, in an inverse regime with T as input quantity, for determining the Boltzmann constant at the TPW. Furthermore, DCGT allows the determination of several important material properties including the polarizability of neon and argon as well as the virial coefficients of helium, neon, and argon. With interpolating DCGT (IDCGT), the ITS-90 has been approximated in the temperature range from 4 K to 25 K. An overview and uncertainty budget for each of these applications of DCGT is provided, accompanied by corroborating evidence from the literature or, for IDCGT, a CIPM key comparison.

  11. Three pion nucleon coupling constants

    NASA Astrophysics Data System (ADS)

    Ruiz Arriola, E.; Amaro, J. E.; Navarro Pérez, R.

    2016-08-01

    There exist four pion nucleon coupling constants, fπ0pp, - fπ0nn, fπ+pn/2 and fπ-np/2 which coincide when up and down quark masses are identical and the electron charge is zero. While there is no reason why the pion-nucleon-nucleon coupling constants should be identical in the real world, one expects that the small differences might be pinned down from a sufficiently large number of independent and mutually consistent data. Our discussion provides a rationale for our recent determination fp2 = 0.0759(4),f 02 = 0.079(1),f c2 = 0.0763(6), based on a partial wave analysis of the 3σ self-consistent nucleon-nucleon Granada-2013 database comprising 6713 published data in the period 1950-2013.

  12. Renormalization constants from string theory.

    NASA Astrophysics Data System (ADS)

    di Vecchia, P.; Magnea, L.; Lerda, A.; Russo, R.; Marotta, R.

    The authors review some recent results on the calculation of renormalization constants in Yang-Mills theory using open bosonic strings. The technology of string amplitudes, supplemented with an appropriate continuation off the mass shell, can be used to compute the ultraviolet divergences of dimensionally regularized gauge theories. The results show that the infinite tension limit of string amplitudes corresponds to the background field method in field theory.

  13. The Greenland gravitational constant experiment.

    NASA Astrophysics Data System (ADS)

    Zumberge, M. A.; Ander, M. E.; Lautzenhiser, T. V.; Parker, R. L.; Aiken, C. L. V.; Gorman, M. R.; Nieto, M. M.; Cooper, A. P. R.; Ferguson, J. F.; Fisher, E.; Greer, J.; Hammer, P.; Hansen, B. L.; McMechan, G. A.; Sasagawa, G. S.; Sidles, C.; Stevenson, J. M.; Wirtz, J.

    1990-09-01

    An Airy-type geophysical experiment was conducted in a 2-km-deep hole in the Greenland ice cap at depths between 213 m and 1673 m to test for possible violations of Newton's inverse square law. Gravity measurements were made at eight depths in 183-m intervals with a LaCoste & Romberg borehole gravity meter. An anomalous variation in gravity totaling 3.87 mGal (3.87x10-5m/s2) in the depth interval of 1460 m was observed. This may be attributed either to a breakdown of Newtonian gravity or to unexpected density variations in the rock below the ice.

  14. On modality and complexity of affine embeddings

    SciTech Connect

    Arzhantsev, I V

    2001-08-31

    Let G be a reductive algebraic group and let H be a reductive subgroup of G. The modality of a G-variety X is the largest number of the parameters in a continuous family of G-orbits in X. A precise formula for the maximum value of the modality over all affine embeddings of the homogeneous space G/H is obtained.

  15. Modern affinity reagents: Recombinant antibodies and aptamers.

    PubMed

    Groff, Katherine; Brown, Jeffrey; Clippinger, Amy J

    2015-12-01

    Affinity reagents are essential tools in both basic and applied research; however, there is a growing concern about the reproducibility of animal-derived monoclonal antibodies. The need for higher quality affinity reagents has prompted the development of methods that provide scientific, economic, and time-saving advantages and do not require the use of animals. This review describes two types of affinity reagents, recombinant antibodies and aptamers, which are non-animal technologies that can replace the use of animal-derived monoclonal antibodies. Recombinant antibodies are protein-based reagents, while aptamers are nucleic-acid-based. In light of the scientific advantages of these technologies, this review also discusses ways to gain momentum in the use of modern affinity reagents, including an update to the 1999 National Academy of Sciences monoclonal antibody production report and federal incentives for recombinant antibody and aptamer efforts. In the long-term, these efforts have the potential to improve the overall quality and decrease the cost of scientific research.

  16. Validation of affinity reagents using antigen microarrays.

    PubMed

    Sjöberg, Ronald; Sundberg, Mårten; Gundberg, Anna; Sivertsson, Asa; Schwenk, Jochen M; Uhlén, Mathias; Nilsson, Peter

    2012-06-15

    There is a need for standardised validation of affinity reagents to determine their binding selectivity and specificity. This is of particular importance for systematic efforts that aim to cover the human proteome with different types of binding reagents. One such international program is the SH2-consortium, which was formed to generate a complete set of renewable affinity reagents to the SH2-domain containing human proteins. Here, we describe a microarray strategy to validate various affinity reagents, such as recombinant single-chain antibodies, mouse monoclonal antibodies and antigen-purified polyclonal antibodies using a highly multiplexed approach. An SH2-specific antigen microarray was designed and generated, containing more than 6000 spots displayed by 14 identical subarrays each with 406 antigens, where 105 of them represented SH2-domain containing proteins. Approximately 400 different affinity reagents of various types were analysed on these antigen microarrays carrying antigens of different types. The microarrays revealed not only very detailed specificity profiles for all the binders, but also showed that overlapping target sequences of spotted antigens were detected by off-target interactions. The presented study illustrates the feasibility of using antigen microarrays for integrative, high-throughput validation of various types of binders and antigens.

  17. Stabilization of the Motion of Affine Systems

    NASA Astrophysics Data System (ADS)

    Babenko, E. A.; Martynyuk, A. A.

    2016-07-01

    Sufficient conditions for the stability of a nonlinear affine system subject to interval initial conditions are established. These conditions are based on new estimates of the norms of the solutions of the systems of perturbed equations of motion. This stabilization method is used to analyze an electromechanical system with permanent magnet

  18. Fan Affinity Laws from a Collision Model

    ERIC Educational Resources Information Center

    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…

  19. Vygotsky's and Buber's Pedagogical Perspectives: Some Affinities

    ERIC Educational Resources Information Center

    Bartholo, Roberto; Tunes, Elizabeth; Tacca, Maria Carmen Villela Rosa

    2010-01-01

    The purpose of this paper is to examine the dialogical and creative character of pedagogic work by analyzing the affinities between Martin Buber's "I-Thou relation" and Lev Semenovich Vygotsky's "Zone of Proximal Development". Backed up by empirical studies on the teacher-student relation, we understand that education can only result in students'…

  20. Predicting Adsorption Affinities of Small Molecules on Carbon Nanotubes Using Molecular Dynamics Simulation.

    PubMed

    Comer, Jeffrey; Chen, Ran; Poblete, Horacio; Vergara-Jaque, Ariela; Riviere, Jim E

    2015-12-22

    Computational techniques have the potential to accelerate the design and optimization of nanomaterials for applications such as drug delivery and contaminant removal; however, the success of such techniques requires reliable models of nanomaterial surfaces as well as accurate descriptions of their interactions with relevant solutes. In the present work, we evaluate the ability of selected models of naked and hydroxylated carbon nanotubes to predict adsorption equilibrium constants for about 30 small aromatic compounds with a variety of functional groups. The equilibrium constants determined using molecular dynamics coupled with free-energy calculation techniques are directly compared to those derived from experimental measurements. The calculations are highly predictive of the relative adsorption affinities of the compounds, with excellent correlation (r ≥ 0.9) between calculated and measured values of the logarithm of the adsorption equilibrium constant. Moreover, the agreement in absolute terms is also reasonable, with average errors of less than one decade. We also explore possible effects of surface loading, although we demonstrate that they are negligible for the experimental conditions considered. Given the degree of reliability demonstrated, we move on to employing the in silico techniques in the design of nanomaterials, using the optimization of adsorption affinity for the herbacide atrazine as an example. Our simulations suggest that, compared to other modifications of graphenic carbon, polyvinylpyrrolidone conjugation gives the highest affinity for atrazine-substantially greater than that of graphenic carbon alone-and may be useful as a nanomaterial for delivery or sequestration of atrazine.

  1. An Alcohol Test for Drifting Constants

    NASA Astrophysics Data System (ADS)

    Jansen, P.; Bagdonaite, J.; Ubachs, W.; Bethlem, H. L.; Kleiner, I.; Xu, L.-H.

    2013-06-01

    The Standard Model of physics is built on the fundamental constants of nature, however without providing an explanation for their values, nor requiring their constancy over space and time. Molecular spectroscopy can address this issue. Recently, we found that microwave transitions in methanol are extremely sensitive to a variation of the proton-to-electron mass ratio μ, due to a fortuitous interplay between classically forbidden internal rotation and rotation of the molecule as a whole. In this talk, we will explain the origin of this effect and how the sensitivity coefficients in methanol are calculated. In addition, we set a limit on a possible cosmological variation of μ by comparing transitions in methanol observed in the early Universe with those measured in the laboratory. Based on radio-astronomical observations of PKS1830-211, we deduce a constraint of Δμ/μ=(0.0± 1.0)× 10^{-7} at redshift z = 0.89, corresponding to a look-back time of 7 billion years. While this limit is more constraining and systematically more robust than previous ones, the methanol method opens a new search territory for probing μ-variation on cosmological timescales. P. Jansen, L.-H. Xu, I. Kleiner, W. Ubachs, and H.L. Bethlem Phys. Rev. Lett. {106}(100801) 2011. J. Bagdonaite, P. Jansen, C. Henkel, H.L. Bethlem, K.M. Menten, and W. Ubachs Science {339}(46) 2013.

  2. Structure-affinity relationship of flavones on binding to serum albumins: effect of hydroxyl groups on ring A.

    PubMed

    Xiao, Jianbo; Cao, Hui; Wang, Yuanfeng; Yamamoto, Koichiro; Wei, Xinlin

    2010-07-01

    Four flavones (flavone, 7-hydroxyflavone, chrysin, and baicalein) sharing the same B- and C-ring structure but a different numbers of hydroxyl groups on the A-ring were studied for their affinities for BSA and HSA. The hydroxylation on ring A of flavones increased the binding constants (K(a)) and the number of binding sites (n) between flavones and serum albumins. The affinities of 7-hydroxyflavone for BSA and HSA were about 800 times and 40 times higher than that of flavone, respectively. It appears that the optimal number of hydroxyl groups introduced to the ring A of flavones is one. As more hydroxyl groups were introduced to positions at C-5, C-6, and/or C-7 of flavones, the affinities for serum albumins decrease. The critical energy transfer distances (R(0)) between the hydroxylated flavones (1-3 OH on the ring A) and serum albumins decreased with the increasing affinities for serum albumins.

  3. Experimental High Resolution (3 km) SMAP Soil Moisture Data Fields With Uncertainty Estimates

    NASA Astrophysics Data System (ADS)

    Das, N. N.

    2015-12-01

    NASA's Soil Moisture Active Passive (SMAP) mission was launched on January 31st, 2015. The objective of the mission is global mapping of surface soil moisture and landscape freeze/thaw state. SMAP utilizes an L-band radar and radiometer sharing a rotating 6-meter mesh reflector antenna. The SMAP spacecraft is in a 685-km Sun-synchronous near-polar orbit, and viewing the surface at a constant 40-degree incidence angle with a 1000-km swath width. Merging of the high-resolution active (radar) and coarse-resolution but high-sensitivity passive (radiometer) L-band observations enable an unprecedented combination of accuracy, resolution, coverage and revisit-time for soil moisture and freeze/thaw state retrievals. However, on July 7th, 2015, the SMAP radar encountered an anomaly and is currently inoperable. Efforts are being made to revive the SMAP radar. Due to the present status of the SMAP observatory, nearly ~2.5 months (from the end of In-Orbit-Check April 13th, 2015 to July 7th, 2015) of the SMAP Active Passive product will be available to public through the NASA DAAC at National Snow and Ice Data Center (NSIDC). The baseline L2_SM_AP product is retrieved soil moisture from the disaggregated/downscaled brightness temperature obtained by merging the coarse-resolution (~36 km) radiometer brightness temperature data and the high-resolution (~3 km) radar backscatter data. The baseline product is intermediate scale 9 km global soil moisture information. Experimentally, a much higher resolution global surface soil moisture data set is also produced at 3 km. This experimental product covering the 2.5 Spring/Summer months is the focus of this presentation. We specifically focus on the analysis of errors and reliability of this data set. The errors in disaggregated brightness temperatures and the retrived soil moisture estimates are discussed. In the presentation the accuracies of the SMAP L2-SM_AP soil moisture retrievals will be shown using summary comparisons with in

  4. WHY IS THE SOLAR CONSTANT NOT A CONSTANT?

    SciTech Connect

    Li, K. J.; Xu, J. C.; Gao, P. X.; Yang, L. H.; Liang, H. F.; Zhan, L. S.

    2012-03-10

    In order to probe the mechanism of variations of the solar constant on the inter-solar-cycle scale, the total solar irradiance (TSI; the so-called solar constant) in the time interval of 1978 November 7 to 2010 September 20 is decomposed into three components through empirical mode decomposition and time-frequency analyses. The first component is the rotation signal, counting up to 42.31% of the total variation of TSI, which is understood to be mainly caused by large magnetic structures, including sunspot groups. The second is an annual-variation signal, counting up to 15.17% of the total variation, the origin of which is not known at this point in time. Finally, the third is the inter-solar-cycle signal, counting up to 42.52%, which is inferred to be caused by the network magnetic elements in quiet regions, whose magnetic flux ranges from (4.27-38.01) Multiplication-Sign 10{sup 19} Mx.

  5. KM3NeT-ARCA project status and plan

    NASA Astrophysics Data System (ADS)

    Coniglione, R.

    2016-04-01

    The KM3NeT Collaboration aims at building a research infrastructure in the depths of the Mediterranean Sea hosting a cubic kilometre neutrino telescope. The KM3NeT/ARCA detector is the ideal instrument to look for high-energy neutrino sources thanks to the latitude of the detector and to the optical characteristics of the sea water. The detector latitude allows for a wide coverage of the observable sky including the region of the Galactic centre and the optical sea water properties allow for the measure of the neutrino direction with excellent angular resolution also for cascade events. The technologically innovative components of the detector and the status of construction will be presented as well as the capability it offers to discover neutrinos.

  6. Remote (250 km) Fiber Bragg Grating Multiplexing System

    PubMed Central

    Fernandez-Vallejo, Montserrat; Rota-Rodrigo, Sergio; Lopez-Amo, Manuel

    2011-01-01

    We propose and demonstrate two ultra-long range fiber Bragg grating (FBG) sensor interrogation systems. In the first approach four FBGs are located 200 km from the monitoring station and a signal to noise ratio of 20 dB is obtained. The second improved version is able to detect the four multiplexed FBGs placed 250 km away, offering a signal to noise ratio of 6–8 dB. Consequently, this last system represents the longest range FBG sensor system reported so far that includes fiber sensor multiplexing capability. Both simple systems are based on a wavelength swept laser to scan the reflection spectra of the FBGs, and they are composed by two identical-lengths optical paths: the first one intended to launch the amplified laser signal by means of Raman amplification and the other one is employed to guide the reflection signal to the reception system. PMID:22164101

  7. Cascade sensitivity studies for KM3NeT

    NASA Astrophysics Data System (ADS)

    Fusco, L. A.; KM3NeT Collaboration

    2016-01-01

    KM3NeT is a future neutrino observatory to be built in the Mediterranean Sea. Its main astrophysical goal it to search for cosmic sources of neutrinos. The status of searches for diffuse fluxes of cosmic neutrinos in the cascade channel are reported in this contribution. A signal analogous to that observed by the IceCube collaboration will be observed with a 5 σ significance within one year of operation of the detector.

  8. The KM3NeT neutrino telescope

    NASA Astrophysics Data System (ADS)

    Coniglione, R.; KM3NeT Collaboration

    2015-08-01

    The construction phase of an underwater high energy neutrino telescope in the Mediterranean Sea, named KM3NeT, has started. The neutrino telescope that will consist of several blocks of instrumented structures will have a size of the order of a cubic-kilometer. In this work the main elements of the detector, the status of the project and the expected performance will be briefly reported.

  9. Towards a 1km resolution global flood risk model

    NASA Astrophysics Data System (ADS)

    Bates, Paul; Neal, Jeff; Sampson, Chris; Smith, Andy

    2014-05-01

    Recent advances in computationally efficient numerical algorithms and new High Performance Computing architectures now make high (1-2km) resolution global hydrodynamic models a realistic proposition. However in many areas of the world the data sets and tools necessary to undertake such modelling do not currently exist. In particular, five major problems need to be resolved: (1) the best globally available terrain data (SRTM) was generated from X-band interferometric radar data which does not penetrate vegetation canopies and which has significant problems in determining ground elevations in urban areas; (2) a global river bathymetry data set does not currently exist; (3) most river channels globally are less than the smallest currently resolvable grid scale (1km) and therefore require a sub-grid treatment; (4) a means to estimate the magnitude of the T year flood at any point along the global river network does not currently exist; and (5) a large proportion of flood losses are generated by off-floodplain surface water flows which are not well represented in current hydrodynamic modelling systems. In this paper we propose solutions to each of these five issues as part of a concerted effort to develop a 1km (or better) resolution global flood hazard model. We describe the new numerical algorithms, computer architectures and computational resources used, and demonstrate solutions to the five previously intractable problems identified above. We conduct a validation study of the modelling against satellite imagery of major flooding on the Mississippi-Missouri confluence plain in the central USA before outlining a proof-of-concept regional study for SE Asia as a step towards a global scale model. For SE Asia we simulate flood hazard for ten different flood return periods over the entire Thailand, Cambodia, Vietnam, Malaysia and Laos region at 1km resolution and show that the modelling produces coherent, consistent and sensible simulations of extent and water depth.

  10. Towards Mapping the Ocean Surface Topography at 1 km Resolution

    NASA Technical Reports Server (NTRS)

    Fu, Lee-Lueng; Rodriquez, Ernesto

    2006-01-01

    We propose to apply the technique of synthetic aperture radar interferometry to the measurement of ocean surface topography at spatial resolution approaching 1 km. The measurement will have wide ranging applications in oceanography, hydrology, and marine geophysics. The oceanographic and related societal applications are briefly discussed in the paper. To meet the requirements for oceanographic applications, the instrument must be flown in an orbit with proper sampling of ocean tides.

  11. Organizations, Paradigms, and People: The Challenge of KM Interventions

    NASA Technical Reports Server (NTRS)

    Bailey, Teresa; Burton, Yvette

    1999-01-01

    This paper presents viewgraphs on Knowledge Management (KM) and how these interventions are put into practice by organizations and society. The topics include: 1) The Multiple Paradigm Tool; 2) Four Paradigms: tool for the Analyzing Organizations; 3) Assumptions About the Nature of Social Science; 4) Assumptions About the Nature of Society; 5) Schools of Sociological and Organizational Theory; 6) Meaning and Metaphors in the Four Paradigms; and 7) Possibilities and Conclusions.

  12. Hypervelocity launch capabilities to over 10 km/s

    SciTech Connect

    Chhabildas, L.C.

    1991-01-01

    Very high pressure and acceleration is necessary to launch flier plates to hypervelocities. In addition, the high pressure loading must be uniform, structured, and shockless, i.e., time-dependent to prevent the flier plate from either fracturing or melting. In this paper, a novel technique is described which allows the use of megabar level loading pressures, and 10{sup 9} g acceleration to launch intact flier plates to velocities of 12.2 km/s. 32 refs., 2 figs.

  13. Saqqar: A 34 km diameter impact structure in Saudi Arabia

    NASA Astrophysics Data System (ADS)

    Kenkmann, Thomas; Afifi, Abdulkader M.; Stewart, Simon A.; Poelchau, Michael H.; Cook, Douglas J.; Neville, Allen S.

    2015-11-01

    Here we present the first proof of an impact origin for the Saqqar circular structure in northwestern Saudi Arabia (Neville et al. ), with an apparent diameter of 34 km, centered at 29°35'N, 38°42'E. The structure is formed in Cambrian-Devonian siliciclastics and is unconformably overlain by undeformed Cretaceous and Paleogene sediments. The age of impact is not well constrained and lies somewhere between 410 and 70 Ma. The subsurface structure is constrained by 2-D reflection seismic profiles and six drilled wells. First-order structural features are a central uplift that rises approximately 2 km above regional datums, surrounded by a ring syncline. The crater rim is defined by circumferential normal faults. The central uplift and ring syncline correspond to a Bouguer gravity high and an annular ring-like low, respectively. The wells were drilled within the central uplift, the deepest among them exceed 2 km depth. Sandstone core samples from these wells show abundant indicators of a shock metamorphic overprint. Planar deformation features (PDFs) were measured with orientations along (0001), {101¯3}, and less frequently along {101¯1} and {101¯4}. Planar fractures (PFs) predominantly occur along (0001) and {101¯1}, and are locally associated with feather features (FFs). In addition, some shocked feldspar grains and strongly deformed mica flakes were found. The recorded shock pressure ranges between 5 and 15 GPa. The preserved level of shock and the absence of an allochthonous crater fill suggest that Saqqar was eroded by 1-2 km between the Devonian and Maastrichtian. The documentation of unequivocal shock features proves the formation of the Saqqar structure by a hypervelocity impact event.

  14. Acceleration of barium ions near 8000 km above an aurora

    NASA Technical Reports Server (NTRS)

    Stenbaek-Nielsen, H. C.; Hallinan, T. J.; Wescott, E. M.; Foeppl, H.

    1984-01-01

    A barium shaped charge, named Limerick, was released from a rocket launched from Poker Flat Research Range, Alaska, on March 30, 1982, at 1033 UT. The release took place in a small auroral breakup. The jet of ionized barium reached an altitude of 8100 km 14.5 min after release, indicating that there were no parallel electric fields below this altitude. At 8100 km the jet appeared to stop. Analysis shows that the barium at this altitude was effectively removed from the tip. It is concluded that the barium was actually accelerated upward, resulting in a large decrease in the line-of-sight density and hence the optical intensity. The parallel electric potential in the acceleration region must have been greater than 1 kV over an altitude interval of less than 200 km. The acceleration region, although presumably auroral in origin, did not seem to be related to individual auroral structures, but appeared to be a large-scale horizontal structure. The perpendicular electric field below, as deduced from the drift of the barium, was temporally and spatially very uniform and showed no variation related to individual auroral structures passing through.

  15. Millikan's measurement of Planck's constant

    NASA Astrophysics Data System (ADS)

    Franklin, Allan

    2013-12-01

    Robert Millikan is famous for measuring the charge of the electron. His result was better than any previous measurement and his method established that there was a fundamental unit of charge, or charge quantization. He is less well-known for his measurement of Planck's constant, although, as discussed below, he is often mistakenly given credit for providing significant evidence in support of Einstein's photon theory of light.1 His Nobel Prize citation was "for his work on the elementary electric charge of electricity and the photoelectric effect," an indication of the significance of his work on the photoelectric effect.

  16. Chandra Independently Determines Hubble Constant

    NASA Astrophysics Data System (ADS)

    2006-08-01

    A critically important number that specifies the expansion rate of the Universe, the so-called Hubble constant, has been independently determined using NASA's Chandra X-ray Observatory. This new value matches recent measurements using other methods and extends their validity to greater distances, thus allowing astronomers to probe earlier epochs in the evolution of the Universe. "The reason this result is so significant is that we need the Hubble constant to tell us the size of the Universe, its age, and how much matter it contains," said Max Bonamente from the University of Alabama in Huntsville and NASA's Marshall Space Flight Center (MSFC) in Huntsville, Ala., lead author on the paper describing the results. "Astronomers absolutely need to trust this number because we use it for countless calculations." Illustration of Sunyaev-Zeldovich Effect Illustration of Sunyaev-Zeldovich Effect The Hubble constant is calculated by measuring the speed at which objects are moving away from us and dividing by their distance. Most of the previous attempts to determine the Hubble constant have involved using a multi-step, or distance ladder, approach in which the distance to nearby galaxies is used as the basis for determining greater distances. The most common approach has been to use a well-studied type of pulsating star known as a Cepheid variable, in conjunction with more distant supernovae to trace distances across the Universe. Scientists using this method and observations from the Hubble Space Telescope were able to measure the Hubble constant to within 10%. However, only independent checks would give them the confidence they desired, considering that much of our understanding of the Universe hangs in the balance. Chandra X-ray Image of MACS J1149.5+223 Chandra X-ray Image of MACS J1149.5+223 By combining X-ray data from Chandra with radio observations of galaxy clusters, the team determined the distances to 38 galaxy clusters ranging from 1.4 billion to 9.3 billion

  17. Assessing uncertainty in physical constants

    NASA Astrophysics Data System (ADS)

    Henrion, Max; Fischhoff, Baruch

    1986-09-01

    Assessing the uncertainty due to possible systematic errors in a physical measurement unavoidably involves an element of subjective judgment. Examination of historical measurements and recommended values for the fundamental physical constants shows that the reported uncertainties have a consistent bias towards underestimating the actual errors. These findings are comparable to findings of persistent overconfidence in psychological research on the assessment of subjective probability distributions. Awareness of these biases could help in interpreting the precision of measurements, as well as provide a basis for improving the assessment of uncertainty in measurements.

  18. Cosmological constant and local gravity

    SciTech Connect

    Bernabeu, Jose; Espinoza, Catalina; Mavromatos, Nick E.

    2010-04-15

    We discuss the linearization of Einstein equations in the presence of a cosmological constant, by expanding the solution for the metric around a flat Minkowski space-time. We demonstrate that one can find consistent solutions to the linearized set of equations for the metric perturbations, in the Lorentz gauge, which are not spherically symmetric, but they rather exhibit a cylindrical symmetry. We find that the components of the gravitational field satisfying the appropriate Poisson equations have the property of ensuring that a scalar potential can be constructed, in which both contributions, from ordinary matter and {Lambda}>0, are attractive. In addition, there is a novel tensor potential, induced by the pressure density, in which the effect of the cosmological constant is repulsive. We also linearize the Schwarzschild-de Sitter exact solution of Einstein's equations (due to a generalization of Birkhoff's theorem) in the domain between the two horizons. We manage to transform it first to a gauge in which the 3-space metric is conformally flat and, then, make an additional coordinate transformation leading to the Lorentz gauge conditions. We compare our non-spherically symmetric solution with the linearized Schwarzschild-de Sitter metric, when the latter is transformed to the Lorentz gauge, and we find agreement. The resulting metric, however, does not acquire a proper Newtonian form in terms of the unique scalar potential that solves the corresponding Poisson equation. Nevertheless, our solution is stable, in the sense that the physical energy density is positive.

  19. Optimal Affine-Invariant Point Matching

    NASA Astrophysics Data System (ADS)

    Costa, Mauro S.; Haralick, Robert M.; Phillips, Tsaiyun I.; Shapiro, Linda G.

    1989-03-01

    The affine-transformation matching scheme proposed by Hummel and Wolfson (1988) is very efficient in a model-based matching system, not only in terms of the computational complexity involved, but also in terms of the simplicity of the method. This paper addresses the implementation of the affine-invariant point matching, applied to the problem of recognizing and determining the pose of sheet metal parts. It points out errors that can occur with this method due to quantization, stability, symmetry, and noise problems. By beginning with an explicit noise model which the Hummel and Wolfson technique lacks, we can derive an optimal approach which overcomes these problems. We show that results obtained with the new algorithm are clearly better than the results from the original method.

  20. Affinity Chromatography in Nonionic Detergent Solutions

    NASA Astrophysics Data System (ADS)

    Robinson, Jack B.; Strottmann, James M.; Wick, Donald G.; Stellwagen, Earle

    1980-10-01

    Anionic dye affinity chromatography is commonly unproductive in the presence of nonionic detergents used to extract particulate proteins. Using lactate dehydrogenase as a model protein, Cibacron blue F3GA as a model dye, and Triton X-100 as a model detergent, we find that the dye is encapsulated in nonionic detergent micelles, rendering the dye incapable of ligation with the enzyme. However, the dye can be liberated from the micelles without altering the nonionic detergent concentration by addition of an anionic detergent, such as deoxycholate or sodium dodecyl sulfate, forming mixed anionic/nonionic micelles that displace the anionic dye. Encapsulation of the anionic detergents prevents their activity as protein denaturants. These observations have been successfully translated to the dye affinity chromatography of a detergent extract of brain particulate cyclic nucleotide phosphodiesterase.

  1. Stability constant estimator user`s guide

    SciTech Connect

    Hay, B.P.; Castleton, K.J.; Rustad, J.R.

    1996-12-01

    The purpose of the Stability Constant Estimator (SCE) program is to estimate aqueous stability constants for 1:1 complexes of metal ions with ligands by using trends in existing stability constant data. Such estimates are useful to fill gaps in existing thermodynamic databases and to corroborate the accuracy of reported stability constant values.

  2. Negative affinity X-ray photocathodes

    NASA Technical Reports Server (NTRS)

    Vanspeybroeck, L.; Kellogg, E.; Murray, S.; Duckett, S.

    1974-01-01

    A new X-ray image intensifier is described. The device should eventually have a quantum efficiency which is an order of magnitude greater than that of presently available high spatial resolution X-ray detectors, such as microchannel plates. The new intesifier is based upon a GaAs crystal photocathode which is activated to achieve negative electron affinity. Details concerning the detector concept are discussed together with the theoretical relations involved, X-ray data, and optical data.

  3. Solar and stellar system tests of the cosmological constant

    SciTech Connect

    Sereno, Mauro; Jetzer, Philippe

    2006-03-15

    Some tests of gravity theories--periastron shift, geodetic precession, change in mean motion and gravitational redshift--are applied in solar and stellar systems to constrain the cosmological constant. We thus consider a length scale range from {approx}10{sup 8} to {approx}10{sup 15} km. Best bounds from the solar system come from perihelion advance and change in mean motion of Earth and Mars, {lambda} < or approx. 10{sup -36} km{sup -2}. Such a limit falls very short to estimates from observational cosmology analyses but a future experiment performing radio ranging observations of outer planets could improve it by 4 orders of magnitude. Beyond the solar system, together with future measurements of periastron advance in wide binary pulsars, gravitational redshift of white dwarfs can provide bounds competitive with Mars data.

  4. On constructing purely affine theories with matter

    NASA Astrophysics Data System (ADS)

    Cervantes-Cota, Jorge L.; Liebscher, D.-E.

    2016-08-01

    We explore ways to obtain the very existence of a space-time metric from an action principle that does not refer to it a priori. Although there are reasons to believe that only a non-local theory can viably achieve this goal, we investigate here local theories that start with Schrödinger's purely affine theory (Schrödinger in Space-time structure. Cambridge UP, Cambridge, 1950), where he gave reasons to set the metric proportional to the Ricci curvature aposteriori. When we leave the context of unified field theory, and we couple the non-gravitational matter using some weak equivalence principle, we can show that the propagation of shock waves does not define a lightcone when the purely affine theory is local and avoids the explicit use of the Ricci tensor in realizing the weak equivalence principle. When the Ricci tensor is substituted for the metric, the equations seem to have only a very limited set of solutions. This backs the conviction that viable purely affine theories have to be non-local.

  5. Phosphopeptide Enrichment by Immobilized Metal Affinity Chromatography.

    PubMed

    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 Fe(3+), Ga(3+), Al(3+), Zr(4+), and Ti(4+) 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 nonspecific binding of non-phosphorylated peptides. This problem is mainly caused by highly acidic peptides that also share high binding affinity towards these metal ions. By lowering the pH of the loading buffer nonspecific binding can be reduced significantly, however with the risk of reducing specific binding capacity. After binding, the enriched phosphopeptides are released from the metal ions using alkaline buffers of pH 10-11, EDTA, or phosphate-containing buffers. Here we describe a protocol for IMAC using Fe(3+) for phosphopeptide enrichment. The principles are illustrated on a semi-complex peptide mixture.

  6. Mapping the global land surface using 1 km AVHRR data

    USGS Publications Warehouse

    Lauer, D.T.; Eidenshink, J.C.

    1998-01-01

    The scientific requirements for mapping the global land surface using 1 km advanced very high resolution radiometer (AVHRR) data have been set forth by the U.S. Global Change Research Program; the International Geosphere Biosphere Programme (IGBP); The United Nations; the National Oceanic and Atmospheric Administration (NOAA); the Committee on Earth Observations Satellites; and the National Aeronautics and Space Administration (NASA) mission to planet Earth (MTPE) program. Mapping the global land surface using 1 km AVHRR data is an international effort to acquire, archive, process, and distribute 1 km AVHRR data to meet the needs of the international science community. A network of AVHRR receiving stations, along with data recorded by NOAA, has been acquiring daily global land coverage since April 1, 1992. A data set of over 70,000 AVHRR images is archived and distributed by the United States Geological Survey (USGS) EROS Data Center, and the European Space Agency. Under the guidance of the IGBP, processing standards have been developed for calibration, atmospheric correction, geometric registration, and the production of global 10-day maximum normalized difference vegetation index (NDVI) composites. The major uses of the composites are for the study of surface vegetation condition, mapping land cover, and deriving biophysical characteristics of terrestrial ecosystems. A time-series of 54 10-day global vegetation index composites for the period of April 1, 1992 through September 1993 has been produced. The production of a time-series of 33 10-day global vegetation index composites using NOAA-14 data for the period of February 1, 1995 through December 31, 1995 is underway. The data products are available from the USGS, in cooperation with NASA's MTPE program and other international organizations.

  7. Constant magnification optical tracking system

    NASA Technical Reports Server (NTRS)

    Frazer, R. E. (Inventor)

    1982-01-01

    A constant magnification optical tracking system for continuously tracking of a moving object is described. In the tracking system, a traveling objective lens maintains a fixed relationship with an object to be optically tracked. The objective lens was chosen to provide a collimated light beam oriented in the direction of travel of the moving object. A reflective surface is attached to the traveling objective lens for reflecting an image of the moving object. The object to be tracked is a free-falling object which is located at the focal point of the objective lens for at least a portion of its free-fall path. A motor and control means is provided for mantaining the traveling objective lens in a fixed relationship relative to the free-falling object, thereby keeping the free-falling object at the focal point and centered on the axis of the traveling objective lens throughout its entire free-fall path.

  8. Philicities, Fugalities, and Equilibrium Constants.

    PubMed

    Mayr, Herbert; Ofial, Armin R

    2016-05-17

    The mechanistic model of Organic Chemistry is based on relationships between rate and equilibrium constants. Thus, strong bases are generally considered to be good nucleophiles and poor nucleofuges. Exceptions to this rule have long been known, and the ability of iodide ions to catalyze nucleophilic substitutions, because they are good nucleophiles as well as good nucleofuges, is just a prominent example for exceptions from the general rule. In a reaction series, the Leffler-Hammond parameter α = δΔG(⧧)/δΔG° describes the fraction of the change in the Gibbs energy of reaction, which is reflected in the change of the Gibbs energy of activation. It has long been considered as a measure for the position of the transition state; thus, an α value close to 0 was associated with an early transition state, while an α value close to 1 was considered to be indicative of a late transition state. Bordwell's observation in 1969 that substituent variation in phenylnitromethanes has a larger effect on the rates of deprotonation than on the corresponding equilibrium constants (nitroalkane anomaly) triggered the breakdown of this interpretation. In the past, most systematic investigations of the relationships between rates and equilibria of organic reactions have dealt with proton transfer reactions, because only for few other reaction series complementary kinetic and thermodynamic data have been available. In this Account we report on a more general investigation of the relationships between Lewis basicities, nucleophilicities, and nucleofugalities as well as between Lewis acidities, electrophilicities, and electrofugalities. Definitions of these terms are summarized, and it is suggested to replace the hybrid terms "kinetic basicity" and "kinetic acidity" by "protophilicity" and "protofugality", respectively; in this way, the terms "acidity" and "basicity" are exclusively assigned to thermodynamic properties, while "philicity" and "fugality" refer to kinetics

  9. Omnidirectional antenna having constant phase

    DOEpatents

    Sena, Matthew

    2017-04-04

    Various technologies presented herein relate to constructing and/or operating an antenna having an omnidirectional electrical field of constant phase. The antenna comprises an upper plate made up of multiple conductive rings, a lower ground-plane plate, a plurality of grounding posts, a conical feed, and a radio frequency (RF) feed connector. The upper plate has a multi-ring configuration comprising a large outer ring and several smaller rings of equal size located within the outer ring. The large outer ring and the four smaller rings have the same cross-section. The grounding posts ground the upper plate to the lower plate while maintaining a required spacing/parallelism therebetween.

  10. Henry's law constants of some environmentally important aldehydes

    SciTech Connect

    Betterton, E.A.; Hoffmann, M.R.

    1988-12-01

    The Henry's law constants of seven aldehydes have been determined as a function of temperature by bubble-column and by head-space techniques. The compounds were chosen for their potential importance in the polluted troposphere and to allow structure-reactivity patterns to be investigated. The results (at 25/degree/C) are as follows (in units of M atm/sup /minus/1/): chloral, 3.44 /times/ 10/sup 5/; glyoxal, greater than or equal to3 /times/ 10/sup 5/; methylglyoxal, 3.71 /times/ 10/sup 3/; formaldehyde, 2.97 /times/ 10/sup 3/; benzaldehyde, 3.74 /times/ 10/sup 1/; hydroxyacetaldehyde, 4.14 /times/ 10/sup 4/; acetaldehyde, 1.14 /times/ 10/sup 1/. A plot of Taft's parameter, ..sigma..sigma*, vs log H* (the apparent Henry's law constant) gives a straight line with a slope of 1.72. H* for formaldehyde is anomalously high, as expected, but the extremely high value for hydroxyacetaldehyde was unexpected and may indicate that ..cap alpha..-hydroxy-substituted aldehydes could have an usually high affinity for the aqueous phase. The intrinsic Henry's law constants, H, corrected for hydration, do not show a clear structure-reactivity pattern for this series of aldehydes.

  11. Quantum electrodynamics and fundamental constants

    NASA Astrophysics Data System (ADS)

    Wundt, Benedikt Johannes Wilhelm

    The unprecedented precision achieved both in the experimental measurements as well as in the theoretical description of atomic bound states make them an ideal study object for fundamental physics and the determination of fundamental constants. This requires a careful study of the effects from quantum electrodynamics (QED) on the interaction between the electron and the nucleus. The two theoretical approaches for the evaluation of QED corrections are presented and discussed. Due to the presence of two energy scales from the binding potential and the radiation field, an overlapping parameter has to be used in both approaches in order to separate the energy scales. The different choices for the overlapping parameter in the two methods are further illustrated in a model example. With the nonrelativistic theory, relativistic corrections in order ( Zalpha)2 to the two-photon decay rate of ionic states are calculated, as well as the leading radiative corrections of alpha( Zalpha)2ln[(Zalpha)-2 ]. It is shown that the corrections is gauge-invariant under a "hybrid" gauge transformation between Coulomb and Yennie gauge. Furthermore, QED corrections for Rydberg states in one-electron ions are investigated. The smallness of the corrections and the absence of nuclear size corrections enable very accurate theoretical predictions. Measuring transition frequencies and comparing them to the theoretical predictions, QED theory can be tested more precisely. In turn, this could yield a more accurate value for the Rydberg constant. Using a transition in a nucleus with a well determined mass, acting as a reference, a comparison to transition in other nuclei can even allow to determined nuclear masses. Finally, in order to avoid an additional uncertainty in nuclei with non zero nuclear spin, QED self-energy corrections to the hyperfine structure up to order alpha(Zalpha)2Delta EHFS are determined for highly excited Rydberg states.

  12. Development of km23-Based Diagnostics and Therapeutics

    DTIC Science & Technology

    2005-05-01

    Attisano, L., Wieser, R., Ventura , F., and Massagu6, J. (1994) Nature 370, 341-347 28. Biggs, J. R., Kraft, A. S. (1999) J. Biol. Chem. 274, 36987-36994...Macias- Silva et al; 1996). Since blockade of km23 could reduce both the levels of phosphorylated Smad2 and the nuclear expression of Smad2, it was of...in TGF-P signaling. Front BioscL. 8, 1280-1303. Macias- Silva , M., Abdollah, S., Hoodless, P. A., Pirone, R., and Attisano, L., Wrana, J. L. (1996

  13. The relational database system of KM3NeT

    NASA Astrophysics Data System (ADS)

    Albert, Arnauld; Bozza, Cristiano

    2016-04-01

    The KM3NeT Collaboration is building a new generation of neutrino telescopes in the Mediterranean Sea. For these telescopes, a relational database is designed and implemented for several purposes, such as the centralised management of accounts, the storage of all documentation about components and the status of the detector and information about slow control and calibration data. It also contains information useful during the construction and the data acquisition phases. Highlights in the database schema, storage and management are discussed along with design choices that have impact on performances. In most cases, the database is not accessed directly by applications, but via a custom designed Web application server.

  14. An evaluation of the global 1-km AVHRR land dataset

    USGS Publications Warehouse

    Teillet, P.M.; El Saleous, N.; Hansen, M.C.; Eidenshink, Jeffery C.; Justice, C.O.; Townshend, J.R.G.

    2000-01-01

    This paper summarizes the steps taken in the generation of the global 1-km AVHRR land dataset, and it documents an evaluation of the data product with respect to the original specifications and its usefulness in research and applications to date. The evaluation addresses data characterization, processing, compositing and handling issues. Examples of the main scientific outputs are presented and options for improved processing are outlined and prioritized. The dataset has made a significant contribution, and a strong recommendation is made for its reprocessing and continuation to produce a long-term record for global change research.

  15. EVLA/NMA: Within and Beyond the 21-km Radius

    NASA Astrophysics Data System (ADS)

    Durand, Steve; Romney, Jonathan D.

    NRAO's Expanded Very Large Array (EVLA) project is being implemented in two phases. Each involves extremely wide- bandwidth data transmission over optical fibers, but the two phases necessarily involve quite different approaches to the required fiber infrastructure, which make for an interesting contrast. Phase 1, formally called the "Ultrasensitive Array", involves replacing almost all of the existing electronics, leaving only the mechanical and track infrastructure of the VLA. The data transmission system being implemented for Phase 1 uses dedicated optical fibers, currently being buried at the VLA site. Twelve standard single-mode fibers will run from each of 72 antenna pads to the central building. One of these fibers will support the wideband data transmission system, using a dense wavelength division multiplexing technique to carry a bandwidth of 96 Gbps (120 Gbps formatted) per antenna. Fibers from the 27 active antenna pads will carry a total bandwidth of 2.6 Tbps. The longest of these fibers will extend the full 21- km length of each arm. Phase 2 will add the "New Mexico Array". Eight new stations will be built, and the electronics of the VLBA Pie Town and Los Alamos stations will be upgraded, to create a medium-resolution array, with sensitivity even higher than Phase 1. All ten NMA stations will lie within the State of New Mexico. The new antennas will range as far as 265 km from the VLA site, and will be located so as to facilitate access to existing fiber trunks installed, primarily, by rural telephone companies. These trunks include numerous unused fibers which, it is anticipated, can be leased economically. The longest fiber run from the VLA is 480 km. The same 96-Gbps total bandwidth per station will be supported, with the same underlying sub-band structure. Signals from up to three NMA stations will be multiplexed onto a single fiber in the existing trunks. This will limit the total length of fiber which must be leased or acquired to about 1240 km.

  16. 157km BOTDA with pulse coding and image processing

    NASA Astrophysics Data System (ADS)

    Qian, Xianyang; Wang, Zinan; Wang, Song; Xue, Naitian; Sun, Wei; Zhang, Li; Zhang, Bin; Rao, Yunjiang

    2016-05-01

    A repeater-less Brillouin optical time-domain analyzer (BOTDA) with 157.68km sensing range is demonstrated, using the combination of random fiber laser Raman pumping and low-noise laser-diode-Raman pumping. With optical pulse coding (OPC) and Non Local Means (NLM) image processing, temperature sensing with +/-0.70°C uncertainty and 8m spatial resolution is experimentally demonstrated. The image processing approach has been proved to be compatible with OPC, and it further increases the figure-of-merit (FoM) of the system by 57%.

  17. Engineering of Bispecific Affinity Proteins with High Affinity for ERBB2 and Adaptable Binding to Albumin

    PubMed Central

    Nilvebrant, Johan; Åstrand, Mikael; Georgieva-Kotseva, Maria; Björnmalm, Mattias; Löfblom, John; Hober, Sophia

    2014-01-01

    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. PMID:25089830

  18. A GSFC alternative to the SLR MERIT constants. [LAGEOS satellite earth orientation monitoring

    NASA Technical Reports Server (NTRS)

    Christodoulidis, Demosthenes C.; Smith, David E.; Klosko, Steven M.; Torrence, Mark H.; Dunn, Peter J.

    1986-01-01

    The use of the Lageos satellite to monitor the earth's orientation is examined. The derivations of long wavelength ocean tidal parameters, a geocentric gravitational constant of 398,600.436 cu km/ sq sec + or - 0.0001 cu km/sq sec, and Love numbers using Lageos laser ranging data are described. The uncertainties of the geopotential model, GEM-L2 of Lerch et al. (1982), are discussed. The calculation of polar motion using the Lageos constants is considered. The Lageos constants are tested by applying them to independent laser ranging data. It is determined that the new constants improve the rms of fit to independent Lageos data and improve the earth orientation parameters compared to VLBI data obtained during the IRIS project.

  19. A nuclear data approach for the Hubble constant measurements

    SciTech Connect

    Pritychenko, B.

    2015-06-09

    An extraordinary number of Hubble constant measurements challenges physicists with selection of the best numerical value. The standard U.S. Nuclear Data Program (USNDP) codes and procedures have been applied to resolve this issue. The nuclear data approach has produced the most probable or recommended Hubble constant value of 67.00(770) (km/sec)/Mpc. This recommended value is based on the last 25 years of experimental research and includes contributions from different types of measurements. The present result implies (14.6±1.7) x 109 years as a rough estimate for the age of the Universe. The complete list of recommended results is given and possible implications are discussed.

  20. KM3NeT/ORCA status and plans

    NASA Astrophysics Data System (ADS)

    Samtleben, Dorothea F. E.

    2016-04-01

    Neutrinos created in interactions of cosmic rays with the atmosphere can serve as a powerful tool to unveil the neutrino mass hierarchy (NMH). At low energies, around a few GeV, matter effects from the transition through the Earth are expected to imprint a distinct but also subtle signature on the oscillation pattern, specific to the ordering of the neutrino masses. KM3NeT/ORCA (Oscillations Research with Cosmics in the Abyss), a densely instrumented building block of the upcoming KM3NeT neutrino telescope, will be designated to measuring this signature in the Mediterranean Sea. Using detailed simulations the sensitivity towards this signature has been evaluated. The multi-PMT detectors allow in the water for an accurate reconstruction of GeV neutrino event signatures and distinction of neutrino flavours. For the determination of the mass hierarchy a median significance of 2-6σ has been estimated for three years of data taking, depending on the actual hierarchy and the oscillation parameters. At the same time the values of several oscillation parameters like θ23 will be determined to unprecedented precision.

  1. CO2 LIDAR measurements over a 20-km slant path

    NASA Astrophysics Data System (ADS)

    Senft, Daniel C.; Fox, Marsha J.; Gonglewski, John D.; Dowling, James A.; Highland, Ronald G.; Shilko, Michael L.

    1997-01-01

    The Air Force Phillips Laboratory conducted a series of measurements in February, May and August 1995 at the Air Force Maui Optical Station (AMOS) facility on Maui, Hawaii, to determine system requirements for an airborne long path CO(subscript 2) DIAL system. The lidar incorporates a cavity-matched mode-locked 3-J laser with the 60 cm diameter AMOS Beam Director Telescope. The one-way beam propagation path length was 21.3 km, originating at the AMOS facility on Haleakala at an altitude of 3.050 km ASL, and terminating at a target site near sea level. Both heterodyne and direct detection techniques are compared with respect to radiometric performance and signal statistics. Minimum detectable absorption levels for DIAL systems using both detection techniques and a variety of targets are estimated from long- range measurements with controlled absorbers. The signal correlation as a function of interpulse temporal separation was determined for long-range direct detection measurements. Radiometric models including system optical characteristics, beam propagation considerations, target reflectivity characteristics,a nd atmospheric effects have been developed and validated experimentally. A new receiver system is currently being fabricated and the laser transmitter is being upgraded for pulse-to-pulse wavelength agility, prior to incorporation into a C-135E airborne platform for future flight experiments.

  2. Sentiment of Search: KM and IT for User Expectations

    NASA Technical Reports Server (NTRS)

    Berndt, Sarah Ann; Meza, David

    2014-01-01

    User perceived value is the number one indicator of a successful implementation of KM and IT collaborations. The system known as "Search" requires more strategy and workflow that a mere data dump or ungoverned infrastructure can provide. Monitoring of user sentiment can be a driver for providing objective measures of success and justifying changes to the user interface. The dynamic nature of information technology makes traditional usability metrics difficult to identify, yet easy to argue against. There is little disagreement, however, on the criticality of adapting to user needs and expectations. The Systems Usability Scale (SUS), developed by John Brook in 1986 has become an industry standard for usability engineering. The first phase of a modified SUS, polls the sentiment of representative users of the JSC Search system. This information can be used to correlate user determined value with types of information sought and how the system is (or is not) meeting expectations. Sentiment analysis by way of the SUS assists an organization in identification and prioritization of the KM and IT variables impacting user perceived value. A secondary, user group focused analysis is the topic of additional work that demonstrates the impact of specific changes dictated by user sentiment.

  3. Quantum crytography over 14km of installed optical fiber

    SciTech Connect

    Hughes, R.J.; Luther, G.G.; Morgan, G.L.; Simmons, C.

    1995-09-01

    We have made the first demonstration that low error rate quantum cryptography over long distances (14km) of installed optical fiber in a real-world environment, subject to uncontrolled temperature and mechanical influences, representing an important new step towards incorporation of quantum cryptography into existing information security systems. We also point out that the high visibility single-photon interference in our experiment allows us to infer a test of the superposition principle of quantum mechanics: a photon reaching the detector has traveled over 14km of optical fiber in a wavepacket comprising a coherent superposition of two components that are spatially separated by about 2m. In principle, there are decoherence processes (or even possible modifications of quantum mechanics) that could cause the photon`s wavefunction to collapse into one component or the other during propagation, leading to a reduction in visibility. However, our results are consistent with no such loss of quantum coherence during the 67-{mu}s propagation time.

  4. Integrin avidity regulation: are changes in affinity and conformation underemphasized?

    PubMed

    Carman, Christopher V; Springer, Timothy A

    2003-10-01

    Integrins play critical roles in development, wound healing, immunity and cancer. Central to their function is their unique ability to modulate dynamically their adhesiveness through both affinity- and valency-based mechanisms. Recent advances have shed light on the structural basis for affinity regulation and on the signaling mechanisms responsible for both affinity and valency modes of regulation.

  5. Importin {beta}-type nuclear transport receptors have distinct binding affinities for Ran-GTP

    SciTech Connect

    Hahn, Silvia; Schlenstedt, Gabriel

    2011-03-18

    Highlights: {yields} Determination of binding properties of nuclear transport receptor/Ran-GTP complexes. {yields} Biosensor measurements provide constants for dissociation, on-rates, and off-rates. {yields} The affinity of receptors for Ran-GTP is widely divergent. {yields} Dissociation constants differ for three orders of magnitude. {yields} The cellular concentration of yeast Ran is not limiting. -- Abstract: Cargos destined to enter or leave the cell nucleus are typically transported by receptors of the importin {beta} family to pass the nuclear pore complex. The yeast Saccharomyces cerevisiae comprises 14 members of this protein family, which can be divided in importins and exportins. The Ran GTPase regulates the association and dissociation of receptors and cargos as well as the transport direction through the nuclear pore. All receptors bind to Ran exclusively in its GTP-bound state and this event is restricted to the nuclear compartment. We determined the Ran-GTP binding properties of all yeast transport receptors by biosensor measurements and observed that the affinity of importins for Ran-GTP differs significantly. The dissociation constants range from 230 pM to 270 nM, which is mostly based on a variability of the off-rate constants. The divergent affinity of importins for Ran-GTP suggests the existence of a novel mode of nucleocytoplasmic transport regulation. Furthermore, the cellular concentration of {beta}-receptors and of other Ran-binding proteins was determined. We found that the number of {beta}-receptors altogether about equals the amounts of yeast Ran, but Ran-GTP is not limiting in the nucleus. The implications of our results for nucleocytoplasmic transport mechanisms are discussed.

  6. Relations between high-affinity binding sites of markers for binding regions on human serum albumin.

    PubMed Central

    Kragh-Hansen, U

    1985-01-01

    Binding of warfarin, digitoxin, diazepam, salicylate and Phenol Red, individually or in different pair combinations, to defatted human serum albumin at ligand/protein molar ratios less than 1:1 was studied at pH 7.0. The binding was determined by ultrafiltration. Some of the experiments were repeated with the use of equilibrium dialysis in order to strengthen the results. Irrespective of the method used, all ligands bind to one high-affinity binding site with an association constant in the range 10(4)-10(6) M-1. High-affinity binding of the following pair of ligands took place independently: warfarin-Phenol Red, warfarin-diazepam, warfarin-digitoxin and digitoxin-diazepam. Simultaneous binding of warfarin and salicylate led to a mutual decrease in binding of one another, as did simultaneous binding of digitoxin and Phenol Red. Both effects could be accounted for by a coupling constant. The coupling constant is the factor by which the primary association constants are affected; in these examples of anti-co-operativity the factor has a value between 0 and 1. In the first example it was calculated to be 0.8 and in the latter 0.5. Finally, digitoxin and salicylate were found to compete for a common high-affinity binding site. The present findings support the proposal of four separate primary binding sites for warfarin, digitoxin (and salicylate), diazepam and Phenol Red. An attempt to correlate this partial binding model for serum albumin with other models in the literature is made. PMID:3977850

  7. Modulation of affinity of a marine pseudomonad for toluene and benzene by hydrocarbon exposure.

    PubMed

    Law, A T; Button, D K

    1986-03-01

    Trace (microgram liter) quantities of either toluene or benzene injected into an amino-acid-limited continuous culture of Pseudomonas sp. strain T2 were utilized immediately with affinities of 2.6 and 6.8 liters g of cells h, respectively, and yielded large amounts of organic products, carbon dioxide, and cells. The immediate utilization of hydrocarbons by hydrocarbon-deprived organisms helps to establish the nutritional value of nonpolar substrates in the environment. The observation of small Michaelis constants for toluene transport led to tests of metabolic competition between hydrocarbons; however, competitive inhibition of toluene metabolism was not found for benzene, naphthalene, xylene, dodecane, or amino acids. Benzene and terpenes were inhibitory at milligram liter concentrations. Toluene was metabolized by a strongly inducible system when compared with benzene. The capacity of toluene to effect larger affinity values increased with exposure time and concentration. The kinetics of induction suggested saturation phenomena, resulting in an induction constant, K(ind), of 96 mug of toluene liter. Maximal induction of amino-acid-grown cells required about 80 h, with the affinity reaching 317 liters g of cells h.

  8. Bisphosphonate binding affinity as assessed by inhibition of carbonated apatite dissolution in vitro

    PubMed Central

    Henneman, Zachary J.; Nancollas, George H.; Ebetino, F. Hal; Russell, R. Graham G.; Phipps, Roger J.

    2009-01-01

    Bisphosphonates (BPs), which display a high affinity for calcium phosphate surfaces, are able to selectively target bone mineral, where they are potent inhibitors of osteoclast-mediated bone resorption. The dissolution of synthetic hydroxyapatite (HAP) has been used previously as a model for BP effects on natural bone mineral. The present work examines the influence of BPs on carbonated apatite (CAP), which mimics natural bone more closely than does HAP. Constant composition dissolution experiments were performed at pH 5.50, physiological ionic strength (0.15M) and temperature (37°C). Selected BPs were added at (0.5 × 10−6) to (50.0 × 10−6)M, and adsorption affinity constants, KL, were calculated from the kinetics data. The BPs showed concentration-dependent inhibition of CAP dissolution, with significant differences in rank order zoledronate > alendronate > risedronate. In contrast, for HAP dissolution at pH 5.50, the differences between the individual BPs were considerably smaller. The extent of CAP dissolution was also dependent on the relative undersaturation, σ, and CAP dissolution rates increased with increasing carbonate content. These results demonstrate the importance of the presence of carbonate in mediating the dissolution of CAP, and the possible involvement of bone mineral carbonate in observed differences in bone affinities of BPs in clinical use. PMID:17907244

  9. High affinity truncated DNA aptamers for the development of fluorescence based progesterone biosensors.

    PubMed

    Alhadrami, Hani A; Chinnappan, Raja; Eissa, Shimaa; Rahamn, Anas Abdel; Zourob, Mohammed

    2017-02-24

    Aptamers have shown a number of potential applications in sensing and therapeutic due to the high affinity and specificity towards their target molecules. Not all the nucleotides in the full length aptamers are involved in the binding with their targets. The non-binding domain of the aptamer may affect the binding affinity of the aptamer-target complex. Mapping the aptamer binding region could increase the affinity and the specificity. In this paper, we designed aptamer-based fluorescence sensors from a truncated progesterone (P4) aptamer. Then, fluorescein and quencher labelled aptamer complementary oligonucleotide sequences were hybridized to the truncated aptamer at different sites to form duplex structures. We used fluorescence-quencher pair displacement assay upon progesterone binding for the determination of P4. One of the truncated sequences has shown high binding affinity with 16 fold increase in the dissociation constant, Kd (2.1 nM) compared to the original aptamer. The aptasensor was highly selective for P4 against similar compounds such as 17-β estradiol, bisphenol-A and vitamin D. The sensor has been applied for the detection of P4 in spiked tap water and in urine samples showing good recovery. This new developed aptamer-based fluorescence biosensor can be applied in food, pharmaceutical, and clinical industries.

  10. Is There a Cosmological Constant?

    NASA Astrophysics Data System (ADS)

    Kochanek, Christopher

    2002-07-01

    The grant contributed to the publication of 18 refereed papers and 5 conference proceedings. The primary uses of the funding have been for page charges, travel for invited talks related to the grant research, and the support of a graduate student, Charles Keeton. The refereed papers address four of the primary goals of the proposal: (1) the statistics of radio lenses as a probe of the cosmological model (#1), (2) the role of spiral galaxies as lenses (#3), (3) the effects of dust on statistics of lenses (#7, #8), and (4) the role of groups and clusters as lenses (#2, #6, #10, #13, #15, #16). Four papers (#4, #5, #11, #12) address general issues of lens models, calibrations, and the relationship between lens galaxies and nearby galaxies. One considered cosmological effects in lensing X-ray sources (#9), and two addressed issues related to the overall power spectrum and theories of gravity (#17, #18). Our theoretical studies combined with the explosion in the number of lenses and the quality of the data obtained for them is greatly increasing our ability to characterize and understand the lens population. We can now firmly conclude both from our study of the statistics of radio lenses and our survey of extinctions in individual lenses that the statistics of optically selected quasars were significantly affected by extinction. However, the limits on the cosmological constant remain at lambda < 0.65 at a 2-sigma confidence level, which is in mild conflict with the results of the Type la supernova surveys. We continue to find that neither spiral galaxies nor groups and clusters contribute significantly to the production of gravitational lenses. The lack of group and cluster lenses is strong evidence for the role of baryonic cooling in increasing the efficiency of galaxies as lenses compared to groups and clusters of higher mass but lower central density. Unfortunately for the ultimate objective of the proposal, improved constraints on the cosmological constant, the next

  11. Is There a Cosmological Constant?

    NASA Technical Reports Server (NTRS)

    Kochanek, Christopher; Oliversen, Ronald J. (Technical Monitor)

    2002-01-01

    The grant contributed to the publication of 18 refereed papers and 5 conference proceedings. The primary uses of the funding have been for page charges, travel for invited talks related to the grant research, and the support of a graduate student, Charles Keeton. The refereed papers address four of the primary goals of the proposal: (1) the statistics of radio lenses as a probe of the cosmological model (#1), (2) the role of spiral galaxies as lenses (#3), (3) the effects of dust on statistics of lenses (#7, #8), and (4) the role of groups and clusters as lenses (#2, #6, #10, #13, #15, #16). Four papers (#4, #5, #11, #12) address general issues of lens models, calibrations, and the relationship between lens galaxies and nearby galaxies. One considered cosmological effects in lensing X-ray sources (#9), and two addressed issues related to the overall power spectrum and theories of gravity (#17, #18). Our theoretical studies combined with the explosion in the number of lenses and the quality of the data obtained for them is greatly increasing our ability to characterize and understand the lens population. We can now firmly conclude both from our study of the statistics of radio lenses and our survey of extinctions in individual lenses that the statistics of optically selected quasars were significantly affected by extinction. However, the limits on the cosmological constant remain at lambda < 0.65 at a 2-sigma confidence level, which is in mild conflict with the results of the Type la supernova surveys. We continue to find that neither spiral galaxies nor groups and clusters contribute significantly to the production of gravitational lenses. The lack of group and cluster lenses is strong evidence for the role of baryonic cooling in increasing the efficiency of galaxies as lenses compared to groups and clusters of higher mass but lower central density. Unfortunately for the ultimate objective of the proposal, improved constraints on the cosmological constant, the next

  12. EGFR kinase possesses a broad specificity for ErbB phosphorylation sites, and ligand increases catalytic-centre activity without affecting substrate binding affinity

    PubMed Central

    2005-01-01

    We previously found that EGF (epidermal growth factor) increases the EGFR (EGF receptor) kinase-binding affinity towards the major tyrosine phosphorylation sites in downstream adaptor proteins such as Gab1 (Grb2-associated binding protein 1) and Shc [Src homology 2 (SH2) domain and collagen containing protein], but not that towards EGFR autophosphorylation sites [Fan, Wong, Deb and Johnson (2004) J. Biol. Chem. 279, 38143–38150]. EGFR activation can also result in transphosphorylation of tyrosine resides in the C-terminal region of the related receptors ErbB2, ErbB3 and ErbB4 in heterodimers which are formed upon ligand stimulation. In the present study, we investigated the specificity of EGFR kinase by comparing the steady state kinetic parameters for peptides derived from all four ErbBs in the absence or presence of EGF. Our results demonstrated that (i) EGFR kinase can efficiently phosphorylate a broad range of diverse peptide sequences representing ErbB sites; (ii) certain ErbB2, ErbB3 and ErbB4 sites had higher specificity constants than any EGFR sequence and (iii) EGF stimulation consistently increases the kcat approx. 5-fold, but does not significantly alter the Km for any ErbB peptides. Furthermore, peptides containing lysine at position −2 or −3 N-terminal to the target tyrosine were found to be poor EGFR kinase substrates, and substitution of these lysines with glutamine decreased the Km and increased the kcat for these substrates. We conclude that EGFR kinase-mediated ErbB transphosphorylations are mostly controlled at the level of oligomerization, and not by a preference of the EGFR kinase for phosphorylation sites in any particular ErbB. The results also demonstrated that, unlike phosphorylation sites in select downstream targets, EGF does not regulate the recognition of phosphorylation sites in the C-terminal region of any of the ErbBs. PMID:16122376

  13. Rate constants of agonist binding to muscarinic receptors in rat brain medulla. Evaluation by competition kinetics

    SciTech Connect

    Schreiber, G.; Henis, Y.I.; Sokolovsky, M.

    1985-07-25

    The method of competition kinetics, which measures the binding kinetics of an unlabeled ligand through its effect on the binding kinetics of a labeled ligand, was employed to investigate the kinetics of muscarinic agonist binding to rat brain medulla pons homogenates. The agonists studied were acetylcholine, carbamylcholine, and oxotremorine, with N-methyl-4-(TH)piperidyl benzilate employed as the radiolabeled ligand. Our results suggested that the binding of muscarinic agonists to the high affinity sites is characterized by dissociation rate constants higher by 2 orders of magnitude than those of antagonists, with rather similar association rate constants. Our findings also suggest that isomerization of the muscarinic receptors following ligand binding is significant in the case of antagonists, but not of agonists. Moreover, it is demonstrated that in the medulla pons preparation, agonist-induced interconversion between high and low affinity bindings sites does not occur to an appreciable extent.

  14. The Greenland gravitational constant experiment

    NASA Astrophysics Data System (ADS)

    Ander, Mark E.; Parker, Robert L.; Aiken, Carlos L. V.; Gorman, Michael R.; Nieto, Michael Martin; Cooper, A. Paul R.; Ferguson, John F.; Fisher, Elizabeth; Greer, James; Hammer, Phil; Hansen, B. Lyle; McMechan, George A.; Sasagawa, Glenn S.; Sidles, Cyndi; Stevenson, J. Mark; Wirtz, Jim

    1990-09-01

    An Airy-type geophysical experiment was conducted in a 2-km-deep hole in the Greenland ice cap at depths between 213 m and 1673 m to test for possible violations of Newton's inverse square law. The experiment was done at Dye 3, the location of a Distant Early Warming Line radar dome and the site of the deepest of the Greenland Ice-Sheet Program (GISP) drill holes. Gravity measurements were made at eight depths in 183-m intervals with a LaCoste & Romberg borehole gravity meter. Prior to the experiment the borehole, gravity meter was calibrated with an absolute gravity meter, and the wireline depth-finding system used in the borehole logging was calibrated in a vertical mine-shaft against a laser geodimeter. The density of the ice in the region was calculated from measurements taken from ice cores obtained from earlier drilling observations. Ice penetrating radar was employed in order to correct the gravity data for the topography of the ice-rock interface. Surface gravity observations were made to assess the extent to which density variations in the sub-ice rock could affect the vertical gravity gradient. The locations of the gravity observation points were determined with a combination of GPS recording, first-order leveling, and EDM surveying. An anomalous variation in gravity totaling 3.87 mGal (3.87×10-5 m/s2) in a depth interval of 1460 m was observed. This may be attributed either to a breakdown of Newtonian gravity or to unexpected density variations in the rock below the ice.

  15. A 700 km long crustal transect across northern Morocco

    NASA Astrophysics Data System (ADS)

    Carbonell, Ramon; Gallart, Josep; Díaz, Jordi; Gil, Alba; Harnafi, Mimoun; Ouraini, Fadila; Ayarza, Puy; Teixell, Antonio; Arboleya, Maria Luisa; Palomeras, Imma; Levander, Alan

    2013-04-01

    Two controlled-source wide angle seismic reflection experiments have been acquired recently (2010 and 2011) in northern Africa across Morocco. A lithospheric scale transect can be constructed by joining both data sets. Hence, an approximately 700 km-long seismic velocity cross section can be derived. From south-to-north the transect goes from the Sahara Platform, south of Merzouga, to Tanger in the north. The first experiment, SIMA, aimed to constrain the crustal structure across the Atlas Mountains. The Rif, the orogenic belt located just south of the coast of Alboran Sea, was the target of the second experiment, RIFSIS. In both cases 900 recording instruments (TEXANS) from the IRIS-PASSCAL instrument center were used to record the acoustic energy generated by explosion shots. In both experiments the shots consisted of 1 TM of explosives fired in ~30 m deep boreholes. Although the data quality varies from shot to shot, key seismic phases as Pg, PmP, Pn, and a few intra-crustal arrivals have been identified to constrain the velocity-depth structure along the whole transect. Forward modelling of the seismic reflection/refraction phases reveals a crust consisting of 3 layers in average. The Moho topography shows from south to north a relatively moderate crustal root beneath the High Atlas, which can reach 40-42 km depth. The crust is thicker beneath the Rif where the Moho is imaged as an asymmetric feature that locally defines a crustal root reaching depths of 50 km and suggesting a crustal imbrication. P wave velocities are rather low in the crust and upper mantle. First arrivals/reflections tomography supports the forward modelling results. Low fold wide-angle stacks obtained by using hyperbolic move-out reveals the geometry of the Moho along the entire transect. Beneath the Atlas, the moderate crustal root inferred is not isostatically consistent with the high surface elevations, hence supporting the idea of a 'mantle plume' as main contributor to the Atlas

  16. The Effect of Water on the 410-km Discontinuity

    NASA Astrophysics Data System (ADS)

    Smyth, J. R.; Frost, D. J.

    2001-12-01

    The H content of the Earth is one of the most poorly constrained compositional variables for the planet. The nominally anhydrous olivine and spinelloid phases thought to compose the bulk of the upper mantle and transition zone may contain many times the amount of H and O that reside in the hydrosphere. The discontinuity at 410 kilometers corresponds to the olivine-wadsleyite transition with an increase in both density and S-wave velocity of about five percent. Previous experiments and calculations in the anhydrous peridotite system indicate an olivine-wadsleyite two-phase interval that is from 10 to 18 km in width. Calculations indicate that the two-phase region would be significantly broader in a hydrous system. We have conducted a series of synthesis experiments in the multi-anvil press on hydrous and anhydrous peridotite compositions and characterized the products by electron microprobe and single-crystal X-ray diffraction. Six experiments were conducted in a hydrous peridotite system, and three in an anhydrous system. The results of our synthesis experiments are consistent with the prediction of Wood (1995) that the presence of H2O extends the stability of wadsleyite to 0.6 to 1.0 GPa lower pressure and would broaden the two-phase loop to as much as 30 km. In the hydrous runs containing both olivine and wadsleyite, there appears a sharp boundary between regions of olivine and regions of wadsleyite. The texture of the run thus does not appear to be a simple chemical equilibrium, but rather a diffusion-controlled boundary. Hydrogen is known to diffuse very rapidly in these materials, raising the possibility that diffusion of H might control the texture and may affect the sharpness of the boundary in the natural system. Hydrous wadsleyite is about five percent denser than anhydrous olivine. In a hypothetical two-phase region consisting of olivine and wadsleyite plus lesser amounts of garnet and clinopyroxene extending over a depth 20 km in a hydrous system

  17. Spatial and temporal variations of fundamental constants

    NASA Astrophysics Data System (ADS)

    Levshakov, S. A.; Agafonova, I. I.; Molaro, P.; Reimers, D.

    2010-11-01

    Spatial and temporal variations in the electron-to-proton mass ratio, μ, and in the fine-structure constant, α, are not present in the Standard Model of particle physics but they arise quite naturally in grant unification theories, multidimensional theories and in general when a coupling of light scalar fields to baryonic matter is considered. The light scalar fields are usually attributed to a negative pressure substance permeating the entire visible Universe and known as dark energy. This substance is thought to be responsible for a cosmic acceleration at low redshifts, z < 1. A strong dependence of μ and α on the ambient matter density is predicted by chameleon-like scalar field models. Calculations of atomic and molecular spectra show that different transitions have different sensitivities to changes in fundamental constants. Thus, measuring the relative line positions, Δ V, between such transitions one can probe the hypothetical variability of physical constants. In particular, interstellar molecular clouds can be used to test the matter density dependence of μ, since gas density in these clouds is ~15 orders of magnitude lower than that in terrestrial environment. We use the best quality radio spectra of the inversion transition of NH3 (J,K)=(1,1) and rotational transitions of other molecules to estimate the radial velocity offsets, Δ V ≡ Vrot - Vinv. The obtained value of Δ V shows a statistically significant positive shift of 23±4stat±3sys m s-1 (1σ). Being interpreted in terms of the electron-to-proton mass ratio variation, this gives Δμ/μ = (22±4stat±3sys)×10-9. A strong constraint on variation of the quantity F = α2/μ in the Milky Way is found from comparison of the fine-structure transition J=1-0 in atomic carbon C i with the low-J rotational lines in carbon monoxide 13CO arising in the interstellar molecular clouds: |Δ F/F| < 3×10-7. This yields |Δ α/α| < 1.5×10-7 at z = 0. Since extragalactic absorbers have gas densities

  18. Latest European coelacanth shows Gondwanan affinities.

    PubMed

    Cavin, Lionel; Forey, Peter L; Buffetaut, Eric; Tong, Haiyan

    2005-06-22

    The last European fossil occurrence of a coelacanth is from the Mid-Cretaceous of the English Chalk (Turonian, 90 million years ago). Here, we report the discovery of a coelacanth from Late Cretaceous non-marine rocks in southern France. It consists of a left angular bone showing structures that imply close phylogenetic affinities with some extinct Mawsoniidae. The closest relatives are otherwise known from Cretaceous continental deposits of southern continents and suggest that the dispersal of freshwater organisms from Africa to Europe occurred in the Late Cretaceous.

  19. On the electron affinity of Be2

    NASA Technical Reports Server (NTRS)

    Bauschlicher, C. W., Jr.; Partridge, H.

    1984-01-01

    Calculations of the electron affinity (EA) of Be2 using a large Slater-type orbital basis set and extensive correlation based upon a CASSCF reference are reported. The adiabatic EAs are estimated to be 0.44 eV for the 2Sigma sub g(+) state and 0.56 eV for the 2Pi sub u state. The extra electron attaches into an empty bonding orbital, causing a shortening of the bond length and an increase in omega(e). The D(e) of the 2Pi sub u state of Be2 is six times as large as the D(e) of Be2.

  20. The ion population between 1300 km and 230000 km in the coma of comet P/Halley

    NASA Technical Reports Server (NTRS)

    Altwegg, K.; Balsiger, H.; Geiss, J.; Goldstein, R.; Ip, W. -H.; Meier, A.; Neugebauer, M.; Rosenbauer, H.; Shelley, E.

    1993-01-01

    During the encounter of the spacecraft Giotto with Comet Halley the two sensors of the ion mass spectrometer (IMS), high energy range spectrometer (HERS) and high intensity spectrometer (HIS), measured the mass and the three-dimensional velocity distributions of cometary ions. HIS looked mainly at the cold, slow part of the distribution close to the nucleus, HERS at the more energetic pick-up ions further out. After a thorough recalibration of the HIS flight spare unit and an extensive data analysis we present here continuous ion density-, composition-, velocity-, and temperature profiles for the water group ion (mass range 16-19 amu/e) along Giotto's inbound trajectory from 230,000 to 1300 km from the comet nucleus. The two sensors are in very good agreement in the region where their measurements overlap thus giving an excellent data base for the discussion of theoretical comet models. The most prominent feature where models and observations disagree is the so called pile up region between 8000 and 15,000 km from the nucleus.

  1. Transport System for Delivery Tourists At Altitude 140 km

    NASA Technical Reports Server (NTRS)

    Bolonkin, Alexander

    2002-01-01

    The author offers a new method and installation for flight in space. This method uses the centrifugal force of a rotating circular cable that provides a means for the launch of a payload into outer space, to keep the fixed space stations at high altitudes (up to 200 km). The method may also be useful for landing to space bodies, for launching of the space ships (crafts), and for moving and accelerating other artificial apparatuses. The offered installation may be used as a propulsion system for space ships and/or probes. This system uses the material of any space body (i.e. stones) for acceleration and change of the space vehicle trajectory. The suggested system may be also used as a high capacity energy accumulator.

  2. Calibration methods and tools for KM3NeT

    NASA Astrophysics Data System (ADS)

    Kulikovskiy, Vladimir

    2016-04-01

    The KM3NeT detectors, ARCA and ORCA, composed of several thousands digital optical modules, are in the process of their realization in the Mediterranean Sea. Each optical module contains 31 3-inch photomultipliers. Readout of the optical modules and other detector components is synchronized at the level of sub-nanoseconds. The position of the module is measured by acoustic piezo detectors inside the module and external acoustic emitters installed on the bottom of the sea. The orientation of the module is obtained with an internal attitude and heading reference system chip. Detector calibration, i.e. timing, positioning and sea-water properties, is overviewed in this talk and discussed in detail in this conference. Results of the procedure applied to the first detector unit ready for installation in the deep sea will be shown.

  3. Measurement-Device-Independent Quantum Key Distribution over 200 km

    NASA Astrophysics Data System (ADS)

    Tang, Yan-Lin; Yin, Hua-Lei; Chen, Si-Jing; Liu, Yang; Zhang, Wei-Jun; Jiang, Xiao; Zhang, Lu; Wang, Jian; You, Li-Xing; Guan, Jian-Yu; Yang, Dong-Xu; Wang, Zhen; Liang, Hao; Zhang, Zhen; Zhou, Nan; Ma, Xiongfeng; Chen, Teng-Yun; Zhang, Qiang; Pan, Jian-Wei

    2014-11-01

    Measurement-device-independent quantum key distribution (MDIQKD) protocol is immune to all attacks on detection and guarantees the information-theoretical security even with imperfect single-photon detectors. Recently, several proof-of-principle demonstrations of MDIQKD have been achieved. Those experiments, although novel, are implemented through limited distance with a key rate less than 0.1 bit /s . Here, by developing a 75 MHz clock rate fully automatic and highly stable system and superconducting nanowire single-photon detectors with detection efficiencies of more than 40%, we extend the secure transmission distance of MDIQKD to 200 km and achieve a secure key rate 3 orders of magnitude higher. These results pave the way towards a quantum network with measurement-device-independent security.

  4. Estimating worldwide solar radiation resources on a 40km grid

    SciTech Connect

    Maxwell, E.L.; George, R.L.; Brady, E.H.

    1996-11-01

    During 1995, the National Renewable Energy Laboratory (NREL), initiated the Data Grid Task under the auspices of DOE`s Resource Assessment Program. A data grid is a framework of uniformly spaced locations (grid points) for which data are available. Estimates of monthly averages of direct normal, diffuse horizontal, and global horizontal daily-total solar radiation energy (kWh/m{sup 2}) are being made for each point on a grid covering the US, Mexico, the Caribbean, and southern Canada. The grid points are separated by approximately 40 km. Using interpolation methods, the digital data grid can be used to estimate solar resources at any location. The most encouraging result to date has been the location of sources providing worldwide data for most of the input parameters required for modeling daily total solar radiation. This is a multiyear task expected to continue through the rest of this century.

  5. Fatal truck-bicycle accident involving dragging for 45 km.

    PubMed

    Klintschar, M; Darok, M; Roll, P

    2003-08-01

    Vehicle-bicycle accidents with subsequent dragging of the rider over long distances are extremely rare. The case reported here is that of a 16-year-old mentally retarded bike rider who was run over by a truck whose driver failed to notice the accident. The legs of the victim became trapped by the rear axle of the trailer and the body was dragged over 45 km before being discovered under the parked truck. The autopsy revealed that the boy had died from the initial impact and not from the dragging injuries which had caused extensive mutilation. The reports of the technical expert and the forensic pathologist led the prosecutor to drop the case against the truck driver for manslaughter.

  6. Wintertime density perturbations near 50 km in relation to latitude

    NASA Technical Reports Server (NTRS)

    Quiroz, R. S.

    1977-01-01

    Standard and reference atmospheres which depict the horizontal distribution of air density in the stratosphere and mesosphere are not realistic in that they do not provide information on the large departures from standard that may occur during a given month, nor on the time- and space-scales of atmospheric perturbations responsible for these departures. In the present paper, it is shown how this information can be obtained from a special analysis of satellite radiance measurements. Plots of the mean zonal radiance, obtained with the VTPR instrument, and the corresponding 50-km density show not only the expected strong poleward gradient of density, but also a strong density surge from late December to early January, affecting all latitudes.

  7. On the structure of self-affine convex bodies

    SciTech Connect

    Voynov, A S

    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.

  8. Affinity filtration coupled with capillary-based affinity purification for the isolation of protein complexes.

    PubMed

    Qureshi, M S; Sheikh, Q I; Hill, R; Brown, P E; Dickman, M J; Tzokov, S B; Rice, D W; Gjerde, D T; Hornby, D P

    2013-08-01

    The isolation of complex macromolecular assemblies at the concentrations required for structural analysis represents a major experimental challenge. Here we present a method that combines the genetic power of site-specific recombination in order to selectively "tag" one or more components of a protein complex with affinity-based rapid filtration and a final step of capillary-based enrichment. This modified form of tandem affinity purification produces highly purified protein complexes at high concentrations in a highly efficient manner. The application of the method is demonstrated for the yeast Arp2/3 heptameric protein complex involved in mediating reorganization of the actin cytoskeleton.

  9. P2X7 receptor activation downmodulates Na(+)-dependent high-affinity GABA and glutamate transport into rat brain cortex synaptosomes.

    PubMed

    Barros-Barbosa, A R; Lobo, M G; Ferreirinha, F; Correia-de-Sá, P; Cordeiro, J M

    2015-10-15

    Sodium-dependent high-affinity amino-acid transporters play crucial roles in terminating synaptic transmission in the central nervous system (CNS). However, there is lack of information about the mechanisms underlying the regulation of amino-acid transport by fast-acting neuromodulators, like ATP. Here, we investigated whether activation of the ATP-sensitive P2X7 receptor modulates Na(+)-dependent high-affinity γ-aminobutyric acid (GABA) and glutamate uptake into nerve terminals (synaptosomes) of the rat cerebral cortex. Radiolabeled neurotransmitter accumulation was evaluated by liquid scintillation spectrometry. The cell-permeant sodium-selective fluorescent indicator, SBFI-AM, was used to estimate Na(+) influx across plasma membrane. 2'(3')-O-(4-benzoylbenzoyl)ATP (BzATP, 3-300 μM), a prototypic P2X7 receptor agonist, concentration-dependently decreased [(3)H]GABA (14%) and [(14)C]glutamate (24%) uptake; BzATP decreased transport maximum velocity (Vmax) without affecting the Michaelis constant (Km) values. The selective P2X7 receptor antagonist, A-438079 (3 μM), prevented inhibition of [(3)H]GABA and [(14)C]glutamate uptake by BzATP (100 μM). The inhibitory effect of BzATP coincided with its ability to increase intracellular Na(+) and was mimicked by Na(+) ionophores, like gramicidin and monensin. Increases in intracellular Na(+) (with veratridine or ouabain) or substitution of extracellular Na(+) by N-methyl-D-glucamine (NMDG)(+) all decreased [(3)H]GABA and [(14)C]glutamate uptake and attenuated BzATP effects. Uptake inhibition by BzATP (100 μM) was also attenuated by calmidazolium, which selectively inhibits Na(+) currents through the P2X7 receptor pore. In conclusion, disruption of the Na(+) gradient by P2X7 receptor activation downmodulates high-affinity GABA and glutamate uptake into rat cortical synaptosomes. Interference with amino-acid transport efficacy may constitute a novel target for therapeutic management of cortical excitability.

  10. Capacitive Cells for Dielectric Constant Measurement

    ERIC Educational Resources Information Center

    Aguilar, Horacio Munguía; Maldonado, Rigoberto Franco

    2015-01-01

    A simple capacitive cell for dielectric constant measurement in liquids is presented. As an illustrative application, the cell is used for measuring the degradation of overheated edible oil through the evaluation of their dielectric constant.

  11. Deconstructing Free Energies in the Law of Matching Water Affinities.

    PubMed

    Shi, Yu; Beck, Thomas

    2017-02-23

    The law of matching water affinities (LMWA) is explored in classical molecular dynamics simulations of several alkali halide ion pairs, spanning the size range from small kosmotropes to large chaotropes. The ion-ion potentials of mean force (PMFs) are computed using three methods: the local molecular field theory (LMFT), the weighted histogram analysis method (WHAM), and integration of the average force. All three methods produce the same total PMF for a given ion pair. In addition, LMFT-based partitioning into van der Waals and local and far-field electrostatic free energies and assessment of the enthalpic, entropic, and ion-water components yield insights into the origins of the observed free energy profiles in water. The results highlight the importance of local electrostatic interactions in determining the shape of the PMFs, while longer-ranged interactions enhance the overall ion-ion attraction, as expected in a dielectric continuum model. The association equilibrium constants are estimated from the smooth WHAM curves and compared to available experimental conductance data. By examining the variations in the average hydration numbers of ions with ion-ion distance, a correlation of the water structure in the hydration shells with the free energy features is found.

  12. Limited proteolysis for assaying ligand binding affinities of nuclear receptors.

    PubMed

    Benkoussa, M; Nominé, B; Mouchon, A; Lefebvre, B; Bernardon, J M; Formstecher, P; Lefebvre, P

    1997-01-01

    The binding of natural or synthetic ligands to nuclear receptors is the triggering event leading to gene transcription activation or repression. Ligand binding to the ligand binding domain of these receptors induces conformational changes that are evidenced by an increased resistance of this domain to proteases. In vitro labeled receptors were incubated with various synthetic or natural agonists or antagonists and submitted to trypsin digestion. Proteolysis products were separated by SDS-PAGE and quantified. The amount of trypsin-resistant fragments was proportional to receptor occupancy by the ligand, and allowed the determination of dissociation constants (kDa). Using the wild-type or mutated human retinoic acid receptor alpha as a model, kDa values determined by classical competition binding assays using tritiated ligands are in agreement with those measured by the proteolytic assay. This method was successfully extended to human retinoic X receptor alpha, glucocorticoid receptor, and progesterone receptor, thus providing a basis for a new, faster assay to determine simultaneously the affinity and conformation of receptors when bound to a given ligand.

  13. Communication: Revised electron affinity of SF6 from kinetic data.

    PubMed

    Troe, Jürgen; Miller, Thomas M; Viggiano, Albert A

    2012-03-28

    Previously determined experimental data for thermal attachment of electrons to SF(6) and thermal detachment from SF(6)(-) over the range 590-670 K are reevaluated by a third-law analysis. Recent high precision calculations of SF(6)(-) harmonic frequences and anharmonicities (for several of the modes) lead to considerable changes in modeled vibrational partition functions which then have to be accommodated for by a smaller value of the derived adiabatic electron affinity EA of SF(6). The previously estimated value of EA = 1.20 (±0.05) eV in this way is reduced to a value of EA = 1.03 (±0.05) eV. In addition, the bond dissociation energy E(0,dis) for SF(6)(-) → SF(5)(-) + F is reduced to E(0,dis) = 1.44 (±0.05) eV. Finally, the consequences for modeled specific rate constants k(det)(E,J) of electron detachment from SF(6)(-) are discussed.

  14. Phosphatidylserine Reversibly Binds Cu2+ with Extremely High Affinity

    PubMed Central

    Monson, Christopher F.; Cong, Xiao; Robison, Aaron; Pace, Hudson P.; Liu, Chunming; Poyton, Matthew F.; Cremer, Paul S.

    2012-01-01

    Phosphatidylserine (PS) embedded within supported lipid bilayers (SLBs) was found to bind Cu2+ from solution with extraordinarily high affinity. In fact, the equilibrium dissociation constant was in the femtomolar range. The resulting complex formed in a 1:2 Cu2+ to PS ratio and quenches a broad spectrum of lipid-bound fluorophores in a reversible and pH-dependent fashion. At acidic pH values, the fluorophores were almost completely unquenched, while at basic pH values significant quenching (85–90%) was observed. The pH at which the transition occurred was dependent on the PS concentration and ranged from approximately pH 5 to 8. The quenching kinetics was slow at low Cu2+ concentrations and basic values pH (up to several hours), while the unquenching reaction was orders of magnitude more rapid upon lowering the pH. This was consistent with diffusion limited complex formation at basic pH, but rapid dissociation under acidic conditions. The tight binding of Cu2+ to PS may have physiological consequences under certain circumstances. PMID:22548290

  15. Quality control of coated antibodies: new, rapid determination of binding affinity.

    PubMed

    Ricoux, R; Chazaud, B; Tresca, J P; Pontet, M

    2000-03-01

    A procedure is described for the determination of the affinity constant between a fluid-phase biotinylated antigen and a solid-phase monoclonal antibody. This procedure allows evaluation of the efficiency of an antibody as a coated tool for an immunoassay. For this purpose, the biotinylation of the antigen and its further quantitative measurement by streptavidin-peroxidase led to a single reversible interaction, the binding affinity of which greatly determines the quality of the assay. The free and bound fractions of the biotinylated antigen were obtained in wells coated with a low level of immobilized antibodies. At the equilibrium state, the free antigen present in the supernatant of these wells was further transferred to high level antibody coated wells which captured all the free antigen molecules. These molecules were quantified using a standard curve established with known concentrations of biotinylated antigen, also incubated in wells coated with the high level of antibody.

  16. A bambusuril macrocycle that binds anions in water with high affinity and selectivity.

    PubMed

    Yawer, Mirza Arfan; Havel, Vaclav; Sindelar, Vladimir

    2015-01-02

    Synthetic receptors that function in water are important for the qualitative and quantitative detection of anions, which may act as pollutants in the environment or play important roles in biological processes. Neutral receptors are particularly appealing because they are often more selective than positively charged receptors; however, their affinity towards anions in pure water is only in range of 1-10(3)  L mol(-1) . The anion-templated synthesis of a water-soluble bambusuril derivative is shown to be an outstanding receptor for various inorganic anions in pure water, with association constants of up to 10(7)  L mol(-1) . Furthermore, the macrocycle discriminates between anions with unprecedented selectivity (up to 500 000-fold). We anticipate that the combination of remarkable affinity and selectivity of this macrocycle will enable the efficient detection and isolation of diverse anions in aqueous solutions, which is not possible with current supramolecular systems.

  17. Preorganized Peptide Scaffolds as Mimics of Phosphorylated Proteins Binding Sites with a High Affinity for Uranyl.

    PubMed

    Starck, Matthieu; Sisommay, Nathalie; Laporte, Fanny A; Oros, Stéphane; Lebrun, Colette; Delangle, Pascale

    2015-12-07

    Cyclic peptides with two phosphoserines and two glutamic acids were developed to mimic high-affinity binding sites for uranyl found in proteins such as osteopontin, which is believed to be a privileged target of this ion in vivo. These peptides adopt a β-sheet structure that allows the coordination of the latter amino acid side chains in the equatorial plane of the dioxo uranyl cation. Complementary spectroscopic and analytical methods revealed that these cyclic peptides are efficient uranyl chelating peptides with a large contribution from the phosphorylated residues. The conditional affinity constants were measured by following fluorescence tryptophan quenching and are larger than 10(10) at physiological pH. These compounds are therefore promising models for understanding uranyl chelation by proteins, which is relevant to this actinide ion toxicity.

  18. Practical strategies for the evaluation of high-affinity protein/nucleic acid interactions

    PubMed Central

    Altschuler, Sarah E.; Lewis, Karen A.; Wuttke, Deborah S.

    2014-01-01

    The quantitative evaluation of binding interactions between proteins and nucleic acids is highly sensitive to a variety of experimental conditions. Optimization of these conditions is critical for obtaining high quality, reproducible data, particularly in the context of very high affinity interactions. Here, we discuss the practical considerations involved in optimizing the apparent binding constant of an interaction as measured by two common quantitative assays, electrophoretic mobility shift assay and double-filter binding when measuring extremely tight protein/nucleic acid interactions with sub-nanomolar binding affinities. We include specific examples from two telomere end-binding protein systems, Schizo -saccharomyces pombe Pot1 and Saccharomyces cerevisiae Cdc13, to demonstrate potential experimental pitfalls and some useful strategies for optimization. PMID:25197549

  19. Guanine nucleotide regulation of dopamine receptor agonist affinity states in rat estradiol-induced pituitary tumors

    SciTech Connect

    Di Paolo, T.; Falardeau, P.

    1987-08-31

    The authors have investigated dopamine (DA) receptor agonist high- and low-affinity states in female rate estradiol-induced prolactin (PRL)-secreting pituitary tumors and intact pituitary tissue. Estradiol treatment increased the anterior pituitary weight 9-fold and plasma prolactin levels 74-fold and these measures are correlated (R = 0.745, n = 73, p < 0.001). Competition for (/sup 3/H)-spiperone binding to the DA receptor by apomorphine was compared in normal and adenomatous pituitary tissue. The inhibition constants (Ki) and the proportions of the two apomorphine sites are unchanged in tumors compared to intact pituitary tissue. Guanosine 5'-(..beta..-..gamma..-imino)triphosphate (Gpp(NH)p) causes complete conversion of the high into low affinity dopaminergic agonist site in normal pituitary and in tumors. These results suggest that rats with primary estradiol-induced pituitary tumors have normal and functional DA receptors. 9 references, 2 tables.

  20. Self-affine and ARX-models zonation of well logging data

    NASA Astrophysics Data System (ADS)

    Shiri, Yousef; Tokhmechi, Behzad; Zarei, Zeinab; Koneshloo, Mohammad

    2012-11-01

    Zonation of time series into models which their parameters are piecewise constant are important and well-studied problems. Geophysical well logging data often show a complex pattern due to their multifractal nature. In a multifractal system, any pieces of it are established by a distinct exponent that can characterize them. This feature has the capability to cluster them. Self-affine zonation by Auto Regressive model with exogenous inputs (ARX) is a new approach which places well logging segments in the clusters which are more self-affine against the other clusters. This approach was performed and compared with a conventional ARX zonation in the well logging data of three different oilfields in southern parts of Iran. The results showed a good accuracy for detecting homogeneous lithological segments and led to a precise interpretation process to update the reservoir architecture.

  1. Conformational Destabilization of Immunoglobulin G Increases the Low pH Binding Affinity with the Neonatal Fc Receptor*

    PubMed Central

    Walters, Benjamin T.; Jensen, Pernille F.; Larraillet, Vincent; Lin, Kevin; Patapoff, Thomas; Schlothauer, Tilman; Rand, Kasper D.; Zhang, Jennifer

    2016-01-01

    Crystallographic evidence suggests that the pH-dependent affinity of IgG molecules for the neonatal Fc receptor (FcRn) receptor primarily arises from salt bridges involving IgG histidine residues, resulting in moderate affinity at mildly acidic conditions. However, this view does not explain the diversity in affinity found in IgG variants, such as the YTE mutant (M252Y,S254T,T256E), which increases affinity to FcRn by up to 10×. Here we compare hydrogen exchange measurements at pH 7.0 and pH 5.5 with and without FcRn bound with surface plasmon resonance estimates of dissociation constants and FcRn affinity chromatography. The combination of experimental results demonstrates that differences between an IgG and its cognate YTE mutant vary with their pH-sensitive dynamics prior to binding FcRn. The conformational dynamics of these two molecules are nearly indistinguishable upon binding FcRn. We present evidence that pH-induced destabilization in the CH2/3 domain interface of IgG increases binding affinity by breaking intramolecular H-bonds and increases side-chain adaptability in sites that form intermolecular contacts with FcRn. Our results provide new insights into the mechanism of pH-dependent affinity in IgG-FcRn interactions and exemplify the important and often ignored role of intrinsic conformational dynamics in a protein ligand, to dictate affinity for biologically important receptors. PMID:26627822

  2. Quantification of hydrophobic interaction affinity of colloids

    NASA Astrophysics Data System (ADS)

    Saini, G.; Nasholm, N.; Wood, B. D.

    2009-12-01

    Colloids play an important role in a wide variety of disciplines, including water and wastewater treatment, subsurface transport of metals and organic contaminants, migration of fines in oil reservoirs, biocolloid (virus and bacteria) transport in subsurface, and are integral to laboratory transport studies. Although the role of hydrophobicity in adhesion and transport of colloids, particularly bacteria, is well known; there is scarcity of literature regarding hydrophobicity measurement of non-bacterial colloids and other micron-sized particles. Here we detail an experimental approach based on differential partitioning of colloids between two liquid phases (hydrocarbon and buffer) as a measure of the hydrophobic interaction affinity of colloids. This assay, known as Microbial adhesion to hydrocarbons or MATH, is frequently used in microbiology and bacteriology for quantifying the hydrophobicity of microbes. Monodispersed colloids and particles, with sizes ranging from 1 micron to 33 micron, were used for the experiments. A range of hydrophobicity values were observed for different particles. The hydrophobicity results are also verified against water contact angle measurements of these particles. This liquid-liquid partitioning assay is quick, easy-to-perform and requires minimal instrumentation. Estimation of the hydrophobic interaction affinity of colloids would lead to a better understanding of their adhesion to different surfaces and subsequent transport in porous media.

  3. Fatigue damage prognosis using affine arithmetic

    NASA Astrophysics Data System (ADS)

    Gbaguidi, Audrey; Kim, Daewon

    2014-02-01

    Among the essential steps to be taken in structural health monitoring systems, damage prognosis would be the field that is least investigated due to the complexity of the uncertainties. This paper presents the possibility of using Affine Arithmetic for uncertainty propagation of crack damage in damage prognosis. The structures examined are thin rectangular plates made of titanium alloys with central mode I cracks and a composite plate with an internal delamination caused by mixed mode I and II fracture modes, under a harmonic uniaxial loading condition. The model-based method for crack growth rates are considered using the Paris Erdogan law model for the isotropic plates and the delamination growth law model proposed by Kardomateas for the composite plate. The parameters for both models are randomly taken and their uncertainties are considered as defined by an interval instead of a probability distribution. A Monte Carlo method is also applied to check whether Affine Arithmetic (AA) leads to tight bounds on the lifetime of the structure.

  4. Affinity-based target deconvolution of safranal

    PubMed Central

    2013-01-01

    Background and the purpose of the study Affinity-based target deconvolution is an emerging method for the identification of interactions between drugs/drug candidates and cellular proteins, and helps to predict potential activities and side effects of a given compound. In the present study, we hypothesized that a part of safranal pharmacological effects, one of the major constituent of Crocus sativus L., relies on its physical interaction with target proteins. Methods Affinity chromatography solid support was prepared by covalent attachment of safranal to agarose beads. After passing tissue lysate through the column, safranal-bound proteins were isolated and separated on SDS-PAGE or two-dimensional gel electrophoresis. Proteins were identified using MALDI-TOF/TOF mass spectrometry and Mascot software. Results and major conclusion Data showed that safranal physically binds to beta actin, cytochrome b-c1 complex sub-unit 1, trifunctional enzyme sub-unit beta and ATP synthase sub-unit alpha and beta. These interactions may explain part of safranal’s pharmacological effects. However, phenotypic and/or biological relevance of these interactions remains to be elucidated by future pharmacological studies. PMID:23514587

  5. Relations between high-affinity binding sites for L-tryptophan, diazepam, salicylate and Phenol Red on human serum albumin.

    PubMed Central

    Kragh-Hansen, U

    1983-01-01

    Binding of L-tryptophan, diazepam, salicylate and Phenol Red to defatted human serum albumin was studied by ultrafiltration at pH 7.0. All ligands bind to one high-affinity binding site with association constants of the order of 10(4)-10(5)M-1. The number of secondary binding sites was found to vary from zero to five, with association constants about 10(3)M-1. Competitive binding studies with different pairs of the ligands were performed. Binding of both ligands was determined simultaneously. L-Tryptophan and diazepam were found to compete for a common high-affinity binding site on albumin. The following combinations of ligands do not bind competitively to albumin: L-tryptophan-Phenol Red, L-tryptophan-salicylate and Phenol Red-salicylate. On the other hand, high-affinity bindings of the three ligands do not take place independently but in such a way that binding of one of the ligands results in a decrease in binding of the other ligands. The decreases in binding are reciprocal and can be accounted for by introducing a coupling constant. The magnitude of the constant is dependent on the ligands being bound. In the present study, the mutual decrease in binding was more pronounced with L-tryptophan-salicylate and Phenol Red-salicylate than with L-tryptophan-Phenol Red. PMID:6847607

  6. Oxygen affinity and amino acid sequence of myoglobins from endothermic and ectothermic fish.

    PubMed

    Marcinek, D J; Bonaventura, J; Wittenberg, J B; Block, B A

    2001-04-01

    Myoglobin (Mb) buffers intracellular O2 and facilitates diffusion of O2 through the cell. These functions of Mb will be most effective when intracellular PO2 is near the partial pressure of oxygen at which Mb is half saturated (P50) of the molecule. We test the hypothesis that Mb oxygen affinity has evolved such that it is conserved when adjusted for body temperature among closely related animals. We measure oxygen P50s tonometrically and oxygen dissociation rate constants with stopped flow and generate amino acid sequence from cDNA of Mbs from fish with different body temperatures. P50s for the endothermic bluefin tuna, skipjack tuna, and blue marlin at 20 degrees C were 0.62 +/- 0.02, 0.59 +/- 0.01, 0.58 +/- 0.04 mmHg, respectively, and were significantly lower than those for ectothermic bonito (1.03 +/- 0.07 mmHg) and mackerel (1.39 +/- 0.03 mmHg). Because the oxygen affinity of Mb decreases with increasing temperature, the above differences in oxygen affinity between endothermic and ectothermic fish are reduced when adjusted for the in vivo muscle temperature of the animal. Oxygen dissociation rate constants at 20 degrees C for the endothermic species ranged from 34.1 to 49.3 s(-1), whereas those for mackerel and bonito were 102 and 62 s(-1), respectively. Correlated with the low oxygen affinity and fast dissociation kinetics of mackerel Mb is a substitution of alanine for proline that would likely result in a more flexible mackerel protein.

  7. Calculating protein-ligand binding affinities with MMPBSA: Method and error analysis.

    PubMed

    Wang, Changhao; Nguyen, Peter H; Pham, Kevin; Huynh, Danielle; Le, Thanh-Binh Nancy; Wang, Hongli; Ren, Pengyu; Luo, Ray

    2016-10-15

    Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) methods have become widely adopted in estimating protein-ligand binding affinities due to their efficiency and high correlation with experiment. Here different computational alternatives were investigated to assess their impact to the agreement of MMPBSA calculations with experiment. Seven receptor families with both high-quality crystal structures and binding affinities were selected. First the performance of nonpolar solvation models was studied and it was found that the modern approach that separately models hydrophobic and dispersion interactions dramatically reduces RMSD's of computed relative binding affinities. The numerical setup of the Poisson-Boltzmann methods was analyzed next. The data shows that the impact of grid spacing to the quality of MMPBSA calculations is small: the numerical error at the grid spacing of 0.5 Å is already small enough to be negligible. The impact of different atomic radius sets and different molecular surface definitions was further analyzed and weak influences were found on the agreement with experiment. The influence of solute dielectric constant was also analyzed: a higher dielectric constant generally improves the overall agreement with experiment, especially for highly charged binding pockets. The data also showed that the converged simulations caused slight reduction in the agreement with experiment. Finally the direction of estimating absolute binding free energies was briefly explored. Upon correction of the binding-induced rearrangement free energy and the binding entropy lost, the errors in absolute binding affinities were also reduced dramatically when the modern nonpolar solvent model was used, although further developments were apparently necessary to further improve the MMPBSA methods. © 2016 Wiley Periodicals, Inc.

  8. Protonation linked equilibria and apparent affinity constants: the thermodynamic profile of the alpha-chymotrypsin-proflavin interaction.

    PubMed

    Bruylants, Gilles; Wintjens, René; Looze, Yvan; Redfield, Christina; Bartik, Kristin

    2007-12-01

    Protonation/deprotonation equilibria are frequently linked to binding processes involving proteins. The presence of these thermodynamically linked equilibria affects the observable thermodynamic parameters of the interaction (K(obs), DeltaH(obs)(0) ). In order to try and elucidate the energetic factors that govern these binding processes, a complete thermodynamic characterisation of each intrinsic equilibrium linked to the complexation event is needed and should furthermore be correlated to structural information. We present here a detailed study, using NMR and ITC, of the interaction between alpha-chymotrypsin and one of its competitive inhibitors, proflavin. By performing proflavin titrations of the enzyme, at different pH values, we were able to highlight by NMR the effect of the complexation of the inhibitor on the ionisable residues of the catalytic triad of the enzyme. Using ITC we determined the intrinsic thermodynamic parameters of the different equilibria linked to the binding process. The possible driving forces of the interaction between alpha-chymotrypsin and proflavin are discussed in the light of the experimental data and on the basis of a model of the complex. This study emphasises the complementarities between ITC and NMR for the study of binding processes involving protonation/deprotonation equilibria.

  9. Survival of Nannochloropsis Phytoplankton in Hypervelocity Impact Events up to Velocities of 6.07 km/s

    NASA Astrophysics Data System (ADS)

    Pasini, D. L. S.; Price, M. C.; Burchell, M. J.; Cole, M. J.

    2013-09-01

    Studies have previously been conducted to verify the survivability of living cells during hypervelocity impact events to test the panspermia and lithopanspermia hypothesis [1], [2]. It has been demonstrated that bacteria survive impacts up to 5.4 km s-1 (approx. shock pressure 30 GPa) - albeit with a low probability of survival [1] whilst larger more complex objects (such as seeds) break up at ~1 km s-1 [2]. The survivability of yeast spores in impacts up to 7.4 km s-1 has also recently been shown [3]. We demonstrate here the survivability of Nannochloropsis Phytoplankton, a eukaryotic photosynthesizing autotroph found in the 'euphotic zone'(sunlit surface layers of oceans) [4] at impact velocities up to 6.07 km s-1. Phytoplankton from a culture sample was frozen and then fired into water (to simulate oceanic impacts, as described in [5]) using a light gas gun (LGG) [6]. The water was then retrieved and placed into a sealed culture vessel and left under a constant light source to check the viability of any remnant organisms.

  10. Evaluation of the 7-km GEOS-5 Nature Run

    NASA Technical Reports Server (NTRS)

    Gelaro, Ronald; Putman, William M.; Pawson, Steven; Draper, Clara; Molod, Andrea; Norris, Peter M.; Ott, Lesley; Prive, Nikki; Reale, Oreste; Achuthavarier, Deepthi; Bosilovich, Michael; Buchard, Virginie; Chao, Winston; Coy, Lawrence; Cullather, Richard; da Silva, Arlindo; Darmenov, Anton; Koster, Randal; McCarty, Will; Schubert, Siegfried

    2015-01-01

    This report documents an evaluation by the Global Modeling and Assimilation Office (GMAO) of a two-year 7-km-resolution non-hydrostatic global mesoscale simulation produced with the Goddard Earth Observing System (GEOS-5) atmospheric general circulation model. The simulation was produced as a Nature Run for conducting observing system simulation experiments (OSSEs). Generation of the GEOS-5 Nature Run (G5NR) was motivated in part by the desire of the OSSE community for an improved high-resolution sequel to an existing Nature Run produced by the European Centre for Medium-Range Weather Forecasts (ECMWF), which has served the community for several years. The intended use of the G5NR in this context is for generating simulated observations to test proposed observing system designs regarding new instruments and their deployments. Because NASA's interest in OSSEs extends beyond traditional weather forecasting applications, the G5NR includes, in addition to standard meteorological components, a suite of aerosol types and several trace gas concentrations, with emissions downscaled to 10 km using ancillary information such as power plant location, population density and night-light information. The evaluation exercise described here involved more than twenty-five GMAO scientists investigating various aspects of the G5NR performance, including time mean temperature and wind fields, energy spectra, precipitation and the hydrological cycle, the representation of waves, tropical cyclones and midlatitude storms, land and ocean surface characteristics, the representation and forcing effects of clouds and radiation, dynamics of the stratosphere and mesosphere, and the representation of aerosols and trace gases. Comparisons are made with observational data sets when possible, as well as with reanalyses and other long model simulations. The evaluation is broad in scope, as it is meant to assess the overall realism of basic aspects of the G5NR deemed relevant to the conduct of OSSEs

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

    PubMed

    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.

  12. 45-km horizontal-path optical link experiment

    NASA Astrophysics Data System (ADS)

    Biswas, Abhijit; Ceniceros, Juan M.; Novak, Matthew J.; Jeganathan, Muthu; Portillo, Angel; Erickson, David M.; de Pew, Jon; Sanii, B.; Lesh, James R.

    1999-04-01

    Mountain-top to mountain-top optical link experiments have been initiated at JPL, in order to perform a systems level evaluation of optical communications. Progress made so far is reported. The NASA, JPL developed optical communications demonstrator (OCD) is used to transmit a laser signal from Strawberry Peak (SP), located in the San Bernadino mountains of California. This laser beam is received by a 0.6 m aperture telescope at JPL's Table Mountain Facility (TMF), located in Wrightwood, California. The optical link is bi-directional with the TMF telescope transmitting a continuous 4-wave (cw) 780 nm beacon and the OCD sending back an 840 nm, 100 - 500 Mbps pseudo noise (PN) modulated, laser beam. The optical link path is at an average altitude of 2 Km above sea level, covers a range of 46.8 Km and provides an atmospheric channel equivalent to approximately 4 air masses. Average received power measured at either end fall well within the uncertainties predicted by link analysis. The reduction in normalized intensity variance ((sigma) I2) for the 4- beam beacon, compared to each individual beam, at SP, was from approximately 0.68 to 0.22. With some allowance for intra-beam mis-alignment, this is consistent with incoherent averaging. The (sigma) I2 measured at TMF approximately 0.43 plus or minus 0.22 exceeded the expected aperture averaged value of less than 0.1, probably because of beam wander. The focused spot sizes of approximately 162 plus or minus 6 micrometer at the TMF Coude and approximately 64 plus or minus 3 micrometer on the OCD compare to the predicted size range of 52 - 172 micrometer and 57 - 93 micrometer, respectively. This is consistent with 4 - 5 arcsec of atmospheric 'seeing.' The preliminary evaluation of OCD's fine tracking indicates that the uncompensated tracking error is approximately 3.3 (mu) rad compared to approximately 1.7 (mu) rad observed in the laboratory. Fine tracking performance was intermittent, primarily due to beacon fades on the

  13. Modulating Uranium Binding Affinity in Engineered Calmodulin EF-Hand Peptides: Effect of Phosphorylation

    PubMed Central

    Pardoux, Romain; Sauge-Merle, Sandrine; Lemaire, David; Delangle, Pascale; Guilloreau, Luc; Adriano, Jean-Marc; Berthomieu, Catherine

    2012-01-01

    To improve our understanding of uranium toxicity, the determinants of uranyl affinity in proteins must be better characterized. In this work, we analyzed the contribution of a phosphoryl group on uranium binding affinity in a protein binding site, using the site 1 EF-hand motif of calmodulin. The recombinant domain 1 of calmodulin from A. thaliana was engineered to impair metal binding at site 2 and was used as a structured template. Threonine at position 9 of the loop was phosphorylated in vitro, using the recombinant catalytic subunit of protein kinase CK2. Hence, the T9TKE12 sequence was substituted by the CK2 recognition sequence TAAE. A tyrosine was introduced at position 7, so that uranyl and calcium binding affinities could be determined by following tyrosine fluorescence. Phosphorylation was characterized by ESI-MS spectrometry, and the phosphorylated peptide was purified to homogeneity using ion-exchange chromatography. The binding constants for uranyl were determined by competition experiments with iminodiacetate. At pH 6, phosphorylation increased the affinity for uranyl by a factor of ∼5, from Kd = 25±6 nM to Kd = 5±1 nM. The phosphorylated peptide exhibited a much larger affinity at pH 7, with a dissociation constant in the subnanomolar range (Kd = 0.25±0.06 nM). FTIR analyses showed that the phosphothreonine side chain is partly protonated at pH 6, while it is fully deprotonated at pH 7. Moreover, formation of the uranyl-peptide complex at pH 7 resulted in significant frequency shifts of the νas(P-O) and νs(P-O) IR modes of phosphothreonine, supporting its direct interaction with uranyl. Accordingly, a bathochromic shift in νas(UO2)2+ vibration (from 923 cm−1 to 908 cm−1) was observed upon uranyl coordination to the phosphorylated peptide. Together, our data demonstrate that the phosphoryl group plays a determining role in uranyl binding affinity to proteins at physiological pH. PMID:22870263

  14. A simple, high-resolution method for establishing DNA binding affinity and sequence selectivity.

    PubMed

    Boger, D L; Fink, B E; Brunette, S R; Tse, W C; Hedrick, M P

    2001-06-27

    Full details of the development of a simple, nondestructive, and high-throughput method for establishing DNA binding affinity and sequence selectivity are described. The method is based on the loss of fluorescence derived from the displacement of ethidium bromide or thiazole orange from the DNA of interest or, in selected instances, the change in intrinsic fluorescence of a DNA binding agent itself and is applicable for assessing relative or absolute DNA binding affinities. Enlisting a library of hairpin deoxyoligonucleotides containing all five base pair (512 hairpins) or four base pair (136 hairpins) sequences displayed in a 96-well format, a compound's rank order binding to all possible sequences is generated, resulting in a high-resolution definition of its sequence selectivity using this fluorescent intercalator displacement (FID) assay. As such, the technique complements the use of footprinting or affinity cleavage for the establishment of DNA binding selectivity and provides the information at a higher resolution. The merged bar graphs generated by this rank order binding provide a qualitative way to compare, or profile, DNA binding affinity and selectivity. The 96-well format assay (512 hairpins) can be conducted at a minimal cost (presently ca. $100 for hairpin deoxyoligonucleotides/assay with ethiduim bromide or less with thiazole orange), with a rapid readout using a fluorescent plate reader (15 min), and is adaptable to automation (Tecan Genesis Workstation 100 robotic system). Its use in generating a profile of DNA binding selectivity for several agents including distamycin A, netropsin, DAPI, Hoechst 33258, and berenil is described. Techniques for establishing binding constants from quantitative titrations are compared, and recommendations are made for use of a Scatchard or curve fitting analysis of the titration binding curves as a reliable means to quantitate the binding affinity.

  15. ASIC design in the KM3NeT detector

    NASA Astrophysics Data System (ADS)

    Gajanana, D.; Gromov, V.; Timmer, P.

    2013-02-01

    In the KM3NeT project [1], Cherenkov light from the muon interactions with transparent matter around the detector, is used to detect neutrinos. Photo multiplier tubes (PMT) used as photon sensor, are housed in a glass sphere (aka Optical Module) to detect single photons from the Cherenkov light. The PMT needs high operational voltage ( ~ 1.5 kV) and is generated by a Cockroft-Walton (CW) multiplier circuit. The electronics required to control the PMT's and collect the signals is integrated in two ASIC's namely: 1) a front-end mixed signal ASIC (PROMiS) for the readout of the PMT and 2) an analog ASIC (CoCo) to generate pulses for charging the CW circuit and to control the feedback of the CW circuit. In this article, we discuss the two integrated circuits and test results of the complete setup. PROMiS amplifies the input charge, converts it to a pulse width and delivers the information via LVDS signals. These LVDS signals carry accurate information on the Time of arrival ( < 2 ns) and Time over Threshold. A PROM block provides unique identification to the chip. The chip communicates with the control electronics via an I2C bus. This unique combination of the ASIC's results in a very cost and power efficient PMT base design.

  16. Stratospheric microbiology at 20 km over the Pacific Ocean

    USGS Publications Warehouse

    Smith, David J.; Griffin, Dale W.; Schuerger, Andrew C.

    2010-01-01

    An aerobiology sampling flight at 20 km was conducted on 28 April 2008 over the Pacific Ocean (36.5° N, 118–149° W), a period of time that coincided with the movement of Asian dust across the ocean. The aim of this study was to confirm the presence of viable bacteria and fungi within a transoceanic, atmospheric bridge and to improve the resolution of flight hardware processing techniques. Isolates of the microbial strains recovered were analyzed with ribosomal ribonucleic acid (rRNA) sequencing to identify bacterial species Bacillus sp., Bacillus subtilis, Bacillus endophyticus, and the fungal genus Penicillium. Satellite imagery and ground-based radiosonde observations were used to measure dust movement and characterize the high-altitude environment at the time of collection. Considering the atmospheric residency time (7–10 days), the extreme temperature regime of the environment (-75°C), and the absence of a mechanism that could sustain particulates at high altitude, it is unlikely that our samples indicate a permanent, stratospheric ecosystem. However, the presence of viable fungi and bacteria in transoceanic stratosphere remains relevant to understanding the distribution and extent of microbial life on Earth.

  17. A 233 km Tunnel for Lepton and Hadron Colliders

    NASA Astrophysics Data System (ADS)

    Summers, D. J.; Cremaldi, L. M.; Datta, A.; Duraisamy, M.; Luo, T.; Lyons, G. T.

    2012-07-01

    A decade ago, a cost analysis was conducted to bore a 233 km circumference Very Large Hadron Collider (VLHC) tunnel passing through Fermilab. Here we outline implementations of $e^+e^-$, $p \\bar{p}$, and $\\mu^+ \\mu^-$ collider rings in this tunnel using recent technological innovations. The 240 and 500 GeV $e^+e^-$ colliders employ Crab Waist Crossings, ultra low emittance damped bunches, short vertical IP focal lengths, superconducting RF, and low coercivity, grain oriented silicon steel/concrete dipoles. Some details are also provided for a high luminosity 240 GeV $e^+ e^-$ collider and 1.75 TeV muon accelerator in a Fermilab site filler tunnel. The 40 TeV $p \\bar{p}$ collider uses the high intensity Fermilab $\\bar{p}$ source, exploits high cross sections for $p \\bar{p}$ production of high mass states, and uses 2 Tesla ultra low carbon steel/YBCO superconducting magnets run with liquid neon. The 35 TeV muon ring ramps the 2 Tesla superconducting magnets at 9 Hz every 0.4 seconds, uses 250 GV of superconducting RF to accelerate muons from 1.75 to 17.5 TeV in 63 orbits with 71% survival, and mitigates neutrino radiation with phase shifting, roller coaster motion in a FODO lattice.

  18. KM3NeT Digital Optical Module electronics

    NASA Astrophysics Data System (ADS)

    Real, Diego

    2016-04-01

    The KM3NeT collaboration is currently building of a neutrino telescope with a volume of several cubic kilometres at the bottom of the Mediterranean Sea. The telescope consists of a matrix of Digital Optical Modules that will detect the Cherenkov light originated by the interaction of the neutrinos in the proximity of the detector. This contribution describes the main components of the read-out electronics of the Digital Optical Module: the Power Board, which delivers all the power supply required by the Digital Optical Molule electronics; the Central Logic Board, the main core of the read-out system, hosting 31 Time to Digital Converters with 1 ns resolution and the White Rabbit protocol embedded in the Central Logic Board Field Programmable Gate Array; the Octopus boards, that transfer the Low Voltage Digital Signals from the PMT bases to the Central Logic Board and finally the PMT bases, in charge of converting the analogue signal produced in the 31 3" PMTs into a Low Voltage Digital Signal.

  19. A 233 km tunnel for lepton and hadron colliders

    SciTech Connect

    Summers, D. J.; Cremaldi, L. M.; Datta, A.; Duraisamy, M.; Luo, T.; Lyons, G. T.

    2012-12-21

    A decade ago, a cost analysis was conducted to bore a 233 km circumference Very Large Hadron Collider (VLHC) tunnel passing through Fermilab. Here we outline implementations of e{sup +}e{sup -}, pp-bar , and {mu}{sup +}{mu}{sup -} collider rings in this tunnel using recent technological innovations. The 240 and 500 GeV e{sup +}e{sup -} colliders employ Crab Waist Crossings, ultra low emittance damped bunches, short vertical IP focal lengths, superconducting RF, and low coercivity, grain oriented silicon steel/concrete dipoles. Some details are also provided for a high luminosity 240 GeV e{sup +}e{sup -} collider and 1.75 TeV muon accelerator in a Fermilab site filler tunnel. The 40 TeV pp-bar collider uses the high intensity Fermilab p-bar source, exploits high cross sections for pp-bar production of high mass states, and uses 2 Tesla ultra low carbon steel/YBCO superconducting magnets run with liquid neon. The 35 TeV muon ring ramps the 2 Tesla superconducting magnets at 9 Hz every 0.4 seconds, uses 250 GV of superconducting RF to accelerate muons from 1.75 to 17.5 TeV in 63 orbits with 71% survival, and mitigates neutrino radiation with phase shifting, roller coaster motion in a FODO lattice.

  20. Structure of a High-Affinity

    SciTech Connect

    Saphire, E.O.; Montero, M.; Menendez, A.; Houten, N.E.van; Irving, M.B.; Pantophlet, R.; Swick, M.B.; Parren, P.W.H.I.; Burton, D.R.; Scott, J.K.; Wilson, I.A.; /Scripps Res. Inst. /Simon Fraser U. /British Columbia U.

    2007-07-13

    The human antibody b12 recognizes a discontinuous epitope on gp120 and is one of the rare monoclonal antibodies that neutralize a broad range of primary human immunodeficiency virus type 1 (HIV-1) isolates. We previously reported the isolation of B2.1, a dimeric peptide that binds with high specificity to b12 and competes with gp120 for b12 antibody binding. Here, we show that the affinity of B2.1 was improved 60-fold over its synthetic-peptide counterpart by fusing it to the N terminus of a soluble protein. This affinity, which is within an order of magnitude of that of gp120, probably more closely reflects the affinity of the phage-borne peptide. The crystal structure of a complex between Fab of b12 and B2.1 was determined at 1.8 Angstrom resolution. The structural data allowed the differentiation of residues that form critical contacts with b12 from those required for maintenance of the antigenic structure of the peptide, and revealed that three contiguous residues mediate B2.1's critical contacts with b12. This single region of critical contact between the B2.1 peptide and the b12 paratope is unlikely to mimic the discontinuous key binding residues involved in the full b12 epitope for gp120, as previously identified by alanine scanning substitutions on the gp120 surface. These structural observations are supported by experiments that demonstrate that B2.1 is an ineffective immunogenic mimic of the b12 epitope on gp120. Indeed, an extensive series of immunizations with B2.1 in various forms failed to produce gp120 cross-reactive sera. The functional and structural data presented here, however, suggest that the mechanism by which b12 recognizes the two antigens is very different. Here, we present the first crystal structure of peptide bound to an antibody that was originally raised against a discontinuous protein epitope. Our results highlight the challenge of producing immunogens that mimic discontinuous protein epitopes, and the necessity of combining

  1. Predicting Stability Constants for Uranyl Complexes Using Density Functional Theory

    SciTech Connect

    Vukovic, Sinisa; Hay, Benjamin P.; Bryantsev, Vyacheslav S.

    2015-04-02

    The ability to predict the equilibrium constants for the formation of 1:1 uranyl:ligand complexes (log K1 values) provides the essential foundation for the rational design of ligands with enhanced uranyl affinity and selectivity. We also use density functional theory (B3LYP) and the IEFPCM continuum solvation model to compute aqueous stability constants for UO22+ complexes with 18 donor ligands. Theoretical calculations permit reasonably good estimates of relative binding strengths, while the absolute log K1 values are significantly overestimated. Accurate predictions of the absolute log K1 values (root mean square deviation from experiment < 1.0 for log K1 values ranging from 0 to 16.8) can be obtained by fitting the experimental data for two groups of mono and divalent negative oxygen donor ligands. The utility of correlations is demonstrated for amidoxime and imide dioxime ligands, providing a useful means of screening for new ligands with strong chelate capability to uranyl.

  2. Predicting Stability Constants for Uranyl Complexes Using Density Functional Theory

    DOE PAGES

    Vukovic, Sinisa; Hay, Benjamin P.; Bryantsev, Vyacheslav S.

    2015-04-02

    The ability to predict the equilibrium constants for the formation of 1:1 uranyl:ligand complexes (log K1 values) provides the essential foundation for the rational design of ligands with enhanced uranyl affinity and selectivity. We also use density functional theory (B3LYP) and the IEFPCM continuum solvation model to compute aqueous stability constants for UO22+ complexes with 18 donor ligands. Theoretical calculations permit reasonably good estimates of relative binding strengths, while the absolute log K1 values are significantly overestimated. Accurate predictions of the absolute log K1 values (root mean square deviation from experiment < 1.0 for log K1 values ranging from 0more » to 16.8) can be obtained by fitting the experimental data for two groups of mono and divalent negative oxygen donor ligands. The utility of correlations is demonstrated for amidoxime and imide dioxime ligands, providing a useful means of screening for new ligands with strong chelate capability to uranyl.« less

  3. Static Stretching Alters Neuromuscular Function and Pacing Strategy, but Not Performance during a 3-Km Running Time-Trial

    PubMed Central

    Damasceno, Mayara V.; Duarte, Marcos; Pasqua, Leonardo A.; Lima-Silva, Adriano E.; MacIntosh, Brian R.; Bertuzzi, Rômulo

    2014-01-01

    Purpose Previous studies report that static stretching (SS) impairs running economy. Assuming that pacing strategy relies on rate of energy use, this study aimed to determine whether SS would modify pacing strategy and performance in a 3-km running time-trial. Methods Eleven recreational distance runners performed a) a constant-speed running test without previous SS and a maximal incremental treadmill test; b) an anthropometric assessment and a constant-speed running test with previous SS; c) a 3-km time-trial familiarization on an outdoor 400-m track; d and e) two 3-km time-trials, one with SS (experimental situation) and another without (control situation) previous static stretching. The order of the sessions d and e were randomized in a counterbalanced fashion. Sit-and-reach and drop jump tests were performed before the 3-km running time-trial in the control situation and before and after stretching exercises in the SS. Running economy, stride parameters, and electromyographic activity (EMG) of vastus medialis (VM), biceps femoris (BF) and gastrocnemius medialis (GA) were measured during the constant-speed tests. Results The overall running time did not change with condition (SS 11:35±00:31 s; control 11:28±00:41 s, p = 0.304), but the first 100 m was completed at a significantly lower velocity after SS. Surprisingly, SS did not modify the running economy, but the iEMG for the BF (+22.6%, p = 0.031), stride duration (+2.1%, p = 0.053) and range of motion (+11.1%, p = 0.0001) were significantly modified. Drop jump height decreased following SS (−9.2%, p = 0.001). Conclusion Static stretch impaired neuromuscular function, resulting in a slow start during a 3-km running time-trial, thus demonstrating the fundamental role of the neuromuscular system in the self-selected speed during the initial phase of the race. PMID:24905918

  4. The affine cohomology spaces and its applications

    NASA Astrophysics Data System (ADS)

    Fraj, Nizar Ben; Laraiedh, Ismail

    2016-12-01

    We compute the nth cohomology space of the affine Lie superalgebra 𝔞𝔣𝔣(1) on the (1,1)-dimensional real superspace with coefficient in a large class of 𝔞𝔣𝔣(1)-modules M. We apply our results to the module of weight densities and the module of linear differential operators acting on a superspace of weighted densities. This work is the generalization of a result by Basdouri et al. [The linear 𝔞𝔣𝔣(n|1)-invariant differential operators on weighted densities on the superspace ℝ1|n and 𝔞𝔣𝔣(n|1)-relative cohomology, Int. J. Geom. Meth. Mod. Phys. 10 (2013), Article ID: 1320004, 9 pp.

  5. High Affinity Binding of Indium and Ruthenium Ions by Gastrins.

    PubMed

    Baldwin, Graham S; George, Graham N; Pushie, M Jake

    2015-01-01

    The peptide hormone gastrin binds two ferric ions with high affinity, and iron binding is essential for the biological activity of non-amidated forms of the hormone. Since gastrins act as growth factors in gastrointestinal cancers, and as peptides labelled with Ga and In isotopes are increasingly used for cancer diagnosis, the ability of gastrins to bind other metal ions was investigated systematically by absorption spectroscopy. The coordination structures of the complexes were characterized by extended X-ray absorption fine structure (EXAFS) spectroscopy. Changes in the absorption of gastrin in the presence of increasing concentrations of Ga3+ were fitted by a 2 site model with dissociation constants (Kd) of 3.3 x 10-7 and 1.1 x 10-6 M. Although the absorption of gastrin did not change upon the addition of In3+ ions, the changes in absorbance on Fe3+ ion binding in the presence of indium ions were fitted by a 2 site model with Kd values for In3+ of 6.5 x 10-15 and 1.7 x 10-7 M. Similar results were obtained with Ru3+ ions, although the Kd values for Ru3+ of 2.6 x 10-13 and 1.2 x 10-5 M were slightly larger than observed for In3+. The structures determined by EXAFS all had metal:gastrin stoichiometries of 2:1 but, while the metal ions in the Fe, Ga and In complexes were bridged by a carboxylate and an oxygen with a metal-metal separation of 3.0-3.3 Å, the Ru complex clearly demonstrated a short range Ru-Ru separation, which was significantly shorter, at 2.4 Å, indicative of a metal-metal bond. We conclude that gastrin selectively binds two In3+ or Ru3+ ions, and that the affinity of the first site for In3+ or Ru3+ ions is higher than for ferric ions. Some of the metal ion-gastrin complexes may be useful for cancer diagnosis and therapy.

  6. File Specification for the 7-km GEOS-5 Nature Run, Ganymed Release Non-Hydrostatic 7-km Global Mesoscale Simulation

    NASA Technical Reports Server (NTRS)

    da Silva, Arlindo M.; Putman, William; Nattala, J.

    2014-01-01

    This document describes the gridded output files produced by a two-year global, non-hydrostatic mesoscale simulation for the period 2005-2006 produced with the non-hydrostatic version of GEOS-5 Atmospheric Global Climate Model (AGCM). In addition to standard meteorological parameters (wind, temperature, moisture, surface pressure), this simulation includes 15 aerosol tracers (dust, sea-salt, sulfate, black and organic carbon), O3, CO and CO2. This model simulation is driven by prescribed sea-surface temperature and sea-ice, daily volcanic and biomass burning emissions, as well as high-resolution inventories of anthropogenic sources. A description of the GEOS-5 model configuration used for this simulation can be found in Putman et al. (2014). The simulation is performed at a horizontal resolution of 7 km using a cubed-sphere horizontal grid with 72 vertical levels, extending up to to 0.01 hPa (approximately 80 km). For user convenience, all data products are generated on two logically rectangular longitude-latitude grids: a full-resolution 0.0625 deg grid that approximately matches the native cubed-sphere resolution, and another 0.5 deg reduced-resolution grid. The majority of the full-resolution data products are instantaneous with some fields being time-averaged. The reduced-resolution datasets are mostly time-averaged, with some fields being instantaneous. Hourly data intervals are used for the reduced-resolution datasets, while 30-minute intervals are used for the full-resolution products. All full-resolution output is on the model's native 72-layer hybrid sigma-pressure vertical grid, while the reduced-resolution output is given on native vertical levels and on 48 pressure surfaces extending up to 0.02 hPa. Section 4 presents additional details on horizontal and vertical grids. Information of the model surface representation can be found in Appendix B. The GEOS-5 product is organized into file collections that are described in detail in Appendix C. Additional

  7. Kinematics of the New Zealand plate boundary: Relative motion by GPS across networks of 1000 km and 50 km spacing

    NASA Technical Reports Server (NTRS)

    Meertens, Charles M.; Rocken, Christian; Perin, Barbara; Walcott, Richard

    1993-01-01

    The NASA/DOSE 'Kinematics of the New Zealand Plate Boundary' experiment is a four-year cooperative Global Positioning System (GPS) experiment involving 6 universities and institutions in New Zealand and the United States. The investigation covers two scales, the first on the scale of plates (approximately 1000 km) and the second is on the scale of the plate boundary zone (approximately 50 km). In the first portion of the experiment, phase A, the objective is to make direct measurements of tectonic plate motion between the Australian and Pacific plates using GPS in order to determine the Euler vector of this plate pair. The phase A portion of this experiment was initiated in December 1992 with the first-epoch baseline measurements on the large scale network. The network will be resurveyed two years later to obtain velocities. The stations which were observed for phase A are shown and listed. Additional regional stations which will be used for this study are listed and are part of either CIGNET or other global tracking networks. The phase A portion of the experiment is primarily the responsibility of the UNAVCO investigators. Therefore, this report concentrates on phase A. The first year of NASA funding for phase A included only support for the field work. Processing and analysis will take place with the second year of funding. The second part of the experiemnt measured relative motion between the Australian and Pacific plates across the pate boundary zone between Hokitika and Christchurch on the South Island of New Zealand. The extent and rate of deformation will be determined by comparisons with historical, conventional surveys and by repeated GPS measurements to be made in two years. This activity was the emphasis of the LDGO portion of the study. An ancillary experiment, phase C, concentrated on plate boundary deformation in the vicinity of Wellington and was done as part of training during the early portion of the field campaign. Details of the objectives of the

  8. Troposphere-stratosphere (surface-55 km) monthly winter general circulation statistics for the Northern Hemisphere Interannual variations

    NASA Technical Reports Server (NTRS)

    Geller, M. A.; Wu, M.-F.; Gelman, M. E.

    1984-01-01

    Individual monthly mean general circulation statistics for the Northern Hemisphere winters of 1978-79, 1979-80, 1980-81, and 1981-82 are examined for the altitude region from the earth's surface to 55 km. Substantial interannual variability is found in the mean zonal geostrophic wind; planetary waves with zonal wavenumber one and two; the heat and momentum fluxes; and the divergence of the Eliassen-Palm flux. These results are compared with previous studies by other workers. This variability in the monthly means is examined further by looking at both time-latitude sections at constant pressure levels and time-height sections at constant latitudes. The implications of this interannual variability for verifying models and interpreting observations are discussed.

  9. Species with negative electron affinity and standard DFT methods. Finding the valence anions.

    PubMed

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

    2008-03-14

    Recently, we have shown that traditional bound-electron DFT models are reliable enough to reproduce negative electron affinities (EA) within a few meV, as long as the valence anion state is found, but they seem to fail in predicting the lowest EA when the ground anion state obtained is non-valence, which holds the extra electron in a diffuse orbital around the molecule; here we propose an alternative approach for finding the valence anion state, based on the stabilization exerted by a polar solvent; the methodology yields correct EA values (i.e. beyond the Koopman's theorem approximation) by gradually decreasing the dielectric constant of the medium.

  10. A high resolution (1 km) groundwater model for Indonesia

    NASA Astrophysics Data System (ADS)

    Sutanudjaja, Edwin; Verkaik, Jarno; de Graaf, Inge; van Beek, Rens; Erkens, Gilles; Bierkens, Marc

    2015-04-01

    Groundwater is important in many parts of Indonesia. It serves as a primary source of drinking water and industrial activities. During times of drought, it sustains water flows in streams, rivers, lakes and wetlands, and thus support ecosystem habitat and biodiversity as well as preventing hazardous forest fire. Besides its importance, groundwater is known as a vulnerable resource as unsustainable groundwater exploitation and management occurs in many areas of the country. Therefore, in order to ensure sustainable management of groundwater resources, monitoring and predicting groundwater changes in Indonesia are imperative. However, large extent groundwater models to assess these changes on a regional scale are almost non-existent and are hampered by the strong topographical and lithological transitions that characterize Indonesia. In this study, we built an 1 km resolution groundwater model for the entire Indonesian archipelago (total inland area: about 2 million km2). We adopted the approaches of Sutanudjaja et al. (2011, 2014a) and de Graaf et al. (2014) in order to make a MODFLOW (Harbaugh et al., 2000) groundwater model by using only global datasets. Aquifer schematization and properties of the groundwater model were developed from available global lithological maps (e.g. Dürr et al., 2005; Gleeson et al., 2011; Hartmann & Moorsdorf, 2012; Gleeson et al., 2014). We forced the groundwater model with the recent output of global hydrological model PCR-GLOBWB version 2.0 (Sutanudjaja et al., 2014b; van Beek et al., 2011), specifically the long term average of groundwater recharge and average surface water levels derived from channel discharge. Simulation results were promising. The MODFLOW model converged with realistic aquifer properties (i.e. transmissivities) and produced reasonable groundwater head spatial distribution reflecting the positions of major groundwater bodies and surface water bodies in the country. In Vienna, we aim to show and demonstrate these

  11. Gastrointestinal distress is common during a 161-km ultramarathon.

    PubMed

    Stuempfle, Kristin Jean; Hoffman, Martin Dean

    2015-01-01

    This study examined the incidence, severity, and timing of gastrointestinal (GI) symptoms in finishers and non-finishers of the 161-km Western States Endurance Run. A total of 272 runners (71.0% of starters) completed a post-race questionnaire that assessed the incidence and severity (none = 0, mild = 1, moderate = 2, severe = 3, very severe = 4) of 12 upper (reflux/heartburn, belching, stomach bloating, stomach cramps/pain, nausea, vomiting) and lower (intestinal cramps/pain, flatulence, side ache/stitch, urge to defecate, loose stool/diarrhoea, intestinal bleeding/bloody faeces) GI symptoms experienced during each of four race segments. GI symptoms were experienced by most runners (96.0%). Flatulence (65.9% frequency, mean value 1.0, s = 0.6 severity), belching (61.3% frequency, mean value 1.0, s = 0.6 severity), and nausea (60.3% frequency, mean value 1.0, s = 0.7 severity) were the most common symptoms. Among race finishers, 43.9% reported that GI symptoms affected their race performance, with nausea being the most common symptom (86.0%). Among race non-finishers, 35.6% reported that GI symptoms were a reason for dropping out of the race, with nausea being the most common symptom (90.5%). For both finishers and non-finishers, nausea was greatest during the most challenging and hottest part of the race. GI symptoms are very common during ultramarathon running, and in particular, nausea is the most common complaint for finishers and non-finishers.

  12. Processing techniques for global land 1-km AVHRR data

    USGS Publications Warehouse

    Eidenshink, Jeffery C.; Steinwand, Daniel R.; Wivell, Charles E.; Hollaren, Douglas M.; Meyer, David

    1993-01-01

    The U.S. Geological Survey's (USGS) Earth Resources Observation Systems (EROS) Data Center (EDC) in cooperation with several international science organizations has developed techniques for processing daily Advanced Very High Resolution Radiometer (AVHRR) 1-km data of the entire global land surface. These techniques include orbital stitching, geometric rectification, radiometric calibration, and atmospheric correction. An orbital stitching algorithm was developed to combine consecutive observations acquired along an orbit by ground receiving stations into contiguous half-orbital segments. The geometric rectification process uses an AVHRR satellite model that contains modules for forward mapping, forward terrain correction, and inverse mapping with terrain correction. The correction is accomplished by using the hydrologic features coastlines and lakes from the Digital Chart of the World. These features are rasterized into the satellite projection and are matched to the AVHRR imagery using binary edge correlation techniques. The resulting coefficients are related to six attitude correction parameters: roll, roll rate, pitch, pitch rate, yaw, and altitude. The image can then be precision corrected to a variety of map projections and user-selected image frames. Because the AVHRR lacks onboard calibration for the optical wavelengths, a series of time-variant calibration coefficients derived from vicarious calibration methods and are used to model the degradation profile of the instruments. Reducing atmospheric effects on AVHRR data is important. A method has been develop that will remove the effects of molecular scattering and absorption from clear sky observations, using climatological measurements of ozone. Other methods to remove the effects of water vapor and aerosols are being investigated.

  13. Determinants of recovery from a 161-km ultramarathon.

    PubMed

    Hoffman, Martin D; Badowski, Natalie; Chin, Joseph; Stuempfle, Kristin J; Parise, Carol A

    2017-04-01

    The primary study objective was to identify determinants of short-term recovery from a 161-km ultramarathon. Participants completed 400 m runs at maximum speed before the race and on days 3 and 5 post-race, provided a post-race blood sample for plasma creatine kinase (CK) concentration, and provided lower body muscle pain and soreness ratings (soreness, 10-point scale) and overall muscular fatigue scores (fatigue, 100-point scale) pre-race and for 7 days post-race. Among 72 race finishers, soreness and fatigue had statistically returned to pre-race levels by 5 days post-race; and 400 m times at days 3 and 5 remained 26% (P = 0.001) and 12% (P = 0.01) slower compared with pre-race, respectively. CK best modelled soreness, fatigue and per cent change in post-race 400 m time. Runners with the highest CKs had 1.5 points higher (P < 0.001) soreness and 11.2 points higher (P = 0.006) fatigue than runners with the lowest CKs. For the model of 400 m time, a significant interaction of time with CK (P < 0.001) indicates that higher CKs were linked with a slower rate of return to pre-race 400 m time. Since post-race CK was the main modifiable determinant of recovery following the ultramarathon, appropriate training appears to be the optimal approach to enhance ultramarathon recovery.

  14. Median statistics estimates of Hubble and Newton's constants

    NASA Astrophysics Data System (ADS)

    Bethapudi, Suryarao; Desai, Shantanu

    2017-02-01

    Robustness of any statistics depends upon the number of assumptions it makes about the measured data. We point out the advantages of median statistics using toy numerical experiments and demonstrate its robustness, when the number of assumptions we can make about the data are limited. We then apply the median statistics technique to obtain estimates of two constants of nature, Hubble constant (H0) and Newton's gravitational constant ( G , both of which show significant differences between different measurements. For H0, we update the analyses done by Chen and Ratra (2011) and Gott et al. (2001) using 576 measurements. We find after grouping the different results according to their primary type of measurement, the median estimates are given by H0 = 72.5^{+2.5}_{-8} km/sec/Mpc with errors corresponding to 95% c.l. (2 σ) and G=6.674702^{+0.0014}_{-0.0009} × 10^{-11} Nm2kg-2 corresponding to 68% c.l. (1σ).

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

    PubMed

    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.

  16. Sperm in poor quality semen from bulls during heat stress have a lower affinity for binding hydrogen-3 heparin

    SciTech Connect

    Ax, R.L.; Gilbert, G.R.; Shook, G.E.

    1987-01-01

    Binding assays with (/sup 3/H) heparin were performed using spermatozoa collected prior to, during, and following summer heat stress to dairy bulls. Ejaculates collected in August 1983 after a period of ambient temperatures exceeding 29.4/sup 0/C exhibited a high frequency of abnormal sperm, and motility was reduced in some samples. Sperm in samples collected during heat stress possessed dissociation constants for binding (/sup 3/H) heparin ranging from 134.5 to 163.2 nmol. In contrast, sperm in semen collected prior to and after heat stress had significantly lower dissociation constants (higher affinity) for (/sup 3/H)heparin, 12.9 to 56.4 nmol. The number of binding sites for (/sup 3/H) heparin on sperm did not change among collection periods. It was concluded that the binding affinity for (/sup 3/H) heparin may reflect membrane integrity of bull sperm.

  17. Emergent cosmological constant from colliding electromagnetic waves

    SciTech Connect

    Halilsoy, M.; Mazharimousavi, S. Habib; Gurtug, O. E-mail: habib.mazhari@emu.edu.tr

    2014-11-01

    In this study we advocate the view that the cosmological constant is of electromagnetic (em) origin, which can be generated from the collision of em shock waves coupled with gravitational shock waves. The wave profiles that participate in the collision have different amplitudes. It is shown that, circular polarization with equal amplitude waves does not generate cosmological constant. We also prove that the generation of the cosmological constant is related to the linear polarization. The addition of cross polarization generates no cosmological constant. Depending on the value of the wave amplitudes, the generated cosmological constant can be positive or negative. We show additionally that, the collision of nonlinear em waves in a particular class of Born-Infeld theory also yields a cosmological constant.

  18. Smooth affine shear tight frames: digitization and applications

    NASA Astrophysics Data System (ADS)

    Zhuang, Xiaosheng

    2015-08-01

    In this paper, we mainly discuss one of the recent developed directional multiscale representation systems: smooth affine shear tight frames. A directional wavelet tight frame is generated by isotropic dilations and translations of directional wavelet generators, while an affine shear tight frame is generated by anisotropic dilations, shears, and translations of shearlet generators. These two tight frames are actually connected in the sense that the affine shear tight frame can be obtained from a directional wavelet tight frame through subsampling. Consequently, an affine shear tight frame indeed has an underlying filter bank from the MRA structure of its associated directional wavelet tight frame. We call such filter banks affine shear filter banks, which can be designed completely in the frequency domain. We discuss the digitization of affine shear filter banks and their implementations: the forward and backward digital affine shear transforms. Redundancy rate and computational complexity of digital affine shear transforms are also investigated in this paper. Numerical experiments and comparisons in image/video processing show the advantages of digital affine shear transforms over many other state-of-art directional multiscale representation systems.

  19. Harmonic undulator radiations with constant magnetic field

    NASA Astrophysics Data System (ADS)

    Jeevakhan, Hussain; Mishra, G.

    2015-01-01

    Harmonic undulators has been analysed in the presence of constant magnetic field along the direction of main undulator field. The spectrum modifications in harmonic undulator radiations and intensity degradation as a function of constant magnetic field magnitude at fundamental and third harmonics have been evaluated with a numerical integration method and generalised Bessel function. The role of harmonic field to overcome the intensity reduction due to constant magnetic field and energy spread in electron beam has also been demonstrated.

  20. Constant voltage electro-slag remelting control

    DOEpatents

    Schlienger, M.E.

    1996-10-22

    A system for controlling electrode gap in an electro-slag remelt furnace has a constant regulated voltage and an electrode which is fed into the slag pool at a constant rate. The impedance of the circuit through the slag pool is directly proportional to the gap distance. Because of the constant voltage, the system current changes are inversely proportional to changes in gap. This negative feedback causes the gap to remain stable. 1 fig.

  1. Noncompetitive affinity assays of glucagon and amylin using mirror-image aptamers as affinity probes.

    PubMed

    Yi, Lian; Wang, Xue; Bethge, Lucas; Klussmann, Sven; Roper, Michael G

    2016-03-21

    The ability to detect picomolar concentrations of glucagon and amylin using fluorescently labeled mirror-image aptamers, so-called Spiegelmers, is demonstrated. Spiegelmers rival the specificity of antibodies and overcome the problem of biostability of natural aptamers in a biological matrix. Using Spiegelmers as affinity probes, noncompetitive capillary electrophoresis affinity assays of glucagon and murine amylin were developed and optimized. The detection limit for glucagon was 6 pM and for amylin was 40 pM. Glucagon-like peptide-1 and -2 did not interfere with the glucagon assay, while the amylin assay showed cross-reactivity to calcitonin gene related peptide. The developed assays were combined with a competitive immunoassay for insulin to measure glucagon, amylin, and insulin secretion from batches of islets after incubation with different glucose concentrations. The development of these assays is an important step towards incorporation into an online measurement system for monitoring dynamic secretion from single islets.

  2. Evaluation of non-covalent interactions between serum albumin and green tea catechins by affinity capillary electrophoresis.

    PubMed

    Zinellu, Angelo; Sotgia, Salvatore; Scanu, Bastianina; Pisanu, Elisabetta; Giordo, Roberta; Cossu, Annalisa; Posadino, Anna Maria; Carru, Ciriaco; Pintus, Gianfranco

    2014-11-07

    The natural antioxidant-associated biological responses appear contradictory since biologically active dosages registered in vitro experiments are considerably higher if compared to concentrations found in vivo. The recent research indicates that natural antioxidants, including the major catechins of green tea epicatechin (EC), epigallocatechin (EGC), epicatechingallate (ECG) and epigallocatechingallate (EGCG) form non-covalent complexes with albumin, a crucial aspect that may modulate their plasma concentration, tissue delivery and biological activity. Affinity capillary electrophoresis (ACE) was used to characterize the binding of the four catechins to human serum albumin (HSA) and bovine serum albumin (BSA) at near-physiological conditions: 10 mmol/L phosphate buffer, HEPES 50 mmol/L (pH 7.5), temperature 37°C. The studied flavonoids displayed affinities toward the albumin with binding constants in the range 10(3)-10(5)M(-1), with a greater affinity of catechins toward HSA than BSA (between 3 and 3.5 fold higher). We also confirmed that catechins having a galloyl moiety (ECG and EGCG) have a higher binding affinity toward albumin than the catechins lacking the galloyl moiety (EC and EGC), and that for both albumins the order of affinity is EC

  3. Identification of the Cardiac Beta-Adrenergic Receptor Protein: Solubilization and Purification by Affinity Chromatography

    PubMed Central

    Lefkowitz, Robert J.; Haber, Edgar; O'Hara, Donald

    1972-01-01

    A protein that binds catecholamines with a specificity parallel to that of their in vivo effects on cardiac contractility (isoproterenol > epinephrine or norepinephrine > dopamine > dihydroxyphenylalanine) was solubilized from a microsomal fraction of canine ventricular myocardium. The binding protein was purified 500 to 800-fold by solubilization and subsequent affinity chromatography with conjugates of norepinephrine linked to agarose beads. Purified β-adrenergic binding protein exists in two forms, corresponding to molecular weights of 40,000 and 160,000. The purified material has a single association constant, 2.3 × 105 liters/mol (as compared to two association constants, 107 and 106 liters/mol, for the binding protein in particulate form) but retains the identical binding specificity for β-adrenergic drugs and antagonists. Images PMID:4507606

  4. Direct detection of antibody concentration and affinity in human serum using microscale thermophoresis.

    PubMed

    Lippok, Svenja; Seidel, Susanne A I; Duhr, Stefan; Uhland, Kerstin; Holthoff, Hans-Peter; Jenne, Dieter; Braun, Dieter

    2012-04-17

    The direct quantification of both the binding affinity and absolute concentration of disease-related biomarkers in biological fluids is particularly beneficial for differential diagnosis and therapy monitoring. Here, we extend microscale thermophoresis to target immunological questions. Optically generated thermal gradients were used to deplete fluorescently marked antigens in 2- and 10-fold-diluted human serum. We devised and validated an autocompetitive strategy to independently fit the concentration and dissociation constant of autoimmune antibodies against the cardiac β1-adrenergic receptor related to dilated cardiomyopathy. As an artificial antigen, the peptide COR1 was designed to mimic the second extracellular receptor loop. Thermophoresis resolved antibody concentrations from 2 to 200 nM and measured the dissociation constant as 75 nM. The approach quantifies antibody binding in its native serum environment within microliter volumes and without any surface attachments. The simplicity of the mix and probe protocol minimizes systematic errors, making thermophoresis a promising detection method for personalized medicine.

  5. Correlation between conformational equilibria of free host and guest binding affinity in non-preorganized receptors.

    PubMed

    Carrillo, Romen; Morales, Ezequiel Q; Martín, Víctor S; Martín, Tomás

    2013-08-16

    Positive cooperativity between host conformational equilibria and guest binding has been widely reported in protein receptors. However, reported examples of this kind of cooperativity in synthetic hosts are scarce and largely serendipitous, among other things because it is hard to envision systems which display this kind of cooperativity. In order to shed some light on the correlation between conformational equilibria of free host and guest binding, selected structural modifications have been performed over a family of nonpreorganized hosts in order to induce conformational changes and to analyze their effect on the binding affinity. The conformational effect was evaluated by a theoretical conformational search and correlated with the ability of the receptors. All data suggest that those receptors that display the best association constants are able to sample folded conformations analogous to the conformational requirements for the binding of the guests. On the contrary, for those receptors where folded conformers are scarce, then the association constant and enantioselectivity clearly drop.

  6. 112 Gb/s PM-QPSK transmission up to 6000 km with 200 km amplifier spacing and a hybrid fiber span configuration.

    PubMed

    Downie, John D; Hurley, Jason; Cartledge, John; Bickham, Scott; Mishra, Snigdharaj

    2011-12-12

    We demonstrate transmission of 112 Gb/s PM-QPSK signals over a system with 200 km span lengths. Amplification is provided by hybrid backward-pumped Raman/EDFA amplifiers and reach lengths up to 6000 km for an 8 channel system and 5400 km for a 32 channel system are shown. As a means of maximizing OSNR, a simple hybrid fiber span configuration is used that combines two ultra-low loss fibers, one having very large effective area.

  7. Focusing of relative plate motion at a continental transform fault: Cenozoic dextral displacement >700 km on New Zealand's Alpine Fault, reversing >225 km of Late Cretaceous sinistral motion

    NASA Astrophysics Data System (ADS)

    Lamb, Simon; Mortimer, Nick; Smith, Euan; Turner, Gillian

    2016-03-01

    The widely accepted ˜450 km Cenozoic dextral strike-slip displacement on New Zealand's Alpine Fault is large for continental strike-slip faults, but it is still less than 60% of the Cenozoic relative plate motion between the Australian and Pacific plates through Zealandia, with the remaining motion assumed to be taken up by rotation and displacement on other faults in a zone up to 300 km wide. We show here that the 450 km total displacement across the Alpine Fault is an artifact of assumptions about the geometry of New Zealand's basement terranes in the Eocene, and the actual Cenozoic dextral displacement across the active trace is greater than 665 km, with more than 700 km (and <785 km since 25 Ma) occurring in a narrow zone less than 10 km wide. This way, the Alpine Fault has accommodated almost all (>94%) of the relative plate motion in the last 25 Ma at an average rate in excess of 28 mm/yr. It reverses more than 225 km (and <300 km) of sinistral shear through Zealandia in the Late Cretaceous, when Zealandia lay on the margin of Gondwana, providing a direct constraint on the kinematics of extension between East and West Antarctica at this time.

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

    PubMed

    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.

  9. Application of Frontal Affinity Chromatography to Study the Biomolecular Interactions with Trypsin.

    PubMed

    Hu, YuanYuan; Qian, Junqing; Guo, Hui; Jiang, ShengLan; Zhang, Zheng

    2015-07-01

    Trypsin is a serine protease that has been proposed as a potential therapeutic target for metabolic disorders and malignancy diseases, thus the identification of biomolecular interactions of compounds to trypsin could be of great therapeutic importance. In this study, trypsin was immobilized on a monolithic silica capillary column via sol-gel. The binding properties of four small molecules (daidzin, genistin, matrine and oxymatrine) to trypsin were examined using the trypsin affinity columns by frontal analysis. The results indicate that the matrine (dissociation constant, Kd = 7.904 μM) has stronger interaction with trypsin than the oxymatrine (Kd = 8.204 μM), whereas daidzin and genistin were nearly have no affinity with trypsin. The results demonstrated that the frontal affinity chromatography can be used for the direct determination of protein-protease inhibitor binding interactions and have several significant advantages, including easy fabricating, reproducible, minimal technological requirements and potential to become a reliable alternative for quantitative studies of biomolecular interactions.

  10. Pancreatic serine protease extraction by affinity partition using a free triazine dye.

    PubMed

    Rocha, Maria Victoria; Romanini, Diana; Nerli, Bibiana B; Tubio, Gisela

    2012-03-01

    Affinity partitioning combines the partitioning behavior of biological macromolecules in aqueous two-phase systems with the principle of biorecognition. Among the numerous substances that have been evaluated as ligands, the reactive dyes constitute a group of low cost textile dyes which have proved to act as biomimetic ligands for many enzymes. The ability of reactive yellow 2 (RY2) to interact with trypsin (TRP) and chymotrypsin (ChTRP) and its behavior in aqueous two-phase systems formed by polyethylene glycol (PEG) and sodium citrate (NaCit) - were investigated. Different variables such as PEG molecular weight, tie line length and dye concentration were analyzed. RY2 showed to bind specifically to both TRP and ChTRP with affinity constants near to 10(3)M(-1). Its partition equilibrium is practically displaced to the top phase in systems formed by PEG of different molecular weight. Addition of this dye to PEG 8000/NaCit systems until a final concentration of 0.196% (w/w) induced an increase in TRP and ChTRP partition coefficients of at least 2 times over that in the absence of the ligand. These findings demonstrate that RY2 fulfils all the requirements to be considered as an affinity ligand in aqueous two-phase partitioning of TRP and ChTRP.

  11. The high-affinity peptidoglycan binding domain of Pseudomonas phage endolysin KZ144

    SciTech Connect

    Briers, Yves; Schmelcher, Mathias; Loessner, Martin J.; Hendrix, Jelle; Engelborghs, Yves; Volckaert, Guido; Lavigne, Rob

    2009-05-29

    The binding affinity of the N-terminal peptidoglycan binding domain of endolysin KZ144 (PBD{sub KZ}), originating from Pseudomonas aeruginosa bacteriophage {phi}KZ, has been examined using a fusion protein of PBD{sub KZ} and green fluorescent protein (PBD{sub KZ}-GFP). A fluorescence recovery after photobleaching analysis of bound PBD{sub KZ}-GFP molecules showed less than 10% fluorescence recovery in the bleached area within 15 min. Surface plasmon resonance analysis confirmed this apparent high binding affinity revealing an equilibrium affinity constant of 2.95 x 10{sup 7} M{sup -1} for the PBD{sub KZ}-peptidoglycan interaction. This unique domain, which binds to the peptidoglycan of all tested Gram-negative species, was harnessed to improve the specific activity of the peptidoglycan hydrolase domain KMV36C. The chimeric peptidoglycan hydrolase (PBD{sub KZ}-KMV36C) exhibits a threefold higher specific activity than the native catalytic domain (KMV36C). These results demonstrate that the modular assembly of functional domains is a rational approach to improve the specific activity of endolysins from phages infecting Gram-negatives.

  12. Reversible immobilization of proteins with streptavidin affinity tags on a surface plasmon resonance biosensor chip.

    PubMed

    Li, Yong-Jin; Bi, Li-Jun; Zhang, Xian-En; Zhou, Ya-Feng; Zhang, Ji-Bin; Chen, Yuan-Yuan; Li, Wei; Zhang, Zhi-Ping

    2006-11-01

    Dissociation of biotin from streptavidin is very difficult due to their high binding affinity. The re-use of streptavidin-modified surfaces is therefore almost impossible, making devices containing them (e.g. surface plasmon resonance (SPR) sensor chips) expensive. This paper describes a new protocol for reversible and site-directed immobilization of proteins with streptavidin affinity tags on the streptavidin-coated SPR biosensor chip (SA chip). Two streptavidin affinity tags, nano-tag and streptavidin-binding peptide (SBP tag), were applied. They both can specifically interact with streptavidin but have weaker binding force compared to the biotin-streptavidin system, thus allowing association and dissociation under controlled conditions. The SA chip surface could be regenerated repeatedly without loss of activity by injection of 50 mM NaOH solution. The fusion construct of a SBP tag and a single-chain antibody to mature bovine prion protein (scFv-Z186-SBP) interacts with the SA chip, resulting in a single-chain-antibody-modified surface. The chip showed kinetic response to the prion antigen with equilibrium dissociation constant K (D) approximately equal to 4.01 x 10(-7). All results indicated that the capture activity of the SA chip has no irreversible loss after repeated immobilization and regeneration cycles. The method should be of great benefit to various biosensors, biochips and immunoassay applications based on the streptavidin capture surface.

  13. Antiparkinson therapeutic potencies correlate with their affinities at dopamine D2(High) receptors.

    PubMed

    Seeman, Philip

    2007-12-01

    To determine whether antiparkinson dopamine agonists preferentially act on the high-affinity or the low-affinity states of dopamine D1 and D2 receptors, the agonist potencies were obtained by competition against [(3)H]SCH23390 for D1(High) and D1(Low), and against [(3)H]domperidone for D2(High) and D2(Low). N-propylnorapomorphine and cabergoline were the most potent at D2(High), with dissociation constants of 0.18 and 0.36 nM, respectively. Other agonists had D2(High)K(i) values of 0.52 nM for quinagolide, 0.6 nM for (+)PHNO, 0.9 for bromocriptine, 1.8 nM for apomorphine, 2.4 nM for pergolide, 3 nM for quinpirole, and 6.2 nM for lergotrile. There was a clear correlation between the K(i) values at D2(High) and their therapeutic concentrations in the plasma water, as derived from the known concentrations after correction for the fraction bound to the human plasma proteins. The data suggest that D2(High) is the primary and common target for the antiparkinson action of dopamine agonists. Bromocriptine, cabergoline, lergotrile, pergolide, and pramipexole had no affinity for D1(High), consistent with the clinical observations that the D2-selective bromocriptine and pramipexole elicit low levels of dyskinesia.

  14. Affinity ligands for glycoprotein purification based on the multi-component Ugi reaction.

    PubMed

    Chen, Chen; Khoury, Graziella El; Lowe, Christopher R

    2014-10-15

    One challenge facing the purification of therapeutic glycoproteins by affinity chromatography is creating ligands specific for the glycan moiety. Affinity chromatography of glycoproteins is currently conducted with immobilized lectins or boronates, although biomimetic ligands could present a more desirable option. This work describes the rational design and combinatorial synthesis of carbohydrate-binding ligands based on the solid phase multi-component Ugi reaction. An aldehyde-functionalized Sepharose™ solid support constitutes one component (aldehyde) in the four-component reaction, while the other three components (a primary/secondary amine, a carboxylic acid and an isocyanide) are varied in a combinatorial fashion to generate a tri-substituted Ugi scaffold which provides a degree of rigidity and is functionally suitable for interacting with the glycan moiety of glycoproteins. An Ugi library containing 48 ligands was initially screened against glucose oxidase (GOx) as the model glycoprotein to identify a candidate ligand, A13C24I8, which showed affinity to GOx through its carbohydrate moiety. Immobilized ligand A13C24I8 demonstrated a static binding capacity of 16.7mg GOx/ml resin and an apparent dissociation constant (Kd) of 1.45×10(-6)M at pH 7.4. The adsorbent can also bind 8.1mg AGP/ml resin and displays an apparent affinity constant Kd=1.44×10(-5)M. The ligand has a sugar specificity in the following sequence: sorbitol>fructose>mannitol>ribose>arabinose>xylose>galactose>mannose>glucose>fructose; however, it did not display any specificity for sialic acid or methyl α-D-glycosides. A control ligand, generated by substitution of C24 (3-carboxyphenylboronic acid) with C7 (4-hydroxyphenyl acetic acid), failed to show affinity to the carbohydrate moiety, supporting the importance of the role that boronic acid group plays in sugar binding. GOx spiked E. coli samples were loaded onto immobilized ligand A13C24I8, 3-aminophenylboronic acid (APBA) and

  15. Affine connection form of Regge calculus

    NASA Astrophysics Data System (ADS)

    Khatsymovsky, V. M.

    2016-12-01

    Regge action is represented analogously to how the Palatini action for general relativity (GR) as some functional of the metric and a general connection as independent variables represents the Einstein-Hilbert action. The piecewise flat (or simplicial) spacetime of Regge calculus is equipped with some world coordinates and some piecewise affine metric which is completely defined by the set of edge lengths and the world coordinates of the vertices. The conjugate variables are the general nondegenerate matrices on the three-simplices which play the role of a general discrete connection. Our previous result on some representation of the Regge calculus action in terms of the local Euclidean (Minkowsky) frame vectors and orthogonal connection matrices as independent variables is somewhat modified for the considered case of the general linear group GL(4, R) of the connection matrices. As a result, we have some action invariant w.r.t. arbitrary change of coordinates of the vertices (and related GL(4, R) transformations in the four-simplices). Excluding GL(4, R) connection from this action via the equations of motion we have exactly the Regge action for the considered spacetime.

  16. [Separation of osteoclasts by lectin affinity chromatography].

    PubMed

    Itokazu, M; Tan, A; Tanaka, S

    1991-09-01

    Newborn rat calvaria bone cells obtained by digestion were fractionated on columns of wheat-germ agglutinin (WGA) sepharose 6MB for osteoclast isolation. The initial nonspecific binding cells which were passed through the WGA sepharose column by a buffer acquired a high enzyme activity of alkaline phosphatase, but not that of acid phosphatase. However, elution of cells using a buffer with the addition of N-acetyl-D-glucosamine resulted in a high acid phosphatase activity but no alkaline phosphatase activity. The former WGA binding negative fraction enriched osteoblasts averaging 30 microns in size. The latter WGA binding positive fraction enriched osteoclasts ranging from 20 microns to 60 microns in size. The electron-microscope clearly demonstrated the cellular details of osteoclasts. Isolated cell counts showed a ratio of six to four. These results indicate that our method of osteoclast isolation is simple and useful in lectin affinity chromatography because all cells have sugar moieties on their surface and the binding of osteoclasts can be reversed by the addition of specific lectin-binding sugars to the eluting buffer.

  17. Prostate Cancer and Bone: The Elective Affinities

    PubMed Central

    2014-01-01

    The onset of metastases dramatically changes the prognosis of prostate cancer patients, determining increased morbidity and a drastic fall in survival expectancy. Bone is a common site of metastases in few types of cancer, and it represents the most frequent metastatic site in prostate cancer. Of note, the prevalence of tumor relapse to the bone appears to be increasing over the years, likely due to a longer overall survival of prostate cancer patients. Bone tropism represents an intriguing challenge for researchers also because the preference of prostate cancer cells for the bone is the result of a sequential series of targetable molecular events. Many factors have been associated with the peculiar ability of prostate cancer cells to migrate in bone marrow and to determine mixed osteoblastic/osteolytic lesions. As anticipated by the success of current targeted therapy aimed to block bone resorption, a better understanding of molecular affinity between prostate cancer and bone microenvironment will permit us to cure bone metastasis and to improve prognosis of prostate cancer patients. PMID:24971315

  18. Multiplexed protein profiling by sequential affinity capture

    PubMed Central

    Ayoglu, Burcu; Birgersson, Elin; Mezger, Anja; Nilsson, Mats; Uhlén, Mathias; Nilsson, Peter

    2016-01-01

    Antibody microarrays enable parallelized and miniaturized analysis of clinical samples, and have proven to provide novel insights for the analysis of different proteomes. However, there are concerns that the performance of such direct labeling and single antibody assays are prone to off‐target binding due to the sample context. To improve selectivity and sensitivity while maintaining the possibility to conduct multiplexed protein profiling, we developed a multiplexed and semi‐automated sequential capture assay. This novel bead‐based procedure encompasses a first antigen capture, labeling of captured protein targets on magnetic particles, combinatorial target elution and a read‐out by a secondary capture bead array. We demonstrate in a proof‐of‐concept setting that target detection via two sequential affinity interactions reduced off‐target contribution, while lowered background and noise levels, improved correlation to clinical values compared to single binder assays. We also compared sensitivity levels with single binder and classical sandwich assays, explored the possibility for DNA‐based signal amplification, and demonstrate the applicability of the dual capture bead‐based antibody microarray for biomarker analysis. Hence, the described concept enhances the possibilities for antibody array assays to be utilized for protein profiling in body fluids and beyond. PMID:26935855

  19. Cambrian trilobites with Siberian affinities, southwestern Alaska

    SciTech Connect

    Palmer, A.R.; Egbert, R.M.; Sullivan, R.; Knoth, J.S.

    1985-02-01

    Cambrian trilobites occur in two levels (about 7 m apart) in the core of a large, complex anticlinal structure in the area between the Taylor Mountains and the Hoholitna River in southwestern Alaska. The lower collection contains Erbia, Macannaia (a species close to Soviet forms described as Pagetia ferox Lermontova), two species of Kootenia (including one perhaps cospecific with forms from the central Brooks range), and several species of ptychoparioid trilobites. It is clear that biogeographic affinities are with the transitional facies of the eastern Siberian platform and the south Siberian foldbelt. In Soviet terms, the age of the collection falls in a disputed interval called latest Early Cambrian (Tojonian) by some authors, and earliest Middle Cambrian (Amgan) by others. In North American terms, Macannaia is known only from early Middle Cambrian beds. The younger collection contains abundant agnostids, a variety of conocoryphids, Paradoxides, and several species of ptychoparioid trilobites. This is an assemblage of undoubted late Middle Cambrian age, comparable to faunas described from the Maya State of the Siberian platform and the Paradoxides paradoxissimus Stage of the Baltic region. Both faunas are from ocean-facing or outer shelf environments. None of the key non-agnostid or non-pagetiid elements have been seen previously in deposits of Cambrian North America.

  20. Affinity of guanosine derivatives for polycytidylate revisited

    NASA Technical Reports Server (NTRS)

    Kanavarioti, A.; Hurley, T. B.; Baird, E. E.

    1995-01-01

    Evidence is presented for complexation of guanosine 5'-monophosphate 2-methylimidazolide (2-MeImpG) with polycytidylate (poly(C)) at pH 8.0 and 23 degrees C in the presence of 1.0 M NaCl2 and 0.2 M MgCl2 in water. The association of 2-MeImpG with poly(C) was investigated using UV-vis spectroscopy as well as by monitoring the kinetics of the nucleophilic substitution reaction of the imidazole moiety by amines. The results of both methods are consistent with moderately strong poly(C) 2-MeImpG complexation and the spectrophotometric measurements allowed the construction of a binding isotherm with a concentration of 2-MeImpG equal to 5.55 +/- 0.15 mM at half occupancy. UV spectroscopy was employed to establish the binding of other guanosine derivatives on poly(C). These derivatives are guanosine 5'-monophosphate (5'GMP), guanosine 5'-monophosphate imidazolide (ImpG), and guanosine 5'-monophosphate morpholidate (morpG). Within experimental error these guanosine derivatives exhibit the same affinity for poly(C) as 2-MeImpG.

  1. Macroporous chitin affinity membranes for lysozyme separation.

    PubMed

    Ruckenstein, E; Zeng, X

    1997-12-20

    Macroporous chitin membranes with high, controlled porosity and good mechanical properties have been prepared using a technique developed in this laboratory based on silica particles as porogen. They were employed for the affinity separation of lysozyme. Chitin membranes (1 mm thickness) can be operated at high fluxes (>/=1.1 mL/min/cm(2)) corresponding to pressure drops >/=2 psi. Their adsorption capacity for lysozyme ( approximately 50 mg/mL membrane) is by an order of magnitude higher than that of the chitin beads employed in column separation. In a binary mixture of lysozyme and ovalbumin, the membranes showed very high selectivity towards lysozyme. The effect of some important operation parameters, such as the flow rates during loading and elution were investigated. Lysozyme of very high purity (>98%) was obtained from a mixture of lysozyme and ovalbumin, and from egg white. The results indicate that the macroporous chitin membranes can be used for the separation, purification, and recovery of lysozyme at large scale. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 56: 610-617, 1997.

  2. The time constant of the somatogravic illusion.

    PubMed

    Correia Grácio, B J; de Winkel, K N; Groen, E L; Wentink, M; Bos, J E

    2013-02-01

    Without visual feedback, humans perceive tilt when experiencing a sustained linear acceleration. This tilt illusion is commonly referred to as the somatogravic illusion. Although the physiological basis of the illusion seems to be well understood, the dynamic behavior is still subject to discussion. In this study, the dynamic behavior of the illusion was measured experimentally for three motion profiles with different frequency content. Subjects were exposed to pure centripetal accelerations in the lateral direction and were asked to indicate their tilt percept by means of a joystick. Variable-radius centrifugation during constant angular rotation was used to generate these motion profiles. Two self-motion perception models were fitted to the experimental data and were used to obtain the time constant of the somatogravic illusion. Results showed that the time constant of the somatogravic illusion was on the order of two seconds, in contrast to the higher time constant found in fixed-radius centrifugation studies. Furthermore, the time constant was significantly affected by the frequency content of the motion profiles. Motion profiles with higher frequency content revealed shorter time constants which cannot be explained by self-motion perception models that assume a fixed time constant. Therefore, these models need to be improved with a mechanism that deals with this variable time constant. Apart from the fundamental importance, these results also have practical consequences for the simulation of sustained accelerations in motion simulators.

  3. Regularizing cosmological singularities by varying physical constants

    SciTech Connect

    Dąbrowski, Mariusz P.; Marosek, Konrad E-mail: k.marosek@wmf.univ.szczecin.pl

    2013-02-01

    Varying physical constant cosmologies were claimed to solve standard cosmological problems such as the horizon, the flatness and the Λ-problem. In this paper, we suggest yet another possible application of these theories: solving the singularity problem. By specifying some examples we show that various cosmological singularities may be regularized provided the physical constants evolve in time in an appropriate way.

  4. Water dimer equilibrium constant of saturated vapor

    NASA Astrophysics Data System (ADS)

    Malomuzh, N. P.; Mahlaichuk, V. N.; Khrapatyi, S. V.

    2014-08-01

    The value and temperature dependence of the dimerization constant for saturated water vapor are determined. A general expression that links the second virial coefficient and the dimerization constant is obtained. It is shown that the attraction between water monomers and dimers is fundamental, especially at T > 350 K. The range of application for the obtained results is determined.

  5. Cosmological constant from the emergent gravity perspective

    NASA Astrophysics Data System (ADS)

    Padmanabhan, T.; Padmanabhan, Hamsa

    2014-05-01

    Observations indicate that our universe is characterized by a late-time accelerating phase, possibly driven by a cosmological constant Λ, with the dimensionless parameter Λ {LP2} ˜= 10-122, where LP = (Għ/c3)1/2 is the Planck length. In this review, we describe how the emergent gravity paradigm provides a new insight and a possible solution to the cosmological constant problem. After reviewing the necessary background material, we identify the necessary and sufficient conditions for solving the cosmological constant problem. We show that these conditions are naturally satisfied in the emergent gravity paradigm in which (i) the field equations of gravity are invariant under the addition of a constant to the matter Lagrangian and (ii) the cosmological constant appears as an integration constant in the solution. The numerical value of this integration constant can be related to another dimensionless number (called CosMIn) that counts the number of modes inside a Hubble volume that cross the Hubble radius during the radiation and the matter-dominated epochs of the universe. The emergent gravity paradigm suggests that CosMIn has the numerical value 4π, which, in turn, leads to the correct, observed value of the cosmological constant. Further, the emergent gravity paradigm provides an alternative perspective on cosmology and interprets the expansion of the universe itself as a quest towards holographic equipartition. We discuss the implications of this novel and alternate description of cosmology.

  6. The Two Km's for ATP of Corn-Root H+-ATPase and the Use of Glucose-6-Phosphate and Hexokinase as an ATP-Regenerating System.

    PubMed Central

    Ramos, R. S.; Caldeira, M. T.; Arruda, P.; De Meis, L.

    1994-01-01

    Plasma membrane vesicles derived from corn (Zea mays L.) roots retain a membrane-bound H+-ATPase that is able to form a H+ gradient across the vesicle membranes. The activity of this ATPase is enhanced 2- to 3-fold when Triton X-100 or lysophosphatidylcholine is added to the medium at a protein:detergent ratio of 2:1 (w/w). In the absence of detergent, the ATPase exhibits only one Km for ATP (0.1-0.2 mM), which is the same as for the pumping of H+. After the addition of either Triton X-100 or lysophosphatidylcholine, two Km's for ATP are detected, one in the range of 1 to 3 [mu]M and a second in the range of 0.1 to 0.2 mM. The Vmax of the second Km for ATP increases as the temperature of the assay medium is raised from 15[deg]C to 38[deg]C. The Arrhenius plot reveals a single break at 30[deg]C, both in the absence and in the presence of detergents. In the presence of Triton X-100 the H+-ATPase catalyzes the cleavage of glucose-6-phosphate when both hexokinase and ADP are included in the assay medium. There is no measurable cleavage when the apparent affinity for ATP of the H+-ATPase is not enhanced by Triton X-100 or when 1 mM glucose is included in the assay medium. These data indicate that when the high-affinity Km for ATP is unmasked with the use of detergent, the ATPase can use glucose-6-phosphate and hexokinase as an ATP-regenerating system. PMID:12232248

  7. Germinal center reaction: antigen affinity and presentation explain it all.

    PubMed

    Oropallo, Michael A; Cerutti, Andrea

    2014-07-01

    The selection and expansion of B cells undergoing affinity maturation in the germinal center is a hallmark of humoral immunity. A recent paper in Nature provides new insights into the relationships between the affinity of the immunoglobulin receptor for antigen, the ability of B cells to present antigen to T cells, and the processes of selection, mutation, and clonal expansion in the germinal center.

  8. Striving for Empathy: Affinities, Alliances and Peer Sexuality Educators

    ERIC Educational Resources Information Center

    Fields, Jessica; Copp, Martha

    2015-01-01

    Peer sexuality educators' accounts of their work reveal two approaches to empathy with their students: affinity and alliance. "Affinity-based empathy" rests on the idea that the more commonalities sexuality educators and students share (or perceive they share), the more they will be able to empathise with one another, while…

  9. Tending to Change: Toward a Situated Model of Affinity Spaces

    ERIC Educational Resources Information Center

    Bommarito, Dan

    2014-01-01

    The concept of affinity spaces, a theoretical construct used to analyze literate activity from a spatial perspective, has gained popularity among scholars of literacy studies and, particularly, video-game studies. This article seeks to expand current notions of affinity spaces by identifying key assumptions that have limited researchers'…

  10. Metal-Mediated Affinity and Orientation Specificity in a Computationally Designed Protein Homodimer

    SciTech Connect

    Der, Bryan S.; Machius, Mischa; Miley, Michael J.; Mills, Jeffrey L.; Szyperski, Thomas; Kuhlman, Brian

    2015-10-15

    Computationally designing protein-protein interactions with high affinity and desired orientation is a challenging task. Incorporating metal-binding sites at the target interface may be one approach for increasing affinity and specifying the binding mode, thereby improving robustness of designed interactions for use as tools in basic research as well as in applications from biotechnology to medicine. Here we describe a Rosetta-based approach for the rational design of a protein monomer to form a zinc-mediated, symmetric homodimer. Our metal interface design, named MID1 (NESG target ID OR37), forms a tight dimer in the presence of zinc (MID1-zinc) with a dissociation constant <30 nM. Without zinc the dissociation constant is 4 {micro}M. The crystal structure of MID1-zinc shows good overall agreement with the computational model, but only three out of four designed histidines coordinate zinc. However, a histidine-to-glutamate point mutation resulted in four-coordination of zinc, and the resulting metal binding site and dimer orientation closely matches the computational model (C{alpha} rmsd = 1.4 {angstrom}).

  11. Protection against anthrax toxin by recombinant antibody fragments correlates with antigen affinity.

    PubMed

    Maynard, Jennifer A; Maassen, Catharina B M; Leppla, Stephen H; Brasky, Kathleen; Patterson, Jean L; Iverson, Brent L; Georgiou, George

    2002-06-01

    The tripartite toxin produced by Bacillus anthracis is the key determinant in the etiology of anthrax. We have engineered a panel of toxin-neutralizing antibodies, including single-chain variable fragments (scFvs) and scFvs fused to a human constant kappa domain (scAbs), that bind to the protective antigen subunit of the toxin with equilibrium dissociation constants (K(d)) between 63 nM and 0.25 nM. The entire antibody panel showed high serum, thermal, and denaturant stability. In vitro, post-challenge protection of macrophages from the action of the holotoxin correlated with the K(d) of the scFv variants. Strong correlations among antibody construct affinity, serum half-life, and protection were also observed in a rat model of toxin challenge. High-affinity toxin-neutralizing antibodies may be of therapeutic value for alleviating the symptoms of anthrax toxin in infected individuals and for medium-term prophylaxis to infection.

  12. Optimal Affinity of a Monoclonal Antibody: Guiding Principles Using Mechanistic Modeling.

    PubMed

    Tiwari, Abhinav; Abraham, Anson K; Harrold, John M; Zutshi, Anup; Singh, Pratap

    2017-03-01

    Affinity optimization of monoclonal antibodies (mAbs) is essential for developing drug candidates with the highest likelihood of clinical success; however, a quantitative approach for setting affinity requirements is often lacking. In this study, we computationally analyzed the in vivo mAb-target binding kinetics to delineate general principles for defining optimal equilibrium dissociation constant ([Formula: see text]) of mAbs against soluble and membrane-bound targets. Our analysis shows that in general [Formula: see text] to achieve 90% coverage for a soluble target is one tenth of its baseline concentration ([Formula: see text]), and is independent of the dosing interval, target turnover rate or the presence of competing ligands. For membrane-bound internalizing targets, it is equal to the ratio of internalization rate of mAb-target complex and association rate constant ([Formula: see text]). In cases where soluble and membrane-bound forms of the target co-exist, [Formula: see text] lies within a range determined by the internalization rate ([Formula: see text]) of the mAb-membrane target complex and the ratio of baseline concentrations of soluble and membrane-bound forms ([Formula: see text]). Finally, to demonstrate practical application of these general rules, we collected target expression and turnover data to project [Formula: see text] for a number of marketed mAbs against soluble (TNFα, RANKL, and VEGF) and membrane-bound targets (CD20, EGFR, and HER2).

  13. Affinity based information diffusion model in social networks

    NASA Astrophysics Data System (ADS)

    Liu, Hongli; Xie, Yun; Hu, Haibo; Chen, Zhigao

    2014-12-01

    There is a widespread intuitive sense that people prefer participating in spreading the information in which they are interested. The affinity of people with information disseminated can affect the information propagation in social networks. In this paper, we propose an information diffusion model incorporating the mechanism of affinity of people with information which considers the fitness of affinity values of people with affinity threshold of the information. We find that the final size of information diffusion is affected by affinity threshold of the information, average degree of the network and the probability of people's losing their interest in the information. We also explore the effects of other factors on information spreading by numerical simulations and find that the probabilities of people's questioning and confirming the information can affect the propagation speed, but not the final scope.

  14. Camelid VHH affinity ligands enable separation of closely related biopharmaceuticals

    PubMed Central

    Pabst, Timothy M.; Wendeler, Michaela; Wang, Xiangyang; Bezemer, Sandra; Hermans, Pim

    2016-01-01

    Abstract Interest in new and diverse classes of molecules such as recombinant toxins, enzymes, and blood factors continues to grow for use a biotherapeutics. Compared to monoclonal antibodies, these novel drugs typically lack a commercially available affinity chromatography option, which leads to greater process complexity, longer development timelines, and poor platformability. To date, for both monoclonal antibodies and novel molecules, affinity chromatography has been mostly reserved for separation of process‐related impurities such as host cell proteins and DNA. Reports of affinity purification of closely related product variants and modified forms are much rarer. In this work we describe custom affinity chromatography development using camelid VHH antibody fragments as "tunable" immunoaffinity ligands for separation of product‐related impurities. One example demonstrates high selectivity for a recombinant immunotoxin where no binding was observed for an undesired deamidated species. Also discussed is affinity purification of a coagulation factor through specific recognition of the gamma‐carboxylglutamic acid domain. PMID:27677057

  15. Affinity Monolith-Integrated Microchips for Protein Purification and Concentration.

    PubMed

    Gao, Changlu; Sun, Xiuhua; Wang, Huaixin; Qiao, Wei; Hu, Bo

    2016-01-01

    Affinity chromatography is a valuable method to purify and concentrate minute amount of proteins. Monoliths with epoxy groups for affinity immobilization were prepared by direct in-situ photopolymerization of glycidyl methacrylate and ethylene glycol dimethacrylate in porogenic solvents consisting of 1-dodecanol and cyclohexanol. By integrating affinity monoliths onto a microfluidic system, targeted biomolecules can be captured and retained on affinity column, while other biomolecules having no specific interactions toward the immobilized ligands flow through the microchannel. Therefore, proteins which remain on the affinity column are purified and concentrated, and then eluted by appropriate solutions and finally, separated by microchip capillary electrophoresis. This integrated microfluidic device has been applied to the purification and separation of specific proteins (FITC-labeled human serum albumin and IgG) in a mixture.

  16. Optimal T-cell receptor affinity for inducing autoimmunity

    PubMed Central

    Koehli, Sabrina; Naeher, Dieter; Galati-Fournier, Virginie; Zehn, Dietmar; Palmer, Ed

    2014-01-01

    T-cell receptor affinity for self-antigen has an important role in establishing self-tolerance. Three transgenic mouse strains expressing antigens of variable affinity for the OVA transgenic-I T-cell receptor were generated to address how TCR affinity affects the efficiency of negative selection, the ability to prime an autoimmune response, and the elimination of the relevant target cell. Mice expressing antigens with an affinity just above the negative selection threshold exhibited the highest risk of developing experimental autoimmune diabetes. The data demonstrate that close to the affinity threshold for negative selection, sufficient numbers of self-reactive T cells escape deletion and create an increased risk for the development of autoimmunity. PMID:25411315

  17. Detection of protein-protein interactions using tandem affinity purification.

    PubMed

    Goodfellow, Ian; Bailey, Dalan

    2014-01-01

    Tandem affinity purification (TAP) is an invaluable technique for identifying interaction partners for an affinity tagged bait protein. The approach relies on the fusion of dual tags to the bait before separate rounds of affinity purification and precipitation. Frequently two specific elution steps are also performed to increase the specificity of the overall technique. In the method detailed here, the two tags used are protein G and a short streptavidin binding peptide; however, many variations can be employed. In our example the tags are separated by a cleavable tobacco etch virus protease target sequence, allowing for specific elution after the first round of affinity purification. Proteins isolated after the final elution step in this process are concentrated before being identified by mass spectrometry. The use of dual affinity tags and specific elution in this technique dramatically increases both the specificity and stringency of the pull-downs, ensuring a low level of background nonspecific interactions.

  18. Affinity Regulates Spatial Range of EGF Receptor Autocrine Ligand Binding

    SciTech Connect

    Dewitt, Ann; Iida, Tomoko; Lam, Ho-Yan; Hill, Virginia; Wiley, H S.; Lauffenburger, Douglas A.

    2002-08-08

    Proper spatial localization of EGFR signaling activated by autocrine ligands represents a critical factor in embryonic development as well as tissue organization and function, and ligand/receptor binding affinity is among the molecular and cellular properties suggested to play a role in governing this localization. The authors employ a computational model to predict how receptor-binding affinity affects local capture of autocrine ligand vis-a-vis escape to distal regions, and provide experimental test by constructing cell lines expressing EGFR along with either wild-type EGF or a low-affinity mutant, EGF{sup L47M}. The model predicts local capture of a lower affinity autocrine ligand to be less efficient when the ligand production rate is small relative to receptor appearance rate. The experimental data confirm this prediction, demonstrating that cells can use ligand/receptor binding affinity to regulate ligand spatial distribution when autocrine ligand production is limiting for receptor signaling.

  19. Determinants of the Differential Antizyme-Binding Affinity of Ornithine Decarboxylase

    PubMed Central

    Liu, Yen-Chin; Hsu, Den-Hua; Huang, Chi-Liang; Liu, Yi-Liang; Liu, Guang-Yaw; Hung, Hui-Chih

    2011-01-01

    Ornithine decarboxylase (ODC) is a ubiquitous enzyme that is conserved in all species from bacteria to humans. Mammalian ODC is degraded by the proteasome in a ubiquitin-independent manner by direct binding to the antizyme (AZ). In contrast, Trypanosoma brucei ODC has a low binding affinity toward AZ. In this study, we identified key amino acid residues that govern the differential AZ binding affinity of human and Trypanosoma brucei ODC. Multiple sequence alignments of the ODC putative AZ-binding site highlights several key amino acid residues that are different between the human and Trypanosoma brucei ODC protein sequences, including residue 119, 124,125, 129, 136, 137 and 140 (the numbers is for human ODC). We generated a septuple human ODC mutant protein where these seven bases were mutated to match the Trypanosoma brucei ODC protein sequence. The septuple mutant protein was much less sensitive to AZ inhibition compared to the WT protein, suggesting that these amino acid residues play a role in human ODC-AZ binding. Additional experiments with sextuple mutants suggest that residue 137 plays a direct role in AZ binding, and residues 119 and 140 play secondary roles in AZ binding. The dissociation constants were also calculated to quantify the affinity of the ODC-AZ binding interaction. The Kd value for the wild type ODC protein-AZ heterodimer ([ODC_WT]-AZ) is approximately 0.22 μM, while the Kd value for the septuple mutant-AZ heterodimer ([ODC_7M]-AZ) is approximately 12.4 μM. The greater than 50-fold increase in [ODC_7M]-AZ binding affinity shows that the ODC-7M enzyme has a much lower binding affinity toward AZ. For the mutant proteins ODC_7M(-Q119H) and ODC_7M(-V137D), the Kd was 1.4 and 1.2 μM, respectively. These affinities are 6-fold higher than the WT_ODC Kd, which suggests that residues 119 and 137 play a role in AZ binding. PMID:22073206

  20. Percent utilization of VO2 max at 5-km competition velocity does not determine time performance at 5 km among elite distance runners.

    PubMed

    Støa, Eva Maria; Støren, Øyvind; Enoksen, Eystein; Ingjer, Frank

    2010-05-01

    The present study investigated to what extent maximum oxygen uptake (VO2 max) and fractional utilization (%VO2 max) in 5-km competition speed correlate with 5-km performance times among elite long distance runners. Eight elite long distance runners with 5-km performance times of 15.10 minutes ( +/- 32 seconds) were tested for VO2 max during an incremental protocol and for %VO2 max during an 8-minute treadmill test at the velocity representing their 5-km seasonal best performance time. There was no correlation between fractional utilization and 5-km performance. The study showed no significant difference between VO2 max obtained during an incremental VO2 max test and %VO2 max when running for 8 minutes at the runner's individual 5-km competition speed. The 5-km time was related to the runner's VO2 max even in a homogenous high-level performance group. In conclusion, the present study found no relationship between fractional utilization and 5-km performance time. Training aiming to increase %VO2 max may thus be of little or no importance in performance enhancement for competitions lasting up to approximately 20 minutes.

  1. Sugar-binding proteins from fish: selection of high affinity "lambodies" that recognize biomedically relevant glycans.

    PubMed

    Hong, Xia; Ma, Mark Z; Gildersleeve, Jeffrey C; Chowdhury, Sudipa; Barchi, Joseph J; Mariuzza, Roy A; Murphy, Michael B; Mao, Li; Pancer, Zeev

    2013-01-18

    Glycan-binding proteins are important for a wide variety of basic research and clinical applications, but proteins with high affinity and selectivity for carbohydrates are difficult to obtain. Here we describe a facile and cost-effective strategy to generate monoclonal lamprey antibodies, called lambodies, that target glycan determinants. We screened a library of yeast surface-displayed (YSD) lamprey variable lymphocyte receptors (VLR) for clones that can selectively bind various biomedically important glycotopes. These glycoconjugates included tumor-associated carbohydrate antigens (Tn and TFα), Lewis antigens (LeA and LeX), N-glycolylneuraminic acid, targets of broadly neutralizing HIV antibodies (poly-Man9 and the HIV gp120), and the glycoproteins asialo-ovine submaxillary mucin (aOSM) and asialo-human glycophorin A (aGPA). We isolated clones that bind each of these targets in a glycan-dependent manner and with very strong binding constants, for example, 6.2 nM for Man9 and 44.7 nM for gp120, determined by surface plasmon resonance (SPR). One particular lambody, VLRB.aGPA.23, was shown by glycan array analysis to be selective for the blood group H type 3 trisaccharide (BG-H3, Fucα1-2Galβ1-3GalNAcα), aGPA, and TFα (Galβ1-3GalNAcα), with affinity constants of 0.2, 1, and 8 nM, respectively. In human tissue microarrays this lambody selectively detected cancer-associated carbohydrate antigens in 14 different types of cancers. It stained 27% of non-small cell lung cancer (NSCLC) samples in a pattern that correlated with poor patient survival. Lambodies with exquisite affinity and selectivity for glycans may find myriad uses in glycobiology and biomedical research.

  2. Performance of dye-affinity beads for aluminium removal in magnetically stabilized fluidized bed

    PubMed Central

    Yavuz, Handan; Say, Ridvan; Andaç, Müge; Bayraktar, Necmi; Denizli, Adil

    2004-01-01

    Background Aluminum has recently been recognized as a causative agent in dialysis encephalopathy, osteodystrophy, and microcytic anemia occurring in patients with chronic renal failure who undergo long-term hemodialysis. Only a small amount of Al(III) in dialysis solutions may give rise to these disorders. Methods Magnetic poly(2-hydroxyethyl methacrylate) (mPHEMA) beads in the size range of 80–120 μm were produced by free radical co-polymerization of HEMA and ethylene dimethacrylate (EDMA) in the presence of magnetite particles (Fe3O4). Then, metal complexing ligand alizarin yellow was covalently attached onto mPHEMA beads. Alizarin yellow loading was 208 μmol/g. These beads were used for the removal of Al(III) ions from tap and dialysis water in a magnetically stabilized fluidized bed. Results Al(III) adsorption capacity of the beads decreased with an increase in the flow-rate. The maximum Al(III) adsorption was observed at pH 5.0. Comparison of batch and magnetically stabilized fluidized bed (MSFB) maximum capacities determined using Langmuir isotherms showed that dynamic capacity (17.5 mg/g) was somewhat higher than the batch capacity (11.8 mg/g). The dissociation constants for Al(III) were determined using the Langmuir isotherm equation to be 27.3 mM (MSFB) and 6.7 mM (batch system), indicating medium affinity, which was typical for pseudospecific affinity ligands. Al(III) ions could be repeatedly adsorbed and desorbed with these beads without noticeable loss in their Al(III) adsorption capacity. Conclusions Adsorption of Al(III) demonstrate the affinity of magnetic dye-affinity beads. The MSFB experiments allowed us to conclude that this inexpensive sorbent system may be an important alternative to the existing adsorbents in the removal of aluminium. PMID:15329149

  3. High affinity binding of [3H]-tyramine in the central nervous system.

    PubMed Central

    Vaccari, A.

    1986-01-01

    Optimum assay conditions for the association of [3H]-para-tyramine [( 3H]-pTA) with rat brain membranes were characterized, and a saturable, reversible, drug-specific, and high affinity binding mechanism for this trace amine was revealed. The binding capacity (Bmax) for [3H]-pTA in the corpus striatum was approximately 30 times higher than that in the cerebellum, with similar dissociation constants (KD). The binding process of [3H]-pTA involved the dopamine system, inasmuch as (a) highest binding capacity was associated with dopamine-rich regions; (b) dopamine and pTA equally displaced specifically bound [3H]-pTA; (c) there was a severe loss in striatal binding capacity for [3H]-pTA and, reportedly, for [3H]-dopamine, following unilateral nigrostriatal lesion; (d) acute in vivo reserpine treatment markedly decreased the density of [3H]-pTA and, reportedly, of [3H]-dopamine binding sites. In competition experiments [3H]-pTA binding sites, though displaying nanomolar affinity for dopamine, revealed micromolar affinities for the dopamine agonists apomorphine and pergolide, and for several dopamine antagonists, while having very high affinity for reserpine, a marker for the catecholamine transporter in synaptic vesicles. The binding process of [3H]-pTA was both energy-dependent (ouabain-sensitive), and ATP-Mg2+-insensitive; furthermore, the potencies of various drugs in competing for [3H]-pTA binding to rat striatal membranes correlated well (r = 0.96) with their reported potencies in inhibiting [3H]-dopamine uptake into striatal synaptosomes. It is concluded that [3H]-pTA binds at a site located on/within synaptic vesicles where it is involved in the transport mechanism of dopamine. PMID:3801770

  4. Surface plasmon resonance imaging for affinity analysis of aptamer-protein interactions with PDMS microfluidic chips.

    PubMed

    Wang, Zhuangzhi; Wilkop, Thomas; Xu, Danke; Dong, Yi; Ma, Guangyu; Cheng, Quan

    2007-10-01

    We report on the use of PDMS multichannels for affinity studies of DNA aptamer-human Immunoglobulin E (IgE) interactions by surface plasmon resonance imaging (SPRi). The sensing surface was prepared with thiol-terminated aptamers through a self-assembling process in the PDMS channels defined on a gold substrate. Cysteamine was codeposited with the thiol aptamers to promote proper spatial arrangement of the aptamers and thus maintain their optimal binding efficiencies. Four aptamers with different nucleic acid sequences were studied to test their interaction affinity toward IgE, and the results confirmed that aptamer I (5'-SH-GGG GCA CGT TTA TCC GTC CCT CCT AGT GGC GTG CCC C-3') has the strongest binding affinity. Control experiments were conducted with a PEG-functionalized surface and IgG was used to replace IgE in order to verify the selective binding of aptamer I to the IgE molecules. A linear concentration-dependent relationship between IgE and aptamer I was obtained, and a 2-nM detection limit was achieved. SPRi data were further analyzed by global fitting, and the dissociation constant of aptamer I-IgE complex was found to be 2.7 x 10(-7) M, which agrees relatively well with the values reported in the literature. Aptamer affinity screening by SPR imaging demonstrates marked advantages over competing methods because it does not require labeling, can be used in real-time, and is potentially high-throughput. The ability to provide both qualitative and quantitative results on a multichannel chip further establishes SPRi as a powerful tool for the study of biological interactions in a multiplexed format.

  5. The serotonin transporter: Examination of the changes in transporter affinity induced by ligand binding

    SciTech Connect

    Humphreys, C.J.

    1989-01-01

    The plasmalemmal serotonin transporter uses transmembrane gradients of Na{sup +}, Cl{sup {minus}} and K{sup +} to accumulate serotonin within blood platelets. Transport is competitively inhibited by the antidepressant imipramine. Like serotonin transport, imipramine binding requires Na{sup +}. Unlike serotonin, however, imipramine does not appear to be transported. To gain insight into the mechanism of serotonin transport the author have analyzed the influences of Na{sup +} and Cl{sup {minus}}, the two ions cotransported with serotonin, on both serotonin transport and the interaction of imipramine and other antidepressant drugs with the plasmalemmal serotonin transporter of human platelets. Additionally, the author have synthesized, purified and characterized the binding of 2-iodoimipramine to the serotonin transporter. Finally, the author have conducted a preliminary study of the inhibition of serotonin transport and imipramine binding produced by dicyclohexylcarbodiimide. My results reveal many instances of positive heterotropic cooperativity in ligand binding to the serotonin transporter. Na{sup +} binding enhances the transporters affinity for imipramine and several other antidepressant drugs, and also increases the affinity for Cl{sup {minus}}. Cl{sup {minus}} enhances the transporters affinity for imipramine, as well as for Na{sup +}. At concentrations in the range of its K{sub M} for transport serotonin is a competitive inhibitor of imipramine binding. At much higher concentrations, however, serotonin also inhibits imipramines dissociation rate constant. This latter effect which is Na{sup +}-independent and species specific, is apparently produced by serotonin binding at a second, low affinity site on, or near, the transporter complex. Iodoimipramine competitively inhibit both ({sup 3}H)imipramine binding and ({sup 3}H)serotonin transport.

  6. Chasing polys: Interdisciplinary affinity and its connection to physics identity

    NASA Astrophysics Data System (ADS)

    Scott, Tyler D.

    This research is based on two motivations that merge by means of the frameworks of interdisciplinary affinity and physics identity. First, a goal of education is to develop interdisciplinary abilities in students' thinking and work. But an often ignored factor is students interests and beliefs about being interdisciplinary. Thus, this work develops and uses a framework called interdisciplinary affinity. It encompasses students interests in making connections across disciplines and their beliefs about their abilities to make those connections. The second motivation of this research is to better understand how to engage more students with physics. Physics identity describes how a student sees themselves in relation to physics. By understanding how physics identity is developed, researchers and educators can identify factors that increase interest and engagement in physics classrooms. Therefore, physics identity was used in conjunction with interdisciplinary affinity. Using a mixed methods approach, this research used quantitative data to identify the relationships interdisciplinary affinity has with physics identity and the physics classroom. These connections were explored in more detail using a case study of three students in a high school physics class. Results showed significant and positive relationships between interdisciplinary affinity and physics identity, including the individual interest and recognition components of identity. It also identified characteristics of physics classrooms that had a significant, positive relationship with interdisciplinary affinity. The qualitative case study highlighted the importance of student interest to the relationship between interdisciplinary affinity and physics identity. It also identified interest and mastery orientation as key to understanding the link between interdisciplinary affinity and the physics classroom. These results are a positive sign that by understanding interdisciplinary affinity and physics identity

  7. Analysis of Free Drug Fractions in Serum by Ultrafast Affinity Extraction and Two-Dimensional Affinity Chromatography using α1-Acid Glycoprotein Microcolumns

    PubMed Central

    Bi, Cong; Zheng, Xiwei; Hage, David S.

    2016-01-01

    In the circulatory system, many drugs are reversibly bound to serum proteins such as human serum albumin (HSA) and alpha1-acid glycoprotein (AGP), resulting in both free and protein-bound fractions for these drugs. This report examined the use of microcolumns containing immobilized AGP for the measurement of free drug fractions by ultrafast affinity extraction and a two-dimensional affinity system. Several drugs known to bind AGP were used as models to develop and evaluate this approach. Factors considered during the creation of this method included the retention of the drugs on the microcolumns, the injection flow rate, the microcolumn size, and the times at which a second AGP column was placed on-line with the microcolumn. The final system had residence times of only 110–830 ms during sample passage through the AGP microcolumns and allowed free drug fractions to be determined within 10–20 min when using only 3–10 µL of sample per injection. This method was used to measure the free fractions of the model drugs at typical therapeutic levels in serum, giving good agreement with the results obtained by ultrafiltration. This approach was also used to estimate the binding constants for each drug with AGP in serum, even for drugs that had significant interactions with both AGP and HSA in such samples. These results indicated that AGP microcolumns could be used with ultrafast affinity extraction to measure free drug fractions in a label-free manner and to study the binding of drugs with AGP in complex samples such as serum. PMID:26797422

  8. Straight as an arrow: humpback whales swim constant course tracks during long-distance migration

    PubMed Central

    Horton, Travis W.; Holdaway, Richard N.; Zerbini, Alexandre N.; Hauser, Nan; Garrigue, Claire; Andriolo, Artur; Clapham, Phillip J.

    2011-01-01

    Humpback whale seasonal migrations, spanning greater than 6500 km of open ocean, demonstrate remarkable navigational precision despite following spatially and temporally distinct migration routes. Satellite-monitored radio tag-derived humpback whale migration tracks in both the South Atlantic and South Pacific include constant course segments of greater than 200 km, each spanning several days of continuous movement. The whales studied here maintain these directed movements, often with better than 1° precision, despite the effects of variable sea-surface currents. Such remarkable directional precision is difficult to explain by established models of directional orientation, suggesting that alternative compass mechanisms should be explored. PMID:21508023

  9. The second acidic constant of salicylic acid.

    PubMed

    Porto, Raffaella; De Tommaso, Gaetano; Furia, Emilia

    2005-01-01

    The second dissociation constant of salicylic acid (H2L) has been determined, at 25 degrees C, in NaCl ionic media by UV spectrophotometric measurements. The investigated ionic strength values were 0.16, 0.25, 0.50, 1.0, 2.0 and 3.0 M. The protolysis constants calculated at the different ionic strengths yielded, with the Specific Interaction Theory, the infinite dilution constant, log beta1(0) = 13.62 +/- 0.03, for the equilibrium L2- + H+ <==> HL-. The interaction coefficient between Na+ and L2-, b(Na+, L2-) = 0.02 +/- 0.07, has been also calculated.

  10. Laser Propulsion and the Constant Momentum Mission

    SciTech Connect

    Larson, C. William; Mead, Franklin B. Jr.; Knecht, Sean D.

    2004-03-30

    We show that perfect propulsion requires a constant momentum mission, as a consequence of Newton's second law. Perfect propulsion occurs when the velocity of the propelled mass in the inertial frame of reference matches the velocity of the propellant jet in the rocket frame of reference. We compare constant momentum to constant specific impulse propulsion, which, for a given specification of the mission delta V, has an optimum specific impulse that maximizes the propelled mass per unit jet kinetic energy investment. We also describe findings of more than 50 % efficiency for conversion of laser energy into jet kinetic energy by ablation of solids.

  11. Improved Lebesgue constants on the triangle

    NASA Astrophysics Data System (ADS)

    Heinrichs, Wilhelm

    2005-08-01

    New sets of points with improved Lebesgue constants in the triangle are calculated. Starting with the Fekete points a direct minimization process for the Lebesgue constant leads to better results. The points and corresponding quadrature weigths are explicitly given. It is quite surprising that the optimal points are not symmetric. The points along the boundary of the triangle are the 1D Gauss-Lobatto points. For all degrees, our points yield the smallest Lebesgue constants currently known. Numerical examples are presented, which show the improved interpolation properties of our nodes.

  12. The cosmological constant and cold dark matter

    NASA Astrophysics Data System (ADS)

    Efstathiou, G.; Sutherland, W. J.; Maddox, S. J.

    1990-12-01

    It is argued here that the success of the cosmological cold dark matter (CDM) model can be retained and the new observations of very large scale cosmological structures can be accommodated in a spatially flat cosmology in which as much as 80 percent of the critical density is provided by a positive cosmological constant. In such a universe, expansion was dominated by CDM until a recent epoch, but is now governed by the cosmological constant. This constant can also account for the lack of fluctuations in the microwave background and the large number of certain kinds of objects found at high redshift.

  13. Developing Knowledge Management (KM): Contributions by Organizational Learning and Total Quality Management (TQM)

    ERIC Educational Resources Information Center

    Hung, Richard Yu-Yuan; Lien, Bella Ya-Hui

    2005-01-01

    Knowledge management is an integral business function for many organizations to manage intellectual resources effectively. From a resource-based perspective, organizational learning and TQM are antecedents that are closely related to KM. The purposes of this study were to explain the contents of KM, and explore the relationship between KM-related…

  14. Constants and Pseudo-Constants of Coupled Beam Motion in the PEP-II Rings

    SciTech Connect

    Decker, F.J.; Colocho, W.S.; Wang, M.H.; Yan, Y.T.; Yocky, G.; /SLAC

    2011-11-01

    Constants of beam motion help as cross checks to analyze beam diagnostics and the modeling procedure. Pseudo-constants, like the betatron mismatch parameter or the coupling parameter det C, are constant till certain elements in the beam line change them. This can be used to visually find the non-desired changes, pinpointing errors compared with the model.

  15. Marshak waves: Constant flux vs constant T-a (slight) paradigm shift

    SciTech Connect

    Rosen, M.D.

    1994-12-22

    We review the basic scaling laws for Marshak waves and point out the differences in results for wall loss, albedo, and Marshak depth when a constant absorbed flux is considered as opposed to a constant absorbed temperature. Comparisons with LASNEX simulations and with data are presented that imply that a constant absorbed flux is a more appropriate boundary condition.

  16. Cratering and penetration experiments in Teflon targets at velocities from 1 to 7 km/s

    NASA Technical Reports Server (NTRS)

    Hoerz, Friedrich; Bernhard, Ronald P.; Cintala, Mark J.; See, Thomas H.

    1995-01-01

    Approximately 20 sq m of protective thermal blankets, largely composed of Teflon, were retrieved from the Long Duration Exposure Facility (LDEF) after the spacecraft had spent approximately 5.7 years in space. Examination of these blankets revealed that they contained thousands of hypervelocity impact features ranging from micron-sized craters to penetration holes several millimeters in diameter. We conducted impact experiments in an effort to reproduce such features and to -- hopefully -- understand the relationships between projectile size and the resulting crater or penetration-hole diameter over a wide range of impact velocity. Such relationships are needed to derive the size- and mass-frequency distribution and flux of natural and man-made particles in low-Earth orbit. Powder propellant and light-gas guns were used to launch soda-lime glass spheres of 3.175 mm (1/8 inch) nominal diameter (Dp) into pure Teflon FEP targets at velocities ranging from 1 to 7 km/s. Target thickness (T) was varied over more than three orders of magnitude from infinite halfspace targets (Dp/T less than 0.1) to very thin films (Dp/T greater than 100). Cratering and penetration of massive Teflon targets is dominated by brittle failure and the development of extensive spall zones at the target's front and, if penetrated, the target's rear side. Mass removal by spallation at the back side of Teflon targets may be so severe that the absolute penetration-hole diameter (Dh) can become larger than that of a standard crater (Dc) at relative target thicknesses of Dp/T = 0.6-0.9. The crater diameter is infinite halfspace Teflon targets increases -- at otherwise constant impact conditions -- with encounter velocity by a factor of V0.44. In contrast, the penetration-hole size is very thin foils (Dp/T greater than 50) is essentially unaffected by impact velocity. Penetrations at target thicknesses intermediate to these extremes will scale with variable exponents of V. Our experimental matrix is

  17. Cratering and penetration experiments in teflon targets at velocities from 1 to 7 km/s

    NASA Technical Reports Server (NTRS)

    Horz, Friedrich; Cintala, Mark; Bernhard, Ronald P.; Cardenas, Frank; Davidson, William; Haynes, Gerald; See, Thomas H.; Winkler, Jerry; Knight, Jeffrey

    1994-01-01

    Approximately 20 sq m of protective thermal blankets, largely composed of Teflon, were retrieved from the Long Duration Exposure Facility after the spacecraft spent approximately 5.7 years in space. Examination of these blankets revealed that they contained thousands of hypervelocity impact features ranging from micron-sized craters to penetration holes several millimeters in diameter. We conducted impact experiments to reproduce such features and to understand the relationships between projectile size and the resulting crater or penetration hole diameter over a wide range of impact velocities. Such relationships are needed to derive the size and mass frequency distribution and flux of natural and man-made particles in low-earth orbit. Powder propellant and light-gas guns were used to launch soda-lime glass spheres into pure Teflon targets at velocities ranging from 1 to 7 km/s. Target thickness varied over more than three orders of magnitude from finite halfspace targets to very thin films. Cratering and penetration of massive Teflon targets is dominated by brittle failure and the development of extensive spall zones at the target's front and, if penetrated, the target's rear side. Mass removal by spallation at the back side of Teflon targets may be so severe that the absolute penetration hole diameter can become larger than that of a standard crater. The crater diameter in infinite halfspace Teflon targets increases, at otherwise constant impact conditions, with encounter velocity by a factor of V (exp 0.44). In contrast, the penetration hole size in very thin foils is essentially unaffected by impact velocity. Penetrations at target thicknesses intermediate to these extremes will scale with variable exponents of V. Our experimental matrix is sufficiently systematic and complete, up to 7 km/s, to make reasonable recommendations for velocity-scaling of Teflon craters and penetrations. We specifically suggest that cratering behavior and associated equations apply

  18. Cratering and penetration experiments in Teflon targets at velocities from 1 to 7 km/s

    NASA Astrophysics Data System (ADS)

    Hoerz, Friedrich; Bernhard, Ronald P.; Cintala, Mark J.; See, Thomas H.

    1995-02-01

    Approximately 20 sq m of protective thermal blankets, largely composed of Teflon, were retrieved from the Long Duration Exposure Facility (LDEF) after the spacecraft had spent approximately 5.7 years in space. Examination of these blankets revealed that they contained thousands of hypervelocity impact features ranging from micron-sized craters to penetration holes several millimeters in diameter. We conducted impact experiments in an effort to reproduce such features and to -- hopefully -- understand the relationships between projectile size and the resulting crater or penetration-hole diameter over a wide range of impact velocity. Such relationships are needed to derive the size- and mass-frequency distribution and flux of natural and man-made particles in low-Earth orbit. Powder propellant and light-gas guns were used to launch soda-lime glass spheres of 3.175 mm (1/8 inch) nominal diameter (Dp) into pure Teflon FEP targets at velocities ranging from 1 to 7 km/s. Target thickness (T) was varied over more than three orders of magnitude from infinite halfspace targets (Dp/T less than 0.1) to very thin films (Dp/T greater than 100). Cratering and penetration of massive Teflon targets is dominated by brittle failure and the development of extensive spall zones at the target's front and, if penetrated, the target's rear side. Mass removal by spallation at the back side of Teflon targets may be so severe that the absolute penetration-hole diameter (Dh) can become larger than that of a standard crater (Dc) at relative target thicknesses of Dp/T = 0.6-0.9. The crater diameter is infinite halfspace Teflon targets increases -- at otherwise constant impact conditions -- with encounter velocity by a factor of V0.44. In contrast, the penetration-hole size is very thin foils (Dp/T greater than 50) is essentially unaffected by impact velocity. Penetrations at target thicknesses intermediate to these extremes will scale with variable exponents of V. Our experimental matrix is

  19. How the cosmological constant affects gravastar formation

    SciTech Connect

    Chan, R.; Silva, M.F.A. da; Rocha, P. E-mail: mfasnic@gmail.com

    2009-12-01

    Here we generalized a previous model of gravastar consisted of an internal de Sitter spacetime, a dynamical infinitely thin shell with an equation of state, but now we consider an external de Sitter-Schwarzschild spacetime. We have shown explicitly that the final output can be a black hole, a ''bounded excursion'' stable gravastar, a stable gravastar, or a de Sitter spacetime, depending on the total mass of the system, the cosmological constants, the equation of state of the thin shell and the initial position of the dynamical shell. We have found that the exterior cosmological constant imposes a limit to the gravastar formation, i.e., the exterior cosmological constant must be smaller than the interior cosmological constant. Besides, we have also shown that, in the particular case where the Schwarzschild mass vanishes, no stable gravastar can be formed, but we still have formation of black hole.

  20. The Cosmological Constant in Quantum Cosmology

    SciTech Connect

    Wu Zhongchao

    2008-10-10

    Hawking proposed that the cosmological constant is probably zero in quantum cosmology in 1984. By using the right configuration for the wave function of the universe, a complete proof is found very recently.

  1. The Rate Constant for Fluorescence Quenching

    ERIC Educational Resources Information Center

    Legenza, Michael W.; Marzzacco, Charles J.

    1977-01-01

    Describes an experiment that utilizes fluorescence intensity measurements from a Spectronic 20 to determine the rate constant for the fluorescence quenching of various aromatic hydrocarbons by carbon tetrachloride in an ethanol solvent. (MLH)

  2. The Solar Constant: A Take Home Lab

    ERIC Educational Resources Information Center

    Eaton, B. G.; And Others

    1977-01-01

    Describes a method that uses energy from the sun, absorbed by aluminum discs, to melt ice, and allows the determination of the solar constant. The take-home equipment includes Styrofoam cups, a plastic syringe, and aluminum discs. (MLH)

  3. Dielectric constant of water in the interface

    NASA Astrophysics Data System (ADS)

    Dinpajooh, Mohammadhasan; Matyushov, Dmitry V.

    2016-07-01

    We define the dielectric constant (susceptibility) that should enter the Maxwell boundary value problem when applied to microscopic dielectric interfaces polarized by external fields. The dielectric constant (susceptibility) of the interface is defined by exact linear-response equations involving correlations of statistically fluctuating interface polarization and the Coulomb interaction energy of external charges with the dielectric. The theory is applied to the interface between water and spherical solutes of altering size studied by molecular dynamics (MD) simulations. The effective dielectric constant of interfacial water is found to be significantly lower than its bulk value, and it also depends on the solute size. For TIP3P water used in MD simulations, the interface dielectric constant changes from 9 to 4 when the solute radius is increased from ˜5 to 18 Å.

  4. Analysis of biomolecular interactions using affinity microcolumns: A review

    PubMed Central

    Zheng, Xiwei; Li, Zhao; Beeram, Sandya; Podariu, Maria; Matsuda, Ryan; Pfaunmiller, Erika L.; White, Christopher J.; Carter, NaTasha; Hage, David S.

    2014-01-01

    Affinity chromatography has become an important tool for characterizing biomolecular interactions. The use of affinity microcolumns, which contain immobilized binding agents and have volumes in the mid-to-low microliter range, has received particular attention in recent years. Potential advantages of affinity microcolumns include the many analysis and detection formats that can be used with these columns, as well as the need for only small amounts of supports and immobilized binding agents. This review examines how affinity microcolumns have been used to examine biomolecular interactions. Both capillary-based microcolumns and short microcolumns are considered. The use of affinity microcolumns with zonal elution and frontal analysis methods are discussed. The techniques of peak decay analysis, ultrafast affinity extraction, split-peak analysis, and band-broadening studies are also explored. The principles of these methods are examined and various applications are provided to illustrate the use of these methods with affinity microcolumns. It is shown how these techniques can be utilized to provide information on the binding strength and kinetics of an interaction, as well as on the number and types of binding sites. It is further demonstrated how information on competition or displacement effects can be obtained by these methods. PMID:24572459

  5. Two high-affinity ligand binding states of uterine estrogen receptor distinguished by modulation of hydrophobic environment

    SciTech Connect

    Hutchens, T.W.; Li, C.M.; Zamah, N.M.; Besch, P.K.

    1987-02-10

    The steroid binding function of soluble (cytosolic) estrogen receptors from calf uteri was evaluated under conditions known to modify the extent of hydrophobic interaction with receptor-associated proteins. Receptor preparations were equilibrated into 6 M urea buffers and control buffers by chromatography through small columns of Sephadex G-25 or by dialysis at 0.6 /sup 0/C. Equilibrium dissociation constants (K/sub d/) and binding capacities (n) of experimental and control receptor preparations were determined by 13-point Scatchard analyses using concentrations of 17..beta..-(/sup 3/H)estradiol from 0.05 to 10 nM. Nonspecific binding was determined at each concentration by parallel incubations with a 200-fold molar excess of the receptor-specific competitor diethylstilbestrol. The control receptor population was consistently found to be a single class of binding sites with a high affinity for estradiol which was unaffected by G-25 chromatography, by dialysis, by dilution, or by the presence of 0.4 M KCl. However, equilibration into 6 M urea induced a discrete (10-fold) reduction in receptor affinity to reveal a second, thermodynamically stable, high-affinity binding state. The presence of 0.4 M KCl did not significantly influence the discrete change in receptor affinity induced by urea. The effects of urea on both receptor affinity and binding capacity were reversible, suggesting a lack of covalent modification. These results demonstrate nonenzymatic means by which not only the binding capacity but also the affinity of receptor for estradiol can be reversibly controlled, suggesting that high concentrations of urea might be more effectively utilized during the physicochemical characterization and purification of steroid receptor proteins.

  6. Beyond lensing by the cosmological constant

    NASA Astrophysics Data System (ADS)

    Faraoni, Valerio; Lapierre-Léonard, Marianne

    2017-01-01

    The long-standing problem of whether the cosmological constant affects directly the deflection of light caused by a gravitational lens is reconsidered. We use a new approach based on the Hawking quasilocal mass of a sphere grazed by light rays and on its splitting into local and cosmological parts. Previous literature restricted to the cosmological constant is extended to any form of dark energy accelerating the universe in which the gravitational lens is embedded.

  7. Low-Dielectric-Constant Polyimide Fibers

    NASA Technical Reports Server (NTRS)

    Dorogy, William E., Jr.; Proctor, K. Mason; St. Clair, Anne K.

    1994-01-01

    In experiments performed at NASA Langley Research Center, low-dielectric-constant polyimide fibers produced by use of resin extrusion. These fibers also have high thermal stability and good tensile properties. Useful in industrial and aerospace applications in which fibers required to have dielectric constants less than 3, high thermal stability, and tensile properties in range of those of standard textile fibers. Potential applications include use in printed circuit-boards and in aircraft composites.

  8. Inflation with a constant rate of roll

    SciTech Connect

    Motohashi, Hayato; Starobinsky, Alexei A.; Yokoyama, Jun'ichi E-mail: alstar@landau.ac.ru

    2015-09-01

    We consider an inflationary scenario where the rate of inflaton roll defined by {sup ··}φ/H φ-dot remains constant. The rate of roll is small for slow-roll inflation, while a generic rate of roll leads to the interesting case of 'constant-roll' inflation. We find a general exact solution for the inflaton potential required for such inflaton behaviour. In this model, due to non-slow evolution of background, the would-be decaying mode of linear scalar (curvature) perturbations may not be neglected. It can even grow for some values of the model parameter, while the other mode always remains constant. However, this always occurs for unstable solutions which are not attractors for the given potential. The most interesting particular cases of constant-roll inflation remaining viable with the most recent observational data are quadratic hilltop inflation (with cutoff) and natural inflation (with an additional negative cosmological constant). In these cases even-order slow-roll parameters approach non-negligible constants while the odd ones are asymptotically vanishing in the quasi-de Sitter regime.

  9. Inflation with a constant rate of roll

    NASA Astrophysics Data System (ADS)

    Motohashi, Hayato; Starobinsky, Alexei A.; Yokoyama, Jun'ichi

    2015-09-01

    We consider an inflationary scenario where the rate of inflaton roll defined by ̈phi/H dot phi remains constant. The rate of roll is small for slow-roll inflation, while a generic rate of roll leads to the interesting case of 'constant-roll' inflation. We find a general exact solution for the inflaton potential required for such inflaton behaviour. In this model, due to non-slow evolution of background, the would-be decaying mode of linear scalar (curvature) perturbations may not be neglected. It can even grow for some values of the model parameter, while the other mode always remains constant. However, this always occurs for unstable solutions which are not attractors for the given potential. The most interesting particular cases of constant-roll inflation remaining viable with the most recent observational data are quadratic hilltop inflation (with cutoff) and natural inflation (with an additional negative cosmological constant). In these cases even-order slow-roll parameters approach non-negligible constants while the odd ones are asymptotically vanishing in the quasi-de Sitter regime.

  10. RNA structure and scalar coupling constants

    SciTech Connect

    Tinoco, I. Jr.; Cai, Z.; Hines, J.V.; Landry, S.M.; SantaLucia, J. Jr.; Shen, L.X.; Varani, G.

    1994-12-01

    Signs and magnitudes of scalar coupling constants-spin-spin splittings-comprise a very large amount of data that can be used to establish the conformations of RNA molecules. Proton-proton and proton-phosphorus splittings have been used the most, but the availability of {sup 13}C-and {sup 15}N-labeled molecules allow many more coupling constants to be used for determining conformation. We will systematically consider the torsion angles that characterize a nucleotide unit and the coupling constants that depend on the values of these torsion angles. Karplus-type equations have been established relating many three-bond coupling constants to torsion angles. However, one- and two-bond coupling constants can also depend on conformation. Serianni and coworkers measured carbon-proton coupling constants in ribonucleosides and have calculated their values as a function of conformation. The signs of two-bond coupling can be very useful because it is easier to measure a sign than an accurate magnitude.

  11. Underwater acoustic positioning system for the SMO and KM3NeT - Italia projects

    SciTech Connect

    Viola, S.; Barbagallo, G.; Cacopardo, G.; Calí, C.; Cocimano, R.; Coniglione, R.; Costa, M.; Cuttone, G.; D'Amato, C.; D'Amato, V.; D'Amico, A.; De Luca, V.; Del Tevere, F.; Distefano, C.; Ferrera, F.; Gmerk, A.; Grasso, R.; Imbesi, M.; Larosa, G.; Lattuada, D.; and others

    2014-11-18

    In the underwater neutrino telescopes, the positions of the Cherenkov light sensors and their movements must be known with an accuracy of few tens of centimetres. In this work, the activities of the SMO and KM3NeT-Italia teams for the development of an acoustic positioning system for KM3NeT-Italia project are presented. The KM3NeT-Italia project foresees the construction, within two years, of 8 towers in the view of the several km{sup 3}-scale neutrino telescope KM3NeT.

  12. The local Hurwitz constant and Diophantine approximation on Hecke groups

    NASA Astrophysics Data System (ADS)

    Lehner, J.

    1990-10-01

    Define the Hecke group by {G_q} = < {( {begin{array}{*{20}{c}} 1 & {{⪉mb... ...{array}{*{20}{c}} 0 & { - 1} 1 & 0 } )} rangle , {λ _q} = 2cos π /q , q = 3,4, ldots . We call {G_q}(∞ ) the {G_q} -rationals, and R - {G_q}(∞ ) the {G_q} -irrationals. The problem we treat here is the approximation of {G_q} -irrationals by {G_q} -rationals. Let M(α ) be the upper bound of numbers c for which \\vertα - k/m\\vert < 1/c{m^2} for all {G_q} -irrationals and infinitely many k/m in {G_q}(∞ ) . Set h_q'= {inf _α }M(α ) . We call h_q' the Hurwitz constant for {G_q} . It is known that h_q'= 2 , q even; h_q'= 2{(1 + {(1 - {λ _q}/2)^2})^{1/2}} , q odd. In this paper we prove this result by using {λ _q} -continued fractions, as developed previously by D. Rosen. Write α - frac{{{P_{n - 1}}}}{{{Q_{n - 1}}}} = frac{{{{( - 1)}^{... ...}{\\varepsilon _2} \\cdots {\\varepsilon _n}}}{{{m_{n - 1}}(α )Q_{n - 1}^2}}, where {\\varepsilon _i} = ± 1 and {P_i}/{Q_i} are the convergents of the {λ _q} -continued fraction for α . Then M(α ) = {overline {lim } _n}{m_n}(α ) . We call {m_n}(α ) the local Hurwitz constant. In the final section we prove some results on the local Hurwitz constant. For example (Theorem 4), it is shown that if q is odd and {\\varepsilon _{n + 1}} = {\\varepsilon _{n + 2}} = + 1 , then {m_i} ≥ {(λ _q^2 + 4)^{1/2}} > h_q' for at least one of i = n - 1,n,n + 1 .

  13. Affinity+: Semi-Structured Brainstorming on Large Displays

    SciTech Connect

    Burtner, Edwin R.; May, Richard A.; Scarberry, Randall E.; LaMothe, Ryan R.; Endert, Alexander

    2013-04-27

    Affinity diagraming is a powerful method for encouraging and capturing lateral thinking in a group environment. The Affinity+ Concept was designed to improve the collaborative brainstorm process through the use of large display surfaces in conjunction with mobile devices like smart phones and tablets. The system works by capturing the ideas digitally and allowing users to sort and group them on a large touch screen manually. Additionally, Affinity+ incorporates theme detection, topic clustering, and other processing algorithms that help bring structured analytic techniques to the process without requiring explicit leadership roles and other overhead typically involved in these activities.

  14. Binding Affinities Controlled by Shifting Conformational Equilibria: Opportunities and Limitations

    PubMed Central

    Michielssens, Servaas; de Groot, Bert L.; Grubmüller, Helmut

    2015-01-01

    Conformational selection is an established mechanism in molecular recognition. Despite its power to explain binding events, it is hardly used in protein/ligand design to modulate molecular recognition. Here, we explore the opportunities and limitations of design by conformational selection. Using appropriate thermodynamic cycles, our approach predicts the effects of a conformational shift on binding affinity and also allows one to disentangle the effects induced by a conformational shift from other effects influencing the binding affinity. The method is assessed and applied to explain the contribution of a conformational shift on the binding affinity of six ubiquitin mutants showing different conformational shifts in six different complexes. PMID:25992736

  15. On the Henry constant and isosteric heat at zero loading in gas phase adsorption.

    PubMed

    Do, D D; Nicholson, D; Do, H D

    2008-08-01

    The Henry constant and the isosteric heat of adsorption at zero loading are commonly used as indicators of the strength of the affinity of an adsorbate for a solid adsorbent. It is assumed that (i) they are observable in practice, (ii) the Van Hoff's plot of the logarithm of the Henry constant versus the inverse of temperature is always linear and the slope is equal to the heat of adsorption, and (iii) the isosteric heat of adsorption at zero loading is either constant or weakly dependent on temperature. We show in this paper that none of these three points is necessarily correct, first because these variables might not be observable since they are outside the range of measurability; second that the linearity of the Van Hoff plot breaks down at very high temperature, and third that the isosteric heat versus loading is a strong function of temperature. We demonstrate these points using Monte Carlo integration and Monte Carlo simulation of adsorption of various gases on a graphite surface. Another issue concerning the Henry constant is related to the way the adsorption excess is defined. The most commonly used equation is the one that assumes that the void volume is the volume extended all the way to a boundary passing through the centres of the outermost solid atoms. With this definition the Henry constant can become negative at high temperatures. Although adsorption at these temperatures may not be practical because of the very low value of the Henry constant, it is more useful to define the Henry constant in such a way that it is always positive at all temperatures. Here we propose the use of the accessible volume; the volume probed by the adsorbate when it is in nonpositive regions of the potential, to calculate the Henry constant.

  16. Comparative Study of Three Methods for Affinity Measurements: Capillary Electrophoresis Coupled with UV Detection and Mass Spectrometry, and Direct Infusion Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Mironov, Gleb G.; Logie, Jennifer; Okhonin, Victor; Renaud, Justin B.; Mayer, Paul M.; Berezovski, Maxim V.

    2012-07-01

    We present affinity capillary electrophoresis and mass spectrometry (ACE-MS) as a comprehensive separation technique for label-free solution-based affinity analysis. The application of ACE-MS for measuring affinity constants between eight small molecule drugs [ibuprofen, s-flurbiprofen, diclofenac, phenylbutazone, naproxen, folic acid, resveratrol, and 4,4'-(propane-1,3-diyl) dibenzoic acid] and β-cyclodextrin is described. We couple on-line ACE with MS to combine the separation and kinetic capability of ACE together with the molecular weight and structural elucidation of MS in one system. To understand the full potential of ACE-MS, we compare it with two other methods: Direct infusion mass spectrometry (DIMS) and ACE with UV detection (ACE-UV). After the evaluation, DIMS provides less reliable equilibrium dissociation constants than separation-based ACE-UV and ACE-MS, and cannot be used solely for the study of noncovalent interactions. ACE-MS determines apparent dissociation constants for all reacting small molecules in a mixture, even in cases when drugs overlap with each other during separation. The ability of ACE-MS to interact, separate, and rapidly scan through m/z can facilitate the simultaneous affinity analysis of multiple interacting pairs, potentially leading to the high-throughput screening of drug candidates.

  17. The Structural Basis of Sirtuin Substrate Affinity

    SciTech Connect

    Cosgrove,M.; Bever, K.; Avalos, J.; Muhammad, S.; Zhang, X.; Wolberger, C.

    2006-01-01

    Sirtuins comprise a family of enzymes that catalyze the deacetylation of acetyllysine side chains in a reaction that consumes NAD+. Although several crystal structures of sirtuins bound to non-native acetyl peptides have been determined, relatively little about how sirtuins discriminate among different substrates is understood. We have carried out a systematic structural and thermodynamic analysis of several peptides bound to a single sirtuin, the Sir2 homologue from Thermatoga maritima (Sir2Tm). We report structures of five different forms of Sir2Tm: two forms bound to the p53 C-terminal tail in the acetylated and unacetylated states, two forms bound to putative acetyl peptide substrates derived from the structured domains of histones H3 and H4, and one form bound to polypropylene glycol (PPG), which resembles the apoenzyme. The structures reveal previously unobserved complementary side chain interactions between Sir2Tm and the first residue N-terminal to the acetyllysine (position -1) and the second residue C-terminal to the acetyllysine (position +2). Isothermal titration calorimetry was used to compare binding constants between wild-type and mutant forms of Sir2Tm and between additional acetyl peptide substrates with substitutions at positions -1 and +2. The results are consistent with a model in which peptide positions -1 and +2 play a significant role in sirtuin substrate binding. This model provides a framework for identifying sirtuin substrates.

  18. Direct detection of thrombin binding to 8-bromodeoxyguanosine-modified aptamer: effects of modification on affinity and kinetics.

    PubMed

    Goji, Shou; Matsui, Jun

    2011-01-01

    The affinity of an 8-bromodeoxyguanosine- (8-BrdG-) substituted thrombin-binding aptamer (TBA-Br), which has the 1st and 10th guanosine residues replaced with 8-BrdG, was estimated using reflectometric interference spectroscopy (RIfS). When comparing TBA-Br with unmodified TBA (TBA-H), it was demonstrated that the modification effectively improved the affinity of TBA; dissociation constants (K(D)) of TBA-H and TBA-Br were 45.4 nM and 1.99 nM, respectively. These values, which were obtained by direct observation of thrombin binding using RIfS, have the same order of magnitude as those obtained in our previous study utilizing conformational changes in TBA to detect thrombin binding, thus confirming the validity of the obtained K(D) values. RIfS measurements also revealed that the 8-BrdG modification resulted in a lower dissociation rate constant (k(d)), which suggests that the enhancement of affinity can be attributed to the stabilization of the G-quadruplex structure on introduction of 8-BrdG.

  19. Rules of RNA specificity of hnRNP A1 revealed by global and quantitative analysis of its affinity distribution.

    PubMed

    Jain, Niyati; Lin, Hsuan-Chun; Morgan, Christopher E; Harris, Michael E; Tolbert, Blanton S

    2017-02-28

    Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a multipurpose RNA-binding protein (RBP) involved in normal and pathological RNA metabolism. Transcriptome-wide mapping and in vitro evolution identify consensus hnRNP A1 binding motifs; however, such data do not reveal how surrounding RNA sequence and structural context modulate affinity. We determined the affinity of hnRNP A1 for all possible sequence variants (n = 16,384) of the HIV exon splicing silencer 3 (ESS3) 7-nt apical loop. Analysis of the affinity distribution identifies the optimal motif 5'-YAG-3' and shows how its copy number, position in the loop, and loop structure modulate affinity. For a subset of ESS3 variants, we show that specificity is determined by association rate constants and that variants lacking the minimal sequence motif bind competitively with consensus RNA. Thus, the results reveal general rules of specificity of hnRNP A1 and provide a quantitative framework for understanding how it discriminates between alternative competing RNA ligands in vivo.

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

    NASA Astrophysics Data System (ADS)

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

    2012-03-01

    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 KD = 2.25×10-9 (M). The secondary structure, contact sites with CRP protein, and application of this aptamer will be described.

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

    PubMed

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

    2016-03-14

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

  2. Rules of RNA specificity of hnRNP A1 revealed by global and quantitative analysis of its affinity distribution

    PubMed Central

    Jain, Niyati; Lin, Hsuan-Chun; Morgan, Christopher E.; Harris, Michael E.; Tolbert, Blanton S.

    2017-01-01

    Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a multipurpose RNA-binding protein (RBP) involved in normal and pathological RNA metabolism. Transcriptome-wide mapping and in vitro evolution identify consensus hnRNP A1 binding motifs; however, such data do not reveal how surrounding RNA sequence and structural context modulate affinity. We determined the affinity of hnRNP A1 for all possible sequence variants (n = 16,384) of the HIV exon splicing silencer 3 (ESS3) 7-nt apical loop. Analysis of the affinity distribution identifies the optimal motif 5′-YAG-3′ and shows how its copy number, position in the loop, and loop structure modulate affinity. For a subset of ESS3 variants, we show that specificity is determined by association rate constants and that variants lacking the minimal sequence motif bind competitively with consensus RNA. Thus, the results reveal general rules of specificity of hnRNP A1 and provide a quantitative framework for understanding how it discriminates between alternative competing RNA ligands in vivo. PMID:28193894

  3. Bidirectional elastic image registration using B-spline affine transformation.

    PubMed

    Gu, Suicheng; Meng, Xin; Sciurba, Frank C; Ma, Hongxia; Leader, Joseph; Kaminski, Naftali; Gur, David; Pu, Jiantao

    2014-06-01

    A registration scheme termed as B-spline affine transformation (BSAT) is presented in this study to elastically align two images. We define an affine transformation instead of the traditional translation at each control point. Mathematically, BSAT is a generalized form of the affine transformation and the traditional B-spline transformation (BST). In order to improve the performance of the iterative closest point (ICP) method in registering two homologous shapes but with large deformation, a bidirectional instead of the traditional unidirectional objective/cost function is proposed. In implementation, the objective function is formulated as a sparse linear equation problem, and a sub-division strategy is used to achieve a reasonable efficiency in registration. The performance of the developed scheme was assessed using both two-dimensional (2D) synthesized dataset and three-dimensional (3D) volumetric computed tomography (CT) data. Our experiments showed that the proposed B-spline affine model could obtain reasonable registration accuracy.

  4. Bidirectional Elastic Image Registration Using B-Spline Affine Transformation

    PubMed Central

    Gu, Suicheng; Meng, Xin; Sciurba, Frank C.; Wang, Chen; Kaminski, Naftali; Pu, Jiantao

    2014-01-01

    A registration scheme termed as B-spline affine transformation (BSAT) is presented in this study to elastically align two images. We define an affine transformation instead of the traditional translation at each control point. Mathematically, BSAT is a generalized form of the affine transformation and the traditional B-Spline transformation (BST). In order to improve the performance of the iterative closest point (ICP) method in registering two homologous shapes but with large deformation, a bi-directional instead of the traditional unidirectional objective / cost function is proposed. In implementation, the objective function is formulated as a sparse linear equation problem, and a sub-division strategy is used to achieve a reasonable efficiency in registration. The performance of the developed scheme was assessed using both two-dimensional (2D) synthesized dataset and three-dimensional (3D) volumetric computed tomography (CT) data. Our experiments showed that the proposed B-spline affine model could obtain reasonable registration accuracy. PMID:24530210

  5. A thermodynamic approach to the affinity optimization of drug candidates.

    PubMed

    Freire, Ernesto

    2009-11-01

    High throughput screening and other techniques commonly used to identify lead candidates for drug development usually yield compounds with binding affinities to their intended targets in the mid-micromolar range. The affinity of these molecules needs to be improved by several orders of magnitude before they become viable drug candidates. Traditionally, this task has been accomplished by establishing structure activity relationships to guide chemical modifications and improve the binding affinity of the compounds. As the binding affinity is a function of two quantities, the binding enthalpy and the binding entropy, it is evident that a more efficient optimization would be accomplished if both quantities were considered and improved simultaneously. Here, an optimization algorithm based upon enthalpic and entropic information generated by Isothermal Titration Calorimetry is presented.

  6. Antibody Affinity Maturation in Fishes—Our Current Understanding

    PubMed Central

    Magor, Brad G.

    2015-01-01

    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. PMID:26264036

  7. Dental affinities of the C-group inhabitants of Hierakonpolis, Egypt: Nubian, Egyptian, or both?

    PubMed

    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.

  8. (In)validity of the constant field and constant currents assumptions in theories of ion transport.

    PubMed Central

    Syganow, A; von Kitzing, E

    1999-01-01

    Constant electric fields and constant ion currents are often considered in theories of ion transport. Therefore, it is important to understand the validity of these helpful concepts. The constant field assumption requires that the charge density of permeant ions and flexible polar groups is virtually voltage independent. We present analytic relations that indicate the conditions under which the constant field approximation applies. Barrier models are frequently fitted to experimental current-voltage curves to describe ion transport. These models are based on three fundamental characteristics: a constant electric field, negligible concerted motions of ions inside the channel (an ion can enter only an empty site), and concentration-independent energy profiles. An analysis of those fundamental assumptions of barrier models shows that those approximations require large barriers because the electrostatic interaction is strong and has a long range. In the constant currents assumption, the current of each permeating ion species is considered to be constant throughout the channel; thus ion pairing is explicitly ignored. In inhomogeneous steady-state systems, the association rate constant determines the strength of ion pairing. Among permeable ions, however, the ion association rate constants are not small, according to modern diffusion-limited reaction rate theories. A mathematical formulation of a constant currents condition indicates that ion pairing very likely has an effect but does not dominate ion transport. PMID:9929480

  9. A robust method for determining DNA binding constants using capillary zone electrophoresis.

    PubMed

    Li, C; Martin, L M

    1998-10-01

    Capillary zone electrophoresis (CZE or CE) with on-line UV detection was utilized to measure the binding constants between purified calf thymus DNA and a library of designed tetrapeptides which had been constructed using unnatural amino acids with thiazole ring side chains. Mixtures containing a constant amount of a tetrapeptide, the neutral marker (mesityl oxide), and varying concentrations of DNA were prepared and equilibrated at 8 degreesC for 12 h. CE was then utilized to separate unbound tetrapeptides from the DNA-peptide complex. The UV absorbance of the peak representing unbound tetrapeptide decreased incrementally as a result of increasing the concentration of DNA in the equilibrium mixture. The absorbance of the peak corresponding to the unbound tetrapeptide was obtained directly from the electropherogram and used in the calculation of the DNA-peptide binding constants. The binding constant for each tetrapeptide to calf thymus DNA was obtained from the negative slope of a Scatchard plot and a comparison of the binding constants for different peptides showed that the tetrapeptides in the library have DNA-binding affinities ranging from 10(2) to 10(6) M-1.

  10. Microcalorimetric study of the anaerobic growth of Escherichia coli: measurements of the affinity of whole cells for various energy substrates.

    PubMed Central

    Belaich, A; Belaich, J P

    1976-01-01

    Microcalorimetry has been used to determine the affinity of whole cells of Escherichia coli for glucose, galactose, fructose, and lactose. Anaerobic growth thermograms were analyzed, and the Km and Vmax values for these energy substrates were measured at pH 7.8. Results obtained with this technique using various organisms growing anaerobically on different sugars are compared. This comparison shows that in practically all cases the cellular rate of catabolic activity is a hyperbolic function of the energy substrate concentrations at low sugar concentrations. In some cases this technique also allows determination of kinetics at high sugar concentrations. PMID:1373

  11. Electrospun polyethersulfone affinity membrane: membrane preparation and performance evaluation.

    PubMed

    Ma, Zuwei; Lan, Zhengwei; Matsuura, Takeshi; Ramakrishna, Seeram

    2009-11-01

    Non-woven polyethersulfone (PES) membranes were prepared by electrospinning. After heat treatment and surface activation, the membranes were covalently functionalized with ligands to be used as affinity membranes. The membranes were characterized in terms of fiber diameter, porosity, specific area, pore size, ligand density and binding capacities. To evaluate the binding efficiency of the membrane, dynamic adsorption of bovine serum albumin (BSA) on the Cibacron blue F3GA (CB) functionalized PES membrane was studied. Experimental breakthrough curves were fitted with the theoretical curves based on the plate model to estimate plate height (H(p)) of the affinity membrane. The high value of H(p) (1.6-8 cm) of the affinity membrane implied a poor dynamic binding efficiency, which can be explained by the intrinsic microstructures of the material. Although the electrospun membrane might not be an ideal candidate for the preparative affinity membrane chromatography for large-scale production, it still can be used for fast small-scale protein purification in which a highly efficient binding is not required. Spin columns packed with protein A/G immobilized PES membranes were demonstrated to be capable of binding IgG specifically. SDS-PAGE results demonstrated that the PES affinity membrane had high specific binding selectivity for IgG molecules and low non-specific protein adsorption. Compared with other reported affinity membranes, the PES affinity membrane had a comparable IgG binding capacity of 4.5 mg/ml, and had a lower flow through pressure drop due to its larger pore size. In conclusion, the novel PES affinity membrane is an ideal spin column packing material for fast protein purification.

  12. Considering affinity: an ethereal conversation (part two of three).

    PubMed

    Winsor, Mary P

    2015-06-01

    In 1840 Hugh Strickland published a diagram showing the relationships of genera of birds in the kingfisher family. Three years later he applied this mapping idea to genera of birds of prey and songbirds, creating a large wall chart that he displayed to colleagues but never published. Both of his diagrams featured a scale of degrees of affinity. The meaning of taxonomic affinity was something Darwin thought about deeply. Details in the chart undermine Strickland's claim that his method was purely inductive.

  13. Proton affinity of methyl nitrate - Less than proton affinity of nitric acid

    NASA Technical Reports Server (NTRS)

    Lee, Timothy J.; Rice, Julia E.

    1992-01-01

    Several state-of-the-art ab initio quantum mechanical methods were used to investigate the equilibrium structure, dipole moments, harmonic vibrational frequencies, and IR intensities of methyl nitrate, methanol, and several structures of protonated methyl nitrate, using the same theoretical methods as in an earlier study (Lee and Rice, 1992) of nitric acid. The ab initio results for methyl nitrate and methanol were found to be in good agreement with available experimental data. The proton affinity (PA) of methyl nitrate was calculated to be 176.9 +/-5 kcal/mol, in excellent agreement with the experimental value 176 kcal/mol obtained by Attina et al. (1987) and less than the PA value of nitric acid. An explanation of the discrepancy of the present results with those of an earlier study on protonated nitric acid is proposed.

  14. Changes in benzodiazepine receptor ligand affinity in the presence of 4,5,6,7-tetrahydroisoxazolo-(5,4-c-)-pyridin-3-ol (THIP)

    SciTech Connect

    Zharkovskii, A.M.; Shavrin, A.S.; Zharkovskaya, T.A.

    1987-07-01

    The authors give data showing that benzodiazepine (BD) receptor ligands change their affinity in the presence of THIP, and that the shift of affinity induced by THIP can be used to predict the activity of these substances in vitro. Rats were used in the experiments and aliquots of the homogenate were incubated with /sup 3/H-flunitrazepam (/sup 3/H-FNZ). THIP inhibited binding of /sup 3/H-FNZ with intact membranes in proportion to its concentration. The inhibitory concentrations and inhibition constants of BD receptor ligands in the absence and presence of THIP are shown.

  15. A measurement of the value of the Hubble constant from the X-ray properties and the Sunyaev-Zel'dovich effect of Abell 665

    NASA Technical Reports Server (NTRS)

    Birkinshaw, M.; Hughes, J. P.; Arnaud, K. A.

    1991-01-01

    A comparison of the X-ray properties and the Sunyaev-Zel'dovich (SZ) effect for a cluster of galaxies can be used to measure the distance of the cluster and hence the Hubble constant. This method was applied to the rich cluster Abell 665. The relative normalization of X-ray and SZ-effect data leads to an estimated Hubble constant of H sub 0 = 40 + or - 9 km/s Mpc if only the random errors are included. When the possible systematic errors are added in quadrature, the range of possible values of the Hubble constants expands to (40 to 50) + or - 12 km/s Mpc.

  16. Functionalized multi-walled carbon nanotubes as affinity ligands

    NASA Astrophysics Data System (ADS)

    Yu, L.; Li, C. M.; Zhou, Q.; Gan, Y.; Bao, Q. L.

    2007-03-01

    Functionalization of carbon nanotubes is very challenging for their applications. The paper here describes a new method to functionalize multi-walled carbon nanotubes (MWCNTs) as specific affinity adsorbents. MWCNTs were acid purified and pretreated with (3-aminopropyl)-triethoxysilane (APTES) in order to introduce abundant amino groups on the surface of MWCNTs. After the conversion of amino groups to carboxyl groups by succinic acid anhydride, MWCNTs were attached to protein A or aminodextran using 1-ethyl-3,3' (dimethylamion)-propylcarbodiimide as a biofunctional crosslinker. The incorporation of aminodextran as a spacer arm noticeably increased the binding capacity of the APTES-modified MWCNTs for protein A. The application of affinity MWCNTs for purification of immunoglobulin G was then evaluated. The affinity of MWCNTs with AMD spacer exhibited a high adsorption capacity of ~361 µg IgG/mg MWCNT (wet basis). About 75% of bound IgG was eluted from affinity MWCNTs (ANT-I and ANT-II) and ELISA confirmed that the biological activity of IgG was well preserved during the course of affinity separation. The functionalized MWCNTs could be potentially used in affinity chromatography.

  17. Second Yamabe constant on Riemannian products

    NASA Astrophysics Data System (ADS)

    Henry, Guillermo

    2017-04-01

    Let (Mm , g) be a closed Riemannian manifold (m ≥ 2) of positive scalar curvature and (Nn , h) any closed manifold. We study the asymptotic behaviour of the second Yamabe constant and the second N-Yamabe constant of (M × N , g + th) as t goes to + ∞. We obtain that lim t → + ∞Y2(M × N , [ g + th ]) =2 2/m+n Y(M ×Rn , [ g +ge ]) . If n ≥ 2, we show the existence of nodal solutions of the Yamabe equation on (M × N , g + th) (provided t large enough). When sg is constant, we prove that lim t → + ∞ YN2 (M × N , g + th) =2 2/m+n YRn(M ×Rn , g +ge) . Also we study the second Yamabe invariant and the second N-Yamabe invariant.

  18. Construction and experimental testing of the constant-bandwidth constant-temperature anemometer.

    PubMed

    Ligeza, P

    2008-09-01

    A classical constant-temperature hot-wire anemometer enables the measurement of fast-changing flow velocity fluctuations, although its transmission bandwidth is a function of measured velocity. This may be a source of significant dynamic errors. Incorporation of an adaptive controller into the constant-temperature system results in hot-wire anemometer operating with a constant transmission bandwidth. The construction together with the results of experimental testing of a constant-bandwidth hot-wire anemometer prototype are presented in this article. During the testing, an approximately constant transmission bandwidth of the anemometer was achieved. The constant-bandwidth hot-wire anemometer can be used in measurements of high-frequency variable flows characterized by a wide range of velocity changes.

  19. Optical turbulence parameters characterized via optical measurements over a 2.33 km free-space laser path.

    PubMed

    Tunick, Arnold

    2008-09-15

    Optical turbulence research contributes to improved laser communications, adaptive optics, and long-range imaging systems. This paper presents experimental measurements of scintillation and focal spot displacement to obtain optical turbulence information along a near-horizontal 2.33 km free-space laser propagation path. Calculated values for the refractive index structure constant (C(n)(2)) and Fried parameter (r0) are compared to scintillometer-based measurements for several cases in winter and spring. Optical measurements were investigated using two different laser sources for the first and second parts of the experiment. Scintillation index estimates from recorded signal intensities were corrected to account for aperture averaging. As a result, we found that an earlier calculation algorithm based on analysis of log-amplitude intensity variance was the best estimator of optical turbulence parameters over the propagation path considered.

  20. Local BLyS production by T follicular cells mediates retention of high affinity B cells during affinity maturation

    PubMed Central

    Goenka, Radhika; Matthews, Andrew H.; Zhang, Bochao; O’Neill, Patrick J.; Scholz, Jean L.; Migone, Thi-Sau; Leonard, Warren J.; Stohl, William; Hershberg, Uri

    2014-01-01

    We have assessed the role of B lymphocyte stimulator (BLyS) and its receptors in the germinal center (GC) reaction and affinity maturation. Despite ample BLyS retention on B cells in follicular (FO) regions, the GC microenvironment lacks substantial BLyS. This reflects IL-21–mediated down-regulation of the BLyS receptor TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) on GC B cells, thus limiting their capacity for BLyS binding and retention. Within the GC, FO helper T cells (TFH cells) provide a local source of BLyS. Whereas T cell–derived BLyS is dispensable for normal GC cellularity and somatic hypermutation, it is required for the efficient selection of high affinity GC B cell clones. These findings suggest that during affinity maturation, high affinity clones rely on TFH-derived BLyS for their persistence. PMID:24367004

  1. Atomic weights: no longer constants of nature

    USGS Publications Warehouse

    Coplen, Tyler B.; Holden, Norman E.

    2011-01-01

    Many of us were taught that the standard atomic weights we found in the back of our chemistry textbooks or on the Periodic Table of the Chemical Elements hanging on the wall of our chemistry classroom are constants of nature. This was common knowledge for more than a century and a half, but not anymore. The following text explains how advances in chemical instrumentation and isotopic analysis have changed the way we view atomic weights and why they are no longer constants of nature

  2. Cosmological constant in scale-invariant theories

    SciTech Connect

    Foot, Robert; Kobakhidze, Archil; Volkas, Raymond R.

    2011-10-01

    The incorporation of a small cosmological constant within radiatively broken scale-invariant models is discussed. We show that phenomenologically consistent scale-invariant models can be constructed which allow a small positive cosmological constant, providing certain relation between the particle masses is satisfied. As a result, the mass of the dilaton is generated at two-loop level. Another interesting consequence is that the electroweak symmetry-breaking vacuum in such models is necessarily a metastable ''false'' vacuum which, fortunately, is not expected to decay on cosmological time scales.

  3. TOPICAL REVIEW The cosmological constant puzzle

    NASA Astrophysics Data System (ADS)

    Bass, Steven D.

    2011-04-01

    The accelerating expansion of the Universe points to a small positive vacuum energy density and negative vacuum pressure. A strong candidate is the cosmological constant in Einstein's equations of general relativity. Possible contributions are zero-point energies and the condensates associated with spontaneous symmetry breaking. The vacuum energy density extracted from astrophysics is 1056 times smaller than the value expected from quantum fields and standard model particle physics. Is the vacuum energy density time dependent? We give an introduction to the cosmological constant puzzle and ideas how to solve it.

  4. Dielectric constants of soils at microwave frequencies

    NASA Technical Reports Server (NTRS)

    Geiger, F. E.; Williams, D.

    1972-01-01

    A knowledge of the complex dielectric constant of soils is essential in the interpretation of microwave airborne radiometer data of the earth's surface. Measurements were made at 37 GHz on various soils from the Phoenix, Ariz., area. Extensive data have been obtained for dry soil and soil with water content in the range from 0.6 to 35 percent by dry weight. Measurements were made in a two arm microwave bridge and results were corrected for reflections at the sample interfaces by solution of the parallel dielectric plate problem. The maximum dielectric constants are about a factor of 3 lower than those reported for similar soils at X-band frequencies.

  5. Environmental dependence of masses and coupling constants

    SciTech Connect

    Olive, Keith A.; Pospelov, Maxim

    2008-02-15

    We construct a class of scalar field models coupled to matter that lead to the dependence of masses and coupling constants on the ambient matter density. Such models predict a deviation of couplings measured on the Earth from values determined in low-density astrophysical environments, but do not necessarily require the evolution of coupling constants with the redshift in the recent cosmological past. Additional laboratory and astrophysical tests of {delta}{alpha} and {delta}(m{sub p}/m{sub e}) as functions of the ambient matter density are warranted.

  6. Microfabricated microengine with constant rotation rate

    DOEpatents

    Romero, Louis A.; Dickey, Fred M.

    1999-01-01

    A microengine uses two synchronized linear actuators as a power source and converts oscillatory motion from the actuators into constant rotational motion via direct linkage connection to an output gear or wheel. The microengine provides output in the form of a continuously rotating output gear that is capable of delivering drive torque at a constant rotation to a micromechanism. The output gear can have gear teeth on its outer perimeter for directly contacting a micromechanism requiring mechanical power. The gear is retained by a retaining means which allows said gear to rotate freely. The microengine is microfabricated of polysilicon on one wafer using surface micromachining batch fabrication.

  7. Microfabricated microengine with constant rotation rate

    SciTech Connect

    Romero, L.A.; Dickey, F.M.

    1999-09-21

    A microengine uses two synchronized linear actuators as a power source and converts oscillatory motion from the actuators into constant rotational motion via direct linkage connection to an output gear or wheel. The microengine provides output in the form of a continuously rotating output gear that is capable of delivering drive torque at a constant rotation to a micromechanism. The output gear can have gear teeth on its outer perimeter for directly contacting a micromechanism requiring mechanical power. The gear is retained by a retaining means which allows said gear to rotate freely. The microengine is microfabricated of polysilicon on one wafer using surface micromachining batch fabrication.

  8. Our Universe from the cosmological constant

    SciTech Connect

    Barrau, Aurélien; Linsefors, Linda E-mail: linda.linsefors@lpsc.in2p3.fr

    2014-12-01

    The issue of the origin of the Universe and of its contents is addressed in the framework of bouncing cosmologies, as described for example by loop quantum gravity. If the current acceleration is due to a true cosmological constant, this constant is naturally conserved through the bounce and the Universe should also be in a (contracting) de Sitter phase in the remote past. We investigate here the possibility that the de Sitter temperature in the contracting branch fills the Universe with radiation that causes the bounce and the subsequent inflation and reheating. We also consider the possibility that this gives rise to a cyclic model of the Universe and suggest some possible tests.

  9. Degravitation of the cosmological constant in bigravity

    NASA Astrophysics Data System (ADS)

    Platscher, Moritz; Smirnov, Juri

    2017-03-01

    In this article the phenomenon of degravitation of the cosmological constant is studied in the framework of bigravity. It is demonstrated that despite a sizable value of the cosmological constant its gravitational effect can be only mild. The bigravity framework is chosen for this demonstration as it leads to a consistent, ghost-free theory of massive gravity. We show that degravitation takes place in the limit where the physical graviton is dominantly a gauge invariant metric combination. We present and discuss several phenomenological consequences expected in this regime.

  10. Porous low dielectric constant materials for microelectronics.

    PubMed

    Baklanov, Mikhail R; Maex, Karen

    2006-01-15

    Materials with a low dielectric constant are required as interlayer dielectrics for the on-chip interconnection of ultra-large-scale integration devices to provide high speed, low dynamic power dissipation and low cross-talk noise. The selection of chemical compounds with low polarizability and the introduction of porosity result in a reduced dielectric constant. Integration of such materials into microelectronic circuits, however, poses a number of challenges, as the materials must meet strict requirements in terms of properties and reliability. These issues are the subject of the present paper.

  11. Atomic Weights No Longer Constants of Nature

    SciTech Connect

    Coplen, T.B.; Holden, N.

    2011-03-01

    Many of us grew up being taught that the standard atomic weights we found in the back of our chemistry textbooks or on the Periodic Table of the Chemical Elements hanging on the wall of our chemistry classroom are constants of nature. This was common knowledge for more than a century and a half, but not anymore. The following text explains how advances in chemical instrumentation and isotopic analysis has changed the way we view atomic weights and why they are no longer constants of nature.

  12. Weyl-Eddington-Einstein affine gravity in the context of modern cosmology

    NASA Astrophysics Data System (ADS)

    Filippov, A. T.

    2010-06-01

    We propose new models of the “affine” theory of gravity in multidimensional space-times with symmetric connections. We use and develop ideas of Weyl, Eddington, and Einstein, in particular, Einstein’s proposed method for obtaining the geometry using the Hamilton principle. More specifically, the connection coefficients are determined using a “geometric” Lagrangian that is an arbitrary function of the generalized (nonsymmetric) Ricci curvature tensor (and, possibly, other fundamental tensors) expressed in terms of the connection coefficients regarded as independent variables. Such a theory supplements the standard Einstein theory with dark energy (the cosmological constant, in the first approximation), a neutral massive (or tachyonic) meson, and massive (or tachyonic) scalar fields. These fields couple only to gravity and can generate dark matter and/or inflation. The new field masses (real or imaginary) have a geometric origin and must appear in any concrete model. The concrete choice of the Lagrangian determines further details of the theory, for example, the nature of the fields that can describe massive particles, tachyons, or even “phantoms.” In “natural” geometric theories, dark energy must also arise. The basic parameters of the theory (cosmological constant, mass, possible dimensionless constants) are theoretically indeterminate, but in the framework of modern “multiverse” ideas, this is more a virtue than a defect. We consider further extensions of the affine models and in more detail discuss approximate effective (“physical”) Lagrangians that can be applied to the cosmology of the early Universe.

  13. Three new defined proton affinities for polybasic molecules in the gas-phase: Proton microaffinity, proton macroaffinity and proton overallaffinity

    NASA Astrophysics Data System (ADS)

    Salehzadeh, Sadegh; Bayat, Mehdi

    2006-08-01

    A theoretical study on complete protonation of a series of tetrabasic molecules with general formula N[(CH 2) nNH 2][(CH 2) mNH 2][(CH 2) pNH 2] (tren, pee, ppe, tpt, epb and ppb) is reported. For first time, three kinds of gas-phase proton affinities for each polybasic molecule are defined as: 'proton microaffinity (PA n, i)', 'proton macroaffinity (PA)' and 'proton overall affinity ( PA)'. The variations of calculated logPA in the series of these molecules is very similar to that of their measured log Kn. There is also a good correlation between the calculated gas-phase proton macroaffinities and proton overallaffinities with corresponding equilibrium macroconstants and overall protonation constants in solution.

  14. Synthesis, characterization and binding affinities of rhenium(I) thiosemicarbazone complexes for the estrogen receptor (α/β).

    PubMed

    Núñez-Montenegro, Ara; Carballo, Rosa; Vázquez-López, Ezequiel M

    2014-11-01

    The binding affinities towards estrogen receptors (ERs) α and β of a set of thiosemicarbazone ligands (HL(n)) and their rhenium(I) carbonyl complexes [ReX(HL(n))(CO)3] (X=Cl, Br) were determined by a competitive standard radiometric assay with [(3)H]-estradiol. The ability of the coordinated thiosemicarbazone ligands to undergo deprotonation and the lability of the ReX bond were used as a synthetic strategy to obtain [Re(hpy)(L(n))(CO)3] (hpy=3- or 4-hydroxypyridine). The inclusion of the additional hpy ligand endows the new thiosemicarbazonate complexes with an improved affinity towards the estrogen receptors and, consequently, the values of the inhibition constant (Ki) could be determined for some of them. In general, the values of Ki for both ER subtypes suggest an appreciable selectivity towards ERα.

  15. Omega-conotoxin GVIA binding to a high-affinity receptor in brain: characterization, calcium sensitivity, and solubilization

    SciTech Connect

    Wagner, J.A.; Snowman, A.M.; Biswas, A.; Olivera, B.M.; Snyder, S.H.

    1988-09-01

    We describe unique, high-affinity binding sites for omega(/sup 125/I)conotoxin GVIA in membranes from rat brain and rabbit sympathetic ganglia which appear to be primarily associated with N-type voltage-dependent calcium channels. The dissociation constant (KD) for the toxin in rat brain membranes is 60 pM. Physiologic extracellular concentrations of calcium inhibit toxin binding noncompetitively (IC50 = 0.2 mM). The regional distribution of the binding sites in rat brain differs markedly from that of dihydropyridine calcium antagonist receptors associated with L-type calcium channels. In detergent-solubilized brain membranes, toxin binding retains the same affinity, specificity, and ionic sensitivity as in particulate preparations.

  16. MODIS 3 Km Aerosol Product: Applications over Land in an Urban/suburban Region

    NASA Technical Reports Server (NTRS)

    Munchak, L. A.; Levy, R. C.; Mattoo, S.; Remer, L. A.; Holben, B. N.; Schafer, J. S.; Hostetler, C. A.; Ferrare, R. A.

    2013-01-01

    MODerate resolution Imaging Spectroradiometer (MODIS) instruments aboard the Terra and Aqua satellites have provided a rich dataset of aerosol information at a 10 km spatial scale. Although originally intended for climate applications, the air quality community quickly became interested in using the MODIS aerosol data. However, 10 km resolution is not sufficient to resolve local scale aerosol features. With this in mind, MODIS Collection 6 is including a global aerosol product with a 3 km resolution. Here, we evaluate the 3 km product over the Baltimore/Washington D.C., USA, corridor during the summer of 2011, by comparing with spatially dense data collected as part of the DISCOVER-AQ campaign these data were measured by the NASA Langley Research Center airborne High Spectral Resolution Lidar (HSRL) and a network of 44 sun photometers (SP) spaced approximately 10 km apart. The HSRL instrument shows that AOD can vary by up to 0.2 within a single 10 km MODIS pixel, meaning that higher resolution satellite retrievals may help to characterize aerosol spatial distributions in this region. Different techniques for validating a high-resolution aerosol product against SP measurements are considered. Although the 10 km product is more statistically reliable than the 3 km product, the 3 km product still performs acceptably, with more than two-thirds of MODIS/SP collocations falling within the expected error envelope with high correlation (R > 0.90). The 3 km product can better resolve aerosol gradients and retrieve closer to clouds and shorelines than the 10 km product, but tends to show more significant noise especially in urban areas. This urban degradation is quantified using ancillary land cover data. Overall, we show that the MODIS 3 km product adds new information to the existing set of satellite derived aerosol products and validates well over the region, but due to noise and problems in urban areas, should be treated with some degree of caution.

  17. Variations in Km(CO2) of Ribulose-1,5-bisphosphate Carboxylase among Grasses

    PubMed Central

    Yeoh, Hock-Hin; Badger, Murray R.; Watson, Leslie

    1980-01-01

    A survey of the Km(CO2) values of ribulose-1,5-bisphosphate carboxylase from 60 grass species shows that enzyme from C3 grasses consistently exhibits lower Km(CO2) than does that from C4 grasses. Systematically ordered variation in Km(CO2) of ribulose-1,5-bisphosphate carboxylases from C3 and C4 grasses is also apparent and, among C4 grasses, this shows some correlation with C4 types. PMID:16661586

  18. Running Performance, Nationality, Sex and Age in 10km, Half-marathon, Marathon and 100km Ultra-marathon IAAF 1999-2015.

    PubMed

    Nikolaidis, Pantelis T; Onywera, Vincent O; Knechtle, Beat

    2016-10-13

    The aim of the present study was to examine the performance of the world's best runners in 10km, half-marathon, marathon and 100km by age, sex and nationality during 1999-2015 using data from International Association of Athletics Federations (IAAF). A total of 38,895 runners (17,136 women and 21,759 men) were considered with 2,594 (1,360 women and 1,234 male) in 10km, 11,595 (5,225 women and 6,370 male) in half-marathon, 23,973 (10,208 women and 13,765 male) in marathon and 733 (343 women and 390 male) in 100km. Most of the runners in 10km (women 40%, men 67%) and half-marathon (women 30%, men 57%) were Kenyans. In marathon, most female and male runners were Ethiopians (women 17%, men 14%) and Kenyans (women 15%, men 43%), respectively. In 100km, most runners were Japanese (20% in women and men). Women were older than men in 10km (32.0±6.0 versus 25.3±4.3 years, p<0.001), half-marathon (27.5±4.7 versus 25.9±4.1 years, p<0.001) and marathon (29.5±5.5 versus 29.1±4.3 years, p<0.001), but not in 100km (36.6±6.1 versus 35.9±5.5 years, p=0.097). Men were faster than women in 10km (28:04±0:17 versus 32:08±0.31 min:sec, p<0.001), half-marathon (1:01:58±0:00:52 versus 1:11:21±0:01:18 h:min:sec, p<0.001), marathon (2:13:42±0:03:01 versus 2:35:04±0:05:21 h:min:s, p<0.001), and 100km (6:48:01±0:11:29 versus 7:53:51±0:16:37 h:min:sec, p<0.001). East-Africans were not the fastest compared to athletes originating from other countries where only Ethiopian men were faster than all other men in marathon. In summary, (i) most runners were from Kenya and Ethiopia in 10km, half-marathon and marathon, but from Japan and Russia in 100km, (ii) women were older than men in all distances except 100km, (iii) men were the fastest in all distances, and (iii) Ethiopian men were faster than all other men in marathon.

  19. Potential of KM3NeT to observe galactic neutrino point-like sources

    NASA Astrophysics Data System (ADS)

    Trovato, Agata

    2016-07-01

    KM3NeT (http://www.km3net.org">http://www.km3net.org) will be the next-generation cubic-kilometre-scale neutrino telescope to be installed in the depths of the Mediterranean Sea. This location will allow for surveying the Galactic Centre, most of the Galactic Plane as well as a large part of the sky. We report KM3NeT discovery potential for the SNR RXJ1713.7-3946 and the PWN Vela X and its sensitivity to point-like sources with an E-2 spectrum.

  20. Protective effect of kombucha mushroom (KM) tea on phenol-induced cytotoxicity in albino mice.

    PubMed

    Yapar, Kursad; Cavusoglu, Kultigin; Oruc, Ertan; Yalcin, Emine

    2010-09-01

    The present study was carried out to evaluate the protective role of kombucha mushroom (KM) tea on cytotoxicity induced by phenol (PHE) in mice. We used weight gain and micronucleus (MN) frequency as indicators of cytotoxicity and supported these parameters with pathological findings. The animals were randomly divided into seven groups: (Group I) only tap water (Group II) 1000 microl kg(-1) b. wt KM-tea, (Group III) 35 mg kg(-1) body wt. PHE (Group IV) 35 mg kg(-1) body wt. PHE + 250 microl kg(-1) b. wt KM-tea (Group V) 35 mg kg(-1) b. wt PHE + 500 microl kg(-1) b. wt KM-tea (Group VI) 35 mg kg(-1) b. wt PHE + 750 microl kg(-1) b. wt KM-tea, (Group VII) 35 mg kg(-1) b. wt PHE + 1000 microl kg(-1) b. wt KM-tea, for 20 consecutive days by oral gavage. The results indicated that all KM-tea supplemented mice showed a lower MN frequency than erythrocytes in only PHE-treated group. There was an observable regression on account of lesions in tissues of mice supplemented with different doses of KM-tea in histopathological observations. In conclusion, the KM-tea supplementation decreases cytotoxicity induced by PHE and its protective role is dose-dependent.

  1. Spray Gun With Constant Mixing Ratio

    NASA Technical Reports Server (NTRS)

    Simpson, William G.

    1987-01-01

    Conceptual mechanism mounted in handle of spray gun maintains constant ratio between volumetric flow rates in two channels leading to spray head. With mechanism, possible to keep flow ratio near 1:1 (or another desired ratio) over range of temperatures, orifice or channel sizes, or clogging conditions.

  2. Variations of the Solar Constant. [conference

    NASA Technical Reports Server (NTRS)

    Sofia, S. (Editor)

    1981-01-01

    The variations in data received from rocket-borne and balloon-borne instruments are discussed. Indirect techniques to measure and monitor the solar constant are presented. Emphasis is placed on the correlation of data from the Solar Maximum Mission and the Nimbus 7 satellites.

  3. Teaching Nanochemistry: Madelung Constants of Nanocrystals

    ERIC Educational Resources Information Center

    Baker, Mark D.; Baker, A. David

    2010-01-01

    The Madelung constants for binary ionic nanoparticles are determined. The computational method described here sums the Coulombic interactions of each ion in the particle without the use of partial charges commonly used for bulk materials. The results show size-dependent lattice energies. This is a useful concept in teaching how properties such as…

  4. Sensing Position With Approximately Constant Contact Force

    NASA Technical Reports Server (NTRS)

    Sturdevant, Jay

    1996-01-01

    Computer-controlled electromechanical system uses number of linear variable-differential transformers (LVDTs) to measure axial positions of selected points on surface of lens, mirror, or other precise optical component with high finish. Pressures applied to pneumatically driven LVDTs adjusted to maintain small, approximately constant contact forces as positions of LVDT tips vary.

  5. A tunable CMOS constant current source

    NASA Technical Reports Server (NTRS)

    Thelen, D.

    1991-01-01

    A constant current source has been designed which makes use of on chip electrically erasable memory to adjust the magnitude and temperature coefficient of the output current. The current source includes a voltage reference based on the difference between enhancement and depletion transistor threshold voltages. Accuracy is +/- 3% over the full range of power supply, process variations, and temperature using eight bits for tuning.

  6. Spectral curve fitting of dielectric constants

    NASA Astrophysics Data System (ADS)

    Ruzi, M.; Ennis, C.; Robertson, E. G.

    2017-01-01

    Optical constants are important properties governing the response of a material to incident light. It follows that they are often extracted from spectra measured by absorbance, transmittance or reflectance. One convenient method to obtain optical constants is by curve fitting. Here, model curves should satisfy Kramer-Kronig relations, and preferably can be expressed in closed form or easily calculable. In this study we use dielectric constants of three different molecular ices in the infrared region to evaluate four different model curves that are generally used for fitting optical constants: (1) the classical damped harmonic oscillator, (2) Voigt line shape, (3) Fourier series, and (4) the Triangular basis. Among these, only the classical damped harmonic oscillator model strictly satisfies the Kramer-Kronig relation. If considering the trade-off between accuracy and speed, Fourier series fitting is the best option when spectral bands are broad while for narrow peaks the classical damped harmonic oscillator and the Triangular basis fitting model are the best choice.

  7. Can compactifications solve the cosmological constant problem?

    SciTech Connect

    Hertzberg, Mark P.; Masoumi, Ali

    2016-06-30

    Recently, there have been claims in the literature that the cosmological constant problem can be dynamically solved by specific compactifications of gravity from higher-dimensional toy models. These models have the novel feature that in the four-dimensional theory, the cosmological constant Λ is much smaller than the Planck density and in fact accumulates at Λ=0. Here we show that while these are very interesting models, they do not properly address the real cosmological constant problem. As we explain, the real problem is not simply to obtain Λ that is small in Planck units in a toy model, but to explain why Λ is much smaller than other mass scales (and combinations of scales) in the theory. Instead, in these toy models, all other particle mass scales have been either removed or sent to zero, thus ignoring the real problem. To this end, we provide a general argument that the included moduli masses are generically of order Hubble, so sending them to zero trivially sends the cosmological constant to zero. We also show that the fundamental Planck mass is being sent to zero, and so the central problem is trivially avoided by removing high energy physics altogether. On the other hand, by including various large mass scales from particle physics with a high fundamental Planck mass, one is faced with a real problem, whose only known solution involves accidental cancellations in a landscape.

  8. Unified Technical Concepts. Module 12: Time Constants.

    ERIC Educational Resources Information Center

    Technical Education Research Center, Waco, TX.

    This concept module on time constants is one of thirteen modules that provide a flexible, laboratory-based physics instructional package designed to meet the specialized needs of students in two-year, postsecondary technical schools. Each of the thirteen concept modules discusses a single physics concept and how it is applied to each energy…

  9. Damping constant estimation in magnetoresistive readers

    SciTech Connect

    Stankiewicz, Andrzej Hernandez, Stephanie

    2015-05-07

    The damping constant is a key design parameter in magnetic reader design. Its value can be derived from bulk or sheet film ferromagnetic resonance (FMR) line width. However, dynamics of nanodevices is usually defined by presence of non-uniform modes. It triggers new damping mechanisms and produces stronger damping than expected from traditional FMR. This work proposes a device-level technique for damping evaluation, based on time-domain analysis of thermally excited stochastic oscillations. The signal is collected using a high bandwidth oscilloscope, by direct probing of a biased reader. Recorded waveforms may contain different noise signals, but free layer FMR is usually a dominating one. The autocorrelation function is a reflection of the damped oscillation curve, averaging out stochastic contributions. The damped oscillator formula is fitted to autocorrelation data, producing resonance frequency and damping constant values. Restricting lag range allows for mitigation of the impact of other phenomena (e.g., reader instability) on the damping constant. For a micromagnetically modeled reader, the technique proves to be much more accurate than the stochastic FMR line width approach. Application to actual reader waveforms yields a damping constant of ∼0.03.

  10. Man's Size in Terms of Fundamental Constants.

    ERIC Educational Resources Information Center

    Press, William H.

    1980-01-01

    Reviews calculations that derive an order of magnitude expression for the size of man in terms of fundamental constants, assuming that man satifies these three properties: he is made of complicated molecules; he requires an atmosphere which is not hydrogen and helium; he is as large as possible. (CS)

  11. The Elastic Constants for Wrought Aluminum Alloys

    NASA Technical Reports Server (NTRS)

    Templin, R L; Hartmann, E C

    1945-01-01

    There are several constants which have been devised as numerical representations of the behavior of metals under the action of loadings which stress the metal within the range of elastic action. Some of these constants, such as Young's modulus of elasticity in tension and compression, shearing modulus of elasticity, and Poisson's ratio, are regularly used in engineering calculations. Precise tests and experience indicate that these elastic constants are practically unaffected by many of the factors which influence the other mechanical properties of materials and that a few careful determinations under properly controlled conditions are more useful and reliable than many determinations made under less favorable conditions. It is the purpose of this paper to outline the methods employed by the Aluminum Research Laboratories for the determination of some of these elastic constants, to list the values that have been determined for some of the wrought aluminum alloys, and to indicate the variations in the values that may be expected for some of the commercial products of these alloys.

  12. Constant capacitance in nanopores of carbon monoliths.

    PubMed

    García-Gómez, Alejandra; Moreno-Fernández, Gelines; Lobato, Belén; Centeno, Teresa A

    2015-06-28

    The results obtained for binder-free electrodes made of carbon monoliths with narrow micropore size distributions confirm that the specific capacitance in the electrolyte (C2H5)4NBF4/acetonitrile does not depend significantly on the micropore size and support the foregoing constant result of 0.094 ± 0.011 F m(-2).

  13. Tuning the Binding Affinities and Reversion Kinetics of a Light Inducible Dimer Allows Control of Transmembrane Protein Localization.

    PubMed

    Zimmerman, Seth P; Hallett, Ryan A; Bourke, Ashley M; Bear, James E; Kennedy, Matthew J; Kuhlman, Brian

    2016-09-20

    Inducible dimers are powerful tools for controlling biological processes through colocalizing signaling molecules. To be effective, an inducible system should have a dissociation constant in the "off" state that is greater (i.e., weaker affinity) than the concentrations of the molecules that are being controlled, and in the "on" state a dissociation constant that is less (i.e., stronger affinity) than the relevant protein concentrations. Here, we reengineer the interaction between the light inducible dimer, iLID, and its binding partner SspB, to better control proteins present at high effective concentrations (5-100 μM). iLID contains a light-oxygen-voltage (LOV) domain that undergoes a conformational change upon activation with blue light and exposes a peptide motif, ssrA, that binds to SspB. The new variant of the dimer system contains a single SspB point mutation (A58V), and displays a 42-fold change in binding affinity when activated with blue light (from 3 ± 2 μM to 125 ± 40 μM) and allows for light-activated colocalization of transmembrane proteins in neurons, where a higher affinity switch (0.8-47 μM) was less effective because more colocalization was seen in the dark. Additionally, with a point mutation in the LOV domain (N414L), we lengthened the reversion half-life of iLID. This expanded suite of light induced dimers increases the variety of cellular pathways that can be targeted with light.

  14. Nanoparticle multivalency counterbalances the ligand affinity loss upon PEGylation.

    PubMed

    Hennig, Robert; Pollinger, Klaus; Veser, Anika; Breunig, Miriam; Goepferich, Achim

    2014-11-28

    The conjugation of receptor ligands to shielded nanoparticles is a widely used strategy to precisely control nanoparticle-cell interactions. However, it is often overlooked that a ligand's affinity can be severely impaired by its attachment to the polyethylene glycol (PEG) chains that are frequently used to protect colloids from serum protein adsorption. Using the model ligand EXP3174, a small-molecule antagonist for the angiotensin II receptor type 1 (AT1R), we investigated the ligand's affinity before and after its PEGylation and when attached to PEGylated nanoparticles. The PEGylated ligand displayed a 580-fold decreased receptor affinity compared to the native ligand. Due to their multivalency, the nanoparticles regained a low nanomolar receptor affinity, which is in the range of the affinity of the native ligand. Moreover, a four orders of magnitude higher concentration of free ligand was required to displace PEGylated nanoparticles carrying EXP3174 from the receptor. On average, one nanoparticle was decorated with 11.2 ligand molecules, which led to a multivalent enhancement factor of 22.5 compared to the monovalent PEGylated ligand. The targeted nanoparticles specifically bound the AT1R and showed no interaction to receptor negative cells. Our study shows that the attachment of a small-molecule ligand to a PEG chain can severely affect its receptor affinity. Concomitantly, when the ligand is tethered to nanoparticles, the immense avidity greatly increases the ligand-receptor interaction. Based on our results, we highly recommend the affinity testing of receptor ligands before and after PEGylation to identify potent molecules for active nanoparticle targeting.

  15. Protein Complex Affinity Capture from Cryomilled Mammalian Cells.

    PubMed

    LaCava, John; Jiang, Hua; Rout, Michael P

    2016-12-09

    Affinity capture is an effective technique for isolating endogenous protein complexes for further study. When used in conjunction with an antibody, this technique is also frequently referred to as immunoprecipitation. Affinity capture can be applied in a bench-scale and in a high-throughput context. When coupled with protein mass spectrometry, affinity capture has proven to be a workhorse of interactome analysis. Although there are potentially many ways to execute the numerous steps involved, the following protocols implement our favored methods. Two features are distinctive: the use of cryomilled cell powder to produce cell extracts, and antibody-coupled paramagnetic beads as the affinity medium. In many cases, we have obtained superior results to those obtained with more conventional affinity capture practices. Cryomilling avoids numerous problems associated with other forms of cell breakage. It provides efficient breakage of the material, while avoiding denaturation issues associated with heating or foaming. It retains the native protein concentration up to the point of extraction, mitigating macromolecular dissociation. It reduces the time extracted proteins spend in solution, limiting deleterious enzymatic activities, and it may reduce the non-specific adsorption of proteins by the affinity medium. Micron-scale magnetic affinity media have become more commonplace over the last several years, increasingly replacing the traditional agarose- and Sepharose-based media. Primary benefits of magnetic media include typically lower non-specific protein adsorption; no size exclusion limit because protein complex binding occurs on the bead surface rather than within pores; and ease of manipulation and handling using magnets.

  16. Protein Complex Affinity Capture from Cryomilled Mammalian Cells

    PubMed Central

    LaCava, John; Jiang, Hua; Rout, Michael P.

    2016-01-01

    Affinity capture is an effective technique for isolating endogenous protein complexes for further study. When used in conjunction with an antibody, this technique is also frequently referred to as immunoprecipitation. Affinity capture can be applied in a bench-scale and in a high-throughput context. When coupled with protein mass spectrometry, affinity capture has proven to be a workhorse of interactome analysis. Although there are potentially many ways to execute the numerous steps involved, the following protocols implement our favored methods. Two features are distinctive: the use of cryomilled cell powder to produce cell extracts, and antibody-coupled paramagnetic beads as the affinity medium. In many cases, we have obtained superior results to those obtained with more conventional affinity capture practices. Cryomilling avoids numerous problems associated with other forms of cell breakage. It provides efficient breakage of the material, while avoiding denaturation issues associated with heating or foaming. It retains the native protein concentration up to the point of extraction, mitigating macromolecular dissociation. It reduces the time extracted proteins spend in solution, limiting deleterious enzymatic activities, and it may reduce the non-specific adsorption of proteins by the affinity medium. Micron-scale magnetic affinity media have become more commonplace over the last several years, increasingly replacing the traditional agarose- and Sepharose-based media. Primary benefits of magnetic media include typically lower non-specific protein adsorption; no size exclusion limit because protein complex binding occurs on the bead surface rather than within pores; and ease of manipulation and handling using magnets. PMID:28060343

  17. Characterization of the ER-Targeted Low Affinity Ca2+ Probe D4ER

    PubMed Central

    Greotti, Elisa; Wong, Andrea; Pozzan, Tullio; Pendin, Diana; Pizzo, Paola

    2016-01-01

    Calcium ion (Ca2+) is a ubiquitous intracellular messenger and changes in its concentration impact on nearly every aspect of cell life. Endoplasmic reticulum (ER) represents the major intracellular Ca2+ store and the free Ca2+ concentration ([Ca2+]) within its lumen ([Ca2+]ER) can reach levels higher than 1 mM. Several genetically-encoded ER-targeted Ca2+ sensors have been developed over the last years. However, most of them are non-ratiometric and, thus, their signal is difficult to calibrate in live cells and is affected by shifts in the focal plane and artifactual movements of the sample. On the other hand, existing ratiometric Ca2+ probes are plagued by different drawbacks, such as a double dissociation constant (Kd) for Ca2+, low dynamic range, and an affinity for the cation that is too high for the levels of [Ca2+] in the ER lumen. Here, we report the characterization of a recently generated ER-targeted, Förster resonance energy transfer (FRET)-based, Cameleon probe, named D4ER, characterized by suitable Ca2+ affinity and dynamic range for monitoring [Ca2+] variations within the ER. As an example, resting [Ca2+]ER have been evaluated in a known paradigm of altered ER Ca2+ homeostasis, i.e., in cells expressing a mutated form of the familial Alzheimer’s Disease-linked protein Presenilin 2 (PS2). The lower Ca2+ affinity of the D4ER probe, compared to that of the previously generated D1ER, allowed the detection of a conspicuous, more clear-cut, reduction in ER Ca2+ content in cells expressing mutated PS2, compared to controls. PMID:27598166

  18. Blood oxygen affinity increases during digestion in the South American rattlesnake, Crotalus durissus terrificus.

    PubMed

    Bovo, Rafael P; Fuga, Adriana; Micheli-Campbell, Mariana A; Carvalho, José E; Andrade, Denis V

    2015-08-01

    Digesting snakes experience massive increases in metabolism that can last for many days and are accompanied by adjustments in the oxygen transport cascade. Accordingly, we examined the oxygen-binding properties of the blood in the South American rattlesnake (Crotalus durissus terrificus) during fasting and 24 and 48h after the snakes have ingested a rodent meal corresponding to 15% (±2%) of its own body mass. In general, oxygen-hemoglobin (Hb-O2) affinity was significantly increased 24h post-feeding, and then returned toward fasting values within 48h post-feeding. Content of organic phosphates ([NTP] and [NTP]/[Hb]), hemoglobin cooperativity (Hill's n), and Bohr Effect (ΔlogP50/ΔpH) were not affected by feeding. The postprandial increase in Hb-O2 affinity in the South American rattlesnake can be almost entirely ascribed by the moderate alkaline tide that follows meal ingestion. In general, digesting snakes were able to regulate blood metabolites at quite constant levels (e.g., plasma osmolality, lactate, glucose, and total protein levels). The level of circulating lipids, however, was considerably increased, which may be related to their mobilization, since lipids are known to be incorporated by the enterocytes after snakes have fed. In conclusion, our results indicate that the exceptional metabolic increment exhibited by C. d. terrificus during meal digestion is entirely supported by the aerobic pathways and that among the attending cardiorespiratory adjustments, pulmonary Hb-O2 loading is likely improved due to the increment in blood O2 affinity.

  19. KW-3902, a selective high affinity antagonist for adenosine A1 receptors.

    PubMed Central

    Nonaka, H.; Ichimura, M.; Takeda, M.; Kanda, T.; Shimada, J.; Suzuki, F.; Kase, H.

    1996-01-01

    1. We demonstrate that 8-(noradamantan-3-yl)-1,3-dipropylxanthine (KW-3902) is a very potent and selective adenosine A1 receptor antagonist, assessed by radioligand binding and cyclic AMP response in cells. 2. In rat forebrain adenosine A1 receptors labelled with [3H]-cyclohexyladenosine (CHA), KW-3902 had a Ki value of 0.19 nM, whereas it showed a Ki value of 170 nM in rat striatal A2A receptors labelled with [3H]-2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamidoad enosine (CGS21680), indicating 890 fold A1 receptor selectivity versus the A2A receptor. KW-3902 at 10 microM showed no effect on recombinant rat A3 receptors expressed on CHO cells. 3. Saturation studies with [3H]-KW-3902 revealed that it bound with high affinity (Kd = 77 pM) and limited capacity (Bmax = 470 fmol mg-1 of protein) to a single class of recognition sites. A high positive correlation was observed between the pharmacological profile of adenosine ligands inhibiting the binding of [3H]-KW-3902 and that of [3H]-CHA. 4. KW-3902 showed potent A1 antagonism against the inhibition of forskolin-induced cyclic AMP accumulation in DDT1 MF-2 cells by the A1-selective agonist, cyclopentyladenosine with a dissociation constant (KB value) of 0.34 nM. KW-3902 antagonized 5'-N-ethylcarboxamidoadenosine-elicited cyclic AMP accumulation via A2B receptors with a KB value of 52 nM. 5. KW-3902 exhibited marked species-dependent differences in the binding affinities. The highest affinity was for the rat A1 receptor (ki = 0.19 nM) and these values for guinea-pig and dog A1 receptors were 1.3 and 10 nM, respectively. PMID:8732272

  20. Selection and affinity maturation of IgNAR variable domains targeting Plasmodium falciparum AMA1.

    PubMed

    Nuttall, Stewart D; Humberstone, Karen S; Krishnan, Usha V; Carmichael, Jennifer A; Doughty, Larissa; Hattarki, Meghan; Coley, Andrew M; Casey, Joanne L; Anders, Robin F; Foley, Michael; Irving, Robert A; Hudson, Peter J

    2004-04-01

    The new antigen receptor (IgNAR) is an antibody unique to sharks and consists of a disulphide-bonded dimer of two protein chains, each containing a single variable and five constant domains. The individual variable (V(NAR)) domains bind antigen independently, and are candidates for the smallest antibody-based immune recognition units. We have previously produced a library of V(NAR) domains with extensive variability in the CDR1 and CDR3 loops displayed on the surface of bacteriophage. Now, to test the efficacy of this library, and further explore the dynamics of V(NAR) antigen binding we have performed selection experiments against an infectious disease target, the malarial Apical Membrane Antigen-1 (AMA1) from Plasmodium falciparum. Two related V(NAR) clones were selected, characterized by long (16- and 18-residue) CDR3 loops. These recombinant V(NAR)s could be harvested at yields approaching 5mg/L of monomeric protein from the E. coli periplasm, and bound AMA1 with nanomolar affinities (K(D)= approximately 2 x 10(-7) M). One clone, designated 12Y-2, was affinity-matured by error prone PCR, resulting in several variants with mutations mapping to the CDR1 and CDR3 loops. The best of these variants showed approximately 10-fold enhanced affinity over 12Y-2 and was Plasmodium falciparum strain-specific. Importantly, we demonstrated that this monovalent V(NAR) co-localized with rabbit anti-AMA1 antisera on the surface of malarial parasites and thus may have utility in diagnostic applications.