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Sample records for affinity constants ka

  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. Determination of acid dissociation constants (pKa) of cephalosporin antibiotics: Computational and experimental approaches.

    PubMed

    Ribeiro, Alyson R; Schmidt, Torsten C

    2017-02-01

    Cefapirin (CEPA) and ceftiofur (CEF) are two examples of widely used veterinarian cephalosporins presenting multiple ionization centers. However, the acid dissociation constants (pKa) of CEF are missing and experimental data about CEPA are rare. The same is true for many cephalosporins, where available data are either incomplete or even wrong. Environmentally relevant biotic and abiotic processes depend primordially on the antibiotic pH-dependent speciation. Consequently, this physicochemical parameter should be reliable, including the correct ionization center identification. In this direction, two experimental techniques, potentiometry and spectrophotometry, along with two well-known pKa predictors, Marvin and ACD/Percepta, were used to study the macro dissociation constants of CEPA and CEF. Additionally, the experimental dissociation constants of 14 cephalosporins available in the literature were revised, compiled and compared with data obtained in silico. Only one value was determined experimentally for CEF (2.68 ± 0.05), which was associated to the carboxylic acid group deprotonation. For CEPA two values were obtained experimentally: 2.74 ± 0.01 for the carboxylic acid deprotonation and 5.13 ± 0.01 for the pyridinium ring deprotonation. In general, experimentally obtained values agree with the in silico predicted data (ACD/Percepta RMSE: 0.552 and Marvin RMSE: 0.706, n = 88). However, for cephalosporins having imine and aminothiazole groups structurally close, Marvin presented problems in pKa predictions. For the biological and environmental fate and effect discussion, it is important to recognize that CEPA and CEF, as well as many other cephalosporins, are present as anionic species in the biologic and environmentally relevant pH values of 6-7.5.

  5. 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.

  6. 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.

  7. 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

  8. Acidity Constant (pKa ) Calculation of Large Solvated Dye Molecules: Evaluation of Two Advanced Molecular Dynamics Methods.

    PubMed

    De Meyer, Thierry; Ensing, Bernd; Rogge, Sven M J; De Clerck, Karen; Meijer, Evert Jan; Van Speybroeck, Veronique

    2016-11-04

    pH-Sensitive dyes are increasingly applied on polymer substrates for the creation of novel sensor materials. Recently, these dye molecules were modified to form a covalent bond with the polymer host. This had a large influence on the pH-sensitive properties, in particular on the acidity constant (pKa ). Obtaining molecular control over the factors that influence the pKa value is mandatory for the future intelligent design of sensor materials. Herein, we show that advanced molecular dynamics (MD) methods have reached the level at which the pKa values of large solvated dye molecules can be predicted with high accuracy. Two MD methods were used in this work: steered or restrained MD and the insertion/deletion scheme. Both were first calibrated on a set of phenol derivatives and afterwards applied to the dye molecule bromothymol blue. Excellent agreement with experimental values was obtained, which opens perspectives for using these methods for designing dye molecules.

  9. Determining Partition Coefficient (Log P), Distribution Coefficient (Log D) and Ionization Constant (pKa) in Early Drug Discovery.

    PubMed

    Bharate, Sonali S; Kumar, Vikas; Vishwakarma, Ram A

    2016-01-01

    An early prediction of physicochemical properties is highly desirable during drug discovery to find out a viable lead candidate. Although there are several methods available to determine partition coefficient (log P), distribution coefficient (log D) and ionization constant (pKa), none of them involves simple and fixed, miniaturized protocols for diverse set of compounds. Therefore, it is necessary to establish simple, uniform and medium-throughput protocols requiring small sample quantities for the determination of these physicochemical properties. Log P and log D were determined by shake flask method, wherein, the compound was partitioned between presaturated noctanol and water phase (water/PBS pH 7.4) and the concentration of compound in each phase was determined by HPLC. The pKa determination made use of UV spectrophotometric analysis in a 96-well microtiter plate containing a series of aqueous buffers ranging from pH 1.0 to 13.0. The medium-throughput miniaturized protocols described herein, for determination of log P, log D and pKa, are straightforward to set up and require very small quantities of sample (< 5 mg for all three properties). All established protocols were validated using diverse set of compounds.

  10. 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.

  11. Application of chemometrics in determination of the acid dissociation constants (pKa) of several benzodiazepine derivatives as poorly soluble drugs in the presence of ionic surfactants.

    PubMed

    Shayesteh, Tavakol Heidary; Radmehr, Moojan; Khajavi, Farzad; Mahjub, Reza

    2015-03-10

    In this study, the acid dissociation constants (pKa) of some benzodiazepine derivatives including chlordiazepoxide, clonazepam, lorazepam, and oxazepam in aqueous micellar solution were determined spectrophotometrically at an ionic strength of 0.1M at 25°C. The effect of cetyl trimethylammonium bromide (CTAB) as a cationic and sodium n-dodecyl sulfate(SDS) as an anionic surfactant on the absorption spectra of benzodiazepine drugs at different pH values were studied. The acidity constants of all related species are estimated by considering the surfactant concept and the application of chemometric methods using the whole spectral fitting of the collected data to an established factor analysis model. DATAN® software (Ver. 5.0, Multid Analyses AB, and Goteborg, Sweden) was applied to determine the acidity constants. In this study, a simple and fast method to determine the ionization constant (pKa) of poorly soluble drugs was developed using surfactants. The acidity constant (i.e. pKa) for chlordiazepoxide, clonazepam, lorazepam, and oxazepam were reported as 4.62, pKa1 value of 1.52 and pKa2 value of 10.51, pKa1 value of 1.53 and pKa2 value of 10.92 and pKa1 value 1.63 and pKa2 value of 11.21 respectively. The results showed that the peak values in the spectrophotometric absorption spectra of drugs are influenced by the presence of anionic and cationic surfactants. According to the results, by changing the SDS concentration from 0 to 0.05M, the pKa of chlordiazepoxide was increased to 5.9, the pKa1 of lorazepam was decreased to 0.1 while the pKa2 was increased to 11.5. Increase in SDS concentration has not shown significant alteration in pKa of clonazepam and oxazepam. Results indicate that by Changing the CTAB concentration from 0 to 0.05M, the pKa of chlordiazepoxide was reduced to 4.4, the pKa1 of clonazepam was decreased to 0.1 and the pKa2 was decreased to 9.1, the pKa1 of lorazepam was decreased to 0.4 and the pKa2 was decreased to 9.4, the pKa1 of oxazepam was

  12. 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.

  13. 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

  14. 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.

  15. 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).

  16. 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.

  17. 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.

  18. 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).

  19. Determination of pKa and Hydration Constants for a Series of α-Keto-Carboxylic Acids Using Nuclear Magnetic Resonance Spectrometry.

    PubMed

    Lopalco, Antonio; Douglas, Justin; Denora, Nunzio; Stella, Valentino J

    2016-02-01

    The determination of the acid-base dissociation constants, and thus the pKa values, of α-keto acids such as pyruvic acid is complex because of the existence of these acids in their hydrated and nonhydrated or oxo state. Equilibria involved in the hydration and dehydration of the α-keto group of pyruvic acid and three other α-keto acids, 3-methyl-2-oxobutanoic acid, 4-methyl-2-oxopentanoic acid, and 2-oxo-2-phenylacetic acid, were investigated by proton and carbon nuclear magnetic resonance spectrometry, at constant ionic strength, 0.15, and 25 °C. Dissociation constants for the oxo (pKa(oxo)) and hydrated (pKa(hyd)) acids of each compound were estimated from the change in the degree of hydration with changes in pH and directly from the changes in chemical shifts of various hydrogen and carbons nuclei with pH. α-Keto acids showed greater hydration in their acidic forms than their carboxylate forms. The degree of hydration was sensitive to steric and electronic/resonance factors. As expected, the oxo forms of the acids were stronger acids compared with their hydrated analogs, and their dissociation constants were also sensitive to steric and electronic factors.

  20. Determination of the dissociation constants (pKa) of secondary and tertiary amines in organic media by capillary electrophoresis and their role in the electrophoretic mobility order inversion.

    PubMed

    Cantu, Marcelo Delmar; Hillebranda, Sandro; Carrilho, Emanuel

    2005-03-11

    Non-aqueous capillary electrophoresis (NACE) may provide a selectivity enhancement in separations since the analyte dissociation constants (pKa) in organic media are different from those in aqueous solutions. In this work, we have studied the inversion in mobility order observed in the separation of tertiary (imipramine (IMI) and amitryptiline (AMI)) and secondary amines (desipramine (DES) and nortryptiline (NOR)) in water, methanol, and acetonitrile. We have determined the pKa values in those solvents and the variation of dissociation constants with the temperature. From these data, and applying the Van't Hoff equation, we have calculated the thermodynamic parameters deltaH and deltaS. The pKa values found in methanol for DES, NOR, IMI, and AMI were 10.80, 10.79, 10.38, and 10.33, respectively. On the other hand, in acetonitrile an opposite relation was found since the values were 20.60, 20.67, 20.74, and 20.81 for DES, NOR, IMI, and AMI. This is the reason why a migration order inversion is observed in NACE for these solvents. The thermodynamic parameters were evaluated and presented a tendency that can be correlated with that observed for pKa values.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Determination of pKa and Hydration Constants for a Series of α-Keto-Carboxylic Acids Using Nuclear Magnetic Resonance Spectrometry

    PubMed Central

    Lopalco, Antonio; Douglas, Justin; Denora, Nunzio; Stella, Valentino J.

    2015-01-01

    The determination of the acid-base dissociation constants, and thus the pKa values, of α-keto acids such as pyruvic acid is complex due to the existence of these acids in their hydrated and non-hydrated or oxo-state. Equilibria involved in the hydration and dehydration of the α-keto group of pyruvic acid and three other α-keto acids, 3-methyl-2-oxobutanoic acid, 4-methyl-2-oxopentanoic acid, and 2-oxo-2-phenylacetic acid, were investigated by proton and carbon nuclear magnetic resonance spectrometry, NMR, at constant ionic strength, 0.15, and 25°C. Dissociation constants for the oxo (pKaoxo) and hydrated (pKahyd) acids of each compound were estimated from the change in the degree of hydration with changes in pH and directly from the changes in chemical shifts of various hydrogen and carbons nuclei with pH. α-Keto acids showed greater hydration in their acidic forms than their carboxylate forms. The degree of hydration was sensitive to steric and electronic/resonance factors. As expected, the oxo forms of the acids were stronger acids compared with their hydrated analogs, and their dissociation constants were also sensitive to steric and electronic factors. PMID:26149194

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. Accurate Three States Model for Amino Acids with Two Chemically Coupled Titrating Sites in Explicit Solvent Atomistic Constant pH Simulations and pKa Calculations.

    PubMed

    Dobrev, Plamen; Donnini, Serena; Groenhof, Gerrit; Grubmüller, Helmut

    2017-01-10

    Correct protonation of titratable groups in biomolecules is crucial for their accurate description by molecular dynamics simulations. In the context of constant pH simulations, an additional protonation degree of freedom is introduced for each titratable site, allowing the protonation state to change dynamically with changing structure or electrostatics. Here, we extend previous approaches for an accurate description of chemically coupled titrating sites. A second reaction coordinate is used to switch between two tautomeric states of an amino acid with chemically coupled titratable sites, such as aspartate (Asp), glutamate (Glu), and histidine (His). To this aim, we test a scheme involving three protonation states. To facilitate charge neutrality as required for periodic boundary conditions and Particle Mesh Ewald (PME) electrostatics, titration of each respective amino acid is coupled to a "water" molecule that is charged in the opposite direction. Additionally, a force field modification for Amber99sb is introduced and tested for the description of carboxyl group protonation. Our three states model is tested by titration simulations of Asp, Glu, and His, yielding a good agreement, reproducing the correct geometry of the groups in their different protonation forms. We further show that the ion concentration change due to the neutralizing "water" molecules does not significantly affect the protonation free energies of the titratable groups, suggesting that the three states model provides a good description of biomolecular dynamics at constant pH.

  19. 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.

  20. p Ka calculation for monoprotonated bipiperidine, bimorpholine and their derivatives in H 2O and MeCN

    NASA Astrophysics Data System (ADS)

    Uudsemaa, Merle; Kanger, Tõnis; Lopp, Margus; Tamm, Toomas

    2010-01-01

    Density-functional theory has been used to estimate the proton affinity (PA) and the acidity constants p Ka of monoprotonated bipiperidine, bimorpholine and their derivatives in water and in acetonitrile (MeCN). Five different conformations of derivatives of bimorpholine and bipiperidine were explored. Monoprotonated bimorpholine has lower p Ka values (9.1 in H 2O and 17.4 in MeCN) than monoprotonated bipiperidine (12.8 in H 2O and 21.0 in MeCN). For N-iPr derivatives of bimorpholine, the p Ka values are 8.8 in H 2O and 17.0 in MeCN and for N-iPr derivatives of bipiperidine the values are 12.5 in H 2O and 20.8 in MeCN.

  1. 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.

  2. Development of Monopole Interaction Models for Ionic Compounds. Part I: Estimation of Aqueous Henry’s Law Constants for Ions and Gas Phase pKa Values for Acidic Compounds

    EPA Science Inventory

    The SPARC (SPARC Performs Automated Reasoning in Chemistry) physicochemical mechanistic models for neutral compounds have been extended to estimate Henry’s Law Constant (HLC) for charged species by incorporating ionic electrostatic interaction models. Combinations of absolute aq...

  3. Assigning the pKa's of Polyprotic Acids.

    ERIC Educational Resources Information Center

    Bodner, George M.

    1986-01-01

    Discusses (1) polyproptic acids for which the difference between K-a's is large; (2) the Henderson-Hasselbach equation; (3) polyprotic acids for which the difference between K-a's is small; (4) analysis of microscopic dissociation constants for cysteine; and (5) analysis of pK-a data. (JN)

  4. 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.

  5. Arginine: Its pKa value revisited

    PubMed Central

    Fitch, Carolyn A; Platzer, Gerald; Okon, Mark; Garcia-Moreno E, Bertrand; McIntosh, Lawrence P

    2015-01-01

    Using complementary approaches of potentiometry and NMR spectroscopy, we have determined that the equilibrium acid dissociation constant (pKa value) of the arginine guanidinium group is 13.8 ± 0.1. This is substantially higher than that of ∼12 often used in structure-based electrostatics calculations and cited in biochemistry textbooks. The revised intrinsic pKa value helps explains why arginine side chains in proteins are always predominantly charged, even at pH values as great as 10. The high pKa value also reinforces the observation that arginine side chains are invariably protonated under physiological conditions of near neutral pH. This occurs even when the guanidinium moiety is buried in a hydrophobic micro-environment, such as that inside a protein or a lipid membrane, thought to be incompatible with the presence of a charged group. PMID:25808204

  6. Arginine: Its pKa value revisited.

    PubMed

    Fitch, Carolyn A; Platzer, Gerald; Okon, Mark; Garcia-Moreno, Bertrand E; McIntosh, Lawrence P

    2015-05-01

    Using complementary approaches of potentiometry and NMR spectroscopy, we have determined that the equilibrium acid dissociation constant (pKa value) of the arginine guanidinium group is 13.8 ± 0.1. This is substantially higher than that of ∼ 12 often used in structure-based electrostatics calculations and cited in biochemistry textbooks. The revised intrinsic pKa value helps explains why arginine side chains in proteins are always predominantly charged, even at pH values as great as 10. The high pKa value also reinforces the observation that arginine side chains are invariably protonated under physiological conditions of near neutral pH. This occurs even when the guanidinium moiety is buried in a hydrophobic micro-environment, such as that inside a protein or a lipid membrane, thought to be incompatible with the presence of a charged group.

  7. 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.

  8. Determination of pKa values of organic bases in aqueous acetonitrile solutions using capillary electrophoresis.

    PubMed

    Buckenmaier, Stephan M C; McCalley, David V; Euerby, Melvin R

    2003-07-04

    Capillary electrophoresis (CE) was used for the determination of ionisation constants (pKa) of a variety of organic bases in aqueous acetonitrile solutions over the range 0-60% (v/v) acetonitrile. These bases are used as test compounds in HPLC column evaluation, thus knowledge of their pKa in hydro-organic solutions is useful. The base pKa decreased with acetonitrile concentration and significant shifts from the aqueous pKa (up to -0.8) were found using 60% acetonitrile. The CE application was confirmed to be very suitable for fast and accurate pKa measurement in aqueous organic solutions.

  9. Determination of pKa of felodipine using UV-Visible spectroscopy

    NASA Astrophysics Data System (ADS)

    Pandey, M. M.; Jaipal, A.; Kumar, A.; Malik, R.; Charde, S. Y.

    2013-11-01

    In the present study, for the first time, experimental pKa value of felodipine is reported. Dissociation constant, pKa, is one of the very important physicochemical properties of drugs. It is of paramount significance from the perspective of pharmaceutical analysis and dosage form design. The method used for the pKa determination of felodipine was essentially a UV-Visible spectrophotometric method. The spectrophotometric method for the pKa determination was opted by acknowledging the established fact that spectrophotometric determination of pKa produces most precise values. The pKa of felodipine was found to be 5.07. Furthermore, the ruggedness of the determined value is also validated in this study in order to produce exact pKa of the felodipine.

  10. Influence of affinity on antibody determination in microtiter ELISA systems

    SciTech Connect

    Peterman, J.H.; Voss, E.W. Jr.; Butler, J.E.

    1986-03-01

    Theoretically, all immunoassays are affinity (Ka) dependent when the product of the antibody (Ab) Ka and the free epitope concentration is less than 10. Thus, the degree of dependence on Ka depends on the concentration of available antigen in the system. The authors examined the binding of /sup 125/I-anti-fluorescein (a-FLU) monoclonal antibodies of different affinities to FLU-gelatin adsorbed on Immunlon 2 microtiter plates. Data obtained were in general agreement with our theoretical predictions; the percent of /sup 125/I-a-FLU which bound correlated with Ka, as did the shape of the titration curves. Measurement of 5 a-FLU monoclonals by the ELISA showed that the determination of Ab concentrations depends on the FLU-gelatin concentration, epitope density, and on the relationship between the Kas of test samples and the reference standard Ab preparation. Thus the ELISA is Ka dependent and should not be used routinely to estimate the absolute amount to Ab in unknown samples. However, the Ka dependency of the ELISA might provide a convenient assay for the estimation of the relative functional Ka (rfKa) of antibody preparations.

  11. Ka-band study: 1988

    NASA Technical Reports Server (NTRS)

    Layland, J. W.; Horttor, R. L.; Clauss, R. C.; Wilcher, J. H.; Wallace, R. J.; Mudgway, D. J.

    1989-01-01

    The Ka-band study team was chartered in late 1987 to bring together all the planning elements for establishing 32 GHz (Ka-band) as the primary downlink frequency for deep-space operation, and to provide a stable baseline from which to pursue that development. This article summarizes the results of that study at its conclusion in mid-1988, and corresponds to material presented to NASA's Office of Space Operations on July 14, 1988. For a variety of reasons, Ka-band is the right next major step in deep-space communications. It offers improved radio metric accuracy through reduced plasma sensitivity and increased bandwidth. Because of these improvements, it offers the opportunity to reduce costs in the flight radio system or in the DSN by allocating part of the overall benefits of Ka-band to this cost reduction. A mission scenario is being planned that can drive at least two and possibly all three of the DSN subnets to provide a Ka-band downlink capability by the turn of the century. The implementation scenario devised by the study team is believed to be feasible within reasonable resource expectations, and capable of providing the needed upgrade as a natural follow-on to the technology development which is already underway.

  12. Exploring binding affinity of oxaliplatin and carboplatin, to nucleoprotein structure of chromatin: spectroscopic study and histone proteins as a target.

    PubMed

    Soori, Hosna; Rabbani-Chadegani, Azra; Davoodi, Jamshid

    2015-01-07

    Platinum drugs are potent chemotherapeutic agents widely used in cancer therapy. They exert their biological activity by binding to DNA, producing DNA adducts; however, in the cell nucleus, DNA is complexed with histone proteins into a nucleoprotein structure known as chromatin. The aim of this study was to explore the binding affinity of oxaliplatin and carboplatin to chromatin using spectroscopic as well as thermal denaturation and equilibrium dialysis techniques. The results showed that the drugs quenched with chromophores of chromatin and the quenching effect for oxaliplatin (Ksv = 3.156) was higher than carboplatin (Ksv = 0.28). The binding of the drugs exhibited hypochromicity both in thermal denaturation profiles and UV absorbance at 210 nm. The binding was positive cooperation with spontaneous reaction and oxaliplatin (Ka = 5.3 × 10(3) M(-1), n = 1.7) exhibited higher binding constant and number of binding sites than carboplatin (Ka = 0.33 × 10(3) M(-1), n = 1.0) upon binding to chromatin. Also secondary structure of chromatin proteins was altered upon drugs binding. It is concluded that oxaliplatin represents higher binding affinity to chromatin compared to carboplatin. In chromatin where DNA is compacted into nucleosomes structure with histones, the affinity of the platinated drugs is reduced and histone proteins may play a fundamental role in this binding process.

  13. Benchmarking pKa prediction

    PubMed Central

    Davies, Matthew N; Toseland, Christopher P; Moss, David S; Flower, Darren R

    2006-01-01

    Background pKa values are a measure of the protonation of ionizable groups in proteins. Ionizable groups are involved in intra-protein, protein-solvent and protein-ligand interactions as well as solubility, protein folding and catalytic activity. The pKa shift of a group from its intrinsic value is determined by the perturbation of the residue by the environment and can be calculated from three-dimensional structural data. Results Here we use a large dataset of experimentally-determined pKas to analyse the performance of different prediction techniques. Our work provides a benchmark of available software implementations: MCCE, MEAD, PROPKA and UHBD. Combinatorial and regression analysis is also used in an attempt to find a consensus approach towards pKa prediction. The tendency of individual programs to over- or underpredict the pKa value is related to the underlying methodology of the individual programs. Conclusion Overall, PROPKA is more accurate than the other three programs. Key to developing accurate predictive software will be a complete sampling of conformations accessible to protein structures. PMID:16749919

  14. 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)

  15. Purification of anti-MUC1 antibodies by peptide mimotope affinity chromatography using peptides derived from a polyvalent phage display library.

    PubMed

    Smith, Richard G; Missailidis, Sotiris; Price, Michael R

    2002-01-05

    A polyvalent, lytic phage display system (T7Select415-1b) displaying a random peptide library has been investigated for its ability to discover novel mimotopes reactive with the therapeutic monoclonal antibody C595. Sequence analysis of enriched phage lead to the identification of a predominant sequence RNREAPRGKICS, and two other consensus sequences RXXP and RXP. The novel synthetic peptide RNREAPRGKICS was linked to beaded agarose and the performance as a mimotope affinity chromatography matrix evaluated. Antibody purified using the novel matrix was found to be of higher specific reactivity than antibody purified using the conventional epitope matrix (peptide APDTRPAPG). The RNREAPRGKICS peptide binding to C595 demonstrated a higher equilibrium association constant (K(A)=0.75 x 10(6)) than the epitope peptide (K(A)=0.16 x 10(6)). Circular dichroism showed that the novel peptide had a more highly ordered structure at 4 degrees C and room temperature, than the epitope peptide.

  16. EFFECTIVE ACIDITY CONSTANT BEHAVIOR NEAR ZERO CHARGE CONDITIONS

    EPA Science Inventory

    Surface site (>SOH group) acidity reactions require expressions of the form: Ka = [>SOHn-1(z-1)]aH+EXP(-DG/RT)/[>SOHnz] (where all variables have their usual meaning). One can rearrange this expression to generate an effective acidity constant historically defined as: Qa = Ka...

  17. 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.

  18. Analysis of Multi-Site Drug-Protein Interactions by High-Performance Affinity Chromatography: Binding by Glimepiride to Normal or Glycated Human Serum Albumin

    PubMed Central

    Matsuda, Ryan; Li, Zhao; Zheng, Xiwei; Hage, David S.

    2015-01-01

    High-performance affinity chromatography (HPAC) was used in a variety of formats to examine multi-site interactions between glimepiride, a third-generation sulfonylurea drug, and normal or in vitro glycated forms of the transport protein human serum albumin (HSA). Frontal analysis revealed that glimepiride interacts with normal HSA and glycated HSA at a group of high affinity sites (association equilibrium constant, or Ka, 9.2–11.8 × 105 M−1 at pH 7.4 and 37°C) and a group of lower affinity regions (Ka, 5.9–16.2 × 103 M−1). Zonal elution competition studies were designed and carried out in both normal- and reversed-role formats to investigate the binding by this drug at specific sites. These experiments indicated that glimepiride was interacting at both Sudlow sites I and II. Allosteric effects were also noted with R-warfarin at Sudlow site I and with tamoxifen at the tamoxifen site on HSA. The binding at Sudlow site I had a 2.1- to 2.3-fold increase in affinity in going from normal HSA to the glycated samples of HSA. There was no significant change in the affinity for glimepiride at Sudlow site II in going from normal HSA to a moderately glycated sample of HSA, but a slight decrease in affinity was seen in going to a more highly glycated HSA sample. These results demonstrated how various HPAC-based methods can be used to profile and characterize multi-site binding by a drug such as glimepiride to a protein and its modified forms. The information obtained from this study should be useful in providing a better understanding of how drug-protein binding may be affected by glycation and of how separation and analysis methods based on HPAC can be employed to study systems with complex interactions or that involve modified proteins. PMID:26189669

  19. 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.

  20. Ka-band MMIC subarray technology program (Ka-Mist)

    NASA Technical Reports Server (NTRS)

    Pottenger, Warren

    1995-01-01

    The broad objective of this program was to demonstrate a proof of concept insertion of Monolithic Microwave Integrated Circuit (MMIC) device technology into an innovative (tile architecture) active phased array antenna application supporting advanced EHF communication systems. Ka-band MMIC arrays have long been considered as having high potential for increasing the capability of space, aircraft, and land mobile communication systems in terms of scan performance, data rate, link margin, and flexibility while offering a significant reduction in size, weight, and power consumption. Insertion of MMIC technology into antenna systems, particularly at millimeter wave frequencies using low power and low noise amplifiers in close proximity to the radiating elements, offers a significant improvement in the array transmit efficiency, receive system noise figure, and overall array reliability. Application of active array technology also leads to the use of advanced beamforming techniques that can improve beam agility, diversity, and adaptivity to complex signal environments.

  1. Ka-band MMIC subarray technology program (Ka-Mist)

    NASA Astrophysics Data System (ADS)

    Pottenger, Warren

    1995-06-01

    The broad objective of this program was to demonstrate a proof of concept insertion of Monolithic Microwave Integrated Circuit (MMIC) device technology into an innovative (tile architecture) active phased array antenna application supporting advanced EHF communication systems. Ka-band MMIC arrays have long been considered as having high potential for increasing the capability of space, aircraft, and land mobile communication systems in terms of scan performance, data rate, link margin, and flexibility while offering a significant reduction in size, weight, and power consumption. Insertion of MMIC technology into antenna systems, particularly at millimeter wave frequencies using low power and low noise amplifiers in close proximity to the radiating elements, offers a significant improvement in the array transmit efficiency, receive system noise figure, and overall array reliability. Application of active array technology also leads to the use of advanced beamforming techniques that can improve beam agility, diversity, and adaptivity to complex signal environments.

  2. Simultaneous high-throughput determination of interaction kinetics for drugs and cyclodextrins by high performance affinity chromatography with mass spectrometry detection.

    PubMed

    Wang, Caifen; Wang, Xiaobo; Xu, Xiaonan; Liu, Botao; Xu, Xu; Sun, Lixin; Li, Haiyan; Zhang, Jiwen

    2016-02-25

    The individual determination of the apparent dissociation rate constant (kd,app) using high performance affinity chromatography (HPAC) is a tedious process requiring numerous separate tests and massive data fitting, unable to provide the apparent association rate constant (ka) and equilibrium binding constant (Ka). In this study, a HPAC with mass spectrometry detection (HPAC-MS/MS) was employed to determine the drug-cyclodextrin (CD) interaction kinetics with low sample loading quantity (<10 ng per injection for single compound) and high-throughput yield as twenty drugs determined in one injection. The kd,app measured by HPAC-MS/MS approach were 0.89 ± 0.07, 4.34 ± 0.01, 1.48 ± 0.01 and 7.77 ± 0.04 s(-1) for ketoprofen, trimethoprim, indapamide and acetaminophen, with kd,app for acetaminophen consistent with that from the HPAC method with UV detector in our previous studies. For twenty drugs with diverse structures and chemical properties, good correlationship was found between kd,app measured by single compound analysis method and high-throughput HPAC-MS/MS approach, with the correlation coefficient of 0.987 and the significance F less than 0.001. Comprehensive quantification of ka,app, kd,app and Ka values was further performed based on the measurement of kd,app by peak profiling method and Ka by the peak fitting method. And the investigation of the drug-CD interaction kinetics under different conditions indicated that the column temperature and mobile phase composition significantly affected the determination of ka,app, kd,app and Ka while also dependent on the acidity and basicity of drugs. In summary, the high-throughput HPAC-MS/MS approach has been demonstrated high efficiency in determination of the drug-CD primary interaction kinetic parameter, especially, kd,app, being proven as a novel tool in screening the right CD for the solubilization of the right drug.

  3. 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.

  4. Biorelevant pKa (37°C) predicted from the 2D structure of the molecule and its pKa at 25°C

    PubMed Central

    Sun, Na; Avdeef, Alex

    2011-01-01

    Values of the ionization constants at 37°C, which are scarcely reported, are more meaningful for interpreting mechanisms of cellular transport by ionizable molecules and in mechanistic dissolution studies, which are often performed at the biorelevant temperature. An equation was developed where the pKa values of drug-like molecules determined at 25°C can be simply converted to values at 37°C, without additional measurement. The differences between the values, ΔpKa = pKa37 − pKa25, were linearly fitted to a function of pKa25 and the standard entropy of ionization, ΔSo, where the latter term was approximated by the five Abraham linear free energy solvation descriptors using multiple linear regression. The Abraham descriptors (H-bond donor and acceptor strengths, dipolar solute-solvent interactions potential, the pi- and n-electrons dispersion force, and molar volume) were determined from the 2-dimensional structure of the molecules. A total of 143 mostly drug-like molecules (207 pKa values at 25°C and at 37°C) were chosen for the study. The pKa values of many were determined here for the first time. Included were 34 weak acids, 85 weak bases, and 24 amphoteric compounds (6 ordinary ampholytes, 18 zwitterions). PMID:21652160

  5. KaVA ESTEMA project

    NASA Astrophysics Data System (ADS)

    Oyadomari, Miyako; Imai, Hiroshi; Cho, Se-Hyung; Asaki, Yoshiharu; Choi, Yoon-Kyong; Kim, Jaeheon; Yun, Youngjoo; Matsumoto, Naoko; Min, Cheul-Hong; Oyama, Tomoaki; Yoon, Sung-Chul; Yoon, Dong-Hwan; Kim, Dong-Jin; Dodson, Richard; Rioja, Maria; Burns, Ross; Orosz, Gabor; Nakagawa, Akiharu; Chibueze O, James; Nakashima, Jun-ichi; Sobolev, Andrey

    2016-07-01

    The ESTEMA (Expanded Study on Stellar Masers) project is one of three Large Programs of the KaVA (the combined array of the Korean VLBI Network and Japanese VLBI Exploration of Radio Astrometry), and conducted in 2015-2016. It aims to publish a database of the largest sample of VLBI images of circumstellar water (H2O) and silicon-monoxide (SiO) maser sources towards circumstellar envelopes (CSEs) of 80 evolved stars in late AGB to early post-AGB phase. Here we present the specifications of the ESTEMA observations and the planned scientific goals in order to share the basic information of the ESTEMA with astronomical community and encourage future collaborations with the ESTEMA and future follow-up observations for the targeted stars.

  6. SARAL/AltiKa Project Overview

    NASA Astrophysics Data System (ADS)

    Picot, Nicolas; Sengenes, Pierre; Lambin, Juliette; Noubel, Jocelyne; Mazeau, Sophie; Verron, Jacques

    2015-04-01

    The SARAL-AltiKa satellite mission is an India-France ISRO-CNES joint project. The satellite has been put into orbit by a PSLV vehicle supplied by ISRO, and launched from Sriharikota, the main ISRO launch base, on Feb. 25, 2013. The SARAL (Satellite for ARgos and ALtika) payload consists of an ARGOS instrument, and an altimetry payload including the AltiKa radiometer-altimeter. SARAL/AltiKa is intended to be a gap filler mission between the RA-2 on-board ENVISAT and Sentinel-3. As such, SARAL/AltiKa is flying on the same orbit as ENVISAT. The special feature of SARAL/AltiKa is mainly related to a wideband Ka-band altimeter (35.75 GHz, 500 MHz), which is the very first satellite altimeter dedicated to oceanography to operate at such a high frequency. The AltiKa instrument consists in a Ka-band altimeter based on already developed subsystems inherited from Siral (CRYOSAT) and Poseidon-3 (JASON-2) in particular, and an embedded dual frequency radiometer. The altimeter and the radiometer share the same antenna. Due to the single frequency Ka-band altimeter, the enhanced bandwidth leads to a better vertical resolution. The spatial resolution is also improved, thanks to the Ka-band smaller footprint and the increased PRF. This talk will present the main characteristics of the mission and the main outcome regarding the data availability and overall quality after 2 years of mission. In particular, we will focus on the main advantages and/or drawbacks of the Ka band frequency compared to the classical Ku band used on other missions like Jason-2. A specific point will be performed on the rain attenuation and corresponding impacts on the altimeter data quality.

  7. A Chemogenomic Analysis of Ionization Constants - Implications for Drug Discovery

    PubMed Central

    Manallack, David T.; Prankerd, Richard J.; Nassta, Gemma C.; Ursu, Oleg; Oprea, Tudor I.; Chalmers, David K.

    2013-01-01

    Chemogenomics methods seek to characterize the interaction between drugs and biological systems and are an important guide for the selection of screening compounds. The acid/base character of drugs has a profound influence on their affinity for the receptor, on their absorption, distribution, metabolism, excretion and toxicity (ADMET) profile and the way the drug can be formulated. In particular, the charge state of a molecule greatly influences its lipophilicity and biopharmaceutical characteristics. This study investigates the acid/base profile of human small molecule drugs, chemogenomics datasets and screening compounds including a natural products set. We estimate the ionization constants (pKa values) of these compounds and determine the identity of the ionizable functional groups in each set. We find substantial differences in acid/base profiles of the chemogenomic classes. In many cases, these differences can be linked to the nature of the target binding site and the corresponding functional groups needed for recognition of the ligand. Clear differences are also observed between the acid/base characteristics of drugs and screening compounds. For example, the proportion of drugs containing a carboxylic acid was 20%, in stark contrast to a value of 2.4% for the screening set sample. The proportion of aliphatic amines was 27% for drugs and only 3.4% for screening compounds. This suggests that there is a mismatch between commercially available screening compounds and the compounds that are likely to interact with a given chemogenomic target family. Our analysis provides a guide for the selection of screening compounds to better target specific chemogenomic families with regard to the overall balance of acids, bases and pKa distributions. PMID:23303535

  8. Explicit solvent models in protein pKa calculations.

    PubMed

    Gibas, C J; Subramaniam, S

    1996-07-01

    Continuum methods for calculation of protein electrostatics treat buried and ordered water molecules by one of two approximations; either the dielectric constant of regions containing ordered water molecules is equal to the bulk solvent dielectric constant, or it is equal to the protein dielectric constant though no fixed atoms are used to represent water molecules. A method for calculating the titration behavior of individual residues in proteins has been tested on models of hen egg white lysozyme containing various numbers of explicit water molecules. Water molecules were included based on hydrogen bonding, solvent accessibility, and/or proximity to titrating groups in the protein. Inclusion of water molecules significantly alters the calculated titration behavior of individual titrating sites, shifting calculated pKa values by up to 0.5 pH unit. Our results suggest that approximately one water molecule within hydrogen-bonding distance of each charged group should be included in protein electrostatics calculations.

  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. Ka-Band MMIC Subarray Technology Program (Ka-Mist)

    NASA Technical Reports Server (NTRS)

    Pottinger, W.

    1995-01-01

    Ka-band monolithic microwave integrated circuit (MMIC) arrays have been considered as having high potential for increasing the capability of space, aircraft, and land mobile communication systems in terms of scan performance, data rate, link margin, and flexibility while offering a significant reduction in size, weight, and power consumption. Insertion of MMIC technology into antenna systems, particularly at millimeter wave frequencies using low power and low noise amplifiers in closed proximity to the radiating elements, offers a significant improvement in the array transmit efficiency, receive system noise figure, and overall array reliability. Application of active array technology also leads to the use of advanced beamforming techniques that can improve beam agility, diversity, and adaptivity to complex signal environments. The objective of this program was to demonstrate the technical feasibility of the 'tile' array packaging architecture at EHF via the insertion of 1990 MMIC technology into a functional tile array or subarray module. The means test of this objective was to demonstrate and deliver to NASA a minimum of two 4 x 4 (16 radiating element) subarray modules operating in a transmit mode at 29.6 GHz. Available (1990) MMIC technology was chosen to focus the program effort on the novel interconnect schemes and packaging requirements rather than focusing on MMIC development. Major technical achievements of this program include the successful integration of two 4 x 4 subarray modules into a single antenna array. This 32 element array demonstrates a transmit EIRP of over 300 watts yielding an effective directive power gain in excess of 55 dB at 29.63 GHz. The array has been actively used as the transmit link in airborne/terrestrial mobile communication experiments accomplished via the ACTS satellite launched in August 1993.

  11. Ka-band MMIC subarray technology program (Ka-Mist)

    NASA Astrophysics Data System (ADS)

    Pottinger, W.

    1995-09-01

    Ka-band monolithic microwave integrated circuit (MMIC) arrays have been considered as having high potential for increasing the capability of space, aircraft, and land mobile communication systems in terms of scan performance, data rate, link margin, and flexibility while offering a significant reduction in size, weight, and power consumption. Insertion of MMIC technology into antenna systems, particularly at millimeter wave frequencies using low power and low noise amplifiers in closed proximity to the radiating elements, offers a significant improvement in the array transmit efficiency, receive system noise figure, and overall array reliability. Application of active array technology also leads to the use of advanced beamforming techniques that can improve beam agility, diversity, and adaptivity to complex signal environments. The objective of this program was to demonstrate the technical feasibility of the 'tile' array packaging architecture at EHF via the insertion of 1990 MMIC technology into a functional tile array or subarray module. The means test of this objective was to demonstrate and deliver to NASA a minimum of two 4 x 4 (16 radiating element) subarray modules operating in a transmit mode at 29.6 GHz. Available (1990) MMIC technology was chosen to focus the program effort on the novel interconnect schemes and packaging requirements rather than focusing on MMIC development. Major technical achievements of this program include the successful integration of two 4 x 4 subarray modules into a single antenna array. This 32 element array demonstrates a transmit EIRP of over 300 watts yielding an effective directive power gain in excess of 55 dB at 29.63 GHz. The array has been actively used as the transmit link in airborne/terrestrial mobile communication experiments accomplished via the ACTS satellite launched in August 1993.

  12. Differences in agonist dissociation constant estimates for 5-HT at 5-HT2-receptors: a problem of acute desensitization?

    PubMed Central

    Leff, P.; Martin, G. R.

    1988-01-01

    1. The agonist dissociation constant for 5-hydroxytryptamine (5-HT) was estimated in the guinea-pig isolated trachea by the method of receptor inactivation. The value obtained (pKA = 6.45) was significantly lower than estimates previously obtained in the rabbit aorta and rat jugular vein, although all three tissues are supposed to contain the same 5-HT2 class of receptor. 2. The antagonist dissociation constant for alpha,alpha-dimethyltryptamine was also estimated in the guinea-pig trachea. The pKB value (5.43) was not significantly different from previous estimates in the rabbit aorta and rat jugular vein, consistent with receptor homogeneity between the three tissues. 3. The effect-time profiles corresponding to individual 5-HT applications were more transient in the guinea-pig trachea than in the rabbit aorta. This difference could be accounted for using a simple model of acute receptor desensitization (Leff, 1986), assuming that the conversion of active agonist-receptor complexes into inactive ones was faster in the guinea-pig trachea than in the rabbit aorta. 4. Computer simulation of the desensitization model showed that the discrepancy of pKA estimates for 5-HT between the rabbit aorta and guinea-pig trachea could also be explained using the same rate constant difference that accounted for the difference in effect-time profiles. This analysis indicated that the estimate made in the trachea was erroneously low, whereas that made in the aorta was concluded to be correct. 5. The apparent association between transience of response and pKA estimates is discussed with particular attention to the reliability of agonist affinity estimates in receptor classification. PMID:3228675

  13. 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.

  14. Computational chemical analysis of unconjugated bilirubin anions and insights into pKa values clarification

    NASA Astrophysics Data System (ADS)

    Vega-Hissi, Esteban G.; Estrada, Mario R.; Lavecchia, Martín J.; Pis Diez, Reinaldo

    2013-01-01

    The pKa, the negative logarithm of the acid dissociation equilibrium constant, of the carboxylic acid groups of unconjugated bilirubin in water is a discussed issue because there are quite different experimental values reported. Using quantum mechanical calculations we have studied the conformational behavior of unconjugated bilirubin species (in gas phase and in solution modeled implicitly and explicitly) to provide evidence that may clarify pKa values because of its pathophysiological relevance. Our results show that rotation of carboxylate group, which is not restricted, settles it in a suitable place to establish stronger interactions that stabilizes the monoanion and the dianion to be properly solvated, demonstrating that the rationalization used to justify the high pKa values of unconjugated bilirubin is inappropriate. Furthermore, low unconjugated bilirubin (UCB) pKa values were estimated from a linear regression analysis.

  15. The Asteroid 2015 KA122

    NASA Astrophysics Data System (ADS)

    Vodniza, Alberto Quijano; Pereira, Mario Rojas

    2015-11-01

    The Asteroid “2015 KA122” was discovered on May 25/2015 by the Catalina Sky Survey. This object is not well known. Its absolute magnitude, of 23.2, indicates a diameter of about 70 meters. The asteroid was at aproximately 3.3 lunar distances from the Earth, on June 6/2015. It has an orbital period of 2.11 years. From our Observatory, located in Pasto-Colombia, we captured several pictures, videos and astrometry data during three days. Our data was published by the Minor Planet Center (MPC) and also appears at the web page of NEODyS. Our observatory’s code at the MPC is “H78”. Pictures of the asteroid were captured with the following equipment: 14” LX200 GPS MEADE (f/10 Schmidt-Cassegrain Telescope) and STL-1001 SBIG camera. Astrometry was carried out, and we calculated the orbital elements. We obtained the following orbital parameters: eccentricity = 0.4089630 +/- 0.00189, semi-major axis = 1.64254884 +/- 0.00505 A.U, orbital inclination = 12.68490 +/- 0.039 deg, longitude of the ascending node = 73.14715 +/- 0.0013 deg, argument of perihelion = 214.82393 +/- 0.007 deg, orbital period = 2.11 years (768.90 days), mean motion = 0.46819485 +/- 0.00216 deg/d, perihelion distance = 0.97080706 +/- 0.000119 A.U, aphelion distance = 2.31429061 +/- 0.0103 A.U. The parameters were calculated based on 81 observations (2015 June 3-5) with mean residual = 0.343 arcseconds. Our videos appear in the following links:http://spaceweathergallery.com/indiv_upload.php?upload_id=113197http://spaceweathergallery.com/indiv_upload.php?upload_id=113238&PHPSESSID=f2lkigjogsfgcmi1rscc9jil36http://spaceweathergallery.com/indiv_upload.php?upload_id=113257

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Development of Methods for the Determination of pKa Values

    PubMed Central

    Reijenga, Jetse; van Hoof, Arno; van Loon, Antonie; Teunissen, Bram

    2013-01-01

    The acid dissociation constant (pKa) is among the most frequently used physicochemical parameters, and its determination is of interest to a wide range of research fields. We present a brief introduction on the conceptual development of pKa as a physical parameter and its relationship to the concept of the pH of a solution. This is followed by a general summary of the historical development and current state of the techniques of pKa determination and an attempt to develop insight into future developments. Fourteen methods of determining the acid dissociation constant are placed in context and are critically evaluated to make a fair comparison and to determine their applications in modern chemistry. Additionally, we have studied these techniques in light of present trends in science and technology and attempt to determine how these trends might affect future developments in the field. PMID:23997574

  1. AltiKa in-flight performances

    NASA Astrophysics Data System (ADS)

    Boy, Francois; Desjonquères, Jean-Damien; Steunou, Nathalie

    2015-04-01

    The SARAL/AltiKa satellite has been launched the 25th of February 2013 from the launch pad of Sriharikota (India). Since this date, AltiKa provides measurements and affords the first altimetry results in Ka band. This paper recalls the instrument design and assesses the in-flight performance. The SARAL/AltiKa mission has been developed in the frame of a cooperation between CNES (French Space Agency) and ISRO (Indian Space Research Organization). AltiKa is a single frequency Ka-band altimeter with a bi-frequency radiometer embedded. Both altimeter and radiometer share the same antenna. Altimeter expertise and routine calibrations performed during assessment phase demonstrate the stability of the instrument. Moreover the performance assessed over ocean are noteworthy such as 0.9 cm on epoch 1 Hz noise for 2 m of SWH, which is fully consistent with simulations and ground pre-flight tests results. The data availability is also very good and very few altimeter measurements are lost due to rain attenuation. Radiometer data analysis shows that the instrument is very stable and its performances are consistent with pre-flight tests results.

  2. 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.

  3. 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.

  4. Evaluation of kinetic constants of biomolecular interaction on optical surface plasmon resonance sensor with Newton Iteration Method

    NASA Astrophysics Data System (ADS)

    Zhao, Yuanyuan; Jiang, Guoliang; Hu, Jiandong; Hu, Fengjiang; Wei, Jianguang; Shi, Liang

    2010-10-01

    In the immunology, there are two important types of biomolecular interaction: antigens-antibodies and receptors-ligands. Monitoring the response rate and affinity of biomolecular interaction can help analyze the protein function, drug discover, genomics and proteomics research. Moreover the association rate constant and dissociation rate constant of receptors-ligands are the important parameters for the study of signal transmission between cells. Recent advances in bioanalyzer instruments have greatly simplified the measurement of the kinetics of molecular interactions. Non-destructive and real-time monitoring the response to evaluate the parameters between antigens and antibodies can be performed by using optical surface plasmon resonance (SPR) biosensor technology. This technology provides a quantitative analysis that is carried out rapidly with label-free high-throughput detection using the binding curves of antigens-antibodies. Consequently, the kinetic parameters of interaction between antigens and antibodies can be obtained. This article presents a low cost integrated SPR-based bioanalyzer (HPSPR-6000) designed by ourselves. This bioanalyzer is mainly composed of a biosensor TSPR1K23, a touch-screen monitor, a microprocessor PIC24F128, a microflow cell with three channels, a clamp and a photoelectric conversion device. To obtain the kinetic parameters, sensorgrams may be modeled using one of several binding models provided with BIAevaluation software 3.0, SensiQ or Autolab. This allows calculation of the association rate constant (ka) and the dissociation rate constant (kd). The ratio of ka to kd can be used to estimate the equilibrium constant. Another kind is the analysis software OriginPro, which can process the obtained data by nonlinear fitting and then get some correlative parameters, but it can't be embedded into the bioanalyzer, so the bioanalyzer don't support the use of OriginPro. This paper proposes a novel method to evaluate the kinetic parameters

  5. 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.

  6. Determination of acidity constants of curcumin in aqueous solution and apparent rate constant of its decomposition.

    PubMed

    Bernabé-Pineda, Margarita; Ramírez-Silva, María Teresa; Romero-Romo, Mario; González-Vergara, Enrique; Rojas-Hernández, Alberto

    2004-04-01

    The stability of curcumin (H3Cur) in aqueous media is improved when the systems in which it is present are at high pH values (higher than 11.7), fitting a model describable by a pseudo-zero order with a rate constant k' for the disappearance of the Cur3- species of 1.39 (10(-9)) Mmin(-1). There were three acidity constants measured for the curcumin as follows: pKA3 = 10.51 +/- 0.01 corresponding to the equilibrium HCur2- = Cur3- + H+, a pKA2 = 9.88 +/- 0.02 corresponding to the equilibrium H2Cur- = HCur-(2) + H+. These pKA values were attributed to the hydrogen of the phenol part of the curcumin, while the pKA1 = 8.38 +/- 0.04 corresponds to the equilibrium H3Cur = H2Cur- + H+ and is attributed the acetylacetone type group. Formation of quinoid structures play an important role in the tautomeric forms of the curcumin in aqueous media, which makes the experimental values differ from the theoretically calculated ones, depending on the conditions adopted in the study.

  7. The pKa of the protonated Schiff bases of gecko cone and octopus visual pigments.

    PubMed Central

    Liang, J; Steinberg, G; Livnah, N; Sheves, M; Ebrey, T G; Tsuda, M

    1994-01-01

    A visual pigment is composed of retinal bound to its apoprotein by a protonated Schiff base linkage. Light isomerizes the chromophore and eventually causes the deprotonation of this Schiff base linkage at the meta II stage of the bleaching cycle. The meta II intermediate of the visual pigment is the active form of the pigment that binds to and activates the G protein transducin, starting the visual cascade. The deprotonation of the Schiff base is mandatory for the formation of meta II intermediate. We studied the proton binding affinity, pKa, of the Schiff base of both octopus rhodopsin and the gecko cone pigment P521 by spectral titration. Several fluorinated retinal analogs have strong electron withdrawing character around the Schiff base region and lower the Schiff base pKa in model compounds. We regenerated octopus and gecko visual pigments with these fluorinated and other retinal analogs. Experiments on these artificial pigments showed that the spectral changes seen upon raising the pH indeed reflected the pKa of the Schiff base and not the denaturation of the pigment or the deprotonation of some other group in the pigment. The Schiff base pKa is 10.4 for octopus rhodopsin and 9.9 for the gecko cone pigment. We also showed that although the removal of Cl- ions causes considerable blue-shift in the gecko cone pigment P521, it affects the Schiff base pKa very little, indicating that the lambda max of visual pigment and its Schiff base pKa are not tightly coupled. PMID:7948697

  8. High Throughput pharmacokinetic modeling using computationally predicted parameter values: dissociation constants (TDS)

    EPA Science Inventory

    Estimates of the ionization association and dissociation constant (pKa) are vital to modeling the pharmacokinetic behavior of chemicals in vivo. Methodologies for the prediction of compound sequestration in specific tissues using partition coefficients require a parameter that ch...

  9. An Ka Bamanankan Kalan: Intermediate Bambara.

    ERIC Educational Resources Information Center

    Bird, Charles; Kante, Mamadou

    This textbook follows the third edition of "Introductory Bambara: An Ka Bamanankan Kalan", and is designed so that Bambara can be used almost exclusively in the classroom. Each of the twenty lessons has a culturally oriented topic and consists of a reading selection, drills on grammar and vocabulary list. The grammar notes are not…

  10. Affinity chromatography on immobilized "biomimetic" ligands. Synthesis, immobilization and chromatographic assessment of an immunoglobulin G-binding ligand.

    PubMed

    Teng, S F; Sproule, K; Husain, A; Lowe, C R

    2000-03-31

    A synthetic bifunctional ligand (22/8) comprising a triazine scaffold substituted with 3-aminophenol (22) and 4-amino-1-naphthol (8) has been designed, synthesised, characterised and immobilized on agarose beads to create a robust, highly selective affinity adsorbent for human immunoglobulin G (IgG). Scatchard analysis of the binding isotherm for IgG on immobilized 22/8 (90 micromol 22/8/g moist weight gel) indicated an affinity constant (Ka) of 1.4 x 10(5) M(-1) and a theoretical maximum capacity of 151.9 mg IgG/g moist weight gel. The adsorbent shows similar selectivity to immobilized protein A and binds IgG from a number of species. An apparent capacity of 51.9 mg human IgG/g moist weight gel was observed under the experimental conditions selected for adsorption. Human IgG was eluted with glycine-HCl buffer with a recovery of 67-69% and a purity of 97.3-99.2%, depending on the pH value of the buffer used for elution. Preparative chromatography of IgG from human plasma showed that under the specified conditions, 94.4% of plasma IgG was adsorbed and 60% subsequently eluted with a purity of 92.5%. The immobilized ligand was able to withstand incubation in 1 M NaOH for 7 days without loss of binding capacity for IgG.

  11. Fluorescence resonance energy-transfer affects the determination of the affinity between ligand and proteins obtained by fluorescence quenching method

    NASA Astrophysics Data System (ADS)

    Xiao, Jianbo; Wei, Xinlin; Wang, Yuanfeng; Liu, Chunxi

    2009-11-01

    The interaction between esculin and serum albumins was investigated to illustrate that the fluorescence resonance energy-transfer (FRET) affects the determination of the binding constants obtained by fluorescence quenching method. The binding constants ( Ka) obtained by the double-logarithm curve for esculin-BSA and esculin-HSA were 1.02 × 10 7 and 2.07 × 10 4 L/mol, respectively. These results from synchronous fluorescence showed that the Tyr and Trp residues of HSA were affected more deeply than those in BSA. The excitation profile of esculin showed that in the presence of BSA and HSA, the S 0 → S 1 transition of esculin ( λexmax≈340 nm) appears, which is similar to the λemmax of BSA and HSA. The critical distance ( R0) between BSA and esculin is higher than that of HSA, which showed that the affinity of esculin and HSA should be higher than that of BSA. After centrifugation, the concentrations of esculin bound to albumins were determined by means of the fluorescence of esculin. It was found that much more esculin was bound to HSA than to BSA. However, the bound models for BSA and HSA are almost the same. The concentration of esculin bound to serum albumin at first decreased with the addition of esculin and then increased. From above results, it can be concluded that the affinity of esculin and HSA should be higher than that of esculin and BSA. This example showed that in the presence of FRET, the binding constants between ligands and proteins based on fluorescence quenching might be deviated.

  12. The Mars Global Surveyor Ka-Band Link Experiment (MGS/KaBLE-II)

    NASA Astrophysics Data System (ADS)

    Morabito, D.; Butman, S.; Shambayati, S.

    1999-01-01

    The Mars Global Surveyor (MGS) spacecraft, launched on November 7, 1996, carries an experimental space-to-ground telecommunications link at Ka-band (32 GHz) along with the primary X-band (8.4-GHz) downlink. The signals are simultaneously transmitted from a 1.5-m-diameter parabolic antenna on MGS and received by a beam-waveguide (BWG) research and development (R&D) 34-meter a ntenna located in NASA's Goldstone Deep Space Network (DSN) complex near Barstow, California. This Ka-band link experiment (KaBLE-II) allows the performances of the Ka-band and X-band signals to be compared under nearly identical conditions. The two signals have been regularly tracked during the past 2 years. This article presents carrier-signal-level data (P_c/N_o) for both X-band and Ka-band acquired over a wide range of station elevation angles, weather conditions, and solar elongation angles. The cruise phase of the mission covered the period from launch (November 7, 1996) to Mars orbit capture (September 12, 1997). Since September 12, 1997, MGS has been in orbit around Mars. The measurements confirm that Ka-band could increase data capacity by at least a factor of three (5 dB) as compared with X-band. During May 1998, the solar corona experiment, in which the effects of solar plasma on the X-band and Ka-band links were studied, was conducted. In addition, frequency and difference frequency (f_x - f_(Ka)/3.8), ranging, and telemetry data results are presented. MGS/KaBLE-II measured signal strengths (for 54 percent of the experiments conducted) that were in reasonable agreement with predicted values based on preflight knowledge, and frequency residuals that agreed between bands and whose statistics were consistent with expected noise sources. For passes in which measured signal strengths disagreed with predicted values, the problems were traced to known deficiencies, for example, equipment operating under certain conditions, such as a cold Ka-band solid-state power amplifier (SSPA

  13. Estimated pKa values for the environmentally relevant C1 through C8 perfluorinated sulfonic acid isomers.

    PubMed

    Rayne, Sierra; Forest, Kaya

    2016-10-14

    In order to estimate isomer-specific acidity constants (pKa) for the perfluorinated sulfonic acid (PFSA) environmental contaminants, the parameterization method 6 (PM6) pKa prediction method was extensively validated against a wide range of carbon oxyacids and related sulfonic/sulfinic acids. Excellent pKa prediction performance was observed for the carbon oxyacids using the PM6 method, but this approach was found to have a severe positive bias for sulfonic/sulfinic acids. To overcome this obstacle, a correlation was developed between non-adjusted PM6 pKa values and the corresponding experimentally obtained/estimated acidity constants for a range of representative alkyl, aryl and halogen-substituted sulfonic acids. Application of this correction to the PM6 values allows for extension of this computational method to a new acid functional group. When used to estimate isomer-specific pKa values for the C1 through C8 PFSAs, the modified PM6 approach suggests an adjusted pKa range from -5.3 to -9.0, indicating that all members of this class of well-known environmental contaminants will be effectively completely dissociated in aquatic systems.

  14. Modulation transfer functions at Ka band

    NASA Astrophysics Data System (ADS)

    Hesany, Vahid; Sistani, Bita; Salam, Asif; Haimov, Samuel; Gogineni, Prasad; Moore, Richard K.

    The modulation transfer function (MTF) is often used to describe the modulation of the radar signal by the long waves. MTFs were measured at 35 GHz (Ka band) with a switched-beam vector slope gauge/scatterometer on the research platform NORDSEE as part of the SAXON-FPN experiment. Three independent measurements of the scattering were available for each height measurement. This provided the opportunity to average the time series to reduce the effects of fading noise and sea spikes, or, alternatively, to append the time series to achieve more degrees of freedom in the spectral estimates. For upwind measurements, the phase of the VV-polarized Ka-band MTF was always positive, which implies that the maximum of the radar return originates from the forward face of the long-scale waves. This phase increases with increasing wind speed. The magnitude of the MTF decreases with increasing wind speed.

  15. Internal standard capillary electrophoresis as a high-throughput method for pKa determination in drug discovery and development.

    PubMed

    Cabot, Joan M; Fuguet, Elisabet; Rosés, Martí

    2014-10-13

    A novel high-throughput method for determining acidity constants (pKa) by capillary electrophoresis (CE) is developed. The method, based on the use of an internal standard (IS-CE), is implemented as a routine method for accurate experimental pKa determination of drugs undergoing physicochemical measurements in drug discovery laboratories. Just two electropherograms at 2 different pH values are needed to calculate an acidity constant. Several ISs can be used in the same buffer and run to enhance precision. With 3 ISs, for example, the pKa of the test compound (TC) can be obtained in triplicate in less than 3 min of electrophoresis. It has been demonstrated that the IS-CE method eliminates some systematic errors, maintaining, or even increasing the precision of the results compared with other methods. Furthermore, pH buffer instability during electrophoretic runs is not a problem in the IS-CE method. It is also proved that after 16 h of electroseparation using the same buffer vial, pH may change by around one unit; but the pKa calculated by the IS-CE method remains constant. Thus, IS-CE is a powerful high-throughput method for pKa determination in drug discovery and development.

  16. Intrinsic surface reaction equilibrium constants of structurally charged amphoteric hydrotalcite-like compounds.

    PubMed

    Hou, Wan-Guo; Song, Shu E

    2004-01-15

    The relative equations among intrinsic surface reaction equilibrium constants (K in 1-pK model, K(a1)(int) and K(a2)(int) in 2-pK model, and *K(Na)(int) and *K(Cl)(int) in inert electrolyte chemical binding model), points of zero charge (PZC), and structural charge density (sigma(st)) for amphoteric solids with structural charge were established to investigate the effects of sigma(st) on intrinsic equilibrium constants and PZC. The intrinsic equilibrium constants of HTlc with general formulas [(Zn,Mg)(1-x)Al(x)(OH)(2)](Cl,OH)(x) and [Mg(1-x)(Fe,Al)(x)(OH)(2)](Cl,OH)(x) were evaluated. The following main conclusions were obtained. For amphoteric solids with structural charge, a point of zero net charge (PZNC) independent of electrolyte concentration (c) exists. A common intersection point (CIP) should appear among the acid-base titration curves at different c, and the pH at the CIP is pH(PZNC). The pK, pK(a1)(int), and pK(a2)(int) may be expressed as a function of pH(PZNC) and sigma(st), and these intrinsic equilibrium constants can be directly calculated from pH(PZNC) and sigma(st). The inert electrolyte chemical binding does not exist for amphoteric surfaces with structural charge. PZNC is not equal to the point of zero net proton charge (PZNPC) when sigma(st) not equal 0. pH(PZNC) > pH(PZNPC) when sigma(st)>0; pH(PZNC) < pH(PZNPC) when sigma(st)<0; and pH(PZNC) = pH(PZNPC) only when sigma(st)=0. With increasing c, the difference between pH(PZNC) and pH(PZNPC) decreases; i.e., pH(PZNPC) moves forward to pH(PZNC) with increasing c. For the HTlc samples studied, with increasing x, the pH(PZNC) and the pK(a1)(int) and pK(a2)(int) decrease, and the pK increases. These results can be explained on the basis of the affinity of metal cations for H(+) or OH(-) and the electrostatic interaction between the charging surface and H(+) or OH(-).

  17. Molecular determinants of KA1 domain-mediated autoinhibition and phospholipid activation of MARK1 kinase

    PubMed Central

    Emptage, Ryan P.; Lemmon, Mark A.; Ferguson, Kathryn M.

    2017-01-01

    Protein kinases are frequently regulated by intramolecular autoinhibitory interactions between protein modules that are reversed when these modules bind other ‘activating’ protein or membrane-bound targets. One group of kinases, the MAP/microtubule affinity-regulating kinases (MARKs) contain a poorly understood regulatory module, the KA1 (kinase associated-1) domain, at their C-terminus. KA1 domains from MARK1 and several related kinases from yeast to humans have been shown to bind membranes containing anionic phospholipids, and peptide ligands have also been reported. Deleting or mutating the C-terminal KA1 domain has been reported to activate the kinase in which it is found — also suggesting an intramolecular autoinhibitory role. Here, we show that the KA1 domain of human MARK1 interacts with, and inhibits, the MARK1 kinase domain. Using site-directed mutagenesis, we identify residues in the KA1 domain required for this auto-inhibitory activity, and find that residues involved in autoinhibition and in anionic phospholipid binding are the same. We also demonstrate that a ‘mini’ MARK1 becomes activated upon association with vesicles containing anionic phospholipids, but only if the protein is targeted to these vesicles by a second signal. These studies provide a mechanistic basis for understanding how MARK1 and its relatives may require more than one signal at the membrane surface to control their activation at the correct location and time. MARK family kinases have been implicated in a plethora of disease states including Alzheimer’s, cancer, and autism, so advancing our understanding of their regulatory mechanisms may ultimately have therapeutic value. PMID:27879374

  18. 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

  19. Predicting the pKa and stability of organic acids and bases at an oil-water interface.

    PubMed

    Andersson, M P; Olsson, M H M; Stipp, S L S

    2014-06-10

    We have used density functional theory and the implicit solvent model, COSMO-RS, to investigate how the acidity constant, pKa, of organic acids and bases adsorbed at the organic compound-aqueous solution interface changes, compared to its value in the aqueous phase. The pKa determine the surface charge density of the molecules that accumulate at the fluid-fluid interface. We have estimated the pKa by comparing the stability of the protonated and unprotonated forms of a series of molecules in the bulk aqueous solution and at an interface where parts of each molecule reside in the hydrophobic phase and the rest remains in the hydrophilic phase. We found that the pKa for acids is shifted by ∼1 pH unit to higher values compared to the bulk water pKa, whereas they are shifted to lower values by a similar amount for bases. Because this pKa shift is similar in magnitude for each of the molecules studied, we propose that the pKa for molecules at a water-organic compound interface can easily be predicted by adding a small shift to the aqueous pKa. This shift is general and correlates with the functional group. We also found that the relative composition of molecules at the fluid-fluid interface is not the same as in the bulk. For example, species such as carboxylic acids are enriched at the interface, where they can dominate surface properties, even when they are a modest component in the bulk fluid. For high surface concentrations of carboxylic acid groups at an interface, such as a self-assembled monolayer, we have demonstrated that the pKa depends on the degree of deprotonation through direct hydrogen bonding between protonated and deprotonated acidic headgroups.

  20. Validation of GPM Ka-Radar Algorithm Using a Ground-based Ka-Radar System

    NASA Astrophysics Data System (ADS)

    Nakamura, Kenji; Kaneko, Yuki; Nakagawa, Katsuhiro; Furukawa, Kinji; Suzuki, Kenji

    2016-04-01

    GPM led by the Japan Aerospace Exploration Agency (JAXA) and the National Aeronautics and Space Administration of US (NASA) aims to observe global precipitation. The core satellite is equipped with a microwave radiometer (GMI) and a dual-frequency radar (DPR) which is the first spaceborne Ku/Ka-band dual-wavelength radar dedicated for precipitation measurement. In the DPR algorithm, measured radar reflectivity is converted to effective radar reflectivity by estimating the rain attenuation. Here, the scattering/attenuation characteristics of Ka-band radiowaves are crucial, particularly for wet snow. A melting layer observation using a dual Ka-band radar system developed by JAXA was conducted along the slope of Mt. Zao in Yamagata Prefecture, Japan. The dual Ka-band radar system consists of two nearly identical Ka-band FM-CW radars, and the precipitation systems between two radars were observed in opposite directions. From this experiment, equivalent radar reflectivity (Ze) and specific attenuation (k) were obtained. The experiments were conducted for two winter seasons. During the data analyses, it was found that k estimate easily fluctuates because the estimate is based on double difference calculation. With much temporal and spatial averaging, k-Ze relationship was obtained for melting layers. One of the results is that the height of the peak of k seems slightly higher than that of Ze. The results are compared with in-situ precipitation particle measurements.

  1. 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.

  2. 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.

  3. 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.

  4. High-power Ka-band amplifier

    NASA Technical Reports Server (NTRS)

    Cormier, R.

    1993-01-01

    Development of a high-power tube suitable to power a Ka-band (34.5-GHz) antenna transmitter located at the Goldstone, California, tracking station is continuing. The University of Maryland Laboratory for Plasma Research and JPL are conducting a joint effort to test the feasibility of phase locking a second-harmonic gyrotron both by direct injection at the output cavity and by using a priming cavity to bunch the electrons in the beam. This article describes several design options and the results of computer simulation testing.

  5. Silicic magma accumulation beneath Mount Mazama, Oregon, 71 ka to 24 ka constrained by SHRIMP measurements of dissolved volatile concentrations in melt inclusions

    NASA Astrophysics Data System (ADS)

    Wright, H. M.; Bacon, C. R.; Vazquez, J. A.; Sisson, T. W.

    2010-12-01

    Dissolved volatile contents of melt inclusions trapped in pyroxene and plagioclase crystals from 7 silicic eruptions preceding the climactic ~7.7 ka Mazama eruption were measured by SIMS with the Stanford-USGS SHRIMP-RG. Melt inclusions in crystals were intersected, polished, and crystals were mounted in indium in Al mounts. A 1.2-3.0 nA (depending on the session), O2- primary beam was accelerated and focused to a 15-25 μm spot on the sample surface, which generated positive secondary ions of analyzed Li, Be, B, C, OH, F, Mg, Si, SiH, S, Cl, Ca, AlO, KO, Rb, and Sr. Measurements were made at high mass resolution (6000-7000). Trace element and volatile concentrations were calculated using a best-fit regression to count rate ratios (normalized to 30Si) vs. variable known concentrations in experimental and natural rhyolite glass standards. Pumiceous samples were chosen from dacitic to rhyodacitic eruptive deposits, consisting of the 71ka dacite of Pumice Castle, 70ka dacite below Llao Rock, 50ka dacite of the Watchman, 35ka dacite of Munson Valley, 35ka Williams Crater tephra, 27ka Redcloud Cliff rhyodacite, and 24ka andesite S of Bear Bluff. Melt inclusions are abundant in spongy, mineral-inclusion-rich interiors of pyroxene crystals in early (71-35ka) eruptive deposits and are less abundant throughout pyroxenes from later eruptions (35-24ka) and in plagioclase crystals. Over the entire time interval, most trace element and volatile concentrations remain approximately constant between melt inclusion populations. However, there are some variations in water and carbon dioxide concentration. A large proportion of inclusions in the smaller eruptive deposits (0.003-0.4 km3) of the dacite of the Watchman, dacite of Munson Valley, and Williams Crater tephra have low water contents, ~1 wt% H2O, corresponding to a saturation pressure of 25MPa, or ~1km depth (at 870°, approximate average temperature for these deposits, e.g., Druitt and Bacon, Contrib Mineral Petrol 1989

  6. Determination of pKa values by capillary zone electrophoresis with a dynamic coating procedure.

    PubMed

    Geiser, Laurent; Henchoz, Yveline; Galland, Alexandra; Carrupt, Pierre-Alain; Veuthey, Jean-Luc

    2005-11-01

    CZE allows to measure the acidic dissociation constant (pKa) of many drug substances. However, determining the EOF intensity may be time-consuming, especially at a low pH. In order to overcome this drawback, a dynamic coating procedure of the capillary was carried out to increase microEOF, and thus to reduce the analysis time. In addition, this coating procedure enhanced migration time stability. The effective mobilities of 15 compounds were measured at different pH, producing pK'a values dependent on BGE ionic strength. The latter values were corrected with the activity coefficient to obtain a "true" pKa value. The 15 investigated compounds were (i) five acids: namely, salicylic acid, benzoic acid, ketoprofen, phenobarbital, and phenol, (ii) four bases: lidocaine, propafenone, propranolol, and quinine, (iii), five ampholytes: sulfanilamide, sulfabenzamide, sulfadimethoxine, sulfadoxine, and sulfisoxazole, and (iv) one zwitterion: cetirizine. The range of determined pKa values was between 1.2 and 11.2, and close to the pKa values available from the literature.

  7. 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.

  8. 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.

  9. 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.

  10. Membrane Environment Modulates the pKa Values of Transmembrane Helices

    PubMed Central

    2015-01-01

    In this work, we apply the recently developed constant pH molecular dynamics technique to study protonation equilibria of titratable side chains in the context of simple transmembrane (TM) helices and explore the effect of pH on their configurations in membrane bilayers. We observe that, despite a significant shift toward neutral states, considerable population of different side chains stay in the charged state that give rise to pKa values around 9.6 for Asp and Glu and 4.5 to 6 for His and Lys side chains, respectively. These charged states are highly stabilized by favorable interactions between head groups, water molecules, and the charged side chains that are facilitated by substantial changes in the configuration of the peptides. The pH dependent configurations and the measured pKa values are in good agreement with relatively recent solid state NMR measurements. Our results presented here demonstrate that all-atom constant pH molecular dynamics can be applied to membrane proteins and peptides to obtain reliable pKa values and pH dependent behavior for these systems. PMID:25734901

  11. Membrane environment modulates the pKa values of transmembrane helices.

    PubMed

    Panahi, Afra; Brooks, Charles L

    2015-04-02

    In this work, we apply the recently developed constant pH molecular dynamics technique to study protonation equilibria of titratable side chains in the context of simple transmembrane (TM) helices and explore the effect of pH on their configurations in membrane bilayers. We observe that, despite a significant shift toward neutral states, considerable population of different side chains stay in the charged state that give rise to pKa values around 9.6 for Asp and Glu and 4.5 to 6 for His and Lys side chains, respectively. These charged states are highly stabilized by favorable interactions between head groups, water molecules, and the charged side chains that are facilitated by substantial changes in the configuration of the peptides. The pH dependent configurations and the measured pKa values are in good agreement with relatively recent solid state NMR measurements. Our results presented here demonstrate that all-atom constant pH molecular dynamics can be applied to membrane proteins and peptides to obtain reliable pKa values and pH dependent behavior for these systems.

  12. p Ka calculation of poliprotic acid: histamine

    NASA Astrophysics Data System (ADS)

    De Abreu, Heitor A.; De Almeida, Wagner B.; Duarte, Hélio A.

    2004-01-01

    Various theoretical studies have been reported addressing the performance of solvation models available to estimate p Ka values. However, no attention has been paid so far to the role played by the electronic, thermal and solvation energy individual contributions to the Gibbs free energy of the deprotonation process. In this work, we decompose the total Gibbs free energy into three distinct terms and then evaluate the dependence of each contribution on the level of theory employed for its determination using different levels of theory. The three possible p Kas of histamine have been estimated and compared with available experimental data. We found that the electronic energy term is sensitive to the level of theory and basis set, and, therefore, could be also a source of error in the theoretical calculation of p Kas.

  13. Aeronautical applications of steerable K/Ka-band antennas

    NASA Technical Reports Server (NTRS)

    Helmken, Henry; Prather, Horton

    1995-01-01

    The expected growth of wideband data and video transmission via satellite will press existing satellite Ku-band services and push development of the Ka-band region. Isolated ground based K/Ka-band terminals can experience severe fading due to rain and weather phenomena. However, since aircraft generally fly above the severe weather, they are attractive platforms for developing commercial K/Ka-band communication links.

  14. Determination of aqueous acid-dissociation constants of aspartic acid using PCM/DFT method

    NASA Astrophysics Data System (ADS)

    Sang-Aroon, Wichien; Ruangpornvisuti, Vithaya

    Determination of acid-dissociation constants, pKa, of aspartic acid in aqueous solution, using density functional theory calculations combined with the conductor-like polarizable continuum model (CPCM) and with integral-equation-formalism polarizable continuum model (IEFPCM) based on the UAKS and UAHF radii, was carried out. The computed pKa values derived from the CPCM and IEFPCM with UAKS cavity model of bare structures of the B3LYP/6-31+G(d,p)-optimized tetrahydrated structures of aspartic acid species are mostly close to the experimental pKa values.0

  15. Elucidating the Conformational Dependence of Calculated pKa Values.

    PubMed

    Livesay, Dennis R; Jacobs, Donald J; Kanjanapangka, Julie; Chea, Eric; Cortez, Hector; Garcia, Jorge; Kidd, Patrick; Marquez, Mario Pulido; Pande, Swati; Yang, David

    2006-07-01

    The variability within calculated protein residue pKa values calculated using Poisson-Boltzmann continuum theory with respect to small conformational fluctuations is investigated. As a general rule, sites buried in the protein core have the largest pKa fluctuations but the least amount of conformational variability; conversely, sites on the protein surface generally have large conformational fluctuations but very small pKa fluctuations. These results occur because of the heterogeneous or uniform nature of the electrostatic microenvironments at the protein core or surface, respectively. Atypical surface sites with large pKa fluctuations occur at the interfaces between significant anionic and cationic potentials.

  16. Study of sea ice regions using AltiKa measurements

    NASA Astrophysics Data System (ADS)

    Poisson, Jean-Christophe; Thibaut, Pierre; Hoang, Duc; Boy, François; Guillot, Amandine; Picot, Nicolas

    2015-04-01

    Since the launch of the SARAL/AltiKa mission on February 25th, 2013, altimeter measurements of excellent quality are acquired all over the globe for the first time in Ka-band. One of the main benefits of the Ka-band is to have a very low penetration length in the ice (unlike the Ku-band historically used by previous altimetry missions), which allows to significantly reduce measurements uncertainties of the sea ice topography. Flying on the Envisat orbit and providing measurements at 40 Hz, the exploitation of AltiKa waveforms on sea ice is of great interest. Sea ice covered regions are characterized by a large number of different surfaces with a multitude of backscattering properties rapidly evolving with time. Thanks to the high resolution and precision of the AltiKa measurements, backscattering properties from each of these surfaces (first year ice, multiyear ice, fast ice, leads, polynyas, etc. …) can be observed through rapid changes of the returned echo shape. In the framework of the PEACHI project (Prototype for Expertise on AltiKa, for Coastal, Hydrology and Ice funded by CNES) which aims at analyzing and improving AltiKa measurements, a waveform processing based on an altimeter echo classification is developed and performed on all available AltiKa data in the Arctic ocean. Through this processing a study is conducted on the the evolution of the sea ice cover observed in Ka-band.

  17. 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.

  18. Reproducing basic pKa values for turkey ovomucoid third domain using a polarizable force field

    PubMed Central

    Click, Timothy H.; Kaminski, George A.

    2009-01-01

    We have extended our previous studies of calculating acidity constants for the acidic residues found in the turkey ovomucoid third domain protein (OMTKY3) by determining the relative pKa values for the basic residues (Lys13, Arg21, Lys29, Lys34, His52, and Lys55). A polarizable force field (PFF) was employed. The values of the pKa were found by direct comparison of energies of solvated protonated and deprotonated forms of the protein. Poisson Boltzmann (PBF) and Generalized Born (SGB) continuum solvation models represent the hydration, and a non-polarizable fixed-charges OPLS-AA force field was used for comparison. Our results indicate that (i) the pKa values of the basic residues can be found in close agreement with the experimental values when a PFF is used in conjunction with the PBF solvation model, (ii) it is sufficient to take into the account only the residues which are in close proximity (hydrogen bonded) to the residue in question, and (iii) The PBF solvation model is superior to the SGB solvation model for these pKa calculations. The average error with the PBF/PFF model is only 0.7 pH units, compared with 2.2 and 6.1 units for the PBF/OPLS and SGB/OPLS, respectively. The maximum deviation of the PBF/PFF results from the experimental values is 1.7 pH units compared with 6.0 pH units for the PBF/OPLS. Moreover, the best results were obtained while using an advanced non-polar energy calculation scheme. The overall conclusion is that this methodology and force field are suitable for accurate assessment of pKa shifts for both acidic basic protein residues. PMID:19432439

  19. Determination of acid dissociation constants of warfarin and hydroxywarfarins by capillary electrophoresis.

    PubMed

    Nowak, Paweł; Olechowska, Paulina; Mitoraj, Mariusz; Woźniakiewicz, Michał; Kościelniak, Paweł

    2015-08-10

    In this work the acid dissociation constants--pKa of warfarin and its all important oxidative metabolites have been determined by capillary electrophoresis-based methods. It has resulted in a complete description of two acid-base dissociation equilibria, yet not investigated experimentally for phase I metabolites of warfarin. The capillary electrophoresis (CE) method based on the relation between effective electrophoretic mobilities and pH has proven to be a suitable tool for pKa determination, while the spectrophotometric (CE-DAD) and the internal standard methods (IS-CE), have appeared to be promising alternative approaches. The CE-DAD approach based on the change in absorbance spectra between the acidic and basic forms is a combination between capillary electrophoresis and spectrophotometric titration, and yields very consistent values of pKa1 with CE. The IS-CE, in turn, enables an estimation of pKa1 and pKa2 from only two analytical runs, however, less accurate than CE and CE-DAD. The Debye-Hückel model has been confirmed experimentally as a good predictor of pKa values at various ionic strengths. Therefore, it has been used in determination of thermodynamic pKa1 and pKa2, referring to the zero ionic strength. The results are important from the analytical, pharmacological, and theoretical points of view.

  20. The impact of antigen density and antibody affinity on antibody-dependent cellular cytotoxicity: relevance for immunotherapy of carcinomas.

    PubMed Central

    Velders, M. P.; van Rhijn, C. M.; Oskam, E.; Fleuren, G. J.; Warnaar, S. O.; Litvinov, S. V.

    1998-01-01

    Antibody-dependent cellular cytotoxicity (ADCC) is considered to be the major mechanism through which tumour cells, upon treatment with anti-tumour MAbs, are eliminated in vivo. However, the relative importance of various parameters that influence the efficacy of ADCC is unclear. Here we present in vitro data on the impact of MAb affinity and antigen density on ADCC, as obtained by comparison of two MAbs against the tumour-associated antigen Ep-CAM. The low-affinity MAb 17-1A (Ka = 5 x 10(7)M(-1)) currently used for therapy, and the high-affinity MAb 323/A3 (Ka = 2 x 10(9) M(-1)), were compared in ADCC experiments against murine and human tumour target cells transfected with the Ep-CAM cDNA under the control of an inducible promoter to enable regulation of the target antigen expression levels. Data obtained from these studies revealed that the high-affinity MAb, in contrast to the low-affinity MAb, could mediate killing of tumour cells with low antigen expression levels. Even at comparable MAb-binding levels, ADCC mediated by the high-affinity MAb was more effective. The kinetics of ADCC was also found to be determined by the level of antigen expression, and by the affinity and the concentration of the MAb used. The efficacy of ADCC with both low- and high-affinity MAbs further depended on adhesive interactions between effector and target cells mediated by CD18. However, at every given MAb concentration these interactions were of less importance for the high-affinity MAb than for the low-affinity MAb. As heterogeneity of a target antigen expression is a common feature of all tumours, and some tumour cells express very low levels of the antigen, the use of high-affinity MAbs in immunotherapy may significantly improve the clinical results obtained to the present date in the treatment of minimal residual disease. PMID:9716030

  1. 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.

  2. 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.

  3. DARHT 2 kA Cathode Development

    SciTech Connect

    Henestroza, E.; Houck, T.; Kwan, J.W.; Leitner, M.; Miram, G.; Prichard, B.; Roy, P.K.; Waldron, W.; Westenskow, G.; Yu, S.; Bieniosek, F.M.

    2009-03-09

    In the campaign to achieve 2 kA of electron beam current, we have made several changes to the DARHT-II injector during 2006-2007. These changes resulted in a significant increase in the beam current, achieving the 2 kA milestone. Until recently (before 2007), the maximum beam current that was produced from the 6.5-inch diameter (612M) cathode was about 1300 A when the cathode was operating at a maximum temperature of 1140 C. At this temperature level, the heat loss was dominated by radiation which is proportional to temperature to the fourth power. The maximum operating temperature was limited by the damage threshold of the potted filament and the capacity of the filament heater power supply, as well as the shortening of the cathode life time. There were also signs of overheating at other components in the cathode assembly. Thus it was clear that our approach to increase beam current could not be simply trying to run at a higher temperature and the preferred way was to operate with a cathode that has a lower work function. The dispenser cathode initially used was the type 612M made by SpectraMat. According to the manufacturer's bulletin, this cathode should be able to produce more than 10 A/cm{sup 2} of current density (corresponding to 2 kA of total beam current) at our operating conditions. Instead the measured emission (space charge limited) was 6 A/cm{sup 2}. The result was similar even after we had revised the activation and handling procedures to adhere more closely to the recommend steps (taking longer time and nonstop to do the out-gassing). Vacuum was a major concern in considering the cathode's performance. Although the vacuum gauges at the injector vessel indicated 10{sup -8} Torr, the actual vacuum condition near the cathode in the central region of the vessel, where there might be significant out-gassing from the heater region, was never determined. Poor vacuum at the surface of the cathode degraded the emission (by raising the work function value). We

  4. "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.

  5. 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.

  6. 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)

  7. Dating loess up to 800 ka by thermoluminescence

    SciTech Connect

    Berger, G.W. ); Pillans, B.J. ); Palmer, A.S. )

    1992-05-01

    Thermoluminescence (TL) ages agreeing with expected ages have been obtained for 13 loess samples spanning the age range from 20 to 800 ka. The authors samples are from Alaska and North Island, New Zealand, and are unusual in TL dating studies of loess older than 80-100 ka by having independent age assignments that are generally well constrained, from ages of associated tephra beds. With the polymineral fine-silt-sized (4-11 {mu}m) grains the partial-bleach TL technique yielded expected ages up to about 350 ka, whereas the total-bleach method gave accurate ages in the range 100 to 800 ka. Thus, the much disputed upper age limit of 100-150 ka for the TL dating of loess now appears to be sample and worker dependent, rather than a global property of the TL signals in the TL-dominant feldspars.

  8. 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.

  9. Ka-Band Autonomous Formation Flying Sensor

    NASA Technical Reports Server (NTRS)

    Tien, Jeffrey; Purcell, George, Jr.; Srinivasan, Jeffrey; Ciminera, Michael; Srinivasan, Meera; Meehan, Thomas; Young, Lawrence; Aung, MiMi; Amaro, Luis; Chong, Yong; Quirk, Kevin

    2004-01-01

    Ka-band integrated range and bearing-angle formation sensor called the Autonomous Formation Flying (AFF) Sensor has been developed to enable deep-space formation flying of multiple spacecraft. The AFF Sensor concept is similar to that of the Global Positioning System (GPS), but the AFF Sensor would not use the GPS. The AFF Sensor would reside in radio transceivers and signal-processing subsystems aboard the formation-flying spacecraft. A version of the AFF Sensor has been developed for initial application to the two-spacecraft StarLight optical-interferometry mission, and several design investigations have been performed. From the prototype development, it has been concluded that the AFF Sensor can be expected to measure distances and directions with standard deviations of 2 cm and 1 arc minute, respectively, for spacecraft separations ranging up to about 1 km. It has also been concluded that it is necessary to optimize performance of the overall mission through design trade-offs among the performance of the AFF Sensor, the field of view of the AFF Sensor, the designs of the spacecraft and the scientific instruments that they will carry, the spacecraft maneuvers required for formation flying, and the design of a formation-control system.

  10. 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

  11. 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.

  12. 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.

  13. On the development of protein pKa calculation algorithms

    SciTech Connect

    Carstensen, Tommy; Farrell, Damien; Huang, Yong; Baker, Nathan A.; Nielsen, Jens E.

    2011-12-01

    Protein pKa calculation algorithms are typically developed to reproduce experimental pKa values and provide us with a better understanding of the fundamental importance of electrostatics for protein structure and function. However, the approximations and adjustable parameters employed in almost all pKa calculation methods means that there is the risk that pKa calculation algorithms are 'over-fitted' to the available datasets, and that these methods therefore do not model protein physics realistically. We employ simulations of the protein pKa calculation algorithm development process to show that careful optimization procedures and non-biased experimental datasets must be applied to ensure a realistic description of the underlying physical terms. We furthermore investigate the effect of experimental noise and find a significant effect on the pKa calculation algorithm optimization landscape. Finally, we comment on strategies for ensuring the physical realism of protein pKa calculation algorithms and we assess the overall state of the field with a view to predicting future directions of development.

  14. NASA SCaN Overview and Ka-Band Actvities

    NASA Technical Reports Server (NTRS)

    Stegeman, James D.; Midon, Marco Mario; Davarian, Faramaz; Geldzahler, Barry

    2014-01-01

    The Ka- and Broadband Communications Conference is an international forum attended by worldwide experts in the area of Ka-Band Propagation and satellite communications. Since its inception, NASA has taken the initiative of organizing and leading technical sections on RF Propagation and satellite communications, solidifying its worldwide leadership in the aforementioned areas. Consequently, participation in this conference through the contributions described below will maintain NASA leadership in Ka- and above RF Propagation as it relates to enhancing current and future satellite communication systems supporting space exploration.

  15. 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.

  16. 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%.

  17. Onboard Interferometric SAR Processor for the Ka-Band Radar Interferometer (KaRIn)

    NASA Technical Reports Server (NTRS)

    Esteban-Fernandez, Daniel; Rodriquez, Ernesto; Peral, Eva; Clark, Duane I.; Wu, Xiaoqing

    2011-01-01

    An interferometric synthetic aperture radar (SAR) onboard processor concept and algorithm has been developed for the Ka-band radar interferometer (KaRIn) instrument on the Surface and Ocean Topography (SWOT) mission. This is a mission- critical subsystem that will perform interferometric SAR processing and multi-look averaging over the oceans to decrease the data rate by three orders of magnitude, and therefore enable the downlink of the radar data to the ground. The onboard processor performs demodulation, range compression, coregistration, and re-sampling, and forms nine azimuth squinted beams. For each of them, an interferogram is generated, including common-band spectral filtering to improve correlation, followed by averaging to the final 1 1-km ground resolution pixel. The onboard processor has been prototyped on a custom FPGA-based cPCI board, which will be part of the radar s digital subsystem. The level of complexity of this technology, dictated by the implementation of interferometric SAR processing at high resolution, the extremely tight level of accuracy required, and its implementation on FPGAs are unprecedented at the time of this reporting for an onboard processor for flight applications.

  18. Aspartate embedding depth affects pHLIP's insertion pKa.

    PubMed

    Fendos, Justin; Barrera, Francisco N; Engelman, Donald M

    2013-07-09

    We have used the pHlow insertion peptide (pHLIP) family to study the role of aspartate embedding depth in pH-dependent transmembrane peptide insertion. pHLIP binds to the surface of a lipid bilayer as a largely unstructured monomer at neutral pH. When the pH is lowered, pHLIP inserts spontaneously across the membrane as a spanning α-helix. pHLIP insertion is reversible when the pH is adjusted back to a neutral value. One of the critical events facilitating pHLIP insertion is the protonation of aspartates in the spanning domain of the peptide: the negative side chains of these residues convert to uncharged, polar forms, facilitating insertion by altering the hydrophobicity of the spanning domain. To examine this protonation mechanism further, we created pHLIP sequence variants in which the two spanning aspartates (D14 and D25) were moved up or down in the sequence. We hypothesized that the aspartate depth in the inserted state would directly affect the proton affinity of the acidic side chains, altering the pKa of pH-dependent insertion. To this end, we also mutated the arginine at position 11 to determine whether arginine snorkeling modulates the insertion pKa by affecting the aspartate depth. Our results indicate that both types of mutations change the insertion pKa, supporting the idea that the aspartate depth is a participating parameter in determining the pH dependence. We also show that pHLIP's resistance to aggregation can be altered with our mutations, identifying a new criterion for improving the performance of pHLIP in vivo when targeting acidic disease tissues such as cancer and inflammation.

  19. Measuring the successes and deficiencies of constant pH molecular dynamics: A blind prediction study

    PubMed Central

    Williams, Sarah L; Blachly, Patrick G; McCammon, J Andrew

    2011-01-01

    A constant pH molecular dynamics method has been used in the blind prediction of pKa values of titratable residues in wild type and mutated structures of the Staphylococcal nuclease (SNase) protein. The predicted values have been subsequently compared to experimental values provided by the laboratory of García-Moreno. CpHMD performs well in predicting the pKa of solvent-exposed residues. For residues in the protein interior, the CpHMD method encounters some difficulties in reaching convergence and predicting the pKa values for residues having strong interactions with neighboring residues. These results show the need to accurately and sufficiently sample conformational space in order to obtain pKa values consistent with experimental results. PMID:22072520

  20. 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.…

  1. 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.

  2. 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

  3. 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

  4. Mars Telecommunications Orbiter Ka-band system design and operations

    NASA Technical Reports Server (NTRS)

    Noreen, Gary; Komarek, Tomas; Diehl, Roger; Shambayati, Shervin; Breidenthal, Julian; Lopez, Saturnino; Jordan, Frank

    2003-01-01

    NASA's Mars Telecommunications Orbiter (MTO) will relay broadband communications from landers, rovers and spacecraft in the vicinity of Mars to Earth. This paper describes the MTO communications system and how the MTO Ka-band system will be operated.

  5. The Mars Observer Ka-band link experiment

    NASA Technical Reports Server (NTRS)

    Rebold, T. A.; Kwok, A.; Wood, G. E.; Butman, S.

    1994-01-01

    The Ka-Band Link Experiment was the first demonstration of a deep-space communications link in the 32- to 35-GHz band (Ka-band). It was carried out using the Mars Observer spacecraft while the spacecraft was in the cruise phase of its mission and using a 34-meter beam-waveguide research and development antenna at the Goldstone complex of the DSN. The DSN has been investigating the performance benefits of a shift from X-band (8.4 GHz) to Ka-band (32 GHz) for deep-space communications. The fourfold increase in frequency is expected to offer a factor of 3 to 10 improvement (5 to 10 dB) in signal strength for a given spacecraft transmitter power and antenna size. Until recently, the expected benefits were based on performance studies, with an eye to implementing such a link, but theory was transformed to reality when a 33.7-GHz Ka-band signal was received from the spacecraft by DSS 13. This article describes the design and implementation of the Ka-Band Link Experiment from the spacecraft to the DSS-13 system, as well as results from the Ka-band telemetry demonstration, ranging demonstration, and long-term tracking experiment. Finally, a preliminary analysis of comparative X- and Ka-band tracking results is included. These results show a 4- to 7-dB advantage for Ka-band using the system at DSS 13, assuming such obstacles as antenna pointing loss and power conversion loss are overcome.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. An 85-ka Paleoclimate Record From Lowland Central America

    NASA Astrophysics Data System (ADS)

    Escobar, J.; Hodell, D. A.; Anselmetti, F. S.; Ariztegui, D.; Brenner, M.; Curtis, J. H.; Gilli, A.; Grzesik, D. A.; Guilderson, T. J.; Müller, A. D.; Bush, M. B.; Correa-Metrio, A.; Kutterolf, S.

    2008-05-01

    Lake sediment cores recovered at seven sites in Lake Peten Itza, northern Guatemala, contain a record of climate change from lowland Central America extending back to ~200 ka. Drill cores at site PI-6 contain a high- resolution record (1 m/ka) for the last ~85 ka. Peten climate generally varied between wetter conditions during interstadials and a drier state during stadials of Marine Isotope Stage (MIS) 3. The most arid periods coincided with Heinrich Events in the North Atlantic and reductions in the strength of meridional overturning circulation. The pattern of clay-gypsum (wet-dry) oscillations during MIS 3 closely resembles the temperature record from Greenland ice cores and North Atlantic marine sediment cores and precipitation proxies from the Cariaco Basin. Previous studies suggested that cool, dry conditions prevailed in the region during the last glacial maximum (LGM) chronozone, ~23 to 18 ka BP. Sedimentologic and palynologic data support a moist climate in the Peten lowlands during this period whenvegetation consisted of a temperate pine-oak forest. This finding contradicts the previous inferences. At the end of the LGM, Peten climate switched abruptly from moist to arid conditions during the so-called "Mystery Period" from 18 to 14.9 ka. Moister conditions prevailed during the warmer Bolling-Allerod (14.7 to 12.8 ka), with the exception of a drier climate, with greater δ18O values between ca. 14.5 and 13.5 ka BP. This drier period in Central America coincided with Meltwater Pulse 1A (14.1- 13.5 ka) (Fairbanks et al., 2005) when a substantial volume of glacial meltwater was introduced to the Gulf of Mexico (e.g. Flower et al., 2004). The greatest δ18O values in Peten Itza occurred at 13.7 ka coinciding with the greatest rate of sea level rise (4.3 cm yr-1) at 13.9 ka. In contrast, sea surface temperature (SST) reconstructions (Lea et al., 2003), color reflectance, and elemental (Fe, Ti) data (Peterson et al., 2000) from Cariaco Basin cores, north of

  17. 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.

  18. 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.

  19. Analysis of agonist dissociation constants as assessed by functional antagonism in guinea pig left atria

    SciTech Connect

    Molenaar, P.; Malta, E.

    1986-04-01

    In electrically driven guinea pig left atria, positive inotropic responses to (-)-isoprenaline and the selective beta 1-adrenoceptor agonist RO363 were obtained in the absence and in the presence of the functional antagonists adenosine, carbachol, gallopamil, nifedipine, and Ro 03-7894. Each of the functional antagonists reduced the maximum response to both agonists and produced nonparallel rightward shifts in the cumulative concentration effect curves. For both agonists, dissociation constants (KA) were calculated using the equation described by Furchgott (1966) for irreversible antagonism. For RO363, which is a partial agonist with high agonist activity, the equations outlined for functional interaction by Mackay (1981) were also employed to calculate KA values. The KA values obtained by each method were compared with the dissociation constants (KD) for the two agonists determined from their ability to displace the radioligand (-)-(/sup 125/I)iodocyanopindolol from beta 1-adrenoceptors in guinea pig left atrial membrane preparations. The estimates of KA varied substantially from KD values. The KD values were taken as more accurate estimates of the true values for the dissociation constants because a high degree of correlation exists between pKD and pD2 values for a number of other beta-adrenoceptor agonists that behave as partial agonists and between pKD and pKB values for a number of beta-adrenoceptor antagonists. Thus, it appears that there are serious limitations in the current theory for using functional antagonism as a means of obtaining agonist dissociation constants.

  20. Characterization of the Dielectric Constant in the Trichoderma reesei Cel7B Active Site.

    PubMed

    Song, Xiangfei; Wang, Yefei; Zhang, Shujun; Yan, Shihai; Li, Tong; Yao, Lishan

    2015-07-27

    An attempt is made to evaluate the dielectric constant of the Trichoderma reesei Cel7B active site. Through kinetic measurements, the pKa value of the catalytic acid E201 is determined. Mutations (away from E201) with net charge changes are introduced to perturb the E201 pKa. It is shown that the mutation with a +1 charge change (including G225R, G230R, and A335R) decreases the pKa of E201, whereas the mutation with a -1 charge change (including Q149E, A222D, G225D, and G230D) increases the pKa. This effect is consistent with the electrostatic interaction between the changed charge and the E201 side chain. The fitting of the experimental data yields an apparent dielectric constant of 25-80. Molecular dynamics simulations with explicit water molecules indicate that the high solvent accessibility of the active site contributes largely to the high dielectric constant. ONIOM calculations show that high dielectric constant benefits the catalysis through decreasing the energy of the transition state relative to that of the enzyme substrate complex.

  1. AN ALTERNATIVE METHOD FOR RELATING MACROSCOPIC TO MICROSCOPIC ACIDITY CONSTANTS WITH ZWITTERIONIC SPECIES

    EPA Science Inventory

    Using the notation of Adams (1916. JACS, 38:1503), zwitterionic microscopic acidity constants defined by: ka = [H+] [+H3NRCOO-]/ [+H3NRCOOH]; kb = [H+] [H2NRCOOH]/ [+H3NRCOOH]; kc = [H+] [H2NRCOO-]/ [+H3NRCOO-]; and kd = [H+] [H2NRCOO-]/ [H2NRCOOH] are historically related to th...

  2. UV/vis, 1H, and 13C NMR spectroscopic studies to determine mangiferin pKa values.

    PubMed

    Gómez-Zaleta, Berenice; Ramírez-Silva, María Teresa; Gutiérrez, Atilano; González-Vergara, Enrique; Güizado-Rodríguez, Marisol; Rojas-Hernández, Alberto

    2006-07-01

    The acid constants of mangiferin (a natural xanthonoid) in aqueous solution were determined through an UV/vis spectroscopic study employing the SQUAD program as a computational tool. A NMR study complements the pK(a) values assignment and evidences a H-bridge presence on 1-C. The chemical model used was consistent with the experimental data obtained. The pK(a) values determined with this procedure were as follows: H(4)(MGF)=H(3)(MGF)(-)+H(+), pKa1 (6-H)=6.52+/-0.06; H(3)(MGF)(-)=H(2)(MGF)(2-)+H(+), pKa2 (3-H)=7.97+/-0.06; H(2)(MGF)(2-)=H(MGF)(3-)+H(+), pKa3 (7-H)=9.44+/-0.04; H(MGF)(3-)=(MGF)(4-)+H(+), pKa4 (1-H)=12.10+/-0.01; where it has been considered mangiferin C(19)H(18)O(11) as H(4)(MGF). Mangiferin UV/vis spectral behavior, stability study in aqueous solution as well as NMR spectroscopy studies: one-dimensional (1)H,(13)C, 2D correlated (1)H/(13)C performed by (g)-HSQC and (g)-HMBC methods; are also presented. pK(a) values determination of H(4)(MGF) in aqueous solution is a necessary contribution to subsequent pharmacokinetic study, and a step towards the understanding of its biological effects.

  3. The Geology of the Ka'u Desert, Hawaii as a Mars Analog

    NASA Astrophysics Data System (ADS)

    Craddock, R. A.; Irwin, R. P.; Williams, R.; Swanson, D.; Howard, A. D.; Quantin, C.; Kuzmin, R.; Zimbelman, J. R.

    2005-12-01

    The Ka'u Desert is located on the western flank of Kilauea volcano on the Big Island of Hawaii. It is a desert because it receives little annual rainfall (about 150 mm/yr) but also because it is subjected to constant outgassing from Kilauea, which creates a harsh, acidic environment. Near the summit of Kilauea the Ka'u Desert is characterized by the Keanakako'i tephra deposit, which is several meters deep thinning out to a discontinuous deposit 1.5 km (1 mile) towards the center of the desert. The deposit itself has been incised by a number of gullies that are flat-floored and terminate in a series of amphitheater-shaped plunge pools. Most of the interior desert contains undulating weathered lava flows, extensive deposits of sand, and several more recent lava flows and volcanic edifices. The southern portion of the desert is bounded by the Hilina Pali fault scarp, which is 500 m (1,500 ft) above the nearby Pacific Ocean and contains a complex series of outwash plains, alluvial fans, and debris flows. We will present a summary of the geology of the Ka'u Desert. Contrary to published interpretations, we will present evidence that the Keanakako'i was not emplaced by two separate catastrophic eruption events but rather by two distinct eruption episodes that included multiple eruption events often interrupted by long hiatuses. Despite the morphology of the gullies contained on the Keanakako'i we will present evidence that the gullies were formed exclusively by surface runoff and not groundwater sapping, including quantitative estimates about the large amounts of discharge that occur during extreme storms. We will also present analyses of the sand deposits and determine the likely provenance of these materials. For the first time, we will also describe alluvial fans and mass wasting features on Hilina Pali and show evidence that they are part of poorly integrated channel system that originates in the Keanakako'i tephra. The Ka'u Desert represents a good Mars analog

  4. Xen clusters in the alpha cages of zeolite KA

    NASA Astrophysics Data System (ADS)

    Jameson, Cynthia J.; Jameson, A. Keith; Gerald, Rex E., II; Lim, Hyung-Mi

    1995-11-01

    We have observed the individual signals of the Xen clusters (n=1-5) trapped in the alpha cages of zeolite KA. The 129Xe NMR chemical shift of each cluster in zeolite KA is larger than that of the corresponding Xen cluster in zeolite NaA. The temperature dependence of the chemical shifts of the clusters vary systematically with cluster size as they do in NaA, but the change of the temperature coefficients with n is somewhat more pronounced for Xen in the cages of KA than in NaA. The Xen chemical shifts and their variation with temperature are reproduced by the grand canonical Monte Carlo (GCMC) simulations. GCMC simulations of the distribution of the Xe atoms among the alpha cages in KA provide the fractions of cages containing n Xe atoms which agree reasonably well with the observed equilibrium distributions. The characteristics of Xe distribution and chemical shifts in KA are compared with that in NaA.

  5. Ku/Ka band observations over polar ice sheets

    NASA Astrophysics Data System (ADS)

    Thibaut, Pierre; Lasne, Yannick; Guillot, Amandine; Picot, Nicolas; Rémy, Frédérique

    2015-04-01

    For the first time, comparisons between Ku and Ka altimeter measurements are possible thanks to the new AltiKa instrument embarked onboard the Saral mission launched on February 25, 2013. This comparison is of particular interest when dealing with ice sheet observations because both frequencies have different penetration characteristics. We propose in this paper to revisit the estimation of the ice sheet topography (and other related parameters) with altimeter systems and to present illustrations of the differences observed in Ku and Ka bands using AltiKa, Envisat/RA-2 but also Cryosat-2 measurements. Working on AltiKa waveforms in the frame of the PEACHI project has allowed us to better understand the impact of the penetration depth on the echo shape, to improve the estimation algorithm and to compare its output with historical results obtained on Envisat and ERS missions. In particular, analyses at cross-overs of the Cryosat-2 and Saral data will be presented. Sentinel-3 mission should be launch during 2015. Operating in Ku band and in delay/doppler mode, it will be crucial to account for penetration effects in order to accurately derive the ice sheet heights and trends. The results of the work presented here, will benefit to the Sentinel-3 mission.

  6. Sea surface temperatures in the North Atlantic Ocean from 30ka to 10ka

    NASA Astrophysics Data System (ADS)

    Barrack, Kerr; Greenop, Rosanna; Burke, Andrea; Barker, Stephen; Chalk, Thomas; Crocker, Anya

    2016-04-01

    Some of the most striking features of the Late Pleistocene interval are the rapid changes in climate between warmer interstadial and cold stadial periods which, when coupled, are termed Dansgaard-Oeschger (D-O) events. This shift between warm and cold climates has been interpreted to result from changes in the thermohaline circulation (Broecker et al., 1985) triggered by, for instance, freshwater input from the collapse of the Laurentide ice sheet (Zahn et al., 1997). However, a recent study suggests that major ice rafting events cannot be the 'trigger' for the centennial to millennial scale cooling events identified over the past 500kyr (Barker at al., 2015). Polar planktic foraminiferal and lithogenic/terrigenous grain counts reveal that the southward migration of the polar front occurs before the deposition of ice rafted debris and therefore the rafting of ice during stadial periods. Based upon this evidence, Barker et al. suggest that the transition to a stadial state is a non-linear response to gradual cooling in the region. In order to test this hypothesis, our study reconstructs sea surface temperature across D-O events and the deglaciation in the North Atlantic between 30ka and 10ka using Mg/ Ca paleothermometry in Globigerina bulloides at ODP Sites 980 and 983 (the same sites as used in Barker et al., 2015) with an average sampling resolution of 300 years. With our new record we evaluate the timing of surface ocean temperature change, frontal shift movement, and ice rafting to investigate variations in the temperature gradient across the polar front over D-O events. References: Barker, S., Chen, J., Gong, X., Jonkers, L., Knorr, G., Thornalley, D., 2015. Icebergs not the trigger for North Atlantic cold events. Nature, 520(7547), pp.333-336. Broecker, W.S., Peteer, D.M., Rind, D., 1985. Does the ocean-atmosphere system have more than one stable mode of operation? Nature, 315 (6014), pp.21-26. Zahn, R., Schönfeld, J., Kudrass, H.-R., Park, M

  7. 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.

  8. A chirality change in XPC- and Sfi1-derived peptides affects their affinity for centrin.

    PubMed

    Grecu, Dora; Irudayaraj, Victor Paul Raj; Martinez-Sanz, Juan; Mallet, Jean-Maurice; Assairi, Liliane

    2016-04-01

    The Ca(2+)-binding protein centrin binds to a hydrophobic motif (W(1)xxL(4)xxxL(8)) included in the sequence of several cellular targets: XPC (xeroderma pigmentosum group C protein), Sfi1 (suppressor of fermentation-induced loss of stress resistance protein1), and Sac3 [the central component of the transcription and mRNA export (TREX-2) complex]. However, centrin binding occurs in a reversed orientation (L(8)xxxL(4)xxW(1)) for Sfi1 and Sac3 compared with XPC. Because D-peptides have been investigated for future therapeutic use, we analyzed their centrin-binding properties. Their affinity for centrin was measured using isothermal titration calorimetry. The chirality change in the target-derived peptides affected their ability to bind centrin in a specific manner depending on the sequence orientation of the centrin-binding motif. In contrast to L-XPC-P10, D-XPC-P10 bound C-HsCen1 in a Ca(2+)-dependent manner and to a lesser extent. D-XPC-P10 exhibited a reduced affinity for C-HsCen1 (Ka=0.064 × 10(6) M(-1)) by a factor of 2000 compared with L-XPC-P10 (Ka=132 × 10(6) M(-1)). D-peptides have a lower affinity than L-peptides for centrin, and the strength of this affinity depends on the sequence orientation of the target-derived peptides. The residual affinity observed for D-XPC suggests that the use of d-peptides represents a promising strategy for inhibiting centrin binding to its targets.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. Design of protonation constant measurement apparatus for carbon dioxide capturing solvents

    NASA Astrophysics Data System (ADS)

    Ma'mun, S.; Amelia, E.; Rahmat, V.; Alwani, D. R.; Kurniawan, D.

    2016-11-01

    Global warming phenomenon has led to world climate change caused by high concentrations of greenhouse gases (GHG), e.g. carbon dioxide (CO2), in the atmosphere. Carbon dioxide is produced in large amount from coal-fired power plants, iron and steel production, cement production, chemical and petrochemical manufacturing, natural gas purification, and transportation. Carbon dioxide emissions seem to rise from year to year; some efforts to reduce the emissions are, therefore, required. Amine-based absorption could be deployed for post-combustion capture. Some parameters, e.g. mass transfer coefficients and chemical equilibrium constants, are required for a vapor-liquid equilibrium modeling. Protonation constant (pKa), as one of those parameters, could then be measured experimentally. Therefore, an experimental setup to measure pKa of CO2 capturing solvents was designed and validated by measuring the pKa of acetic acid at 30 to 70 °C by a potentiometric titration method. The set up was also used to measure the pKa of MEA at 27 °C. Based on the validation results and due to low vapor pressure of CO2 capturing solvents in general, e.g. alkanolamines, the setup could therefore be used for measuring pKa of the CO2 capturing solvents at temperatures up to 70 °C.

  16. Base-sequence specificity of Hoechst 33258 and DAPI binding to five (A/T)4 DNA sites with kinetic evidence for more than one high-affinity Hoechst 33258-AATT complex.

    PubMed

    Breusegem, Sophia Y; Clegg, Robert M; Loontiens, Frank G

    2002-02-01

    The binding of Hoechst 33258 and DAPI to five different (A/T)4 sequences in a stable DNA hairpin was studied exploiting the substantial increase in dye fluorescence upon binding. The two dyes have comparable affinities for the AATT site (e.g. association constant K(a)=5.5 x 10(8) M(-1) for DAPI), and their affinities decrease in the series AATT > TAAT approximately equal to ATAT > TATA approximately equal to TTAA. The extreme values of K(a) differ by a factor of 200 for Hoechst 33258 but only 30 for DAPI. The binding kinetics of Hoechst 33258 were measured by stopped-flow under pseudo-first order conditions with an (A/T)4 site in excess. The lower-resolution experiments can be well represented by single exponential processes, corresponding to a single-step binding mechanism. The calculated association-rate parameters for the five (A/T)4 sites are similar (2.46 x 10(8) M(-1) s(-1) to 0.86 x 10(8) M(-1) s(-1)) and nearly diffusion-controlled, while the dissociation-rate parameters vary from 0.42 s(-1) to 96 s(-1). Thus the association constants are kinetically controlled and are close to their equilibrium-determined values. However, when obtained with increased signal-to-noise ratio, the kinetic traces for Hoechst 33258 binding at the AATT site reveal two components. The concentration dependencies of the two time constants and amplitudes are consistent with two different kinetically equivalent two-step models. In the first model, fast bimolecular binding is followed by an isomerization of the initial complex. In the second model, two single-step associations form two complexes that mutually exclude each other. For both models the four reaction-rate parameters are calculated. Finally, specific dissociation kinetics, using poly[d(A-5BrU)], show that the kinetics are even more complex than either two-step model. We correlate our results with the different binding orientations and locations of Hoechst 33258 in the DNA minor groove found in several structural studies in

  17. Probing the binding affinity of plasma proteins adsorbed on Au nanoparticles.

    PubMed

    Zhang, Xiaoning; Zhang, Junting; Zhang, Fan; Yu, Shaoning

    2017-04-06

    Nanoparticle (NP) surfaces are modified immediately by the adsorption of proteins when exposed to human blood, leading to the formation of a protein corona. The adsorption of serum proteins is the key process for exploring the bioapplication and biosafety of NPs. In this study, NP-protein binding affinity (Ka) was investigated. Some serum proteins, such as human serum albumin (HSA), trypsin (TRP), hemoglobin (Hb), myoglobin (MB), immunoglobulin G (IgG), carbonic anhydrase (CA), fibrinogen (FIB), chymotrypsin and r-globulin, were used with gold nanoparticles (AuNPs) to address binding affinity according to isothermal titration calorimetry (ITC) combined with dynamic light scattering (DLS) and fluorescence quenching. The NP protein binding affinities determined by the two methods were in agreement, and depended on the protein properties and size of the NPs. The two methods are convenient, and the results are highly comparable. These methods can be extended to determine the binding affinity of NP protein interactions. The adsorption of proteins upon the AuNP surface is a complex process and depends on several factors, but the binding affinities are higher for proteins with more cysteine residues located on the surface.

  18. Ka-band MMIC microstrip array for high rate communications

    NASA Technical Reports Server (NTRS)

    Lee, R. Q.; Raquet, C. A.; Tolleson, J. B.; Sanzgiri, S. M.

    1991-01-01

    In a recent technology assessment of alternative communication systems for the space exploration initiative (SEI), Ka-band (18 to 40 GHz) communication technology was identified to meet the mission requirements of telecommunication, navigation, and information management. Compared to the lower frequency bands, Ka-band antennas offer higher gain and broader bandwidths; thus, they are more suitable for high data rate communications. Over the years, NASA has played an important role in monolithic microwave integrated circuit (MMIC) phased array technology development, and currently, has an ongoing contract with Texas Instrument (TI) to develop a modular Ka-band MMIC microstrip subarray (NAS3-25718). The TI contract emphasizes MMIC integration technology development and stipulates using existing MMIC devices to minimize the array development cost. The objective of this paper is to present array component technologies and integration techniques used to construct the subarray modules.

  19. 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.

  20. 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.

  1. X-/Ka-Band Dichroic Plate Noise Temperature Reduction

    NASA Astrophysics Data System (ADS)

    Veruttipong, W.; Lee, P.

    1994-07-01

    The X-/Ka-band (8.4-GHz/32.0-GHz) dichroic plate installed at DSS 13 contributes an estimated 3 K to the system noise temperature at 32.0 GHz. Approximately 1 percent of the Ka-band incident field is reflected by the plate into the 300-K environment of the DSS-13 pedestal room. A low-cost, easily implemented method of reducing the noise temperature is presented. Using a curved reflector, the reflected field can be refocused into an 80-K cold load, reducing the noise temperature contribution of the dichroic plate by about 2 K.

  2. X-/Ka-band dichroic plate noise temperature reduction

    NASA Astrophysics Data System (ADS)

    Veruttipong, W.; Lee, P.

    1994-11-01

    The X-/Ka-band (8.4 GHz/32.0 GHz) dichroic plate installed as DSS 13 contributes an estimated 3 K to the system noise temperature at 32.0 GHz. Approximately 1 percent of the Ka-band incident field is reflected by the plate into the 300-K environment of the DSS-13 pedestal room. A low-cost, easily implemented method of reducing the noise temperature is presented. Using a curved reflector, the reflected field can be re-focused into an 80-K cold load, reducing the noise temperature contribution of the dichroic plate by about 2 K.

  3. X-/Ka-band dichroic plate noise temperature reduction

    NASA Technical Reports Server (NTRS)

    Veruttipong, W.; Lee, P.

    1994-01-01

    The X-/Ka-band (8.4 GHz/32.0 GHz) dichroic plate installed as DSS 13 contributes an estimated 3 K to the system noise temperature at 32.0 GHz. Approximately 1 percent of the Ka-band incident field is reflected by the plate into the 300-K environment of the DSS-13 pedestal room. A low-cost, easily implemented method of reducing the noise temperature is presented. Using a curved reflector, the reflected field can be re-focused into an 80-K cold load, reducing the noise temperature contribution of the dichroic plate by about 2 K.

  4. Screening and Isolation of Penicillinase Inhibitor, KA-107

    PubMed Central

    Iwai, Y.; Ohno, H.; Takeshima, H.; Yamaguchi, N.; Ōmura, S.; Hata, T.

    1973-01-01

    It is known that penicillin resistance of bacteria is mainly caused by the inactivation of penicillin by penicillinase derived from such strains. We have developed a screening procedure for penicillinase inhibitors. Several microorganisms were found to produce such inhibitors, and from the culture filtrate of Streptomyces gedanensis ATCC 4880 a penicillinase inhibitor, named KA-107, was isolated. The characteristics of this inhibitor were revealed by an in vitro test by using penicillinase derived from penicillin resistant Staphylococcus aureus, FS-1277. When KA-107 was used in combination with penicillin-G, ampicillin, d- or l-phenethicillin, the growth inhibitory activity of these penicillins was maintained. PMID:4202340

  5. Cold climate deglaciation prior to termination 2 implied by new evidence for high sea-levels at 132 KA

    SciTech Connect

    Johnson, R.G. . Dept. of Geology and Geophysics)

    1992-01-01

    Radioisotope dating of corals from reefs and beaches suggests a high sea stand just prior to termination 2. Lack of precision in the ages, stratigraphic uncertainties, and possible diagenetic alterations in the corals have prevented a widespread acceptance of this sea stand. These disadvantages can be avoided by an approach that uses differential uplift measurements to determine the duration of the interval of generally high sea-levels. The last interglacial terrace on Barbados has features indicating two intervals of constant sea-level: an older wave-cut at the inshore edge of the terrace, and a younger cut formed near present eustatic sea-level, below the crest, and just before the earliest Wisconsin glacial buildup. The differential uplift between these two features, measured at five locations having uplift rates between 0.18 and 0.39m/ka, yields a eustatic sea-level differences of 5.4m and a minimal duration of 12.1 [+-] 0.6ka between the two still stands. The assigned age of the younger wave-cut is 120 [+-] 0.5ka, based on sea-level regression due to ice sheet buildup implied by a Little Ice Age analog and rapidly falling Milankovitch summer insolation. The resulting minimal age of the first high sea-stand is 132.1 [+-] 1.1ka, about 7ka before termination 2. This age implies a major early deglaciation caused by a deficit of moisture transported to the great ice sheets, and occurring under relatively cold climate conditions.

  6. Pollen-climate relationships in time (9 ka, 6 ka, 0 ka) and space (upland vs. lowland) in eastern continental Asia

    NASA Astrophysics Data System (ADS)

    Tian, Fang; Cao, Xianyong; Dallmeyer, Anne; Zhao, Yan; Ni, Jian; Herzschuh, Ulrike

    2017-01-01

    Temporal and spatial stability of the vegetation-climate relationship is a basic ecological assumption for pollen-based quantitative inferences of past climate change and for predicting future vegetation. We explore this assumption for the Holocene in eastern continental Asia (China, Mongolia). Boosted regression trees (BRT) between fossil pollen taxa percentages (Abies, Artemisia, Betula, Chenopodiaceae, Cyperaceae, Ephedra, Picea, Pinus, Poaceae and Quercus) and climate model outputs of mean annual precipitation (Pann) and mean temperature of the warmest month (Mtwa) for 9 and 6 ka (ka = thousand years before present) were set up and results compared to those obtained from relating modern pollen to modern climate. Overall, our results reveal only slight temporal differences in the pollen-climate relationships. Our analyses suggest that the importance of Pann compared with Mtwa for taxa distribution is higher today than it was at 6 ka and 9 ka. In particular, the relevance of Pann for Picea and Pinus increases and has become the main determinant. This change in the climate-tree pollen relationship parallels a widespread tree pollen decrease in north-central China and the eastern Tibetan Plateau. We assume that this is at least partly related to vegetation-climate disequilibrium originating from human impact. Increased atmospheric CO2 concentration may have permitted the expansion of moisture-loving herb taxa (Cyperaceae and Poaceae) during the late Holocene into arid/semi-arid areas. We furthermore find that the pollen-climate relationship between north-central China and the eastern Tibetan Plateau is generally similar, but that regional differences are larger than temporal differences. In summary, vegetation-climate relationships in China are generally stable in space and time, and pollen-based climate reconstructions can be applied to the Holocene. Regional differences imply the calibration-set should be restricted spatially.

  7. 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.

  8. 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.

  9. Acid Dissociation Constants of Melamine Derivatives from Density Functional Theory Calculations

    NASA Astrophysics Data System (ADS)

    Jang, Yun Hee; Hwang, Sungu; Chang, Seo Bong; Ku, Jamin; Chung, Doo Soo

    2009-10-01

    Melamine and its hydrolysis products (ammeline, ammelide, and cyanuric acid) recently attracted great attention as major food contaminants. Developing analytical tools to quantify them requires exact knowledge of their acid dissociation constants (pKa values). Herein, we calculated the pKa values of these melamine derivatives in water, using a density functional theory quantum mechanical method [B3LYP/6-311++G(d,p)] in combination with the Poisson-Boltzmann continuum solvation model. The excellent agreement of the calculated values with the experimental ones shows that our method can be used to predict such properties of other food contaminants.

  10. 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

  11. 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.

  12. Ferroelectric switch for a high-power Ka-band active pulse compressor

    SciTech Connect

    Hirshfield, Jay L.

    2013-12-18

    Results are presented for design of a high-power microwave switch for operation at 34.3 GHz, intended for use in an active RF pulse compressor. The active element in the switch is a ring of ferroelectric material, whose dielectric constant can be rapidly changed by application of a high-voltage pulse. As envisioned, two of these switches would be built into a pair of delay lines, as in SLED-II at SLAC, so as to allow 30-MW μs-length Ka-band pulses to be compressed in time by a factor-of-9 and multiplied in amplitude to generate 200 MW peak power pulses. Such high-power pulses could be used for testing and evaluation of high-gradient mm-wave accelerator structures, for example. Evaluation of the switch design was carried out with an X-band (11.43 GHz) prototype, built to incorporate all the features required for the Ka-band version.

  13. Multi-Step Ka/Ka Dichroic Plate with Rounded Corners for NASA's 34m Beam Waveguide Antenna

    NASA Technical Reports Server (NTRS)

    Veruttipong, Watt; Khayatian, Behrouz; Hoppe, Daniel; Long, Ezra

    2013-01-01

    A multi-step Ka/Ka dichroic plate Frequency Selective Surface (FSS structure) is designed, manufactured and tested for use in NASA's Deep Space Network (DSN) 34m Beam Waveguide (BWG) antennas. The proposed design allows ease of manufacturing and ability to handle the increased transmit power (reflected off the FSS) of the DSN BWG antennas from 20kW to 100 kW. The dichroic is designed using HFSS and results agree well with measured data considering the manufacturing tolerances that could be achieved on the dichroic.

  14. Anatomically modern human in Southeast Asia (Laos) by 46 ka

    PubMed Central

    Demeter, Fabrice; Shackelford, Laura L.; Bacon, Anne-Marie; Duringer, Philippe; Westaway, Kira; Sayavongkhamdy, Thongsa; Braga, José; Sichanthongtip, Phonephanh; Khamdalavong, Phimmasaeng; Ponche, Jean-Luc; Wang, Hong; Lundstrom, Craig; Patole-Edoumba, Elise; Karpoff, Anne-Marie

    2012-01-01

    Uncertainties surround the timing of modern human emergence and occupation in East and Southeast Asia. Although genetic and archeological data indicate a rapid migration out of Africa and into Southeast Asia by at least 60 ka, mainland Southeast Asia is notable for its absence of fossil evidence for early modern human occupation. Here we report on a modern human cranium from Tam Pa Ling, Laos, which was recovered from a secure stratigraphic context. Radiocarbon and luminescence dating of the surrounding sediments provide a minimum age of 51–46 ka, and direct U-dating of the bone indicates a maximum age of ∼63 ka. The cranium has a derived modern human morphology in features of the frontal, occipital, maxillae, and dentition. It is also differentiated from western Eurasian archaic humans in aspects of its temporal, occipital, and dental morphology. In the context of an increasingly documented archaic–modern morphological mosaic among the earliest modern humans in western Eurasia, Tam Pa Ling establishes a definitively modern population in Southeast Asia at ∼50 ka cal BP. As such, it provides the earliest skeletal evidence for fully modern humans in mainland Southeast Asia. PMID:22908291

  15. Marine04 Marine radiocarbon age calibration, 26 ? 0 ka BP

    SciTech Connect

    Hughen, K; Baille, M; Bard, E; Beck, J; Bertrand, C; Blackwell, P; Buck, C; Burr, G; Cutler, K; Damon, P; Edwards, R; Fairbanks, R; Friedrich, M; Guilderson, T; Kromer, B; McCormac, F; Manning, S; Bronk-Ramsey, C; Reimer, P; Reimer, R; Remmele, S; Southon, J; Stuiver, M; Talamo, S; Taylor, F; der Plicht, J v; Weyhenmeyer, C

    2004-11-01

    New radiocarbon calibration curves, IntCal04 and Marine04, have been constructed and internationally ratified to replace the terrestrial and marine components of IntCal98. The new calibration datasets extend an additional 2000 years, from 0-26 ka cal BP (Before Present, 0 cal BP = AD 1950), and provide much higher resolution, greater precision and more detailed structure than IntCal98. For the Marine04 curve, dendrochronologically dated tree-ring samples, converted with a box-diffusion model to marine mixed-layer ages, cover the period from 0-10.5 ka cal BP. Beyond 10.5 ka cal BP, high-resolution marine data become available from foraminifera in varved sediments and U/Th-dated corals. The marine records are corrected with site-specific {sup 14}C reservoir age information to provide a single global marine mixed-layer calibration from 10.5-26.0 ka cal BP. A substantial enhancement relative to IntCal98 is the introduction of a random walk model, which takes into account the uncertainty in both the calendar age and the radiocarbon age to calculate the underlying calibration curve. The marine datasets and calibration curve for marine samples from the surface mixed layer (Marine04) are discussed here. The tree-ring datasets, sources of uncertainty, and regional offsets are presented in detail in a companion paper by Reimer et al.

  16. Cassini Downlink Ka-Band Carrier Signal Analysis

    NASA Astrophysics Data System (ADS)

    Morabito, D. D.; Kahan, D.; Oudrhiri, K.; Lee, C.-A.

    2017-02-01

    Lower frequency telemetry bands are becoming more limited in bandwidth with more competition between flight projects and other entities. Higher frequency bands offer significantly more bandwidth and hence the prospect of much higher data rates. Future or prospective flight projects considering Ka-band (32-GHz) telemetry data links are interested in past flight experience with received Ka-band data. Over 10 years of Cassini closed-loop received Ka-band carrier data involving over 2 million individual measurements were acquired at all three Deep Space Network (DSN) sites. We analyzed these data to characterize link performance over a wide range of weather conditions and as a function of elevation angle. Based on this analysis, we have derived a recommendation for telecommunications link margin for preflight planning purposes. These results suggest that a 4-dB margin will ensure a 94 percent data return at a minimum 20-deg elevation angle under 90 percent weather conditions at 32 GHz (Ka-band).

  17. Mars Global Surveyor Ka-Band Frequency Data Analysis

    NASA Technical Reports Server (NTRS)

    Morabito, D.; Butman, S.; Shambayati, S.

    2000-01-01

    The Mars Global Surveyor (MGS) spacecraft, launched on November 7, 1996, carries an experimental space-to-ground telecommunications link at Ka-band (32 GHz) along with the primary X-band (8.4 GHz) downlink. The signals are simultaneously transmitted from a 1.5-in diameter parabolic high gain antenna (HGA) on MGS and received by a beam-waveguide (BWG) R&D 34-meter antenna located in NASA's Goldstone Deep Space Network (DSN) complex near Barstow, California. The projected 5-dB link advantage of Ka-band relative to X-band was confirmed in previous reports using measurements of MGS signal strength data acquired during the first two years of the link experiment from December 1996 to December 1998. Analysis of X-band and Ka-band frequency data and difference frequency (f(sub x)-f(sub ka)/3.8) data will be presented here. On board the spacecraft, a low-power sample of the X-band downlink from the transponder is upconverted to 32 GHz, the Ka-band frequency, amplified to I-W using a Solid State Power Amplifier, and radiated from the dual X/Ka HGA. The X-band signal is amplified by one of two 25 W TWTAs. An upconverter first downconverts the 8.42 GHz X-band signal to 8 GHz and then multiplies using a X4 multiplier producing the 32 GHz Ka-band frequency. The frequency source selection is performed by an RF switch which can be commanded to select a VCO (Voltage Controlled Oscillator) or USO (Ultra-Stable Oscillator) reference. The Ka-band frequency can be either coherent with the X-band downlink reference or a hybrid combination of the USO and VCO derived frequencies. The data in this study were chosen such that the Ka-band signal is purely coherent with the X-band signal, that is the downconverter is driven by the same frequency source as the X-band downlink). The ground station used to acquire the data is DSS-13, a 34-meter BWG antenna which incorporates a series of mirrors inside beam waveguide tubes which guide the energy to a subterranean pedestal room, providing a stable

  18. Experimental radio frequency link for Ka-band communications applications

    NASA Technical Reports Server (NTRS)

    Fujikawa, Gene; Conray, Martin J.; Saunders, Alan L.; Pope, Dale E.

    1988-01-01

    An experimental radio frequency link has been demonstrated to provide two-way communication between a remote user ground terminal and a ground-based Ka-band transponder. Bit-error-rate performance and radio frequency characteristics of the communication link were investigated.

  19. Anatomically modern human in Southeast Asia (Laos) by 46 ka.

    PubMed

    Demeter, Fabrice; Shackelford, Laura L; Bacon, Anne-Marie; Duringer, Philippe; Westaway, Kira; Sayavongkhamdy, Thongsa; Braga, José; Sichanthongtip, Phonephanh; Khamdalavong, Phimmasaeng; Ponche, Jean-Luc; Wang, Hong; Lundstrom, Craig; Patole-Edoumba, Elise; Karpoff, Anne-Marie

    2012-09-04

    Uncertainties surround the timing of modern human emergence and occupation in East and Southeast Asia. Although genetic and archeological data indicate a rapid migration out of Africa and into Southeast Asia by at least 60 ka, mainland Southeast Asia is notable for its absence of fossil evidence for early modern human occupation. Here we report on a modern human cranium from Tam Pa Ling, Laos, which was recovered from a secure stratigraphic context. Radiocarbon and luminescence dating of the surrounding sediments provide a minimum age of 51-46 ka, and direct U-dating of the bone indicates a maximum age of ~63 ka. The cranium has a derived modern human morphology in features of the frontal, occipital, maxillae, and dentition. It is also differentiated from western Eurasian archaic humans in aspects of its temporal, occipital, and dental morphology. In the context of an increasingly documented archaic-modern morphological mosaic among the earliest modern humans in western Eurasia, Tam Pa Ling establishes a definitively modern population in Southeast Asia at ~50 ka cal BP. As such, it provides the earliest skeletal evidence for fully modern humans in mainland Southeast Asia.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. Modeling and predicting pKa values of mono-hydroxylated polychlorinated biphenyls (HO-PCBs) and polybrominated diphenyl ethers (HO-PBDEs) by local molecular descriptors.

    PubMed

    Yu, Haiying; Wondrousch, Dominik; Yuan, Quan; Lin, Hongjun; Chen, Jianrong; Hong, Huachang; Schüürmann, Gerrit

    2015-11-01

    Hydroxylated polychlorinated biphenyls (HO-PCBs) and polybrominated diphenyl ethers (HO-PBDEs) are attracting considerable concerns because of their multiple endocrine-disrupting effects and wide existence in environment and organisms. The hydroxyl groups enable these chemicals to be ionizable, and dissociation constant, pKa, becomes an important parameter for investigating their environmental behavior and biological activities. In this study, a new pKa prediction model was developed using local molecular descriptors. The dataset contains 21 experimental pKa values of HO-PCBs and HO-PBDEs. The optimized geometries by ab initio HF/6-31G(∗∗) algorithm were used to calculate the site-specific molecular readiness to accept or donate electron charges. The developed model obtained good statistical performance, which significantly outperformed commercial software ACD and SPARC. Mechanism analysis indicates that pKa values increase with the charge-limited donor energy EQocc on hydroxyl oxygen atom and decrease with the energy-limited acceptor charge QEvac on hydroxyl hydrogen atom. The regression model was also applied to calculate pKa values for all 837 mono-hydroxylated PCBs and PBDEs in each class, aiming to provide basic data for the ecological risk assessment of these chemicals.

  6. 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.

  7. Mars Global Surveyor Ka-Band Frequency Data Analysis

    NASA Astrophysics Data System (ADS)

    Morabito, D.; Butman, S.; Shambayati, S.

    2000-01-01

    The Mars Global Surveyor (MGS) spacecraft, launched on November 7, 1996, carries an experimental space-to-ground telecommunications link at Ka-band (32 GHz) along with the primary X-band (8.4 GHz) downlink. The signals are simultaneously transmitted from a 1.5-in diameter parabolic high gain antenna (HGA) on MGS and received by a beam-waveguide (BWG) R&D 34-meter antenna located in NASA's Goldstone Deep Space Network (DSN) complex near Barstow, California. The projected 5-dB link advantage of Ka-band relative to X-band was confirmed in previous reports using measurements of MGS signal strength data acquired during the first two years of the link experiment from December 1996 to December 1998. Analysis of X-band and Ka-band frequency data and difference frequency (fx-fka)/3.8 data will be presented here. On board the spacecraft, a low-power sample of the X-band downlink from the transponder is upconverted to 32 GHz, the Ka-band frequency, amplified to I-W using a Solid State Power Amplifier, and radiated from the dual X/Ka HGA. The X-band signal is amplified by one of two 25 W TWTAs. An upconverter first downconverts the 8.42 GHz X-band signal to 8 GHz and then multiplies using a X4 multiplier producing the 32 GHz Ka-band frequency. The frequency source selection is performed by an RF switch which can be commanded to select a VCO (Voltage Controlled Oscillator) or USO (Ultra-Stable Oscillator) reference. The Ka-band frequency can be either coherent with the X-band downlink reference or a hybrid combination of the USO and VCO derived frequencies. The data in this study were chosen such that the Ka-band signal is purely coherent with the X-band signal, that is the downconverter is driven by the same frequency source as the X-band downlink). The ground station used to acquire the data is DSS-13, a 34-meter BWG antenna which incorporates a series of mirrors inside beam waveguide tubes which guide the energy to a subterranean pedestal room, providing a stable environment

  8. 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.

  9. 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.

  10. 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).

  11. 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.

  12. Calibration of the radiocarbon time scale at 37ka BP

    SciTech Connect

    Southon, J.R.; Deino, A.L.; Orsi, G.

    1995-12-01

    Results from radiocarbon and U-Th measurements on corals have provided a radiocarbon calibration beyond the range covered by tree ring series, but the uncertainties in the measurements beyond 20ka BP are very large. We have obtained new calibration data from radiocarbon dates on material associated with the catastrophic Campanian Ignimbrite eruption from the Phlegrean Fields near Naples. The eruption has been well dated by {sup 40}Ar/{sup 39}Ar to 37ka BP. Radiocarbon measurements were carried out on charcoal from a carbonized branch exposed within the ignimbrite tuff on the wall of an active quarry. The sample was split and analyzed at both the Naples and Lawrence Livermore AMS facilities. The offset between the Ar-Ar data and the radiocarbon results (recalculated using the true 5730-year half life for {sup 14}C) is consistent with predictions from paleomagnetic data and carbon cycle modeling.

  13. EUReKA! A Conceptual Model of Emotion Understanding.

    PubMed

    Castro, Vanessa L; Cheng, Yanhua; Halberstadt, Amy G; Grühn, Daniel

    2016-07-01

    The field of emotion understanding is replete with measures, yet lacks an integrated conceptual organizing structure. To identify and organize skills associated with the recognition and knowledge of emotions, and to highlight the focus of emotion understanding as localized in the self, in specific others, and in generalized others, we introduce the conceptual framework of Emotion Understanding in Recognition and Knowledge Abilities (EUReKA). We then categorize fifty-six existing methods of emotion understanding within this framework to highlight current gaps and future opportunities in assessing emotion understanding across the lifespan. We hope the EUReKA model provides a systematic and integrated framework for conceptualizing and measuring emotion understanding for future research.

  14. Ka-band MMIC arrays for ACTS Aero Terminal Experiment

    NASA Technical Reports Server (NTRS)

    Raquet, C.; Zakrajsek, R.; Lee, R.; Turtle, J.

    1992-01-01

    An antenna system consisting of three experimental Ka-band active arrays using GaAs MMIC devices at each radiating element for electronic beam steering and distributed power amplification is presented. The MMIC arrays are to be demonstrated in the ACTS Aeronautical Terminal Experiment, planned for early 1994. The experiment is outlined, with emphasis on a description of the antenna system. Attention is given to the way in which proof-of-concept MMIC arrays featuring three different state-of-the-art approaches to Ka-band MMIC insertion are being incorporated into an experimental aircraft terminal for the demonstration of an aircraft-to-satellite link, providing a basis for follow-on MMIC array development.

  15. Interim Findings of ACTS Ka-Band Propagation Campaign

    NASA Technical Reports Server (NTRS)

    Golshan, N.

    1997-01-01

    The ACTS propagation campaign is focusing on two broad areas: 1) Rain/signal attenuation data collection at seven sites in North America, 2) Theoretical and empirical consideratons for a global model to predict first & second order temporal and spatial statistics on attenuation, scintillation, conherence bandwidth, and depolarization due to weather (precipitation and atmospheric including interaction of weather with the antenna) for satellite systems at Ka-band.

  16. 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

  17. The general pattern of Kač Moody extensions in supergravity and the issue of cosmic billiards

    NASA Astrophysics Data System (ADS)

    Fré, Pietro; Gargiulo, Floriana; Rulik, Ksenya; Trigiante, Mario

    2006-05-01

    In this paper we study the systematics of the affine extension of supergravity duality algebras when one steps down from D=4 to D=2 which is instrumental for the study of cosmic billiards. For all D=4 supergravities (with N⩾3) there is a universal field theoretical mechanism promoting the extension, which relies on the coexistence of two non-locally related Lagrangian descriptions of the corresponding D=2 degrees of freedom: the Ehlers Lagrangian and the Matzner-Misner one. This and the existence of a generalized Kramer-Neugebauer non-local transformation relating the two models, provide a Chevalley-Serre presentation of the affine Kač-Moody algebra which follows a universal pattern for all supergravities. This is an extension of the mechanism considered by Nicolai for pure N=1 supergravity, but has general distinctive features in extended theories ( N⩾3) related to the presence of vector fields and to their symplectic description. Moreover the novelty is that in the general case the Matzner-Misner Lagrangian is structurally different from the Ehlers one, since half of the scalars are replaced by gauge 0-forms subject to SO(2n,2n) electric-magnetic duality rotations representing in D=2 the Sp(2n,R) rotations of D=4. The role played by the symplectic bundle of vectors in this context suggests that the mechanism of the affine extension can be studied also for N=2 supergravity, where one deals with geometries rather than with algebras, the scalar manifold being not necessarily a homogeneous manifold U/H. We also show that the mechanism of the affine extension commutes with the Tits-Satake projection of the relevant duality algebras.

  18. 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.

  19. Rain Fade Compensation Alternatives for Ka Band Communication Satellites

    NASA Technical Reports Server (NTRS)

    Acosta, Roberto J.

    1997-01-01

    Future satellite communications systems operating in Ka-band frequency band are subject to degradation produced by the troposphere which is much more severe than those found at lower frequency bands. These impairments include signal absorption by rain, clouds and gases, and amplitude scintillation's arising from refractive index irregularities. For example, rain attenuation at 20 GHz is almost three times that at 11 GHz. Although some of these impairments can be overcome by oversizing the ground station antennas and high power amplifiers, the current trend is using small (less than 20 inches apertures), low-cost ground stations (less than $1000) that can be easily deployed at user premises. As a consequence, most Ka-band systems are expected to employ different forms of fade mitigation that can be implemented relatively easily and at modest cost. The rain fade mitigation approaches are defined by three types of Ka-band communications systems - a low service rate (less than 1.5 Mb/s), a moderate service rate (1.5 to 6 Mb/s) system and a high service rate (greater than 43 Mb/s) system. The ACTS VSAT network, which includes an adaptive rain fade technique, is an example of a moderate service rate.

  20. X/Ka Celestial Frame Improvements: Vision to Reality

    NASA Technical Reports Server (NTRS)

    Jacobs, C. S.; Bagri, D. S.; Britcliffe, M. J.; Clark, J. E.; Franco, M. M.; Garcia-Miro, C.; Goodhart, C. E.; Horiuchi, S.; Lowe, S. T.; Moll, V. E.; Navarro, R.; Rogstad, S. P.; Proctor, R. C.; Sigman, E. H.; Skjerve, L. J.; Soriano, M. A.; Sovers, O. J.; Tucker, B. C.; Wang, D.; White, L. A.

    2010-01-01

    In order to extend the International Celestial Reference Frame from its S/X-band (2.3/8.4 GHz) basis to a complementary frame at X/Ka-band (8.4/32 GHz), we began in mid-2005 an ongoing series of X/Ka observations using NASA s Deep Space Network (DSN) radio telescopes. Over the course of 47 sessions, we have detected 351 extra-galactic radio sources covering the full 24 hours of right ascension and declinations down to -45 degrees. Angular source position accuracy is at the part-per-billion level. We developed an error budget which shows that the main errors arise from limited sensitivity, mismodeling of the troposphere, uncalibrated instrumental effects, and the lack of a southern baseline. Recent work has improved sensitivity by improving pointing calibrations and by increasing the data rate four-fold. Troposphere calibration has been demonstrated at the mm-level. Construction of instrumental phase calibrators and new digital baseband filtering electronics began in recent months. We will discuss the expected effect of these improvements on the X/Ka frame.

  1. X/Ka Celestial Reference Frame Improvements: Vision to Reality

    NASA Astrophysics Data System (ADS)

    Jacobs, Christopher S.; Bagri, D. S.; Brticliffe, M. J.; Clark, J. E.; Franco, M. M.; García-Miró, C.; Goodhart, C. E.; Horiuchi, S.; Lowe, S. T.; Moll, V. E.; Navarro, R.; Rogstad, S. P.; Proctor, R. C.; Skjerve, L. J.; Soriano, M. A.; Sovers, O. J.; Tucker, B. C.; Wang, D.; White, L. A.

    2010-12-01

    In order to extend the International Celestial Reference Frame from its S/X-band (2.3/8.4 GHz) basis to a complementary frame at X/Ka-band (8.4/32 GHz), we began in mid-2005 an ongoing series of X/Ka observations using NASA's Deep Space Network (DSN) radio telescopes. Over the course of 47 sessions, we have detected 351 extra-galactic radio sources covering the full 24 hours of right ascension and declinations down to -45 degrees. Angular source position accuracy is at the part-per-billion level. We developed an error budget which shows that the main errors arise from limited sensitivity, mismodeling of the troposphere, uncalibrated instrumental effects, and the lack of a southern baseline. Recent work has improved sensitivity by improving pointing calibrations and by increasing the data rate four-fold. Troposphere calibration has been demonstrated at the mm-level. Construction of instrumental phase calibrators and new digital baseband filtering electronics began in recent months. We will discuss the expected effect of these improvements on the X/Ka frame.

  2. 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.

  3. Spectrophotometric determination of acidity constants of salicylaldoxime in aqueous solution at 25 °C and ionic strength of 0.5 M controlled with NaCl

    NASA Astrophysics Data System (ADS)

    Tshuma, Joel; Alarcón-Ángeles, Georgina; Palacios-Beas, Elia; Vargas-García, Roberto; Ramírez-Silva, María Teresa; Rojas-Hernández, Alberto

    2007-04-01

    The equilibrium constants of salicylaldoxime in water at 25 °C, 0.5 M of ionic strength with NaCl and concentration of 1 × 10 -4 M were determined spectrophotometrically. The spectral data were processed using SQUAD program. The salicylaldoxime in acid medium has the value of p Ka1 = 1.224 ± 0.027. In alkaline medium the salicylaldoxime has the values of p Ka2 = 8.551 ± 0.024 and p Ka3 = 11.728 ± 0.016.

  4. Spectrophotometric determination of acidity constants of salicylaldoxime in aqueous solution at 25 degrees C and ionic strength of 0.5 M controlled with NaCl.

    PubMed

    Tshuma, Joel; Alarcón-Angeles, Georgina; Palacios-Beas, Elia; Vargas-García, Roberto; Ramírez-Silva, María Teresa; Rojas-Hernández, Alberto

    2007-04-01

    The equilibrium constants of salicylaldoxime in water at 25 degrees C, 0.5 M of ionic strength with NaCl and concentration of 1x10(-4) M were determined spectrophotometrically. The spectral data were processed using SQUAD program. The salicylaldoxime in acid medium has the value of pKa1=1.224+/-0.027. In alkaline medium the salicylaldoxime has the values of pKa2=8.551+/-0.024 and pKa3=11.728+/-0.016.

  5. 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.

  6. 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.

  7. Identification of an Orthogonal Peptide Binding Motif for Biarsenical Multiuse Affinity Probes

    SciTech Connect

    Chen, Baowei; Cao, Haishi; Yan, Ping; Mayer, M. Uljana; Squier, Thomas C.

    2007-07-01

    Biarsenical multiuse affinity probes (MAPs) complexed with ethanedithiol (EDT) permit the selective cellular labeling of proteins engineered with tetracysteine motifs, but are limited by the availability of a single binding motif (i.e., CCPGCC or PG tag) that prevents the differential labeling of co-expressed proteins. To overcome this problem, we have used a high-throughput peptide screen to identify an alternate binding motif (i.e., CCKACC or KA tag), which has a similar brightness to the classical sequence upon MAP binding, but displays altered rates and affinities of association that permit the differential labeling of these peptide sequences by the red probe 4,5-bis(1,3,2-dithiarsolan-2-yl)-resorufin (ReAsH-EDT2) or its green cognate 4’,5’-bis(1,3,2-dithoarsolan-2-yl)fluorescein-(1,2-ethanedithiol)2 (FLAsH-EDT2). The utility of this labeling strategy was demonstrated following the expression of PG- and KA-tagged subunits of RNA polymerase expressed in E. coli. Specific labeling of two subunits of RNA polymerase in cellular lysates was achieved, whereby ReAsH-EDT2 is shown to selectively label the PG-tag on RNA polymerase alpha subunit prior to the labeling of the KA-tag sequence of the beta subunit of RNA polymerase with FlAsH-EDT2. These results demonstrate the ability to selectively label multiple individual proteins with orthogonal sequence tags in complex cellular lystates with spectroscopically distinct MAPs, and indicate the absolute specificity of ReAsH to target expressed proteins with essentially no nonspecific binding interactions.

  8. AltiKa: a Ka-band Altimetry Payload and System for Operational Altimetry during the GMES Period

    PubMed Central

    Vincent, Patrick; Steunou, Nathalie; Caubet, Eric; Phalippou, Laurent; Rey, Laurent; Thouvenot, Eric; Verron, Jacques

    2006-01-01

    This paper describes the Ka-band altimetry payload and system that has been studied for several years by CNES, ALCATEL SPACE and some science laboratories. Altimetry is one of the major elements of the ocean observing system to be made sustainable through the GEOSS (Global Earth Observation System of Systems) and GMES (Global Monitoring of the Environment and Security) programs. A short review of some mission objectives to be fulfilled in terms of mesoscale oceanography in the frame of the GEOSS and GMES programs is performed. To answer the corresponding requirements, the approach consisting in a constellation of nadir altimeter is discussed. A coupled Ka-band altimeter-radiometer payload is then described; technical items are detailed to explain how this payload shall meet the science and operational requirements, and expected performances are displayed. The current status of the payload development and flight perspectives are given.

  9. Late Paleogene terrestrial fauna and paleoenvironments in Eastern Anatolia: New insights from the Kağızman-Tuzluca Basin

    NASA Astrophysics Data System (ADS)

    Métais, Grégoire; Sen, Sevket; Sözeri, Koray; Peigné, Stéphane; Varol, Baki

    2015-08-01

    In Eastern Turkey, relatively little work has been undertaken to characterize the sedimentologic and stratigraphical context of the Kağızman-Tuzluca Basin until now. Extending across the Turkey-Armenian border, this basin documents the syn- and post-collisional evolution of Eastern Anatolia, resulting from the closure of the Neotethyan Seaways and the final collision of the Afro-Arabian and Eurasian plates. From detailed sedimentological and paleontological studies, we propose an interpretation of the lithology and depositional environment of the Late Paleogene Alhan Formation located on the western bank of the Aras River. This sequence of terrestrial clastics rests directly and unconformably onto the ophiolitic mélange, and it documents several depositional sequences deposited in alluvial plain and lacustrine environments. At this stage, the age of the Alhan Formation can only be calibrated by fossil evidence. Several stratigraphic levels yielding fossil data along the section have been identified, but these poor assemblages of fauna and flora hamper extensive comparisons with roughly contemporaneous localities of Central and Southern Asia. Carnivorous and ruminant mammal remains are reported for the first time from the supposed Late Oligocene Güngörmez Formation. The identified fossil mammal taxa reveal biogeographic affinities between Central Anatolia and southern Asia, thus suggesting dispersal between these areas during the Oligocene or earlier. Further studies of the fossil assemblages from the Kağızman-Tuzluca Basin and other basins of Eastern Anatolia and lesser Caucasus regions are needed to better constrain the paleobiogeographic models.

  10. The role of reaction affinity and secondary minerals in regulating chemical weathering rates at the Santa Cruz Soil Chronosequence, California

    SciTech Connect

    Maher, K.; Steefel, C. I.; White, A.F.; Stonestrom, D.A.

    2009-02-25

    In order to explore the reasons for the apparent discrepancy between laboratory and field weathering rates and to determine the extent to which weathering rates are controlled by the approach to thermodynamic equilibrium, secondary mineral precipitation and flow rates, a multicomponent reactive transport model (CrunchFlow) was used to interpret soil profile development and mineral precipitation and dissolution rates at the 226 ka marine terrace chronosequence near Santa Cruz, CA. Aqueous compositions, fluid chemistry, transport, and mineral abundances are well characterized (White et al., 2008, GCA) and were used to constrain the reaction rates for the weathering and precipitating minerals in the reactive transport modeling. When primary mineral weathering rates are calculated with either of two experimentally determined rate constants, the nonlinear, parallel rate law formulation of Hellmann and Tisser and [2006] or the aluminum inhibition model proposed by Oelkers et al. [1994], modeling results are consistent with field-scale observations when independently constrained clay precipitation rates are accounted for. Experimental and field rates, therefore, can be reconciled at the Santa Cruz site. Observed maximum clay abundances in the argillic horizons occur at the depth and time where the reaction fronts of the primary minerals overlap. The modeling indicates that the argillic horizon at Santa Cruz can be explained almost entirely by weathering of primary minerals and in situ clay precipitation accompanied by undersaturation of kaolinite at the top of the profile. The rate constant for kaolinite precipitation was also determined based on model simulations of mineral abundances and dissolved Al, SiO{sub 2}(aq) and pH in pore waters. Changes in the rate of kaolinite precipitation or the flow rate do not affect the gradient of the primary mineral weathering profiles, but instead control the rate of propagation of the primary mineral weathering fronts and thus total

  11. First Airswot Ka-Band Radar Backscatter Returns over a Complex California Wetland

    NASA Astrophysics Data System (ADS)

    Baney, O. N.; Smith, L. C.; Pitcher, L. H.; Gleason, C. J.; Chu, V. W.; Bennett, M. M.; Pavelsky, T.; Sadowy, G. A.

    2014-12-01

    In anticipation of the launch of the NASA Surface Water Ocean Topography (SWOT) mission, this project was conducted around the Piute Ponds of Edwards Air Force Base within the Mojave Desert, California to characterize ground conditions simultaneously with two AirSWOT flights collected May 14th, 2014. Both SWOT and AirSWOT employ a Ka-band interferometer to map water surface elevations and extent, but the ability of Ka-band radar to discriminate shorelines and flooded vegetation is not well known. Presumed bright returns from moist soils surrounding surface water bodies have also been speculated to confound interpretation of SWOT/AirSWOT data. The Piute Ponds are a dynamic area of constantly changing water conditions, providing a convenient test site for field studies to assess open water, dry shorelines, vegetation edges, islands, flooded vegetation and soil moisture in conjunction with AirSWOT backscatter and visible/near-infrared camera imagery. Islands were characterized into dry islands and flooded vegetation stands including species such as bulrush (Scripus acutus) and tamarisk (Tammarix ramosissima). Results demonstrate that full water extent can be determined by near-range backscatter returns which are strong for both open water and flooded vegetation. Far-range backscatter returns over open water were unreliable for flooded extent. Comparing near-range and far-range backscatter results to the soil moisture transect shows correlation, however as soil moisture increases, discriminating between wet sediment and water becomes difficult. In sum, first results suggest near-return backscatter results prove most useful in distinguishing open water from non-water, with a strong correlation between soil moisture and backscatter returns.

  12. 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

  13. 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.

  14. 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

  15. 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)

  16. 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

  17. 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...

  18. 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.

  19. 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

  20. Ka-Band ARM Zenith Radar (KAZR) Instrument Handbook

    SciTech Connect

    Widener, K; Bharadwaj, N; Johnson, K

    2012-03-06

    The Ka-band ARM zenith radar (KAZR) is a zenith-pointing Doppler cloud radar operating at approximately 35 GHz. The KAZR is an evolutionary follow-on radar to ARM's widely successful millimeter-wavelength cloud radar (MMCR). The main purpose of the KAZR is to provide vertical profiles of clouds by measuring the first three Doppler moments: reflectivity, radial Doppler velocity, and spectra width. At the sites where the dual-polarization measurements are made, the Doppler moments for the cross-polarization channel are also available. In addition to the moments, velocity spectra are also continuously recorded for each range gate.

  1. Ka- and W-band PM-HFET DRO's

    NASA Astrophysics Data System (ADS)

    Wenger, J.; Guettich, U.

    1993-06-01

    Dielectric resonator stabilized oscillators have been designed, fabricated, and investigated. The oscillators consist of microstrip matching and biasing circuits on alumina substrate, a dielectric resonator puck, and a low-noise quarter-micron InGaAs-GaAs pseudomorphic (PM) HFET as the active device. At 37 GHz and 81 GHz, output powers of 10 dBm and 0 dBm have been measured. The phase noise of the Ka-band and W-band oscillators has been determined to be -97 dBc/Hz at 100 kHz and -90 dBc/Hz at 1 MHz off carrier, respectively.

  2. Four-Way Ka-Band Power Combiner

    NASA Technical Reports Server (NTRS)

    Perez, Raul; Li, Samuel

    2007-01-01

    A waveguide structure for combining the outputs of four amplifiers operating at 35 GHz (Ka band) is based on a similar prior structure used in the X band. The structure is designed to function with low combining loss and low total reflected power at a center frequency of 35 GHz with a 160 MHz bandwidth. The structure (see figure) comprises mainly a junction of five rectangular waveguides in a radial waveguide. The outputs of the four amplifiers can be coupled in through any four of the five waveguide ports. Provided that these four signals are properly phased, they combine and come out through the fifth waveguide port.

  3. Ka-band mobile and personal systems development at JPL

    NASA Technical Reports Server (NTRS)

    Dessouky, K.; Estabrook, P.; Jedrey, T.; Sue, M. K.

    1991-01-01

    Expanding the commercial applications of space is one of the primary goals of NASA. Throughout the eighties NASA has pursued this objective by sponsoring and undertaking the development of system concepts, enabling high risk technologies, and actual proof of concept demonstration hardware. In the mobile and personal arena, or the so-called low data rate applications area, JPL is NASA's lead center. JPL's focus of activities has been the Mobile Satellite-Experiment (MSAT-X) project, which developed mobile communication technologies at L-band, and its present successors, which aim to expand the mobile arena by exploiting Ka-band.

  4. 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.

  5. 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.

  6. 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

  7. Estimating the acidity of transition metal hydride and dihydrogen complexes by adding ligand acidity constants.

    PubMed

    Morris, Robert H

    2014-02-05

    A simple equation (pKa(THF) = ∑AL + Ccharge + Cnd + Cd6) can be used to obtain an estimate of the pKa of diamagnetic transition metal hydride and dihydrogen complexes in tetrahydrofuran, and, by use of conversion equations, in other solvents. It involves adding acidity constants AL for each of the ligands in the 5-, 6-, 7-, or 8-coordinate conjugate base complex of the hydride or dihydrogen complex along with a correction for the charge (Ccharge = -15, 0 or 30 for x = +1, 0 or -1 charge, respectively) and the periodic row of the transition metal (Cnd = 0 for 3d or 4d metal, 2 for 5d metal) as well as a correction for d(6) octahedral acids (Cd6 = 6 for d(6) metal ion in the acid, 0 for others) that are not dihydrogen complexes. Constants AL are provided for 13 commonly occurring ligand types; of these, nine neutral ligands are correlated with Lever's electrochemical ligand parameters EL. This method gives good estimates of the over 170 literature pKa values that range from less than zero to 50 with a standard deviation of 3 pKa units for complexes of the metals chromium to nickel, molybdenum, ruthenium to palladium, and tungsten to platinum in the periodic table. This approach allows a quick assessment of the acidity of hydride complexes found in nature (e.g., hydrogenases) and in industry (e.g., catalysis and hydrogen energy applications). The pKa values calculated for acids that have bulky or large bite angle chelating ligands deviate the most from this correlation. The method also provides an estimate of the base strength of the deprotonated form of the complex.

  8. Investigation of mechanics properties of an awl-shaped serpentine microspring for in-plane displacement with low spring constant-to-layout area

    NASA Astrophysics Data System (ADS)

    Chou, Hui-Min; Lin, Meng-Ju; Chen, Rongshun

    2016-07-01

    The design, fabrication, and experimental test of an awl-shaped serpentine microspring (ASSM) for providing in-plane motion and low spring constant-to-layout area are investigated. The ASSM can provide low stiffness for in-plane motion under a restricted layout area. The spring constants of ASSMs for in-plane motion are theoretically analyzed by using Castigliano's theorem, and validated through simulation using COMSOL Multiphysics. These ASSMs are successfully fabricated on a silicon-on-insulator wafer. The parameter K/A (spring constant-to-layout area) is used as the performance index. Smaller K/A induces larger deformation under the same layout area. It shows that K/A of ASSM is smaller than the classic one with the same dimensions (total length and number of turns). Geometric sizes having effect on K/A are discussed. The spring constants for in-plane and out-of-plane motion are compared and discussed. The taper angle and beam width-to-thickness ratio (w/h) are two key factors. As w/h being >1, the spring constant of in-plane motion (ky) is always larger than that of out-of-plane motion (kz). If w/h is <1, the spring constant kz would be larger than ky if the taper angle are larger than its critical angle φr.

  9. Acidity constant determination of novel drug precursor benzothiazolon derivatives including acyl and piperazine moieties

    NASA Astrophysics Data System (ADS)

    Sıdır, İsa; Gülseven Sıdır, Yadigar; Berber, Halil

    2013-07-01

    In this study, protonation and deprotonation behaviors of eight new drug precursor benzothiazolon derivatives in all of acidic and basic scale (super acidic, pH, super basic regions) are analyzed by using UV-visible spectrophotometric technique. Acidity constants (pKa), elucidation of the structure and protonation mechanisms of the studied molecules are obtained. Substituent effect on acidity constant values is discussed. These molecules are protonated from oxygen atom of acetamide group in the keto form. The protonation is found to be considerably contributed by the keto form.

  10. 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

  11. 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.

  12. Filling the gap. Human cranial remains from Gombore II (Melka Kunture, Ethiopia; ca. 850 ka) and the origin of Homo heidelbergensis.

    PubMed

    Profico, Antonio; Di Vincenzo, Fabio; Gagliardi, Lorenza; Piperno, Marcello; Manzi, Giorgio

    2016-06-20

    African archaic humans dated to around 1,0 Ma share morphological affinities with Homo ergaster and appear distinct in cranio-dental morphology from those of the Middle Pleistocene that are referred to Homo heidelbergensis. This observation suggests a taxonomic and phylogenetic discontinuity in Africa that ranges across the Matuyama/Brunhes reversal (780 ka). Yet, the fossil record between roughly 900 and 600 ka is notoriously poor. In this context, the Early Stone Age site of Gombore II, in the Melka Kunture formation (Upper Awash, Ethiopia), provides a privileged case-study. In the Acheulean layer of Gombore II, somewhat more recent than 875 ±10 ka, two large cranial fragments were discovered in 1973 and 1975 respectively: a partial left parietal (Melka Kunture 1) and a right portion of the frontal bone (Melka Kunture 2), which probably belonged to the same cranium. We present here the first detailed description and computer-assisted reconstruction of the morphology of the cranial vault pertaining to these fossil fragments. Our analysis suggest that the human fossil specimen from Gombore II fills a phenetic gap between Homo ergaster and Homo heidelbergensis. This appears in agreement with the chronology of such a partial cranial vault, which therefore represents at present one of the best available candidates (if any) for the origin of Homo heidelbergensis in Africa.

  13. K/Ka-band channel characterization for mobile satellite systems

    NASA Technical Reports Server (NTRS)

    Pinck, Deborah S.; Rice, Michael D.

    1995-01-01

    Mobile satellite systems allow truly ubiquitous wireless communications to users anywhere and anytime. NASA's Advanced Communications Technology Satellite (ACTS) provides an ideal space-based platform for the measurement of K/Ka band propagation characteristics in a land mobile satellite application. Field tests conducted in Southern California during the first seven months of 1994 using JPL's ACTS Mobile Terminal (AMT) provided channel characterization data for the K/Ka-band link. A pilot tone was transmitted from a fixed station in Cleveland, Ohio through the satellite and downlinked at 20 GHz in the Southern California spot beam. The AMT was equipped with a narrow beam, high gain antenna which tracked the satellite in azimuth for a fixed elevation angle (46 degrees for this case). The field tests were conducted in three basic environments: clear line-of-sight (LOS) highways, lightly shadowed suburban, and heavily shadowed suburban. Preliminary results of these field tests indicate very little multipath for rural environments and for clear LOS links (as expected with a narrow beam antenna). Deep fades were experienced in shadowed areas, especially those where tree canopies covered the road.

  14. Ka-Band, Multi-Gigabit-Per-Second Transceiver

    NASA Technical Reports Server (NTRS)

    Simons, Rainee N.; Wintucky, Edwin G.; Smith, Francis J.; Harris, Johnny M.; Landon, David G.; Haddadin, Osama S.; McIntire, William K.; Sun, June Y.

    2011-01-01

    A document discusses a multi-Gigabit-per-second, Ka-band transceiver with a software-defined modem (SDM) capable of digitally encoding/decoding data and compensating for linear and nonlinear distortions in the end-to-end system, including the traveling-wave tube amplifier (TWTA). This innovation can increase data rates of space-to-ground communication links, and has potential application to NASA s future spacebased Earth observation system. The SDM incorporates an extended version of the industry-standard DVB-S2, and LDPC rate 9/10 FEC codec. The SDM supports a suite of waveforms, including QPSK, 8-PSK, 16-APSK, 32- APSK, 64-APSK, and 128-QAM. The Ka-band and TWTA deliver an output power on the order of 200 W with efficiency greater than 60%, and a passband of at least 3 GHz. The modem and the TWTA together enable a data rate of 20 Gbps with a low bit error rate (BER). The payload data rates for spacecraft in NASA s integrated space communications network can be increased by an order of magnitude (>10 ) over current state-of-practice. This innovation enhances the data rate by using bandwidth-efficient modulation techniques, which transmit a higher number of bits per Hertz of bandwidth than the currently used quadrature phase shift keying (QPSK) waveforms.

  15. Stability measurements on the 50 kA SMES conductor

    NASA Astrophysics Data System (ADS)

    Pfotenhauer, M. J.

    Stability measurements have been made on a large aluminium stabilized conductor designed for use in a superconducting magnetic energy storage (SMES) coil. The conductor has been built to carry 50 kA at 1.8 K and in 4.6 T field. It consists of a 25.4 mm diameter, high purity aluminium stabilizer with eight superconducting strands of 2.8 mm diameter each, composed of 60% Cu, 40% NbTi. The strands are set in eight helical grooves, evenly spaced around the outer diameter of the aluminium. The conductor is designed for use in full scale SMES units and has been tested in the 1 m diameter, three-turn test coil of the University of Wisconsin proof of principle experiment (POPE). The POPE facility includes the test coil, a 4 T background magnet, a dewar for a 1.8 K, 1 atm environment and a 100 kA d.c. power supply. Test results demonstrate good agreement with a new dynamic stability model. The balance of time-dependent heat generation during current diffusion and time-dependent cooling to the helium produces three new features of stability: 1, a threshold current for propagation; 2, large propagation velocities; and 3, a finite length travelling normal zone. POPE measurements verify all three features of the dynamic stability model.

  16. ITIL and Grid services at GridKa

    NASA Astrophysics Data System (ADS)

    Marten, H.; Koenig, T.

    2010-04-01

    The Steinbuch Centre for Computing (SCC) is a new organizational unit of the Karlsruhe Institute of Technology (KIT). Founded in February 2008 as a merger of the previous Institute for Scientific Computing of Forschungszentrum Karlsruhe and the Computing Centre of the Technical University Karlsruhe, SCC provides a broad spectrum of IT services for 8.000 employees and 18.000 students and carries out research and development in key areas of information technology under the same roof. SCC is also known to host the German WLCG [1] Tier-1 centre GridKa. In order to accompany the merging of the two existing computing centres located at a distance of about 10 km and to provide common first class services for science, SCC has selected the IT service management according to the industrial quasi-standard "IT Infrastructure Library (ITIL)" [3] as a strategic element. The paper discusses the implementation of a few ITIL key components from the perspective of a Scientific Computing Centre using examples of Grid services at GridKa.

  17. 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.

  18. 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

  19. 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.

  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.

    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

  1. Antibody Fragments for On-Site Testing of Cannabinoids Generated via in Vitro Affinity Maturation.

    PubMed

    Morita, Izumi; Oyama, Hiroyuki; Yasuo, Mayumi; Matsuda, Kazuhisa; Katagi, Kengo; Ito, Aya; Tatsuda, Hiroka; Tanaka, Hiroyuki; Morimoto, Satoshi; Kobayashi, Norihiro

    2017-01-01

    Law enforcement against illicit use of cannabis and related substances requires rapid, feasible, and reliable tools for on-site testing of cannabinoids. Notably, methods based on cannabinoid-specific antibodies enable efficient screening of multiple specimens. Antibody engineering may accelerate development of modern and robust testing systems. Here, we used in vitro affinity maturation to generate a single-chain Fv fragment (scFv) that recognizes with high affinity the psychoactive cannabinoid, Δ(9)-tetrahydrocannabinol (THC). A mouse monoclonal antibody against THC, Ab-THC#33, with Ka 6.2×10(7) M(-1) (as Fab fragment) was established by the hybridoma technique. Then, a "wild-type" scFv (wt-scFv) with Ka, 1.1×10(7) M(-1) was prepared by bacterial expression of a fusion gene combining the VH and VL genes for Ab-THC#33. Subsequently, random point mutations in VH and VL were generated separately, and the resulting products were assembled into mutant scFv genes, which were then phage-displayed. Repeated panning identified a mutant scFv (scFv#m1-36) with 10-fold enhanced affinity (Ka 1.1×10(8) M(-1)) for THC, in which only a single conservative substitution (Ser50Thr) was present at the N-terminus of the VH-complementarity-determining region 2 (CDR2) sequence. In competitive enzyme-linked immunosorbent assay (ELISA), the mutant scFv generated dose-response curves with midpoint 0.27 ng/assay THC, which was 3-fold lower than that of wt-scFv. Even higher reactivity with a major THC metabolite, 11-nor-9-carboxy-Δ(9)-tetrahydrocannabinol, indicated that the mutant scFv will be useful for testing not only THC in confiscated materials, but also the metabolite in urine. Indeed, the antibody fragment is potentially suitable for use in advanced on-site testing platforms for cannabinoids.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Thermodynamic proton-ligand and metal-ligand stability constants of some drugs.

    PubMed

    Agrawal, Y K; Patel, D R

    1986-02-01

    The thermodynamic proton-ligand (pKa) and metal-ligand stability constants of clioquinol, clofibrate, nitrofurazone, and tetracycline with Cu2+, Zn2+, Mn2+, Mg2+, and Ca2+ have been determined at 35 degrees C in 50% ethanol-water media. An empirical pH correction for mixed-aqueous media has been applied. The metal-ligand stability constants were determined by following the Bjerrum Calvin titration technique as applied by Agrawal to mixed-aqueous solvents. The effect of the basicity of the ligand and the order of stability constants is discussed. The stability constants of the divalent metals follow the order: Cu2+ greater than Zn2+ greater than Mn2+ greater than Mg2+ greater than Ca2+ with all the drugs.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. Malama I Ka `Aina: Fostering the Culture-Science connection

    NASA Astrophysics Data System (ADS)

    Bruno, B.; Chinn, P.

    2005-12-01

    The Malama I Ka `Aina Project (Caring for the land, or sustainability) aims to improve and expand the education of Hawai`i's children by developing and disseminating standards-based, culturally relevant science curricular materials based on an understanding and appreciation of the ways in which traditional Hawaiians interacted with their environment for sustainability. Key concepts include the role of water and the ahupua`a (traditional Hawaiian system of land management), and a culture-based sense of place that includes knowledge of and connection to the land. Elementary, middle, high school and University of Hawai`i teachers work together to develop and implement curricula that are especially relevant to a particular school's science program and issues, e.g., invasive species, students, community and/or geographical location. Participants (typically a mix of teachers, education majors and science majors) enroll in Malama I Ka `Aina, a three-credit course offered through the University of Hawai`i`s Dept. of Curriculum Studies and applicable toward a Bachelor's or Master's degree. This course (team taught by scientists, cultural experts and educational professionals) enables participants to: (1) Study Hawai`i`s unique geology, geography and environmental issues in the context of Hawaiian culture and post Western contact; (2) Use course knowledge to develop, teach and assess Hawaii-oriented, project-based, inquiry activities that address the Hawaii Science Content Standards; (3) Gain an appreciation for the scientific method, and the curiosity that drives science (4) Use educational technology such as PowerPoint, graphing packages and web authoring software to develop electronic resources for educational activities. A sample of the lessons developed by course participants can be found on http://malama.hawaii.edu/schools/index2.html. This project is based at the University of Hawai`i College of Education and funded by an award to P. Chinn by the US Department of

  15. The 8.2 ka event in the northern Alps

    NASA Astrophysics Data System (ADS)

    Luetscher, M.; Hoffmann, D. L.; Müller, W.; Spötl, C.

    2012-04-01

    The 8.2 ka event has been identified as a widespread climate excursion affecting most of the Northern Hemisphere. High-resolution records from ice cores and speleothems constrain the chronology of this event to between 8.21±0.02 and 8.08±0.03 ka BP (Vinther et al. 2006, Cheng et al. 2009). A distinctive asymmetrical pattern in d18O is consistent with modelling results suggesting rapid input of freshwater into the northern Atlantic due to catastrophic drainage of ice-marginal lakes (LeGrande et al., 2008). Despite an increasing amount of data, the regional expression of this event is still poorly understood. Here, we present a new speleothem record from Gasselhöhle in the Northern Calcareous Alps, Austria. The 205 mm-long GAS19 stalagmite was analysed at high resolution for stable isotopes (100 µm) and trace elements (~10-15 µm; continuous LA-ICPMS profiles). Twelve individual MC-ICP-MS U/Th ages underline an annual growth rate of ca. 60 µm during the Early Holocene. The d18O averages -8.9‰, only slightly more depleted than modern carbonate precipitates from the same cave chamber. The 8.2 ka event is marked in GAS19 by a ca. 1‰ excursion with a minimum value of -9.9‰. Largely invariant trace element concentrations (e.g. Mg, U, Sr, Ba) indicate essentially no changes in the local hydrological regime and therefore support the hypothesis of a temperature-dominated signal. The proximity to the lacustrine isotope record from Mondsee (eg. Lauterbach et al. 2011) opens new perspectives for the interpretation of the oxygen isotope signal using two archives at different elevations. Moreover, several coeval speleothem records are available across the Eastern Alps fostering a spatial comparison of the proxy signals associated with this event. Cheng, H. et al. (2009), Geology, 37, 1007-1010 Lauterbach, S. et al. (2011), JQS, 26, 253-267 LeGrande, A.N., Schmidt, G.A. (2008), Paleoceanography, 23, doi: 10.1029/2008PA001610 Vinther, B. et al. (2006), JGR, 111, D13103

  16. Ka-Band Multibeam Aperture Phased Array Being Developed

    NASA Technical Reports Server (NTRS)

    Reinhart, Richard C.; Kacpura, Thomas J.

    2004-01-01

    Phased-array antenna systems offer many advantages to low-Earth-orbiting satellite systems. Their large scan angles and multibeam capabilities allow for vibration-free, rapid beam scanning and graceful degradation operation for high rate downlink of data to users on the ground. Technology advancements continue to reduce the power, weight, and cost of these systems to make phased arrays a competitive alternative in comparison to the gimbled reflector system commonly used in science missions. One effort to reduce the cost of phased arrays is the development of a Ka-band multibeam aperture (MBA) phased array by Boeing Corporation under a contract jointly by the NASA Glenn Research Center and the Office of Naval Research. The objective is to develop and demonstrate a space-qualifiable dual-beam Ka-band (26.5-GHz) phased-array antenna. The goals are to advance the state of the art in Ka-band active phased-array antennas and to develop and demonstrate multibeam transmission technology compatible with spacecraft in low Earth orbit to reduce the cost of future missions by retiring certain development risks. The frequency chosen is suitable for space-to-space and space-to-ground communication links. The phased-array antenna has a radiation pattern designed by combining a set of individual radiating elements, optimized with the type of radiating elements used, their positions in space, and the amplitude and phase of the currents feeding the elements. This arrangement produces a directional radiation pattern that is proportional to the number of individual radiating elements. The arrays of interest here can scan the main beam electronically with a computerized algorithm. The antenna is constructed using electronic components with no mechanical parts, and the steering is performed electronically, without any resulting vibration. The speed of the scanning is limited primarily by the control electronics. The radiation performance degrades gracefully if a portion of the elements

  17. 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…

  18. 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…

  19. 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.

  20. 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.

  1. The role of reaction affinity and secondary minerals in regulating chemical weathering rates at the Santa Cruz Soil Chronosequence, California

    USGS Publications Warehouse

    Maher, K.; Steefel, Carl; White, A.F.; Stonestrom, D.A.

    2009-01-01

    In order to explore the reasons for the apparent discrepancy between laboratory and field weathering rates and to determine the extent to which weathering rates are controlled by the approach to thermodynamic equilibrium, secondary mineral precipitation, and flow rates, a multicomponent reactive transport model (CrunchFlow) was used to interpret soil profile development and mineral precipitation and dissolution rates at the 226 ka Marine Terrace Chronosequence near Santa Cruz, CA. Aqueous compositions, fluid chemistry, transport, and mineral abundances are well characterized [White A. F., Schulz M. S., Vivit D. V., Blum A., Stonestrom D. A. and Anderson S. P. (2008) Chemical weathering of a Marine Terrace Chronosequence, Santa Cruz, California. I: interpreting the long-term controls on chemical weathering based on spatial and temporal element and mineral distributions. Geochim. Cosmochim. Acta 72 (1), 36-68] and were used to constrain the reaction rates for the weathering and precipitating minerals in the reactive transport modeling. When primary mineral weathering rates are calculated with either of two experimentally determined rate constants, the nonlinear, parallel rate law formulation of Hellmann and Tisserand [Hellmann R. and Tisserand D. (2006) Dissolution kinetics as a function of the Gibbs free energy of reaction: An experimental study based on albite feldspar. Geochim. Cosmochim. Acta 70 (2), 364-383] or the aluminum inhibition model proposed by Oelkers et al. [Oelkers E. H., Schott J. and Devidal J. L. (1994) The effect of aluminum, pH, and chemical affinity on the rates of aluminosilicate dissolution reactions. Geochim. Cosmochim. Acta 58 (9), 2011-2024], modeling results are consistent with field-scale observations when independently constrained clay precipitation rates are accounted for. Experimental and field rates, therefore, can be reconciled at the Santa Cruz site. Additionally, observed maximum clay abundances in the argillic horizons occur at

  2. 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.

  3. 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’.

  4. 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.

  5. 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.

  6. A Ka-band GaAs monolithic phase shifter

    NASA Technical Reports Server (NTRS)

    Sokolov, V.; Geddes, J. J.; Contolatis, A.; Bauhahn, P. E.; Chao, C.

    1983-01-01

    The design and performance of a GaAs monolithic 180-degree one-bit switched line phase shifter test circuit for Ka-band operation is presented. A self-aligned gate (SAG) fabrication technique is also described that reduces resistive parasitics in the switching FET's. Over the 27.5-30 GHz band, typical measured differential insertion phase is within 10-20 deg of the ideal time delay characteristic. Over the same band, the insertion loss for the SAG phase shifter is about 2.5-3 dB per bit. The SAG fabrication technique holds promise in reducing phase shifter insertion loss to about 1.5 dB/bit for 30-GHz operation.

  7. Advanced Ka-Band Transceiver With Monopulse Tracking

    NASA Technical Reports Server (NTRS)

    Khan, Abdur; Hoppe, Dan; Epp, Larry; Perez, Raul

    2006-01-01

    A proposed Ka-band transmitting/ receiving system would embody a unique combination of established and semi-proven design features. The proposed system (see figure) would include a monopulse receiving feedback loop and a mirror that could be moved by piezoelectric actuators in the feedback loop to adjust the aim of the transmitted and received radio beams. Unlike in a phased-array tracking system, phase shifters (which can be complex and expensive) would not be needed in this monopulse tracking system. Moreover, the monopulse-tracking loop could be combined with other subsystems used in established subreflector and antenna designs. The final transmitter power amplifier in the proposed system would be a quasi-optical power amplifier (QOPA) -- a combination of a planar array of 25 amplifiers and corresponding planar arrays of antenna elements, such that free-space power combining would take place at the output.

  8. A personal communications network using a Ka-band satellite

    NASA Technical Reports Server (NTRS)

    Palmer, Larry C.; Laborde, Enrique; Stern, Alan; Sohn, Philip Y.

    1992-01-01

    The feasibility of a personal communications network using portable terminals that can provide 4.8-kb/s voice communications to a hub station via a Ka-band geosynchronous satellite has been investigated. Tradeoffs are examined so that the combined system of hub and gateway earth stations, the satellite, and the personal terminals can provide a competitive service in terms of cost, availability, and quality. A baseline system that uses a spacecraft with approximately 140 spot beams to cover the contiguous US (CONUS) and 5-W power amplifiers in each beam is described. Satellite access in both the forward and return directions uses frequency-division multiple-access/code-division multiple-access (FDMA/CDMA) with a chip rate of 2.5 Mchip/s.

  9. A personal communications network using a Ka-band satellite

    NASA Technical Reports Server (NTRS)

    Palmer, L. C.; Stern, A.; Sohn, P. Y.

    1991-01-01

    The feasibility of portable communications terminals that can provide 4.8-kbps voice communications to a hub station via a Ka-band geosynchronous satellite was investigated. Tradeoffs are examined so that the combined system of the hub and gateway earth stations, the satellite, and the personal terminals can provide a competitive service in terms of cost, availability, and quality. A baseline system is described using a spacecraft with approximately 140 spot beams that cover CONUS with 5-watt power amplifiers in each beam. Satellite access in both the forward and return directions uses Frequency Division Multiple Access/Code Division Multiple Access (FDMA/CDMA) with a chip rate of 2.5 Mchip/sec. An experiment is recommended using the Advanced Communications Technology Satellite (ACTS) to demonstrate some of the features of the portable terminal concept.

  10. Miniaturized Ka-Band Dual-Channel Radar

    NASA Technical Reports Server (NTRS)

    Hoffman, James P.; Moussessian, Alina; Jenabi, Masud; Custodero, Brian

    2011-01-01

    Smaller (volume, mass, power) electronics for a Ka-band (36 GHz) radar interferometer were required. To reduce size and achieve better control over RFphase versus temperature, fully hybrid electronics were developed for the RF portion of the radar s two-channel receiver and single-channel transmitter. In this context, fully hybrid means that every active RF device was an open die, and all passives were directly attached to the subcarrier. Attachments were made using wire and ribbon bonding. In this way, every component, even small passives, was selected for the fabrication of the two radar receivers, and the devices were mounted relative to each other in order to make complementary components isothermal and to isolate other components from potential temperature gradients. This is critical for developing receivers that can track each other s phase over temperature, which is a key mission driver for obtaining ocean surface height. Fully hybrid, Ka-band (36 GHz) radar transmitter and dual-channel receiver were developed for spaceborne radar interferometry. The fully hybrid fabrication enables control over every aspect of the component selection, placement, and connection. Since the two receiver channels must track each other to better than 100 millidegrees of RF phase over several minutes, the hardware in the two receivers must be "identical," routed the same (same line lengths), and as isothermal as possible. This level of design freedom is not possible with packaged components, which include many internal passive, unknown internal connection lengths/types, and often a single orientation of inputs and outputs.

  11. 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.…

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Experimental correlation between the p Ka value of sulfonphthaleins with the nature of the substituents groups

    NASA Astrophysics Data System (ADS)

    Balderas-Hernández, Patricia; Ramírez-Silva, María Teresa; Romero-Romo, Mario; Palomar-Pardavé, Manuel; Roa-Morales, Gabriela; Barrera-Diaz, Carlos; Rojas-Hernández, Alberto

    2008-04-01

    This work presents the results obtained from a spectrophotometry study performed on some indicators of the sulfonphtaleins like phenol red (PR), thymol blue (TB), bromothymol blue (BTB), xylenol orange (XO) and methylthymol blue (MTB). During the first stage the acidity constants of some of the indicators were determined using the data from spectrophotometry, potentiometry and with the use of the software SQUAD. These were as follows: for the equilibrium 2H + BTB ↔ H 2BTB, log β2 = 15.069 ± 0.046 and for H + BTB ↔ HBTB, log β1 = 8.311 ± 0.044. For the XO and the MTB five values were calculated for each, namely, for MTB: log β5 = 42.035, log β4 = 38.567 ± 0.058, log β3 = 32.257 ± 0.057, log β2 = 23.785 ± 0.057, and log β1 = 12.974 ± 0.045 while for XO: log β5 = 40.120 ± 0.102, log β4 = 35.158 ± 0.062, log β3 = 29.102 ± 0.053, log β2 = 21.237 ± 0.044, and log β1 = 11.682 ± 0.044. During the second stage, a study was conducted on the effect of the substituents present in the indicators to determine the effect of different functional groups on the p Ka value corresponding to the last indicator's dissociation.

  20. The Use of Pseudo-equilibrium Constant Affords Improved QSAR Models of Human Plasma Protein Binding

    PubMed Central

    Zhu, Xiangwei; Sedykh, Alexander; Zhu, Hao; Liu, Shushen; Tropsha, Alexander

    2015-01-01

    Purpose To develop accurate in silico predictors of Plasma Protein Binding (PPB). Methods Experimental PPB data were compiled for over 1,200 compounds. Two endpoints have been considered: (1) fraction bound (%PPB); and (2) the logarithm of a pseudo binding constant (lnKa) derived from %PPB. The latter metric was employed because it reflects the PPB thermodynamics and the distribution of the transformed data is closer to normal. Quantitative Structure-Activity Relationship (QSAR) models were built with Dragon descriptors and three statistical methods. Results Five-fold external validation procedure resulted in models with the prediction accuracy (R2) of 0.67±0.04 and 0.66±0.04, respectively, and the mean absolute error (MAE) of 15.3±0.2% and 13.6±0.2%, respectively. Models were validated with two external datasets: 173 compounds from DrugBank, and 236 chemicals from the US EPA ToxCast project. Models built with lnKa were significantly more accurate (MAE of 6.2–10.7%) than those built with %PPB (MAE of 11.9–17.6%) for highly bound compounds both for the training and the external sets. Conclusion The pseudo binding constant (lnKa) is more appropriate for characterizing PPB binding than conventional %PPB. Validated QSAR models developed herein can be applied as reliable tools in early drug development and in chemical risk assessment. PMID:23568522

  1. The kinetics of acylation and deacylation of penicillin acylase from Escherichia coli ATCC 11105: evidence for lowered pKa values of groups near the catalytic centre.

    PubMed Central

    Morillas, M; Goble, M L; Virden, R

    1999-01-01

    Penicillin G acylase catalysed the hydrolysis of 4-nitrophenyl acetate with a kcat of 0.8 s-1 and a Km of 10 microM at pH 7.5 and 20 degreesC. Results from stopped-flow experiments fitted a dissociation constant of 0.16 mM for the Michaelis complex, formation of an acetyl enzyme with a rate constant of 32 s-1 and a subsequent deacylation step with a rate constant of 0.81 s-1. Non-linear Van't Hoff and Arrhenius plots for these parameters, measured at pH 7.5, may be partly explained by a conformational transition affecting catalytic groups, but a linear Arrhenius plot for the ratio of the rate constant for acylation relative to KS was consistent with energy-compensation between the binding of the substrate and catalysis of the formation of the transition state. At 20 degreesC, the pH-dependence of kcat was similar to that of kcat/Km, indicating that formation of the acyl-enzyme did not affect the pKa values (6.5 and 9.0) of an acidic and basic group in the active enzyme. The heats of ionization deduced from values of pKa for kcat, which measures the rate of deacylation, are consistent with alpha-amino and guanidinium groups whose pKa values are decreased in a non-polar environment. It is proposed that, for catalytic activity, the alpha-amino group of the catalytic SerB1 and the guanidinium group of ArgB263 are required in neutral and protonated states respectively. PMID:9931321

  2. 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.

  3. Determination of acid-base dissociation constants of amino- and guanidinopurine nucleotide analogs and related compounds by capillary zone electrophoresis.

    PubMed

    Solínová, Veronika; Kasicka, Václav; Koval, Dusan; Cesnek, Michal; Holý, Antonín

    2006-03-01

    CZE has been applied for determination of acid-base dissociation constants (pKa) of ionogenic groups of newly synthesized amino- and (amino)guanidinopurine nucleotide analogs, such as acyclic nucleoside phosphonate, acyclic nucleoside phosphonate diesters and other related compounds. These compounds bear characteristic pharmacophores contained in various important biologically active substances, such as cytostatics and antivirals. The pKa values of ionogenic groups of the above compounds were determined by nonlinear regression analysis of the experimentally measured pH dependence of their effective electrophoretic mobilities. The effective mobilities were measured by CZE performed in series of BGEs in a broad pH range (3.50-11.25), at constant ionic strength (25 mM) and temperature (25 degrees C). pKa values were determined for the protonated guanidinyl group in (amino)guanidino 9-alkylpurines and in (amino)guanidinopurine nucleotide analogs, such as acyclic nucleoside phosphonates and acyclic nucleoside phosphonate diesters, for phosphonic acid to the second dissociation degree (-2) in acyclic nucleoside phosphonates of amino and (amino)guanidino 9-alkylpurines, and for protonated nitrogen in position 1 (N1) of purine moiety in acyclic nucleoside phosphonates of amino 9-alkylpurines. Thermodynamic pKa of protonated guanidinyl group was estimated to be in the range of 7.75-10.32, pKa of phosphonic acid to the second dissociation degree achieved values of 6.64-7.46, and pKa of protonated nitrogen in position 1 of purine was in the range of 4.13-4.89, depending on the structure of the analyzed compounds.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. Accurate proton affinity and gas-phase basicity values for molecules important in biocatalysis

    PubMed Central

    Moser, Adam; Range, Kevin; York, Darrin M.

    2010-01-01

    Benchmark quantum calculations of proton affinities and gas phase basicities of molecules relevant to biochemical processes, particulsarly acid/base catalysis, are presented and compared for a variety of multi-level and density-functional quantum models. Included are nucleic acid bases in both keto and enol tautomeric forms, ribose in B-form and A-form sugar pucker conformations, amino acid side chains and backbone molecules, and various phosphates and phosphoranes including thio substitutions. This work presents a high-level thermodynamic characterization of biologically relevant protonation states, and provides a benchmark database for development of next-generation semiempirical and approximate density-functional quantum models, and parameterization of methods to predict pKa values and relative solvation energies. PMID:20942500

  9. 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.

  10. Dating North European mammoths (Mammuthus primigenius Blum.): a nearly continuous record from 53 ka to 11 ka

    NASA Astrophysics Data System (ADS)

    Ukkonen, P.; Aaris-Sørensen, K.; Arppe, L.; Clark, P. U.; Daugnora, L.; Lister, A.; Lõugas, L.; Seppä, H. A.; Stuart, A. J.; Wojtal, P.; Zupins, I.

    2010-05-01

    nearly continuously from 53 ka to 11 ka, completely disappearing from the area only during the Last Glacial Maximum (LGM). From the northern parts of the study area, mammoths disappeared ca. 27 ka ago. In the south they survived until the LGM, and occupied the area again during deglaciation. Mammoths survived in the eastern part of the study area until the end of Younger Dryas. References Weninger, B., Jöris, O., 2008. A 14C age calibration curve for the last 60 ka: the Greenland-Hulu U/Th timescale and its impact on understanding the Middle to Upper Paleolithic transition in Western Eurasia. Journal of Human Evolution 55,772-781. Weninger, B., Jöris, O., Danzeglocke, U., 2008. CalPal-2007. Cologne Radiocarbon Calibration & Palaeoclimate Research Package. http://www.calpal.de/ [2008-09-18].

  11. Increasing Diversity in STEM through Ka Hikina O Ka Lā Summer Bridge Program for Native Hawaiian Students

    NASA Astrophysics Data System (ADS)

    Coopersmith, A.; Cie, D. K.; Calder, S.; Naho`olewa, D.; Rai, B.

    2014-12-01

    The Advanced Technology Solar Telescope (ATST) Mitigation Initiative and the Kahikina O Ka Lā Program are NSF-funded projects at the University of Hawai`i Maui College. These projects offer instruction and activities intended to increase diversity in STEM careers. Ke Alahaka, the 2014 summer bridge program, was offered to Native Hawaiian high-school students who indicated an interest in STEM areas. Content workshops were offered in Marine Science, Physics, Biotechnology, and Computer Science and Engineering as well as a Hawaiian Studies course designed to provide a cultural context for the STEM instruction. Focus groups and other program assessments indicate that 50% of the students attending the workshops intend to pursue a STEM major during their undergraduate studies.

  12. 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.

  13. 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.

  14. 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.

  15. Determination of the acid dissociation constant of the biosurfactant monorhamnolipid in aqueous solution by potentiometric and spectroscopic methods.

    PubMed

    Lebrón-Paler, Ariel; Pemberton, Jeanne E; Becker, Bridget A; Otto, William H; Larive, Cynthia K; Maier, Raina M

    2006-11-15

    The acid dissociation constant in water for a monorhamnolipid mixture extracted from Pseudomonas aeruginosa ATCC 9027 has been determined using potentiometry and two spectroscopic approaches at concentrations below and above the critical micelle concentration (cmc). Potentiometric titrations resulted in pKa values ranging from 4.28 +/- 0.16 to 5.50 +/- 0.06 depending on concentration. 1H NMR spectrochemical titrations at concentrations below the cmc revealed a pKa value of 4.39 +/- 0.06. ATR-FT-IR spectrochemical titrations on solutions well above the cmc gave a pKa value of 4.84 +/- 0.05. The value of 4.28 for the free rhamnolipid molecule for concentrations below the cmc differs markedly from that reported previously. However, the pKa of 5.50 for surface-adsorbed and solution aggregates correlates closely to that previously reported. Differences in these pKa values are rationalized in terms of the pH- and concentration-dependent aggregation behavior of rhamnolipids in aqueous solution.

  16. New insights on water level variability for Lake Turkana for the past 15 ka and at 150 ka from relict beaches

    NASA Astrophysics Data System (ADS)

    Forman, S. L.; Wright, D.

    2015-12-01

    Relict beaches adjacent to Lake Turkana provide a record of water level variability for the Late Quaternary. This study focused on deciphering the geomorphology, sedimentology, stratigraphy and 14C chronology of strand plain sequences in the Kalokol and Lothagam areas. Nine >30 m oscillations in water level were documented between ca. 15 and 4 ka. The earliest oscillation between ca. 14.5 and 13 ka is not well constrained with water level to at least 70 m above the present surface and subsequently fell to at least 50 m. Lake level increased to ~ 90 m between ca. 11.2 and 10.4 ka, post Younger Dryas cooling. Water level fell by >30 m by 10.2 ka, with another potential rise at ca. 8.5 ka to >70 m above current level. Lake level regressed by > 40 m at 8.2 ka coincident with cooling in the equatorial Eastern Atlantic Ocean. Two major >70 m lake level oscillations centered at 6.6 and 5.2 ka may reflect enhanced convection with warmer sea surface temperatures in the Western Indian Ocean. The end of the African Humid Period occurred from ca. 8.0 to 4.5 ka and was characterized by variable lake level (± > 40 m), rather than one monotonic fall in water level. This lake level variability reflects a complex response to variations in the extent and intensity of the East and West African Monsoons near geographic and topographic limits within the catchment of Lake Turkana. Also, for this closed lake basin excess and deficits in water input are amplified with a cascading lake effect in the East Rift Valley and through the Chew Bahir Basin. The final regression from a high stand of > 90 m began at. 5.2 ka and water level was below 20 m by 4.5 ka; and for the remainder of the Holocene. This sustained low stand is associated with weakening of the West African Monsoon, a shift of the mean position of Congo Air Boundary west of the Lake Turkana catchment and with meter-scale variability in lake level linked to Walker circulation across the Indian Ocean. A surprising observation is

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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…

  2. 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'…

  3. 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.

  4. Photometric method for determination of acidity constants through integral spectra analysis.

    PubMed

    Zevatskiy, Yuriy Eduardovich; Ruzanov, Daniil Olegovich; Samoylov, Denis Vladimirovich

    2015-04-15

    An express method for determination of acidity constants of organic acids, based on the analysis of the integral transmittance vs. pH dependence is developed. The integral value is registered as a photocurrent of photometric device simultaneously with potentiometric titration. The proposed method allows to obtain pKa using only simple and low-cost instrumentation. The optical part of the experimental setup has been optimized through the exclusion of the monochromator device. Thus it only takes 10-15 min to obtain one pKa value with the absolute error of less than 0.15 pH units. Application limitations and reliability of the method have been tested for a series of organic acids of various nature.

  5. Photometric method for determination of acidity constants through integral spectra analysis

    NASA Astrophysics Data System (ADS)

    Zevatskiy, Yuriy Eduardovich; Ruzanov, Daniil Olegovich; Samoylov, Denis Vladimirovich

    2015-04-01

    An express method for determination of acidity constants of organic acids, based on the analysis of the integral transmittance vs. pH dependence is developed. The integral value is registered as a photocurrent of photometric device simultaneously with potentiometric titration. The proposed method allows to obtain pKa using only simple and low-cost instrumentation. The optical part of the experimental setup has been optimized through the exclusion of the monochromator device. Thus it only takes 10-15 min to obtain one pKa value with the absolute error of less than 0.15 pH units. Application limitations and reliability of the method have been tested for a series of organic acids of various nature.

  6. Evaluation of the acidity constants of the 4-hidroxy-5-6salicylideneamino9-2-7-naphthalenedisulfonic acid (Azomethine-H) using UV?vis spectrophotometry

    NASA Astrophysics Data System (ADS)

    Alarcón-Angeles, G.; Corona-Avendaño, S.; Rojas-Hernández, A.; Romero-Romo, M. A.; Ramírez-Silva, M. T.

    2005-01-01

    The time stability of the azomethine-H species was determined not to be better than 10 min in the absence of oxygen and light, however under phosphate buffered conditions the azomethine-H species remained stable for longer periods, as indicated by the spectrophotometric behaviour. Nevertheless, the analysis time still exceeded the stability allowance. Therefore, the determination of the acidity constants of the Azomethine-H species was studied by means of UV-vis spectrophotometry in buffered media by means of the point-by-point analysis and data processing with SQUAD to refine the resulting constants, which were: p Ka1=3.39, p Ka2 7.36 and p Ka3 8.73. The latter were associated to the corresponding acid-base equilibria of the amine and hydroxy groups constituting the molecule.

  7. A method for computing association rate constants of atomistically represented proteins under macromolecular crowding

    NASA Astrophysics Data System (ADS)

    Qin, Sanbo; Cai, Lu; Zhou, Huan-Xiang

    2012-12-01

    In cellular environments, two protein molecules on their way to form a specific complex encounter many bystander macromolecules. The latter molecules, or crowders, affect both the energetics of the interaction between the test molecules and the dynamics of their relative motion. In earlier work (Zhou and Szabo 1991 J. Chem. Phys. 95 5948-52), it has been shown that, in modeling the association kinetics of the test molecules, the presence of crowders can be accounted for by their energetic and dynamic effects. The recent development of the transient-complex theory for protein association in dilute solutions makes it possible to easily incorporate the energetic and dynamic effects of crowders. The transient complex refers to a late on-pathway intermediate, in which the two protein molecules have near-native relative separation and orientation, but have yet to form the many short-range specific interactions of the native complex. The transient-complex theory predicts the association rate constant as ka = ka0exp( - ΔG*el/kBT), where ka0 is the ‘basal’ rate constant for reaching the transient complex by unbiased diffusion, and the Boltzmann factors captures the influence of long-range electrostatic interactions between the protein molecules. Crowders slow down the diffusion, therefore reducing the basal rate constant (to kac0), and induce an effective interaction energy ΔGc. We show that the latter interaction energy for atomistic proteins in the presence of spherical crowders is ‘long’-ranged, allowing the association rate constant under crowding to be computed as kac = kac0exp[ - (ΔG*el + ΔG*c)/kBT]. Applications demonstrate that this computational method allows for realistic modeling of protein association kinetics under crowding.

  8. Highly Efficient Amplifier for Ka-Band Communications

    NASA Technical Reports Server (NTRS)

    1996-01-01

    An amplifier developed under a Small Business Innovation Research (SBIR) contract will have applications for both satellite and terrestrial communications. This power amplifier uses an innovative series bias arrangement of active devices to achieve over 40-percent efficiency at Ka-band frequencies with an output power of 0.66 W. The amplifier is fabricated on a 2.0- by 3.8-square millimeter chip through the use of Monolithic Microwave Integrated Circuit (MMIC) technology, and it uses state-of-the-art, Pseudomorphic High-Electron-Mobility Transistor (PHEMT) devices. Although the performance of the MMIC chip depends on these high-performance devices, the real innovations here are a unique series bias scheme, which results in a high-voltage chip supply, and careful design of the on-chip planar output stage combiner. This design concept has ramifications beyond the chip itself because it opens up the possibility of operation directly from a satellite power bus (usually 28 V) without a dc-dc converter. This will dramatically increase the overall system efficiency. Conventional microwave power amplifier designs utilize many devices all connected in parallel from the bias supply. This results in a low-bias voltage, typically 5 V, and a high bias current. With this configuration, substantial I(sup 2) R losses (current squared times resistance) may arise in the system bias-distribution network. By placing the devices in a series bias configuration, the total current is reduced, leading to reduced distribution losses. Careful design of the on-chip planar output stage power combiner is also important in minimizing losses. Using these concepts, a two-stage amplifier was designed for operation at 33 GHz and fabricated in a standard MMIC foundry process with 0.20-m PHEMT devices. Using a 20-V bias supply, the amplifier achieved efficiencies of over 40 percent with an output power of 0.66 W and a 16-dB gain over a 2-GHz bandwidth centered at 33 GHz. With a 28-V bias, a power

  9. 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.

  10. Determination of the pKa of ionizable enzyme groups by nonlinear regression using a second degree equation.

    PubMed

    O'Reilly, S; Riveros, M C

    1994-01-01

    A second degree equation fitted by nonlinear regression for the analysis of the pH effect on enzyme activity is proposed for diprotic enzyme systems. This method allows the calculation of two molecular dissociation constants (KE1 and KE2 for the free enzyme, KES1 and KES2 for the ES complex) and the pH independent parameters (Vmax and Vmax/Km). The method is validated by bibliographic (alpha-chymotrypsin) and experimental data (almond beta-D-glucosidase). No significant differences were found between present data and those previously reported in the literature using similar experimental conditions. This method works using comparatively few [H+] concentration values within a narrow pH range, preferentially around the optimum, being adequate for diprotic systems with close pKa values.

  11. Ka Hana `Imi Na`auao: A Science Curriculum Project

    NASA Astrophysics Data System (ADS)

    Napeahi, K.; Roberts, K. D.; Galloway, L. M.; Stodden, R. A.; Akuna, J.; Bruno, B.

    2005-12-01

    In antiquity, the first people to step foot on what are now known as the Hawaiian islands skillfully traversed the Pacific Ocean using celestial navigation and learned observations of scientific phenomena. Long before the Western world ventured beyond the horizon, Hawaiians had invented the chronometer, built aqueduct systems (awai) that continue to amaze modern engineers, and had preventive health systems as well as a comprehensive knowledge of medicinal plants (including antivirals) which only now are working their way through trials for use in modern pharmacopia. Yet, today, Native Hawaiians are severely underrepresented in science-related fields, reflecting (in part) a failure of the Western educational system to nurture the potential of these resourceful students, particularly the many "at-risk" students who are presently over-represented in special education. A curriculum which draws from and incorporates traditional Hawaiian values and knowledge is needed to reinforce links to the inquiry process which nurtured creative thinking during the renaissance of Polynesian history. The primary goal of the Ka Hana `Imi Na`auao Project (translation: `science` or `work in which you seek enlightenment, knowledge or wisdom`) is to increase the number of Native Hawaiian adults in science-related postsecondary education and employment fields. Working closely with Native Hawaiian cultural experts and our high school partners, we will develop and implement a culturally responsive 11th and 12th grade high school science curriculum, infused with math, literacy and technology readiness skills. Software and assistive technology will be used to adapt instruction to individual learners` reading levels, specific disabilities and learning styles. To ease the transition from secondary to post-secondary education, selected grade 12 students will participate in planned project activities that link high school experiences with college science-related programs of study. Ka Hana `Imi Na

  12. Radiocarbon dating from 40 to 60 ka BP at Border Cave, South Africa

    NASA Astrophysics Data System (ADS)

    Bird, M. I.; Fifield, L. K.; Santos, G. M.; Beaumont, P. B.; Zhou, Y.; di Tada, M. L.; Hausladen, P. A.

    2003-04-01

    We present 21 radiocarbon dates on 19 charcoal samples from the sedimentary sequence preserved in Border Cave, South Africa. The background radiocarbon activity for charcoal from the cave was determined to be 0.050±0.018 percent modern carbon, from the analysis of a radiocarbon-dead sample from unit 5WA. Radiocarbon ages for individual samples ranged from 25.2 to >58.2 ka BP. The error-weighted mean ages for successively older strata are 38.5+0.85/-0.95 ka BP for unit 1WA, 50.2+1.1/-1.0 ka BP for units 2BS.LR.A and 2BS.LR.B, 56.5+2.7/-2.0 ka BP for unit 2BS.LR.C and 59.2+3.4/-2.4 ka BP for unit 2WA. This radiocarbon chronology is consistent with independent chronologies derived from electron spin resonance and amino acid racemization dating. The results therefore provide further evidence that radiocarbon dating of charcoal by the ABOX-SC technique can yield reliable radiocarbon ages beyond 40 ka BP. They also imply that Border Cave 5, a modern human mandible, predates >58.2 ka BP and that the Middle Stone Age (Mode 3)—Later Stone Age (Mode 5) transition of Border Cave was largely effected between ˜56.5 and ˜41.6 ka ago.

  13. X/X/Ka-band prime focus feed antenna for the Mars Observer beacon spacecraft

    NASA Technical Reports Server (NTRS)

    Stanton, P.; Reilly, H.; Esquivel, M.

    1988-01-01

    The results of an X/X/Ka-band feed design concept demonstration are presented. The purpose is to show the feasibility of adding a Ka-band beacon to the Mars Observer spacecraft. Scale model radiation patterns were made and analyzed.

  14. Electrostatic forces in two lysozymes: calculations and measurements of histidine pKa values.

    PubMed

    Takahashi, T; Nakamura, H; Wada, A

    1992-08-01

    In order to examine the electrostatic forces in globular proteins, pKa values and their ionic strength dependence of His residues of hen egg white lysozyme (HEWL) and human lysozyme (HUML) were measured, and they were compared with those calculated numerically. pKa values of His residues in HEWL, HUML, and short oligopeptides were determined from chemical shift changes of His side chains by 1H-nmr measurements. The associated changes in pKa values in HEWL and HUML were calculated by solving the Poisson-Boltzmann equations numerically for macroscopic dielectric models. The calculated pKa changes and their ionic strength dependence agreed fairly well with the observed ones. The contribution from each residue of each alpha-helix dipole to the pKa values and their ionic strength dependence was analyzed using Green's reciprocity theorem. The results indicate that (1) the pKa of His residues are largely affected by surrounding ionized and polar groups; (2) the ionic strength dependence of the pKa values is determined by the overall charge distributions and their accessibilities to solvent; and (3) alpha-helix dipoles make a significant contribution to the pKa, when the His residue is close to the helix terminus and not fully exposed to the solvent.

  15. A View from the Cocoon--Space Categorization in the Korean Verb [na-ka-ta].

    ERIC Educational Resources Information Center

    Kim, Alan Hyun-Oak

    1996-01-01

    Analysis of the Korean verb "na-ka-ta" ("to get out, exit") focuses on why an expression such as "kyengkicang-ey na-ka-ta" ("someone goes out/in to the sports arena") is acceptable only in the context that the person's entering the arena is for the purpose of a contest, while it becomes semantically…

  16. 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.

  17. 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

  18. 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.

  19. Detecting small seamounts in AltiKa repeat cycle data

    NASA Astrophysics Data System (ADS)

    Marks, K. M.; Smith, W. H. F.

    2016-12-01

    We present a technique of stacking repeat cycles of satellite altimeter sea surface height profiles that lowers the noise and improves the resolution of small seamounts. Our approach differs from other studies because it uses the median (not the mean) of the stacks, which suppresses outliers. Seamounts as small as 720 m tall are easily detected in stacked 40 Hz AltiKa data profiles, and a 500 m tall seamount is perceptible. Noise variance decreases with an increase in the number of cycles stacked, and RMS noise dips below 2 cm when 11 or more cycles are stacked. Coherence analyses between geoid height and bathymetry show that full wavelengths down to about 10 km can be resolved. Comparisons of study areas with and without seamounts find that signal from small seamounts lies in the 10-28 km waveband. A simple Gaussian band-pass filter based on the seamount waveband passes signals that can be used in seamount detection studies. Such studies may find seamounts <2 km tall that are predicted to be abundant on the ocean floor.

  20. A transportable 50 kA dual mode lightning simulator

    NASA Technical Reports Server (NTRS)

    Salisbury, K.; Lloyd, S.; Chen, Y. G.

    1991-01-01

    A transportable lightning simulator was designed, built and tested, which is capable of delivering more than 50 kA to an 8 micro-H test object. The simulator was designed to be a versatile device in the lightning laboratory while meeting the requirements of MIL-STD-1757A for component E current waveforms. The system is capable of operating in either a ringing mode with a Q greater than 5 and a nominal frequency of 160 kHz, or a unipolar mode with no hardware configuration changes. The ringing mode is obtained by the LCR series circuit formed by the pulse generator and test object. The unipolar mode is obtained by closing an electrically triggered crowbar switch at peak current. The simulator exceeds the peak current requirement and rate of rise requirements for MIL-STD-1757A in both the ringing and unipolar modes. The pulse half width in the unipolar mode is in excess of 50 microsec and the action is in excess of 10(exp 5) A(exp 2)s. The design, component values, and test results are presented.

  1. Ka-Band Transponder for Deep-Space Radio Science

    NASA Technical Reports Server (NTRS)

    Dennis, Matthew S.; Mysoor, Narayan R.; Folkner, William M.; Mendoza, Ricardo; Venkatesan, Jaikrishna

    2008-01-01

    A one-page document describes a Ka-band transponder being developed for use in deep-space radio science. The transponder receives in the Deep Space Network (DSN) uplink frequency band of 34.2 to 34.7 GHz, transmits in the 31.8- to 32.3 GHz DSN downlink band, and performs regenerative ranging on a DSN standard 4-MHz ranging tone subcarrier phase-modulated onto the uplink carrier signal. A primary consideration in this development is reduction in size, relative to other such transponders. The transponder design is all-analog, chosen to minimize not only the size but also the number of parts and the design time and, thus, the cost. The receiver features two stages of frequency down-conversion. The receiver locks onto the uplink carrier signal. The exciter signal for the transmitter is derived from the same source as that used to generate the first-stage local-oscillator signal. The ranging-tone subcarrier is down-converted along with the carrier to the second intermediate frequency, where the 4-MHz tone is demodulated from the composite signal and fed into a ranging-tone-tracking loop, which regenerates the tone. The regenerated tone is linearly phase-modulated onto the downlink carrier.

  2. Thomson Scattering on exploding wires at 800 kA

    NASA Astrophysics Data System (ADS)

    Greenly, John; Seyler, Charles; Banasek, Jacob; Potter, William

    2016-10-01

    Laser Thomson scattering measurements have been carried out on a single 0.25 mm diameter Al wire load driven with an 800 kA, 100 ns risetime pulse on the COBRA pulsed power facility. The 527 nm, 10 J, 5 ns laser is brought to a line focus on a chord across the unstable, roughly cylindrical plasma column of the wire, which reaches 8mm outer diameter at 100 ns. The laser path is either on axis or 2mm or 4mm off axis. Scattered signals are collected on a fiber array yielding data across the laser path through the plasma. The scattered light is easily visible over the wire plasma self-emission. The scattered spectra have highly complex structures comprised of as many as four distinct spectral peaks spread over 1 nm in wavelength, both red-and blue-shifted. On axis, the laser does not reach the far side of the plasma, being totally absorbed and/or refracted out of its path. 2 mm off-axis the beam is severely refracted, probably from near the critical surface in the plasma, appearing in images taken with cameras 45 degrees off its entering path. The scattering should be in the collective regime, and analysis is underway to extract information on flow velocities and temperatures within the volume, of 0.5mm radius, imaged by each fiber. Work supported by US DOE NNSA Grant DE-NA0001855.

  3. Absolute paleointensity from Hawaiian lavas younger than 35 ka

    USGS Publications Warehouse

    Valet, J.-P.; Tric, E.; Herrero-Bervera, E.; Meynadier, L.; Lockwood, J.P.

    1998-01-01

    Paleointensity studies have been conducted in air and in argon atmosphere on nine lava flows with radiocarbon ages distributed between 3.3 and 28.2 ka from the Mauna Loa volcano in the big island of Hawaii. Determinations of paleointensity obtained at eight sites depict the same overall pattern as the previous results for the same period in Hawaii, although the overall average field intensity appears to be lower. Since the present results were determined at higher temperatures than in the previous studies, this discrepancy raises questions regarding the selection of low versus high-temperature segments that are usually made for absolute paleointensity. The virtual dipole moments are similar to those displayed by the worldwide data set obtained from dated lava flows. When averaged within finite time intervals, the worldwide values match nicely the variations of the Sint-200 synthetic record of relative paleointensity and confirm the overall decrease of the dipole field intensity during most of this period. The convergence between the existing records at Hawaii and the rest of the world does not favour the presence of persistent strong non-dipole components beneath Hawaii for this period.

  4. Rain Fade Compensation for Ka-Band Communications Satellites

    NASA Technical Reports Server (NTRS)

    Mitchell, W. Carl; Nguyen, Lan; Dissanayake, Asoka; Markey, Brian; Le, Anh

    1997-01-01

    This report provides a review and evaluation of rain fade measurement and compensation techniques for Ka-band satellite systems. This report includes a description of and cost estimates for performing three rain fade measurement and compensation experiments. The first experiment deals with rain fade measurement techniques while the second one covers the rain fade compensation techniques. The third experiment addresses a feedback flow control technique for the ABR service (for ATM-based traffic). The following conclusions were observed in this report; a sufficient system signal margin should be allocated for all carriers in a network, that is a fixed clear-sky margin should be typically in the range of 4-5 dB and should be more like 15 dB in the up link for moderate and heavy rain zones; to obtain a higher system margin it is desirable to combine the uplink power control technique with the technique that implements the source information rate and FEC code rate changes resulting in a 4-5 dB increase in the dynamic part of the system margin. The experiments would assess the feasibility of the fade measurements and compensation techniques, and ABR feedback control technique.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Mars Reconnaissance Orbiter Ka-band (32 GHz) Demonstration: Cruise Phase Operations

    NASA Technical Reports Server (NTRS)

    Shambayati, Shervin; Morabito, David; Border, James S.; Davarian, Faramaz; Lee, Dennis; Mendoza, Ricardo; Britcliffe, Michael; Weinreb, Sander

    2006-01-01

    The X-band (8.41 GHz) frequency currently used for deep space telecommunications is too narrow (50 MHz) to support future high rate missions. Because of this NASA has decided to transition to Ka-band (32 GHz) frequencies. As weather effects cause much larger fluctuations on Ka-band than on X-band, the traditional method of using a few dBs of margin to cover these fluctuations is wasteful of power for Ka-band; therefore, a different operations concept is needed for Ka-band links. As part of the development of the operations concept for Ka-band, NASA has implemented a fully functioning Ka-band communications suite on its Mars Reconnaissance Orbiter (MRO). This suite will be used during the primary science phase to develop and refine the Ka-band operations concept for deep space missions. In order to test the functional readiness of the spacecraft and the Deep Space Network's (DSN) readiness to support the demonstration activities a series of passes over DSN 34-m Beam Waveguide (BWG) antennas were scheduled during the cruise phase of the mission. MRO was launched on August 12, 2005 from Kennedy Space Center, Cape Canaveral, Florida, USA and went into Mars Orbit on March 10, 2006. A total of ten telemetry demonstration and one high gain antenna (HGA) calibration passes were allocated to the Ka-band demonstration. Furthermore, a number of "shadow" passes were also scheduled where, during a regular MRO track over a Ka-band capable antenna, Ka-band was identically configured as the X-band and tracked by the station. In addition, nine Ka-band delta differential one way ranging ((delta)DOR) passes were scheduled. During these passes, the spacecraft and the ground system were put through their respective paces. Among the highlights of these was setting a single day record for data return from a deep space spacecraft (133 Gbits) achieved during one 10-hour pass; achieving the highest data rate ever from a planetary mission (6 Mbps) and successfully demonstrating Ka-band DDOR

  13. The rise and fall of Lake Bonneville between 45 and 10.5 ka

    USGS Publications Warehouse

    Benson, L.V.; Lund, S.P.; Smoot, J.P.; Rhode, D.E.; Spencer, R.J.; Verosub, K.L.; Louderback, L.A.; Johnson, C.A.; Rye, R.O.; Negrini, R.M.

    2011-01-01

    A sediment core taken from the western edge of the Bonneville Basin has provided high-resolution proxy records of relative lake-size change for the period 45.1-10.5 calendar ka (hereafter ka). Age control was provided by a paleomagnetic secular variation (PSV)-based age model for Blue Lake core BL04-4. Continuous records of ??18O and total inorganic carbon (TIC) generally match an earlier lake-level envelope based on outcrops and geomorphic features, but with differences in the timing of some hydrologic events/states. The Stansbury Oscillation was found to consist of two oscillations centered on 25 and 24 ka. Lake Bonneville appears to have reached its geomorphic highstand and began spilling at 18.5 ka. The fall from the highstand to the Provo level occurred at 17.0 ka and the lake intermittently overflowed at the Provo level until 15.2 ka, at which time the lake fell again, bottoming out at ~14.7 ka. The lake also fell briefly below the Provo level at ~15.9 ka. Carbonate and ??18O data indicate that between 14.7 and 13.1 ka the lake slowly rose to the Gilbert shoreline and remained at about that elevation until 11.6 ka, when it fell again. Chemical and sedimentological data indicate that a marsh formed in the Blue Lake area at 10.5 ka.Relatively dry periods in the BL04-4 records are associated with Heinrich events H1-H4, suggesting that either the warming that closely followed a Heinrich event increased the evaporation rate in the Bonneville Basin and (or) that the core of the polar jet stream (PJS) shifted north of the Bonneville Basin in response to massive losses of ice from the Laurentide Ice Sheet (LIS) during the Heinrich event. The second Stansbury Oscillation occurred during Heinrich event H2, and the Gilbert wet event occurred during the Younger Dryas cold interval. Several relatively wet events in BL04-4 occur during Dansgaard-Oeschger (DO) warm events.The growth of the Bear River glacier between 32 and 17 ka paralleled changes in the values of proxy

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. Multi-wavelength spectrophotometric determination of the protolytic constants of tetracycline hydrochloride in some nonaqueous-water mixed solvents: A solvatochromism study

    NASA Astrophysics Data System (ADS)

    Ghasemi, Jahan B.; Jalalvand, Ali R.

    2011-01-01

    Annihilation of the contribution of one chemical component from the original data matrix is a general method in rank annihilation factor analysis (RAFA). However, RAFA is not applicable for studying the protonation equilibria of multiprotic acids but in this study two-rank annihilation factor analysis (TRAFA) was used as an efficient chemometrics algorithm for determination of the protolytic constants (p Ka) of tetracycline hydrochloride (TCHC) in some nonaqueous-water mixed solvents such as acetonitrile (AN)-water and methanol (MeOH)-water from the spectral pH-absorbance data. The spectral data was obtained from spectrophotometric acid-base titrations of different solutions of TCHC at (25.0 ± 0.10) °C and an ionic strength of 0.10 M. In TRAFA algorithm the p Ka values were obtained with relationship between residual standard deviation (R.S.D.) and hypothetical p Ka values. In the case of TCHC, the spectra were divided in two consecutive subdivisions according to their pH range having two p Ka and TRAFA was run twice. The validity of the obtained p Ka values was checked with well-known chemometrics algorithms such as DATAN, EQUSPEC, SPECFIT/32 and SQUAD. The effects of changing solvent composition on the protolytic constants were explained by linear solvation energy relationships (LSER) utilizing solvatochromic parameters.

  19. 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.

  20. Analysis of Fade Detection and Compensation Experimental Results in a Ka-Band Satellite System. Degree awarded by Akron Univ., May 2000

    NASA Technical Reports Server (NTRS)

    Johnson, Sandra

    2001-01-01

    The frequency bands being used for new satellite communication systems are constantly increasing to accommodate the requirements for additional capacity. At these higher frequencies, propagation impairments that did not significantly affect the signal at lower frequencies begin to have considerable impact. In Ka-band, the next logical commercial frequency band to be used for satellite communication, attenuation of the signal due to rain is a primary concern. An experimental satellite built by NASA, the Advanced Communication Technology Satellite (ACTS), launched in September 1993, is the first US communication satellite operating in the Ka-band. In addition to higher carrier frequencies, a number of other new technologies, including onboard baseband processing, multiple beam antennas, and rain fade detection and compensation techniques, were designed into the ACTS. Verification experiments have been conducted since the launch to characterize the new technologies. The focus of this thesis is to describe and validate the method used by the ACTS Very Small Aperture Terminal (VSAT) ground stations in detecting the presence of fade in the communication signal and to adaptively compensate for it by the addition of burst rate reduction and forward error correction. Measured data obtained from the ACTS program is used to validate the compensation technique. In this thesis, models in MATLAB are developed to statistically characterize the increased availability achieved by the compensation techniques in terms of the bit error rate time enhancement factor. Several improvements to the ACTS technique are discussed and possible implementations for future Ka-band systems are also presented.

  1. 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

  2. Cyclone Xaver seen by SARAL/AltiKa

    NASA Astrophysics Data System (ADS)

    Scharroo, Remko; Fenoglio, Luciana; Annunziato, Alessandro

    2014-05-01

    During the first week of December 2013, Cyclone Xaver pounded the coasts and the North Sea. On 6 December, all along the Wadden Sea, the barrier islands along the north of the Netherlands and the northwest of Germany experienced record storm surges. We show a comparison of the storm surge measured by the radar altimeter AltiKa on-board the SARAL satellite and various types of in-situ data and models. Two tide gauges along the German North Sea coast, one in the southern harbour of the island of Helgoland and one on an offshore lighthouse Alte Weser, confirmed that the storm drove sea level to about three meters above the normal tide level. Loading effects during the storm are also detected by the GPS measurements at several tide gauge stations. The altimeter in the mean time shows that the storm surge was noticeable as far as 400 km from the coast. The altimeter measured wind speeds of 20 m/s nearly monotonically throughout the North Sea. An offshore anemometer near the island of Borkum corroborated this value. A buoy near the FINO1 offshore platform measured wave heights of 8 m, matching quite well the measurements from the altimeter, ranging from 6 m near the German coast to 12 m further out into the North Sea. Furthermore we compare the altimeter-derived and in-situ sea level, wave height and wind speed products with outputs from the Operation Circulation and Forecast model of the Bundesamt für Seeschifffahrt und Hydrographie (BSH) and with a global storm surge forecast and inundation model of the Joint Research Centre (JRC) of the European Commission. The Operational circulation model of BSH (BSHcmod) and its component, the surge model (BSHsmod), perform daily predictions for the next 72 hours based on the meteorological model of the Deutsche Wetterdienst (DWD). The JRC Storm Surge Calculation System is a new development that has been established at the JRC in the framework of the Global Disasters Alerts and Coordination System (GDACS). The system uses

  3. A 75 ka Stalagmite Paleoclimate Record from Northern Venezuela

    NASA Astrophysics Data System (ADS)

    Retrum, J. B.; Gonzalez, L. A.; Edwards, R.; Tincher, S. M.; Cheng, H.; Urbani, F.

    2011-12-01

    A stalagmite collected from Cueva Zarraga in the northern Venezuelan Andes was analyzed to determine local paleoclimatic history and help examine climate change in the Caribbean. Ages were determined by U/Th disequilibrium and the stalagmite shows a nearly complete record for ~ 75 ka. Two significant periods of non-deposition have been identified. The first period ranges between the Last Glacial Maximum at 19,820 ± 149 cal yr BP and a brief resumption of stalagmite growth at 15,409 ± 747 cal yr BP, likely representing the Bølling-Allerød interstadial. After the brief period of deposition, growth does not resume unil the Holocene at 10,408 ± 78 cal yr BP. Carbon and oxygen isotopes show a major depletion shift from the last glacial period to the Holocene, suggesting warmer and wetter conditions during the Holocene. The oxygen isotope depletion shift is also seen in the Cariaco Basin foraminifera record off the northern coast of Venezuela. While tempting to attribute δ13C depletion to decrease of the C4 plant contribution, there is no evidence that the area experience major vegetation changes. We attribute the δ13C depletion to enhanced recycling of soil CO2 resulting from canopy effects. Today, Cueva Zarraga is at the northern extent of the Inter-Tropical Convergence Zone (ITCZ). The cooler and drier conditions of the last glacial period suggest a southern displacement of the ITCZ. The close proximity of Cueva Zarraga to Cariaco Basin may allow for a high resolution tropical terrestrial and oceanic climatic response comparison.

  4. KA-SB: from data integration to large scale reasoning

    PubMed Central

    Roldán-García, María del Mar; Navas-Delgado, Ismael; Kerzazi, Amine; Chniber, Othmane; Molina-Castro, Joaquín; Aldana-Montes, José F

    2009-01-01

    Background The analysis of information in the biological domain is usually focused on the analysis of data from single on-line data sources. Unfortunately, studying a biological process requires having access to disperse, heterogeneous, autonomous data sources. In this context, an analysis of the information is not possible without the integration of such data. Methods KA-SB is a querying and analysis system for final users based on combining a data integration solution with a reasoner. Thus, the tool has been created with a process divided into two steps: 1) KOMF, the Khaos Ontology-based Mediator Framework, is used to retrieve information from heterogeneous and distributed databases; 2) the integrated information is crystallized in a (persistent and high performance) reasoner (DBOWL). This information could be further analyzed later (by means of querying and reasoning). Results In this paper we present a novel system that combines the use of a mediation system with the reasoning capabilities of a large scale reasoner to provide a way of finding new knowledge and of analyzing the integrated information from different databases, which is retrieved as a set of ontology instances. This tool uses a graphical query interface to build user queries easily, which shows a graphical representation of the ontology and allows users o build queries by clicking on the ontology concepts. Conclusion These kinds of systems (based on KOMF) will provide users with very large amounts of information (interpreted as ontology instances once retrieved), which cannot be managed using traditional main memory-based reasoners. We propose a process for creating persistent and scalable knowledgebases from sets of OWL instances obtained by integrating heterogeneous data sources with KOMF. This process has been applied to develop a demo tool , which uses the BioPax Level 3 ontology as the integration schema, and integrates UNIPROT, KEGG, CHEBI, BRENDA and SABIORK databases. PMID:19796402

  5. Resilient FTS3 service at GridKa

    NASA Astrophysics Data System (ADS)

    Hartmann, T.; Bubeliene, J.; Hoeft, B.; Obholz, L.; Petzold, A.; Wisniewski, K.

    2015-12-01

    The FTS (File Transfer Service) service provides a transfer job scheduler to distribute and replicate vast amounts of data over the heterogeneous WLCG infrastructures. Compared to the channel model of the previous versions, the most recent version of FTS simplifies and improves the flexibility of the service while reducing the load to the service components. The improvements allow to handle a higher number of transfers with a single FTS3 setup. Covering now continent-wide transfers compared to the previous version, whose installations handled only transfers within specific clouds, a resilient system becomes even more necessary with the increased number of depending users. Having set up a FTS3 services at the German T1 site GridKa at KIT in Karlsruhe, we present our experiences on the preparations for a high-availability FTS3 service. Trying to avoid single points of failure, we rely on a database cluster as fault tolerant data back-end and the FTS3 service deployed on an own cluster setup to provide a resilient infrastructure for the users. With the database cluster providing a basic resilience for the data back-end, we ensure on the FTS3 service level a consistent and reliable database access through a proxy solution. On each FTS3 node a HAproxy instance is monitoring the integrity of each database node and distributes database queries over the whole cluster for load balancing during normal operations; in case of a broken database node, the proxy excludes it transparently to the local FTS3 service. The FTS3 service itself consists of a main and a backup instance, which takes over the identity of the main instance, i.e., IP, in case of an error using a CTDB (Cluster Trivial Database) infrastructure offering clients a consistent service.

  6. Coeval ages of Australasian, Central American and Western Canadian tektites reveal multiple impacts 790 ka ago

    NASA Astrophysics Data System (ADS)

    Schwarz, Winfried H.; Trieloff, Mario; Bollinger, Klemens; Gantert, Niklas; Fernandes, Vera A.; Meyer, Hans-Peter; Povenmire, Hal; Jessberger, Elmar K.; Guglielmino, Massimo; Koeberl, Christian

    2016-04-01

    High resolution 40Ar-39Ar step heating dating of australites and indochinites, representing a large area of the Australasian strewn field, and more recently discovered tektite-like glasses from Central America (Belize) and Western Canada, were carried out. Precise plateau ages were obtained in all cases, yielding indistinguishable ages of 789 ± 9 ka for four australites, 783 ± 5 ka for four indochinites, 783 ± 17 ka for one Western Canadian and 769 ± 16 ka for one Belize impact glass. Concerning major elements and REEs, australites and the Western Canadian impact glass are indistinguishable. If the Western Canadian sample was transported by impact ejection and belongs to the Australasian strewn field, this implies extremely far ballistic transport of 9000 km distance, assuming a source crater in southern Asia. The distinct major element and REE composition of the Belize impact glass suggests formation in another separate impact event. We conclude that the Australasian/Western Canadian impact glasses formed 785 ± 7 ka ago in a single event and Belize impact glass in a separate event 769 ± 16 ka ago. The two impact events forming these two strewn fields occurred remarkably closely related in time, i.e., separated by <30 ka.

  7. Studying NASA's Transition to Ka-Band Communications for Low Earth Orbit

    NASA Technical Reports Server (NTRS)

    Chelmins, David T.; Reinhart, Richard C.; Mortensen, Dale; Welch, Bryan; Downey, Joseph; Evans, Michael

    2014-01-01

    As the S-band spectrum becomes crowded, future space missions will need to consider moving command and telemetry services to Ka-band. NASA's Space Communications and Navigation (SCaN) Testbed provides a software-defined radio (SDR) platform that is capable of supporting investigation of this service transition. The testbed contains two S-band SDRs and one Ka-band SDR. Over the past year, SCaN Testbed has demonstrated Ka-band communications capabilities with NASAs Tracking and Data Relay Satellite System (TDRSS) using both open- and closed-loop antenna tracking profiles. A number of technical areas need to be addressed for successful transition to Ka-band. The smaller antenna beamwidth at Ka-band increases the criticality of antenna pointing, necessitating closed loop tracking algorithms and new techniques for received power estimation. Additionally, the antenna pointing routines require enhanced knowledge of spacecraft position and attitude for initial acquisition, versus an S-band antenna. Ka-band provides a number of technical advantages for bulk data transfer. Unlike at S-band, a larger bandwidth may be available for space missions, allowing increased data rates. The potential for high rate data transfer can also be extended for direct-to-ground links through use of variable or adaptive coding and modulation. Specific examples of Ka-band research from SCaN Testbeds first year of operation will be cited, such as communications link performance with TDRSS, and the effects of truss flexure on antenna pointing.

  8. Standard Observing Bands: Is Now the Time to Replace S/X with X/Ka?

    NASA Technical Reports Server (NTRS)

    Jacobs, C. S.; Lanyi, G. E.; Naudet, C. J.

    2004-01-01

    In this paper we will argue that the VLBI community should be developing a road map to transition from S/X to simultaneous X and Ka-band (32 GHz) observations. There are both negative and positive reasons for planning such a transition. On the negative side, we will outline concerns that S-band observations may be headed toward obsolescence. On the positive side, we will refer to evidence that X/Ka has potential for providing a more stable reference frame than S/X. We will propose timetables for a transition to X/Ka observing starting from the current status of X/Ka and plans that are now taking shape. First X/Ka fringes were obtained in 2001 with the Deep Space Network. Future plans will be discussed including a proposed X/Ka-band upgrade to the VLBA. Lastly, we will consider the need for a period of overlap between S/X and X/Ka so that the long and rich history of astrometric and geodetic VLBI is not compromised.

  9. Tephrochronology of a 70 ka-long marine record in the Marsili Basin (southern Tyrrhenian Sea)

    NASA Astrophysics Data System (ADS)

    Tamburrino, S.; Insinga, D. D.; Pelosi, N.; Kissel, C.; Laj, C.; Capotondi, L.; Sprovieri, M.

    2016-11-01

    A sequence of tephra layers is studied in a 13.9 m-long deep-sea core (MD01-2474G) from the southern Tyrrhenian Sea. The chronology of the succession is provided by a high-resolution age-depth model based on isotope stratigraphy and AMS radiocarbon dating, which place the succession of events in a time interval spanning the last 70 ka. Based on a precise chronological framework and proximal-distal correlations, the Y-1, Y-6 and Y-7 main marker tephras were identified. Compositional data on fresh micro-pumice or glass shards of selected tephras were correlated with the coeval volcanic activity of Aeolian Arc (Vulcano and Salina), Mt. Etna, Phlegrean Fields Pantelleria and Ischia. The tephra sequence contains a number of deposits documenting recurrent activity on Vulcano Island at ca. 6.9 ka BP (MD3), ca. 16.7 ka BP (MD11), ca. 23.2 ka BP (MD14), ca. 29.6 ka BP (MD15), ca. 36.9 ka BP (MD22) and ca. 42.5 ka BP (MD27). The results presented in this study improve the southern Tyrrhenian Sea tephrostratigraphic framework and provide new insights into chemistry and dispersal area of Aeolian Arc pyroclastic deposits in this sector of the Central Mediterranean.

  10. Performance of a Ka-Band Transponder Breadboard for Deep-Space Applications

    NASA Astrophysics Data System (ADS)

    Mysoor, N. R.; Lane, J. P.; Kayalar, S.; Kermode, A. W.

    1995-04-01

    This article summarizes the design concepts applied in the development of an advanced Ka-band (34.4 GHz/32 GHz) transponder breadboard for the next generation of space communications systems applications. The selected architecture upgrades the X-band (7.2 GHz/8.4 GHz) deep-space transponder (DST) to provide Ka-band up/Ka- and X-band down capability. In addition, it can also be configured to provide X-band up/Ka- and X-band down capability. The Ka-band transponder breadboard incorporates several state-of-the-art components, including sampling mixers, a Ka-band dielectric resonator oscillator, and microwave monolithic integrated circuits (MMICs). The MMICs that were tested in the breadboard include upconverters, downconverters, automatic gain control circuits, mixers, phase modulators, and amplifiers. The measured receiver dynamic range, tracking range, acquisition rate, static phase error, and phase jitter characteristics of the Ka-band breadboard interfaced to the advanced engineering model X-band DST are in good agreement with the expected performance. The results show a receiver tracking threshold of -149 dBm with a dynamic range of 80 dB and a downlink phase jitter of 7-deg rms. The analytical results of phase noise and Allan standard deviation are in good agreement with the experimental results.

  11. Standard Observing Bands: Is Now the Time to Replace S/X with X/Ka?

    NASA Astrophysics Data System (ADS)

    Jacobs, Christopher S.; Lanyi, G. E.; Naudet, C. J.

    2004-06-01

    In this paper we will argue that the VLBI community should be developing a road map to transition from S/X to simultaneous X and Ka-band (32 GHz) observations. There are both negative and positive reasons for planning such a transition. On the negative side, we will outline concerns that S-band observations may be headed toward obsolescence. On the positive side, we will refer to evidence that X/Ka has potential for providing a more stable reference frame than S/X. We will propose timetables for a transition to X/Ka observing starting from the current status of X/Ka and plans that are now taking shape. First X/Ka fringes were obtained in 2001 with the Deep Space Network. Future plans will be discussed including a proposed X/Ka-band upgrade to the VLBA. Lastly, we will consider the need for a period of overlap between S/X and X/Ka so that the long and rich history of astrometric and geodetic VLBI is not compromised.

  12. Studying NASA's Transition to Ka-Band Communications for Low Earth Orbit

    NASA Technical Reports Server (NTRS)

    Chelmins, David; Reinhart, Richard; Mortensen, Dale; Welch, Bryan; Downey, Joseph; Evans, Mike

    2014-01-01

    As the S-band spectrum becomes crowded, future space missions will need to consider moving command and telemetry services to Ka-band. NASAs Space Communications and Navigation (SCaN) Testbed provides a software-defined radio (SDR) platform that is capable of supporting investigation of this service transition. The testbed contains two S-band SDRs and one Ka-band SDR. Over the past year, SCaN Testbed has demonstrated Ka-band communications capabilities with NASAs Tracking and Data Relay Satellite System (TDRSS) using both open- and closed-loop antenna tracking profiles. A number of technical areas need to be addressed for successful transition to Ka-band. The smaller antenna beamwidth at Ka-band increases the criticality of antenna pointing, necessitating closed loop tracking algorithms and new techniques for received power estimation. Additionally, the antenna pointing routines require enhanced knowledge of spacecraft position and attitude for initial acquisition, versus an S-band antenna. Ka-band provides a number of technical advantages for bulk data transfer. Unlike at S-band, a larger bandwidth may be available for space missions, allowing increased data rates. The potential for high rate data transfer can also be extended for direct-to-ground links through use of variable or adaptive coding and modulation. Specific examples of Ka-band research from SCaN Testbeds first year of operation will be cited, such as communications link performance with TDRSS, and the effects of truss flexure on antenna pointing.

  13. The Potential for a Ka-band (32 GHz) Worldwide VLBI Network

    NASA Technical Reports Server (NTRS)

    Jacobs, C. S.; Bach, U.; Colomer, F.; Garcia-Miro, C.; Gomez-Gonzalez, J.; Gulyaev, S.; Horiuchi, S.; Ichikawa, R.; Kraus, A.; Kronschnabl, G.; Lopez-Fernandez, J. A.; Lovell, J.; Majid, W.; Natusch, T.; Neidhardt, A.; Phillips, C.; Porcas, R.; Romero-Wolf, A.; Saldana, L.; Schreiber, U.; Sotuela, I.; Takeuchi, H.; Trinh, J.; Tzioumis, A.; deVincente, P.

    2012-01-01

    Ka-band (32 GHz, 9mm) Very Long Baseline Interferometric (VLBI) networking has now begun and has tremendous potential for expansion over the next few years. Ka-band VLBI astrometry from NASA's Deep Space Network has already developed a catalog of 470 observable sources with highly accurate positions. Now, several antennas worldwide are planning or are considering adding Ka-band VLBI capability. Thus, there is now an opportunity to create a worldwide Ka-band network with potential for high resolution imaging and astrometry. With baselines approaching a Giga-lambda, a Ka-band network would be able to probe source structure at the nano-radian (200 as) level ( 100X better than Hubble) and thus gain insight into the astrophysics of the most compact regions of emission in active galactic nuclei. We discuss the advantages of Ka-band, show the known sources and candidates, simulate projected baseline (uv) coverage, and discuss potential radio frequency feeds. The combination of these elements demonstrates the feasibility of a worldwide Ka network within the next few years!

  14. Prediction of Absolute Hydroxyl pKa Values for 3-Hydroxypyridin-4-ones.

    PubMed

    Chen, Yu-Lin; Doltsinis, Nikos L; Hider, Robert C; Barlow, Dave J

    2012-10-18

    pKa values have been calculated for a series of 3-hydroxypyridin-4-one (HPO) chelators in aqueous solution using coordination constrained ab initio molecular dynamics (AIMD) in combination with thermodynamic integration. This dynamics-based methodology in which the solvent is treated explicitly at the ab initio level has been compared with more commonly used simple, static, approaches. Comparison with experimental numbers has confirmed that the AIMD-based approach predicts the correct trend in the pKa values and produces the lowest average error (∼0.3 pKa units). The corresponding pKa predictions made via static quantum mechanical calculations overestimate the pKa values by 0.3-7 pKa units, with the extent of error dependent on the choice of thermodynamic cycle employed. The use of simple quantitative structure property relationship methods gives prediction errors of 0.3-1 pKa units, with some values overestimated and some underestimated. Beyond merely calculating pKa values, the AIMD simulations provide valuable additional insight into the atomistic details of the proton transfer mechanism and the solvation structure and dynamics at all stages of the reaction. For all HPOs studied, it is seen that proton transfer takes place along a chain of three H2O molecules, although direct hydrogen bonds are seen to form transiently. Analysis of the solvation structure before and after the proton transfer event using radial pair distribution functions and integrated number densities suggests that the trends in the pKa values correlate with the strength of the hydrogen bond and the average number of solvent molecules in the vicinity of the donor oxygen.

  15. 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.

  16. 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.

  17. 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

  18. A Novel Ku-Band/Ka-Band and Ka-Band/E-Band Multimode Waveguide Couplers for Power Measurement of Traveling-Wave Tube Amplifier Harmonic Frequencies

    NASA Technical Reports Server (NTRS)

    Wintucky, Edwin G.; Simons, Rainee N.

    2015-01-01

    This paper presents the design, fabrication and test results for a novel waveguide multimode directional coupler (MDC). The coupler, fabricated from two dissimilar frequency band waveguides, is capable of isolating power at the second harmonic frequency from the fundamental power at the output port of a traveling-wave tube (TWT) amplifier. Test results from proof-of-concept demonstrations are presented for a Ku-band/Ka-band MDC and a Ka-band/E-band MDC. In addition to power measurements at harmonic frequencies, a potential application of the MDC is in the design of a satellite borne beacon source for atmospheric propagation studies at millimeter-wave (mm-wave) frequencies (Ka-band and E-band).

  19. A Ka-band (32 GHz) beacon link experiment (KABLE) with Mars Observer

    NASA Astrophysics Data System (ADS)

    Riley, A. L.; Hansen, D. M.; Mileant, A.; Hartop, R. W.

    1987-02-01

    A proposal for a Ka-Band (32 GHz) Link Experiment (KABLE) with the Mars Observer mission was submitted to NASA. The experiment will rely on the fourth harmonic of the spacecraft X-band transmitter to generate a 33.6 GHz signal. The experiment will rely also on the Deep Space Network (DSN) receiving station equipped to simultaneously receive X- and Ka-band signals. The experiment will accurately measure the spacecraft-to-Earth telecommunication link performance at Ka-band and X-band (8.4 GHz).

  20. A Ka-band (32 GHz) beacon link experiment (KABLE) with Mars Observer

    NASA Technical Reports Server (NTRS)

    Riley, A. L.; Hansen, D. M.; Mileant, A.; Hartop, R. W.

    1987-01-01

    A proposal for a Ka-Band (32 GHz) Link Experiment (KABLE) with the Mars Observer mission was submitted to NASA. The experiment will rely on the fourth harmonic of the spacecraft X-band transmitter to generate a 33.6 GHz signal. The experiment will rely also on the Deep Space Network (DSN) receiving station equipped to simultaneously receive X- and Ka-band signals. The experiment will accurately measure the spacecraft-to-Earth telecommunication link performance at Ka-band and X-band (8.4 GHz).

  1. A ˜50 ka record of monsoonal variability in the Darjeeling foothill region, eastern Himalayas

    NASA Astrophysics Data System (ADS)

    Ghosh, Ruby; Bera, Subir; Sarkar, Anindya; Paruya, Dipak Kumar; Yao, Yi-Feng; Li, Cheng-Sen

    2015-04-01

    Pollen, phytoliths and δ 13C signatures of soil organic matter from two fluvial sedimentary sequences of the Darjeeling foothill region, eastern Himalayas are used to portray palaeoclimatic oscillations and their impact on regional plant communities over the last ˜50 ka. Quantitative palaeoclimate estimation using coexistence approach on pollen data and other proxies indicate significant oscillations in precipitation during the late part of MIS 3 (46.4-25.9 ka), early and middle part of MIS 2 (25.9-15.6 ka), and 5.4 to 3.5 ka. Middle to late MIS 3 (ca 46.4-31 ka.) was characterized by a comparatively low monsoonal activity and slightly higher temperature than that during ca 31 ka onwards. Simultaneous expansion of deciduous trees and chloridoid grasses also imply a drier and warmer phase. Between 31 and 22.3 ka (late MIS 3 to mid-MIS 2), higher precipitation and a slightly cooler temperature led to an increase in evergreen elements over deciduous taxa and wet-loving panicoid grasses over dry-loving chloridoid grasses than earlier. After ca 22.3 ka, shrinking of forest cover, expansion of C4 chloridoid grasses, Asteraceae and Cheno-ams in the vegetation with lowering of temperature and precipitation characterized the onset of the LGM which continued till 18.3 ka. End of the LGM is manifested by a restoration in the forest cover and in the temperature and precipitation regime. Later, during 5.4 to 4.3 ka, a strong monsoonal activity supported a dense moist evergreen forest cover that subsequently declined during 4.3 to 3.5 ka. A further increase in deciduous elements and non-arboreals might be a consequence of reduced precipitation and higher temperature during this phase. A comparison between monsoonal rainfall, MAT and palaeoatmospheric CO2 with floral dynamics since last ˜50 ka indicates that these fluctuations in plant succession were mainly driven by monsoonal variations.

  2. Validation Studies for CHRISTINE-CC Using a Ka-Band Coupled-Cavity TWT

    DTIC Science & Technology

    2006-04-01

    Cavity TWT for 29-31 GHz Figure 3: Output power vs. input power at f=30.0 Communications Systems," I Ith Ka and Broadband GHz for the VTA-6430A1 Ka...Coupled-Cavity TWT DISTRIBUTION: Approved for public release, distribution unlimited This paper is part of the following report: TITLE: 2006 IEEE...Studies for CHRISTINE-CC Using a Ka-Band Coupled-Cavity TWT * D. Chernin, D. Dialetis, T. M. Antonsen, Jr.t, Science Applications International Corp McLean

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. Climate and hillslope degradation vary in concert; 85 ka to present, eastern Sierra Nevada, CA, USA

    NASA Astrophysics Data System (ADS)

    Madoff, Risa D.; Putkonen, Jaakko

    2016-08-01

    Degradation in the landscape results when the interactions of climate, substrate, and biota dislodge and transport sediment that is mantling landforms. Rates of degradation through time control landform stability and resiliency. Therefore, records of past degradation rates can be used to inform us on how a given landscape responded to significant changes in past climates. For example, climate has varied at many temporal scales, and some of the largest recent shifts enabled the glacial advances and retreats in time scales of 20-100 ka. Therefore, it is reasonable to expect that the rate of landscape degradation has also varied at similar time scales. However, the general hillslope diffusion equation that is commonly used to model cross-profiles of hillslopes on time scales of thousands to tens of thousands of years typically relies on a constant and optimized rate parameter to generate a model cross-profile approximating the current observed landform cross-profile. Using a time-varying diffusivity parameter, we generated three separate degradation scenarios for the Mono Basin moraine in the eastern Sierra Nevada, CA, USA, in order to assess the potential impact of varying past climates on sediment transport. We used published paleoclimate records in the study area and modern rates of surface degradation from climates that correspond broadly to those paleoclimates. The results indicate that, in this case, the climate driven and, therefore, time-dependent degradation model produces a good fit between the modeled and observed landform profiles. Results showed that, when the surface elevations of the reference case (constant optimized diffusivity) were compared through time to the surface elevations of the time-dependent model, the differences were relatively small. The largest deviation was found to occur during the Last Glacial Maximum (LGM). We found that for investigations into the geological effects of climate change in glacial and polar regions, the use of time

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Bond-valence methods for p Ka prediction. II. Bond-valence, electrostatic, molecular geometry, and solvation effects

    NASA Astrophysics Data System (ADS)

    Bickmore, Barry R.; Rosso, Kevin M.; Tadanier, Christopher J.; Bylaska, Eric J.; Doud, Darrin

    2006-08-01

    In a previous contribution, we outlined a method for predicting (hydr)oxy-acid and oxide surface acidity constants based on three main factors: bond valence, Me-O bond ionicity, and molecular shape. Here, electrostatics calculations and ab initio molecular dynamics simulations are used to qualitatively show that Me-O bond ionicity controls the extent to which the electrostatic work of proton removal departs from ideality, bond valence controls the extent of solvation of individual functional groups, and bond valence and molecular shape control local dielectric response. These results are consistent with our model of acidity, but completely at odds with other methods of predicting acidity constants for use in multisite complexation models. In particular, our ab initio molecular dynamics simulations of solvated monomers clearly indicate that hydrogen bonding between (hydr)oxo-groups and water molecules adjusts to obey the valence sum rule, rather than maintaining a fixed valence based on the coordination of the oxygen atom as predicted by the standard MUSIC model. However, we also show how our method for p Ka prediction could be improved using ab initio molecular dynamics simulations of solvated surfaces.

  15. 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.

  16. Design and Validation of High Date Rate Ka-Band Software Defined Radio for Small Satellite

    NASA Technical Reports Server (NTRS)

    Xia, Tian

    2016-01-01

    The Design and Validation of High Date Rate Ka- Band Software Defined Radio for Small Satellite project will develop a novel Ka-band software defined radio (SDR) that is capable of establishing high data rate inter-satellite links with a throughput of 500 megabits per second (Mb/s) and providing millimeter ranging precision. The system will be designed to operate with high performance and reliability that is robust against various interference effects and network anomalies. The Ka-band radio resulting from this work will improve upon state of the art Ka-band radios in terms of dimensional size, mass and power dissipation, which limit their use in small satellites.

  17. Advances in Ka-Band Communication System for CubeSats and SmallSats

    NASA Technical Reports Server (NTRS)

    Kegege, Obadiah; Wong, Yen F.; Altunc, Serhat

    2016-01-01

    A study was performed that evaluated the feasibility of Ka-band communication system to provide CubeSat/SmallSat high rate science data downlink with ground antennas ranging from the small portable 1.2m/2.4m to apertures 5.4M, 7.3M, 11M, and 18M, for Low Earth Orbit (LEO) to Lunar CubeSat missions. This study included link analysis to determine the data rate requirement, based on the current TRL of Ka-band flight hardware and ground support infrastructure. Recent advances in Ka-band transceivers and antennas, options of portable ground stations, and various coverage distances were included in the analysis. The link/coverage analysis results show that Cubesat/Smallsat missions communication requirements including frequencies and data rates can be met by utilizing Near Earth Network (NEN) Ka-band support with 2 W and high gain (>6 dBi) antennas.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. Global calibration/validation of 2 years of SARAL/AltiKa data

    NASA Astrophysics Data System (ADS)

    Scharroo, Remko; Lillibridge, John; Leuliette, Eric; Bonekamp, Hans

    2015-04-01

    The AltiKa altimeter flying onboard the French/Indian SARAL satellite provides the first opportunity to examine Ka-band measurements of sea surface height, significant wave height and ocean surface wind speed. In this presentation we provide the results from our global calibration/validation analysis of the AltiKa measurements, with an emphasis on near real-time applications of interest to both EUMETSAT and NOAA. Traditional along-track SSHA, and single as well as dual-satellite crossover assessments of the AltiKa performance are be provided. Unique aspects of the AltiKa mission such as improved along-track resolution, reduced ionospheric path delay corrections, mission-specific wind speed and sea state bias corrections, and sensitivity to liquid moisture and rain are also explored. In February 2014, a major update to the ground processing was introduced. "Patch-2" improved the way wind speed was derived from altimeter backscatter, as suggested by Lillibridge et al. (1). The backscatter attenuation is now derived from the radiometer measurements via neural network algorithms, which also determine the wet tropospheric correction. We emphasize these improvements in our analysis. After 2 years in flight, SARAL/AltiKa is already providing a significant contribution to the constellation of operational radar altimetry missions, demonstrating the large benefits of high-rate Ka-band altimetry. (1) Lillibridge, John, Remko Scharroo, Saleh Abdalla, Doug Vandemark, 2014: One- and Two-Dimensional Wind Speed Models for Ka-Band Altimetry. J. Atmos. Oceanic Technol., 31, 630-638. doi: http://dx.doi.org/10.1175/JTECH-D-13-00167.1

  10. An abrupt and prominent climatic reversal at 9.2 ka in the northeastern North America

    NASA Astrophysics Data System (ADS)

    Hou, J.; Huang, Y.; Shuman, B. N.; Oswald, W.; Foster, D. R.

    2008-12-01

    Continental climate during the early Holocene (from 10 to 7 ka) is characterized by multiple abrupt climatic reversals such as the well-known 8.2 ka event that has been observed worldwide and attributed to the terminal collapse of the Laurentide Ice Sheet (LIS) in the North American continent. However, many episodes of meltwater releases occurred prior to the final collapse of LIS, their impact on the continental climate is much less understood. We present in this paper decadal-scale hydrogen isotopic records of aquatic and terrestrial plant biomarkers from Blood Pond, Massachusetts during the early Holocene. Our isotopic records infer a cooling of 3~4 degree between 9.3 and 9.1 ka against the millennial scale climate background, mainly induced by changes in precipitation seasonality. In comparison, the 8.2 ka event displays smaller amplitude of temperature cooling of 1~2 degree at our southern New England site. We interpret our observed climatic reversal at ~ 9.2 ka as representing increased proportion of winter precipitation in conjunction with a drier and cooler summer, triggered by slowdown in thermohaline circulation as a result of freshwater release from the proglacial lakes. We attribute the difference in climate response at 8.2 ka and 9.2 ka events to the configuration of LIS, with 9.2 ka LIS having a much stronger blocking effect on the moisture from the Gulf of Mexico during the summer. Our data suggest that the seasonality of the precipitation at the southern New England was highly sensitive to meltwater releases, especially prior to the final collapse of the LIS.

  11. NASA's Evolution to Ka-Band Space Communications for Near-Earth Spacecraft

    NASA Technical Reports Server (NTRS)

    McCarthy, Kevin; Stocklin, Frank; Geldzahler, Barry; Friedman, Daniel; Celeste, Peter

    2010-01-01

    This slide presentation reviews the exploration of NASA using a Ka-band system for spacecraft communications in Near-Earth orbits. The reasons for changing to Ka-band are the higher data rates, and the current (X-band spectrum) is becoming crowded. This will require some modification to the current ground station antennas systems. The results of a Request for Information (RFI) are discussed, and the recommended solution is reviewed.

  12. Complete Genome Sequence of the Thermophilic, Piezophilic, Heterotrophic Bacterium Marinitoga piezophila KA3

    SciTech Connect

    Lucas, Susan; Han, James; Lapidus, Alla L.; Cheng, Jan-Fang; Goodwin, Lynne A.; Pitluck, Sam; Peters, Lin; Mikhailova, Natalia; Teshima, Hazuki; Detter, J. Chris; Han, Cliff; Tapia, Roxanne; Land, Miriam L; Hauser, Loren John; Kyrpides, Nikos C; Ivanova, N; Pagani, Ioanna; Vannier, Pauline; Oger, Phil; Bartlett, Douglas; Noll, Kenneth M; Woyke, Tanja; Jebbar, Mohamed

    2012-01-01

    Marinitoga piezophila KA3 is a thermophilic, anaerobic, chemoorganotrophic, sulfur-reducing bacterium isolated from the Grandbonum deep-sea hydrothermal vent site at the East Pacific Rise (13 degrees N, 2,630-m depth). The genome of M. piezophila KA3 comprises a 2,231,407-bp circular chromosome and a 13,386-bp circular plasmid. This genome was sequenced within Department of Energy Joint Genome Institute CSP 2010.

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. Forest cover change and fragmentation using Landsat data in Maçka State Forest Enterprise in Turkey.

    PubMed

    Cakir, Günay; Sivrikaya, Fatih; Keleş, Sedat

    2008-02-01

    Monitoring forest cover change and understanding the dynamic of forest cover is increasingly important in sustainable development and management of forest ecosystems. This paper uses remote sensing (RS) techniques to monitor forest cover change in Maçka State Forest Enterprise (MSFE) located in NE of Turkey through 1975 to 2000 and then analyses spatial and temporal changes in forest cover by Geographical Information Systems (GIS) and FRAGSTATStrade mark. Forest cover changes were detected from a time series of satellite images of Landsat MSS in 1975, Landsat TM in 1987, and Landsat ETM+ in 2000 using RS and GIS. The results showed that total forest area, productive forest area and degraded forest area increased while broadleaf forest area and non forest area decreased. Mixed forest and degraded forest increased during the first (1975-1987) period, but decreased during the second (1987-2000) period. During the whole study period, the annual forestation rate was 152 ha year(-1), equivalent to 0.27% year(-1) using the compound-interest-rate formula. The total number of patches increased from 36,204 to 48,092 (33%), and mean size of forest patch (MPS) decreased from 2.8 ha to 2.1 ha during a 25 year period. Number of smaller patches (patches in 0-100 ha size class) increased, indicating more fragmented landscape over time that might create a risk for the maintenance of biodiversity of the area. While total population increased from 1975 to 2000 (3.7%), rural population constantly decreased. The increase of forest areas may well be explained by the fact that demographic movement of rural areas concentrated into Maçka City Center. These figures also indicated that decrease in the rural population might likely lead to the release of human pressure to forest areas, probably resulting in a positive development of forest areas.

  18. How Does the Methodology of 3D Structure Preparation Influence the Quality of pKa Prediction?

    PubMed

    Geidl, Stanislav; Svobodová Vařeková, Radka; Bendová, Veronika; Petrusek, Lukáš; Ionescu, Crina-Maria; Jurka, Zdeněk; Abagyan, Ruben; Koča, Jaroslav

    2015-06-22

    The acid dissociation constant is an important molecular property, and it can be successfully predicted by Quantitative Structure-Property Relationship (QSPR) models, even for in silico designed molecules. We analyzed how the methodology of in silico 3D structure preparation influences the quality of QSPR models. Specifically, we evaluated and compared QSPR models based on six different 3D structure sources (DTP NCI, Pubchem, Balloon, Frog2, OpenBabel, and RDKit) combined with four different types of optimization. These analyses were performed for three classes of molecules (phenols, carboxylic acids, anilines), and the QSPR model descriptors were quantum mechanical (QM) and empirical partial atomic charges. Specifically, we developed 516 QSPR models and afterward systematically analyzed the influence of the 3D structure source and other factors on their quality. Our results confirmed that QSPR models based on partial atomic charges are able to predict pKa with high accuracy. We also confirmed that ab initio and semiempirical QM charges provide very accurate QSPR models and using empirical charges based on electronegativity equalization is also acceptable, as well as advantageous, because their calculation is very fast. On the other hand, Gasteiger-Marsili empirical charges are not applicable for pKa prediction. We later found that QSPR models for some classes of molecules (carboxylic acids) are less accurate. In this context, we compared the influence of different 3D structure sources. We found that an appropriate selection of 3D structure source and optimization method is essential for the successful QSPR modeling of pKa. Specifically, the 3D structures from the DTP NCI and Pubchem databases performed the best, as they provided very accurate QSPR models for all the tested molecular classes and charge calculation approaches, and they do not require optimization. Also, Frog2 performed very well. Other 3D structure sources can also be used but are not so robust, and

  19. Improving Cry8Ka toxin activity towards the cotton boll weevil (Anthonomus grandis)

    PubMed Central

    2011-01-01

    Background The cotton boll weevil (Anthonomus grandis) is a serious insect-pest in the Americas, particularly in Brazil. The use of chemical or biological insect control is not effective against the cotton boll weevil because of its endophytic life style. Therefore, the use of biotechnological tools to produce insect-resistant transgenic plants represents an important strategy to reduce the damage to cotton plants caused by the boll weevil. The present study focuses on the identification of novel molecules that show improved toxicity against the cotton boll weevil. In vitro directed molecular evolution through DNA shuffling and phage display screening was applied to enhance the insecticidal activity of variants of the Cry8Ka1 protein of Bacillus thuringiensis. Results Bioassays carried out with A. grandis larvae revealed that the LC50 of the screened mutant Cry8Ka5 toxin was 3.15-fold higher than the wild-type Cry8Ka1 toxin. Homology modelling of Cry8Ka1 and the Cry8Ka5 mutant suggested that both proteins retained the typical three-domain Cry family structure. The mutated residues were located mostly in loops and appeared unlikely to interfere with molecular stability. Conclusions The improved toxicity of the Cry8Ka5 mutant obtained in this study will allow the generation of a transgenic cotton event with improved potential to control A. grandis. PMID:21906288

  20. Pre-Flight Testing and Performance of a Ka-Band Software Defined Radio

    NASA Technical Reports Server (NTRS)

    Downey, Joseph A.; Reinhart, Richard C.; Kacpura, Thomas

    2012-01-01

    National Aeronautics and Space Administration (NASA) has developed a space-qualified, reprogrammable, Ka-band Software Defined Radio (SDR) to be utilized as part of an on-orbit, reconfigurable testbed. The testbed will operate on the truss of the International Space Station beginning in late 2012. Three unique SDRs comprise the testbed, and each radio is compliant to the Space Telecommunications Radio System (STRS) Architecture Standard. The testbed provides NASA, industry, other Government agencies, and academic partners the opportunity to develop communications, navigation, and networking applications in the laboratory and space environment, while at the same time advancing SDR technology, reducing risk, and enabling future mission capability. Designed and built by Harris Corporation, the Ka-band SDR is NASA's first space-qualified Ka-band SDR transceiver. The Harris SDR will also mark the first NASA user of the Ka-band capabilities of the Tracking Data and Relay Satellite System (TDRSS) for on-orbit operations. This paper describes the testbed's Ka-band System, including the SDR, travelling wave tube amplifier (TWTA), and antenna system. The reconfigurable aspects of the system enabled by SDR technology are discussed and the Ka-band system performance is presented as measured during extensive pre-flight testing.

  1. Stratigraphic constraints for explosive activity in the past 100 ka at Etna Volcano, Italy

    NASA Astrophysics Data System (ADS)

    Coltelli, Mauro; Del Carlo, Paola; Vezzoli, Luigina

    2000-08-01

    The pyroclastic deposits of Etna have been correlated over the whole volcanic edifice for the first time, allowing the construction of a continuous record of tephra-producing events, which extends from approximately 100 ka to the Present. In this interval, five main periods of explosive activity have been identified: (a) 100-ka strombolian to subplinian activity; (b) 80- to 100-ka plinian benmoreitic activity; (c) 16- to 80-ka strombolian to subplinian from basaltic to mugearitic activity; (d) 15.5- to 15-ka plinian benmoreitic activity accompanying the caldera-forming eruptions of the Ellittico Volcano; and (e) the most recent 13-ka basaltic explosive activity of strombolian and subplinian type of the present edifice that also includes the 122-B.C. plinian eruption. This study results in a semi-quantitative and in some cases quantitative definition of the intensity and chronology of the explosive activity at Etna. Moreover, this work gives a new significance to the volcanic hazards of Etna, a volcano generally considered to be the site of gentle effusive eruptions.

  2. Progress in the prediction of pKa values in proteins

    SciTech Connect

    Alexov, Emil; Mehler, Ernest L.; Baker, Nathan A.; Baptista, Antonio; Huang, Yong; Milletti, Francesca; Nielsen, Jens E.; Farrell, Damien; Carstensen, Tommy; Olsson, Mats H.; Shen, Jana K.; Warwicker, Jim; Williams, Sarah; Word, J Michael

    2011-12-15

    The pKa-cooperative aims to provide a forum for experimental and theoretical researchers interested in protein pKa values and protein electrostatics in general. The first round of the pKa -cooperative, which challenged computational labs to carry out blind predictions against pKas experimentally determined in the laboratory of Bertrand Garcia-Moreno, was completed and results discussed at the Telluride meeting (July 6-10, 2009). This paper serves as an introduction to the reports submitted by the blind prediction participants that will be published in a special issue of PROTEINS: Structure, Function and Bioinformatics. Here we briefly outline existing approaches for pKa calculations, emphasizing methods that were used by the participants in calculating the blind pKa values in the first round of the cooperative. We then point out some of the difficulties encountered by the participating groups in making their blind predictions, and finally try to provide some insights for future developments aimed at improving the accuracy of pKa calculations.

  3. A Ka-band Celestial Reference Frame with Applications to Deep Space Navigation

    NASA Astrophysics Data System (ADS)

    Jacobs, Christopher S.; Clark, J. E.; García-Miró, C.; Horiuchi, S.; Sotuela, I.

    2011-10-01

    The Ka-band radio spectrum is now being used for a wide variety of applications. This paper highlights the use of Ka-band as a frequency for precise deep space navigation based on a set of reference beacons provided by extragalactic quasars which emit broadband noise at Ka-band. This quasar-based celestial reference frame is constructed using X/Ka-band (8.4/32 GHz) from fifty-five 24-hour sessions with the Deep Space Network antennas in California, Australia, and Spain. We report on observations which have detected 464 sources covering the full 24 hours of Right Ascension and declinations down to -45 deg. Comparison of this X/Ka-band frame to the international standard S/X-band (2.3/8.4 GHz) ICRF2 shows wRMS agreement of ~200 micro-arcsec (μas) in α cos δ and ~300 μas in δ. There is evidence for systematic errors at the 100 μas level. Known errors include limited SNR, lack of instrumental phase calibration, tropospheric refraction mis-modeling, and limited southern geometry. The motivation for extending the celestial reference frame to frequencies above 8 GHz is to access more compact source morphology for improved frame stability and to support spacecraft navigation for Ka-band based NASA missions.

  4. A Ka-Band Celestial Reference Frame with Applications to Deep Space Navigation

    NASA Technical Reports Server (NTRS)

    Jacobs, Christopher S.; Clark, J. Eric; Garcia-Miro, Cristina; Horiuchi, Shinji; Sotuela, Ioana

    2011-01-01

    The Ka-band radio spectrum is now being used for a wide variety of applications. This paper highlights the use of Ka-band as a frequency for precise deep space navigation based on a set of reference beacons provided by extragalactic quasars which emit broadband noise at Ka-band. This quasar-based celestial reference frame is constructed using X/Ka-band (8.4/32 GHz) from fifty-five 24-hour sessions with the Deep Space Network antennas in California, Australia, and Spain. We report on observations which have detected 464 sources covering the full 24 hours of Right Ascension and declinations down to -45 deg. Comparison of this X/Ka-band frame to the international standard S/X-band (2.3/8.4 GHz) ICRF2 shows wRMS agreement of approximately 200 micro-arcsec in alpha cos(delta) and approximately 300 micro-arcsec in delta. There is evidence for systematic errors at the 100 micro-arcsec level. Known errors include limited SNR, lack of instrumental phase calibration, tropospheric refraction mis-modeling, and limited southern geometry. The motivation for extending the celestial reference frame to frequencies above 8 GHz is to access more compact source morphology for improved frame stability and to support spacecraft navigation for Ka-band based NASA missions.

  5. The GridKa Tier-1 Computing Center within the ALICE Grid Framework

    NASA Astrophysics Data System (ADS)

    Park, WooJin J.; Christopher, Jung; Heiss, Andreas; Petzold, Andreas; Schwarz, Kilian

    2014-06-01

    The GridKa computing center, hosted by Steinbuch Centre for Computing at the Karlsruhe Institute for Technology (KIT) in Germany, is serving as the largest Tier-1 center used by the ALICE collaboration at the LHC. In 2013, GridKa provides 30k HEPSPEC06, 2.7 PB of disk space, and 5.25 PB of tape storage to ALICE. The 10Gbit/s network connections from GridKa to CERN, several Tier-1 centers and the general purpose network are used by ALICE intensively. In 2012 a total amount of ~1 PB was transferred to and from GridKa. As Grid framework, AliEn (ALICE Environment) is being used to access the resources, and various monitoring tools including the MonALISA (MONitoring Agent using a Large Integrated Services Architecture) are always running to alert in case of any problem. GridKa on-call engineers provide 24/7 support to guarantee minimal loss of availability of computing and storage resources in case of hardware or software problems. We introduce the GridKa Tier-1 center from the viewpoint of ALICE services.

  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. Application of the Goldilocks Effect to the Design of Potent and Selective Inhibitors of Phenylethanolamine N-Methyltransferase: Balancing pKa and Steric Effects in the Optimization of 3-Methyl-1,2,3,4-tetrahydroisoquinoline Inhibitors by β-Fluorination

    PubMed Central

    Grunewald, Gary L.; Seim, Mitchell R.; Lu, Jian; Makboul, Mariam; Criscione, Kevin R.

    2008-01-01

    3-Methyl-1,2,3,4-tetrahydroisoquinolines (3-methyl-THIQs) are potent inhibitors of phenylethanolamine N-methyltransferase (PNMT), but are not selective due to significant affinity for the α2-adrenoceptor. Fluorination of the methyl group lowers the pKa of the THIQ amine from 9.53 (CH3) to 7.88 (CH2F), 6.42 (CHF2), and 4.88 (CF3). This decrease in pKa results in a reduction in affinity for the α2-adrenoceptor. However, increased fluorination also results in a reduction in PNMT inhibitory potency, apparently due to steric and electrostatic factors. Biochemical evaluation of a series of 3-fluoromethyl-THIQs and 3-trifluoromethyl-THIQs showed that the former were highly potent inhibitors of PNMT, but were often non-selective due to significant affinity for the α2-adrenoceptor, while the latter were devoid of α2-adrenoceptor affinity, but also lost potency at PNMT. 3-Difluoromethyl-7-substituted-THIQs have the proper balance of both steric and pKa properties and thus have enhanced selectivity versus the corresponding 3-fluoromethyl-7-substituted-THIQs and enhanced PNMT inhibitory potency versus the corresponding 3-trifluoromethyl-7-substituted-THIQs. Using the “Goldilocks Effect” analogy, the 3-fluoromethyl-THIQs are too potent (too hot) at the α2-adrenoceptor and the 3-trifluoromethyl-THIQs are not potent enough (too cold) at PNMT, but the 3-difluoromethyl-THIQs are just right. They are both potent inhibitors of PNMT and highly selective due to low affinity for the α2-adrenoceptor. This seems to be the first successful use of the β-fluorination of aliphatic amines to impart selectivity to a pharmacological agent while maintaining potency at the site of interest. PMID:16686536

  9. 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.

  10. 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.

  11. Spectral slope and Kolmogorov constant of MHD turbulence.

    PubMed

    Beresnyak, A

    2011-02-18

    The spectral slope of strong MHD turbulence has recently been a matter of controversy. While the Goldreich-Sridhar model predicts a -5/3 slope, shallower slopes have been observed in numerics. We argue that earlier numerics were affected by driving due to a diffuse locality of energy transfer. Our highest-resolution simulation (3072(2)×1024) exhibited the asymptotic -5/3 scaling. We also discover that the dynamic alignment, proposed in models with -3/2 slope, saturates and cannot modify the asymptotic, high Reynolds number slope. From the observed -5/3 scaling we measure the Kolmogorov constant C(KA)=3.27±0.07 for Alfvénic turbulence and C(K)=4.2±0.2 for full MHD turbulence, which is higher than the hydrodynamic value of 1.64. This larger C(K) indicates inefficient energy transfer in MHD turbulence, which is in agreement with diffuse locality.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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

  18. The Effect of Past Climate Change on Regolith Erosion Rates for the Past 100 ka in the Eastern Sierra Nevada

    NASA Astrophysics Data System (ADS)

    Madoff, R. D.; Putkonen, J.

    2014-12-01

    Global climate change over the last 100 ka is known to have resulted in glacial fluctuations in the eastern Sierra Nevada evidenced today by moraines. The effect of past climate on regolith erosion rates is quantified by modeling hillslope diffusion and evolution of a profile cross-section of Mono Basin moraine in the eastern Sierra Nevada. The degradation in the model is described by the linear transport law, q = -κ(dz/dx), where the diffusivity coefficient, κ, is a parameter to account for factors affecting regolith transport rate (q) unrelated to slope (dz/dx), such as climate and substrate. Three scenarios were modeled with respective κ values. In the first, κ is held constant through the age of the landform and optimized to reproduce the current moraine cross-section. In the second, κ varies with time based on the documented variation in the paleoclimate and related degradation rate. In the third, κ is held constant and defined by present-day degradation values measured in the region. In all the scenarios the moraine initial slopes are at the angle of repose. Comparisons of the first (constant κ) and second (variable κ) scenarios show that the former can generate erosion rates that overestimate crest elevation by 30% during the first quarter of the landform age and underestimate it by 20% during the latter three-quarters. However, the third (current κ) scenario underestimates the degradation up to 58% of the current profile. This indicates that the past erosion rates were higher than what is observed today. Increased regolith erosion rates in the past were driven by climates colder and wetter than the present.

  19. 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.

  20. 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.

  1. 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.

  2. Determination of acidity constants of sparingly soluble drugs in aqueous solution by the internal standard capillary electrophoresis method.

    PubMed

    Cabot, Joan Marc; Fuguet, Elisabet; Rosés, Martí

    2014-12-01

    A set of 33 drugs with different solubilities, ranging from soluble to very insoluble, has been chosen in order to evaluate the performance of the internal standard CE method to determine acidity constants of compounds with limited solubility. The set of drugs tested in this work has been chosen as a function of their intrinsic solubility. For the most insoluble compounds, several analytical conditions to overcome the insolubility in aqueous buffers have been tested. This paper assesses the compound solubility limits for the IS-CE method in aqueous pKa determinations, and also compares the determined pKa s with the results from the literature data obtained by other methods. It is proved that IS-CE method determines acidity constants of sparingly soluble drugs in aqueous media (compounds with logS down to around -6), whereas other reference methods require the use of aqueous-organic solvent buffers and extrapolation procedures to obtain the aqueous pKa for the same compounds.

  3. Molecular Paleoclimate Reconstructions over the Last 9 ka from a Peat Sequence in South China

    PubMed Central

    Wang, Xinxin; Huang, Xianyu; Sachse, Dirk; Ding, Weihua; Xue, Jiantao

    2016-01-01

    To achieve a better understanding of Holocene climate change in the monsoon regions of China, we investigated the molecular distributions and carbon and hydrogen isotope compositions (δ13C and δD values) of long-chain n-alkanes in a peat core from the Shiwangutian (SWGT) peatland, south China over the last 9 ka. By comparisons with other climate records, we found that the δ13C values of the long-chain n-alkanes can be a proxy for humidity, while the δD values of the long-chain n-alkanes primarily recorded the moisture source δD signal during 9–1.8 ka BP and responded to the dry climate during 1.8–0.3 ka BP. Together with the average chain length (ACL) and the carbon preference index (CPI) data, the climate evolution over last 9 ka in the SWGT peatland can be divided into three stages. During the first stage (9–5 ka BP), the δ13C values were depleted and CPI and Paq values were low, while ACL values were high. They reveal a period of warm and wet climate, which is regarded as the Holocene optimum. The second stage (5–1.8 ka BP) witnessed a shift to relatively cool and dry climate, as indicated by the more positive δ13C values and lower ACL values. During the third stage (1.8–0.3 ka BP), the δ13C, δD, CPI and Paq values showed marked increase and ACL values varied greatly, implying an abrupt change to cold and dry conditions. This climate pattern corresponds to the broad decline in Asian monsoon intensity through the latter part of the Holocene. Our results do not support a later Holocene optimum in south China as suggested by previous studies. PMID:27505008

  4. Molecular Paleoclimate Reconstructions over the Last 9 ka from a Peat Sequence in South China.

    PubMed

    Wang, Xinxin; Huang, Xianyu; Sachse, Dirk; Ding, Weihua; Xue, Jiantao

    2016-01-01

    To achieve a better understanding of Holocene climate change in the monsoon regions of China, we investigated the molecular distributions and carbon and hydrogen isotope compositions (δ13C and δD values) of long-chain n-alkanes in a peat core from the Shiwangutian (SWGT) peatland, south China over the last 9 ka. By comparisons with other climate records, we found that the δ13C values of the long-chain n-alkanes can be a proxy for humidity, while the δD values of the long-chain n-alkanes primarily recorded the moisture source δD signal during 9-1.8 ka BP and responded to the dry climate during 1.8-0.3 ka BP. Together with the average chain length (ACL) and the carbon preference index (CPI) data, the climate evolution over last 9 ka in the SWGT peatland can be divided into three stages. During the first stage (9-5 ka BP), the δ13C values were depleted and CPI and Paq values were low, while ACL values were high. They reveal a period of warm and wet climate, which is regarded as the Holocene optimum. The second stage (5-1.8 ka BP) witnessed a shift to relatively cool and dry climate, as indicated by the more positive δ13C values and lower ACL values. During the third stage (1.8-0.3 ka BP), the δ13C, δD, CPI and Paq values showed marked increase and ACL values varied greatly, implying an abrupt change to cold and dry conditions. This climate pattern corresponds to the broad decline in Asian monsoon intensity through the latter part of the Holocene. Our results do not support a later Holocene optimum in south China as suggested by previous studies.

  5. [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.

  6. 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.

  7. Real-time association rate constant measurement using combination tapered fiber-optic biosensor (CTFOB) dip-probes

    NASA Astrophysics Data System (ADS)

    Simmonds, Boris; Wang, Chun-Wei; Kapoor, Rakesh

    2010-02-01

    This document reports a novel method of measuring association rate constant (ka) for antibody-antigen interaction using evanescent wave-based combination tapered fiber-optic biosensor (CTFOB) dip-probes. The method was demonstrated by measuring association rate constant for bovine serum albumin (BSA) and anti-BSA antibody interaction. "Direct method" was used for detection; goat anti-BSA "capture" antibodies were immobilized on the probe surfaces while the antigen (BSA) was directly labeled with Alexa 488 dye. The probes were subsequently submerged in 3nM Labeled BSA in egg albumin (1 mg/ml). The fluorescence signal recorded was proportional to BSA anti-BSA conjugates and continuous signal was acquired suing a fiber optic spectrometer (Ocean Optics, Inc.). A 476 nm diode laser was use as an excitation source. Association constant was estimated from a plot of signal as a function of time. Measured association rate constant ka for the binding of BSA with anti-BSA at room temperature is (8.33 +/- 0.01) x 104 M-1s-1.

  8. Records of the paleoclimate during the fast transgression period (13 ka BP-8 ka BP) from the mud area on the inner shelf of the East China Sea

    NASA Astrophysics Data System (ADS)

    Liu, S.

    2015-12-01

    A 35.30m-long core (MZ02) recovered from a water depth of 32.4m from the inner shelf mud deposit of the East China Sea was analyzed for sedimentary characteristics, color reflectance, clay mineral, and element geochemistry components as well as by AMS 14C dating to research the sedimentation rate, sediment provenance and paleocwan mountainous river and clay fralimate evolution during the fast transgression period in the study area. Rare earth element and clay mineral proxies indicated that the mixed provenance sediment accumulated in the foreshore-nearshore region at the beginning of the fast transgression period, with a higher sedimentation rate of 5.58m/ka. While from 9800-9500 a B.P., the sedimentation rate keep lower about 1.73m/ka, and the sediment provenance changed obviously, silt fraction were apt to Taiction prone to be transported from the Yangtze River. Multiple proxy system including sediment redness (a*), chemical index of alteration (CIA), clay mineral proxy (smectite/kaolinite), major and trace element proxy (CaO/MgO, Ba/Sr) also showed a good paleoclimate record during the fast transgression period, which could be divided into three units. All the proxies changed little during Unit I (13-11.3ka B.P.) and revealed the climate kept in a relative stable level. Obvious fluctuation happened in Unit II (11.3-10.1ka B.P.) and the temperature kept decreasing more than 1ka till the Younger Dryas event, showed a well regional response to global climate changes. While continuous warming trend resumed again in Unit III (10.1-8 ka B.P.), which may be the signal for Holocene warm period. In addition, we also found significant 80yr, 89yr and 100yr cycles in our CIA, CaO/MgO and Ba/Sr records that imply a possible solar influence on the regional climate changes during the fast transgression period. Keywords: East China Sea, provenance, transgression, mud deposit, late Pleistocene, paleoclimate

  9. 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.

  10. Intrinsic absolute bioavailability prediction in rats based on in situ absorption rate constants and/or in vitro partition coefficients: 6-fluoroquinolones.

    PubMed

    Sánchez-Castaño, G; Ruíz-García, A; Bañón, N; Bermejo, M; Merino, V; Freixas, J; Garriguesx, T M; Plá-Delfina, J M

    2000-11-01

    A preliminary study attempting to predict the intrinsic absolute bioavailability of a group of antibacterial 6-fluoroquinolones-including true and imperfect homologues as well as heterologues-was carried out. The intrinsic absolute bioavailability of the test compounds, F, was assessed on permanently cannulated conscious rats by comparing the trapezoidal normalized areas under the plasma concentration-time curves obtained by intravenous and oral routes (n = 8-12). The high-performance liquid chromatography analytical methods used for plasma samples are described. Prediction of the absolute bioavailability of the compounds was based on their intrinsic rat gut in situ absorption rate constant, k(a). The working equation was: where T represents the mean absorbing time. A T value of 0.93 (+/-0.06) h provides the best correlation between predicted and experimentally obtained bioavailabilities (F' and F, respectively) when k(a) values are used (slope a = 1.10; intercept b = -0.05; r = 0.991). The k(a) values can also be expressed in function of the in vitro partition coefficients, P, between n-octanol and a phosphate buffer. In this case, theoretical k(a) values can be determined with the parameters of a standard k(a)/P correlation previously established for a group of model compounds. When P values are taken instead of k(a) values, reliable bioavailability predictions can also be made. These and other relevant features of the method are discussed.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. IntCal04: A New Consensus Radiocarbon Calibration Dataset from 0-26 ka BP

    NASA Astrophysics Data System (ADS)

    Reimer, P. J.; Baillie, M. G.; Bard, E.; Beck, J. W.; Buck, C. E.; Blackwell, P. G.; Burr, G. S.; Cutler, K. B.; Damon, P. E.; Edwards, R. L.; Fairbanks, R. G.; Friedrich, M.; Guilderson, T. P.; Hogg, A. G.; Hughen, K. A.; Kromer, B.; McCormac, G.; Ramsey, C. B.; Reimer, R. W.; Remmele, S.; Southon, J. R.; Stuiver, M.; Taylor, F. W.; van der Plicht, J.; Weyhenmeyer, C. E.

    2003-12-01

    Because atmosphere 14C levels have not been constant through time, it is necessary to calibrate radiocarbon dates with known age radiocarbon datasets in order to compare paleorecords based on 14C ages and those based on other timescales. The need for a consensus calibration dataset was acknowledged by the radiocarbon community as a way of preventing confusion and the subjective use of selected datasets (1). Since then, radiocarbon calibration datasets have been developed by international collaborations and presented for ratification at the International Radiocarbon Conference (2-4). The IntCal04 Radiocarbon Calibration/Comparison Working Group has put together a dataset which incorporates existing and new measurements of tree-ring records, foraminifera from varved sediments, and corals that meet a strict set of acceptance criteria (5). Uncertainties for both the calendar time scale and the radiocarbon ages have been quantified and included in the dataset combination using a statistical technique based on the ideas of Christen and Nicholls (6) and Gomez Portugal Aguilar (7). The IntCal04 dataset, which covers the range of 0 to 26 ka BP, was presented for ratification at the 19th International Radiocarbon Conference in Wellington, New Zealand, in September, 2003. This paper will highlight the differences between IntCal98 and the new IntCal04 dataset and give an example showing the effect on the calibrated age for a Younger Dryas age sample. 1. J. Klein, J. C. Lerman, P. E. Damon, E. K. Ralph, Radiocarbon 24, 103-150 (1982). 2. M. Stuiver, Radiocarbon 28, R2-R2 (1986). 3. M. Stuiver et al., Radiocarbon 40, 1041-1083 (1998). 4. M. Stuiver, P. J. Reimer, Radiocarbon 35, 215-230 (1993). 5. P. J. Reimer et al., Radiocarbon 44, 653-661. (2002). 6. J. A. Christen, G. Nicholls, "Random-walk radiocarbon calibration." (Mathematics Department, University of Auckland, 2000). 7.D. G. P. Aguilar, C. D. Litton, A. O'Hagan, Radiocarbon 44, 195-212 (2002).

  16. 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

  17. Proton affinity of the histidine-tryptophan cluster motif from the influenza A virus from ab initio molecular dynamics

    NASA Astrophysics Data System (ADS)

    Bankura, Arindam; Klein, Michael L.; Carnevale, Vincenzo

    2013-08-01

    Ab initio molecular dynamics calculations have been used to compare and contrast the deprotonation reaction of a histidine residue in aqueous solution with the situation arising in a histidine-tryptophan cluster. The latter is used as a model of the proton storage unit present in the pore of the M2 proton conducting ion channel. We compute potentials of mean force for the dissociation of a proton from the Nδ and Nɛ positions of the imidazole group to estimate the pKas. Anticipating our results, we will see that the estimated pKa for the first protonation event of the M2 channel is in good agreement with experimental estimates. Surprisingly, despite the fact that the histidine is partially desolvated in the M2 channel, the affinity for protons is similar to that of a histidine in aqueous solution. Importantly, the electrostatic environment provided by the indoles is responsible for the stabilization of the charged imidazolium.

  18. Equatorial Precession in the Control Software of the Ka-Band Object Observation and Monitoring Experiment

    NASA Technical Reports Server (NTRS)

    Jakeman, Hali L.

    2013-01-01

    The Ka-Band Object Observation and Monitoring, or KaBOOM, project is designed mainly to track and characterize near Earth objects. However, a smaller goal of the project would be to monitor pulsars and study their radio frequency signals for use as a clock in interstellar travel. The use of pulsars and their timing accuracy has been studied for decades, but never in the Ka-band of the radio frequency spectrum. In order to begin the use of KaBOOM for this research, the control systems need to be analyzed to ensure its capability. Flaws in the control documentation leave it unclear as to whether the control software processes coordinates from the J200 epoch. This experiment will examine the control software of the Intertronic 12m antennas used for the KaBOOM project and detail its capabilities in its "equatorial mode." The antennas will be pointed at 4 chosen points in the sky on several days while probing the virtual azimuth and elevation (horizon coordinate) registers. The input right ascension and declination coordinates will then be converted separately from the control software to horizontal coordinates and compared, thus determining the ability of the control software to process equatorial coordinates.

  19. Ka-band monopulse antenna-pointing systems analysis and simulation

    NASA Technical Reports Server (NTRS)

    Lo, V. Y.

    1996-01-01

    NASA 's Deep Space Network (DSN) has been using both 70-m and 34-m reflector antennas to communicate with spacecraft at S-band (2.3 GHz) and X-band (8.45 GHz). To improve the quality of telecommunication and to meet future mission requirements, JPL has been developing 34-m Ka-band (32-GHz) beam waveguide antennas. Presently, antenna pointing operates in either the open-loop mode with blind pointing using navigation predicts or the closed-loop mode with conical scan (conscan). Pointing accuracy under normal conscan operating conditions is in the neighborhood of 5 mdeg. This is acceptable at S- and X-bands, but not enough at Ka-band. Due to the narrow beamwidth at Ka-band, it is important to improve pointing accuracy significantly (approximately 2 mdeg). Monopulse antenna tracking is one scheme being developed to meet the stringent pointing-accuracy requirement at Ka-band. Other advantages of monopulse tracking include low sensitivity to signal amplitude fluctuations as well as single-pulse processing for acquisition and tracking. This article presents system modeling, signal processing, simulation, and implementation of Ka-band monopulse tracking feed for antennas in NASA/DSN ground stations.

  20. A 600-ka Arctic sea-ice record from Mendeleev Ridge based on ostracodes

    NASA Astrophysics Data System (ADS)

    Cronin, T. M.; Polyak, L.; Reed, D.; Kandiano, E. S.; Marzen, R. E.; Council, E. A.

    2013-11-01

    Arctic paleoceanography and sea-ice history were reconstructed from epipelagic and benthic ostracodes from a sediment core (HLY0503-06JPC, 800 m water depth) located on the Mendeleev Ridge, Western Arctic Ocean. The calcareous microfaunal record (ostracodes and foraminifers) covers several glacial/interglacial cycles back to estimated Marine Isotope Stage 13 (MIS 13, ˜500 ka) with an average sedimentation rate of ˜0.5 cm/ka for most of the stratigraphy (MIS 5-13). Results based on ostracode assemblages and an unusual planktic foraminiferal assemblage in MIS 11 dominated by a temperate-water species Turborotalita egelida show that extreme interglacial warmth, high surface ocean productivity, and possibly open ocean convection characterized MIS 11 and MIS 13 (˜400 and 500 ka, respectively). A major shift in western Arctic Ocean environments toward perennial sea ice occurred after MIS 11 based on the distribution of an ice-dwelling ostracode Acetabulastoma arcticum. Spectral analyses of the ostracode assemblages indicate sea ice and mid-depth ocean circulation in western Arctic Ocean varied primarily at precessional (˜22 ka) and obliquity (˜40 ka) frequencies.

  1. A 600-ka Arctic sea-ice record from Mendeleev Ridge based on ostracodes

    USGS Publications Warehouse

    Cronin, Thomas M.; Polyak, L.V.; Reed, D.; Kandiano, E. S.; Marzen, R. E.; Council, E. A.

    2013-01-01

    Arctic paleoceanography and sea-ice history were reconstructed from epipelagic and benthic ostracodes from a sediment core (HLY0503-06JPC, 800 m water depth) located on the Mendeleev Ridge, Western Arctic Ocean. The calcareous microfaunal record (ostracodes and foraminifers) covers several glacial/interglacial cycles back to estimated Marine Isotope Stage 13 (MIS 13, ∼500 ka) with an average sedimentation rate of ∼0.5 cm/ka for most of the stratigraphy (MIS 5–13). Results based on ostracode assemblages and an unusual planktic foraminiferal assemblage in MIS 11 dominated by a temperate-water species Turborotalita egelida show that extreme interglacial warmth, high surface ocean productivity, and possibly open ocean convection characterized MIS 11 and MIS 13 (∼400 and 500 ka, respectively). A major shift in western Arctic Ocean environments toward perennial sea ice occurred after MIS 11 based on the distribution of an ice-dwelling ostracode Acetabulastoma arcticum. Spectral analyses of the ostracode assemblages indicate sea ice and mid-depth ocean circulation in western Arctic Ocean varied primarily at precessional (∼22 ka) and obliquity (∼40 ka) frequencies.

  2. Geological record of meltwater events at Qinghai Lake, China from the past 40 ka

    NASA Astrophysics Data System (ADS)

    Zhou, Weijian; Liu, Taibei; Wang, Hao; An, Zhisheng; Cheng, Peng; Zhu, Yizhi; Burr, G. S.

    2016-10-01

    We report here on a previously unpublished sediment core from Qinghai Lake, China, that preserves a continuous record of sedimentation for the past 40 ka. A striking feature of the record is a set of distinct meltwater events recorded at 35, 19 and 14 ka respectively. These events are manifest as distinct pulses of relatively old organic radiocarbon in the sediments. We interpret these as a signal of glacial melting in the Qinghai Lake watershed. The meltwater signals are closely correlated to temperature and precipitation records associated with deglaciation. The events at 19 ka and 14 ka correspond to well-established high latitude Melt Water Pulse (MWP) events during Marine Isotope Stage (MIS) 2, and the 35 ka event corresponds to a period of pervasive high lake levels in western China during late MIS 3. We interpret these anomalous dates as the result of relatively old carbon that was destabilized by the glaciers, and released into the lake as the glaciers melted. The data indicate that this process takes thousands of years. We expect that the approach employed here to identify these events is generally applicable to any lake system with a significant glacial meltwater component.

  3. Performance of a Ka-band transponder breadboard for deep-space applications

    NASA Technical Reports Server (NTRS)

    Mysoor, N. R.; Lane, J. P.; Kayalar, S.; Kermode, A. W.

    1995-01-01

    This article summarizes the design concepts applied in the development of and advanced Ka-band (34.4 GHz/32 GHz) transponder breadboard for the next generation of space communications systems applications. The selected architecture upgrades the X-band (7.2 GHz/8.4 GHz) deep-space transponder (DST) to provide Da-band up/Ka- and X-band down capability. The Ka-band transponder breadboard incorporates several state-of-the-art components, including sampling mixers, a Ka-band dielectric resonator oscillator, and microwave monolithic integrated circuits (MMICs). The MMICs that were tested in the breadboard include upconverters, downconverters, automatic gain control circuits, mixers, phase modulators, and amplifiers. The measured receiver dynamic range, tracking range, acquisition rate, static phase error, and phase jitter characteristics of the Ka-band breadboard interfaced to the advanced engineering model X-band DST are in good agreement with the expected performance. The results show a receiver tracking threshold of -149 dBm with a dynamic range of 80 dB and a downlink phase jitter of 7 deg rms. The analytical results of phase noise and Allan standard deviation are in good agreement with the experimental results.

  4. Overview of Ka-band communications technology requirements for the space exploration initiative

    NASA Astrophysics Data System (ADS)

    Miller, Edward F.

    1991-12-01

    In the Space Exploration Initiative, Ka-band frequencies are likely to carry the bulk of the communications traffic both in the vicinity of and on the return links from the moon and Mars. The four exploration architectures identified by the Synthesis Group are examined and Ka-band technology requirements to meet the data traffic needs and schedule are identified. Specific Ka-band technology requirements identified are: transmitters - 0.5 to 200 W with high efficiency; antennas - 5m and 9m diameter, with multiple beams and/or scanning beams; and spacecraft receivers - noise figure of 2 dB. For each component, the current state of technology is assessed and needed technology development programs are identified. It is concluded that to meet the schedules of lunar and Mars precursor missions beginning in approximately the year 2000, aggressive technology development and advanced development programs are required immediately for Ka-band communications systems components. Additionally, the greater data transmission rates for the cargo and piloted phases of the exploration program require further Ka-band communications technology developments targeted for operations beginning in about 2010.

  5. Performance of a Ka-band transponder breadboard for deep-space applications

    NASA Astrophysics Data System (ADS)

    Mysoor, N. R.; Lane, J. P.; Kayalar, S.; Kermode, A. W.

    1995-08-01

    This article summarizes the design concepts applied in the development of and advanced Ka-band (34.4 GHz/32 GHz) transponder breadboard for the next generation of space communications systems applications. The selected architecture upgrades the X-band (7.2 GHz/8.4 GHz) deep-space transponder (DST) to provide Da-band up/Ka- and X-band down capability. The Ka-band transponder breadboard incorporates several state-of-the-art components, including sampling mixers, a Ka-band dielectric resonator oscillator, and microwave monolithic integrated circuits (MMICs). The MMICs that were tested in the breadboard include upconverters, downconverters, automatic gain control circuits, mixers, phase modulators, and amplifiers. The measured receiver dynamic range, tracking range, acquisition rate, static phase error, and phase jitter characteristics of the Ka-band breadboard interfaced to the advanced engineering model X-band DST are in good agreement with the expected performance. The results show a receiver tracking threshold of -149 dBm with a dynamic range of 80 dB and a downlink phase jitter of 7 deg rms. The analytical results of phase noise and Allan standard deviation are in good agreement with the experimental results.

  6. Overview of Ka-band communications technology requirements for the space exploration initiative

    NASA Technical Reports Server (NTRS)

    Miller, Edward F.

    1991-01-01

    In the Space Exploration Initiative, Ka-band frequencies are likely to carry the bulk of the communications traffic both in the vicinity of and on the return links from the moon and Mars. The four exploration architectures identified by the Synthesis Group are examined and Ka-band technology requirements to meet the data traffic needs and schedule are identified. Specific Ka-band technology requirements identified are: transmitters - 0.5 to 200 W with high efficiency; antennas - 5m and 9m diameter, with multiple beams and/or scanning beams; and spacecraft receivers - noise figure of 2 dB. For each component, the current state of technology is assessed and needed technology development programs are identified. It is concluded that to meet the schedules of lunar and Mars precursor missions beginning in approximately the year 2000, aggressive technology development and advanced development programs are required immediately for Ka-band communications systems components. Additionally, the greater data transmission rates for the cargo and piloted phases of the exploration program require further Ka-band communications technology developments targeted for operations beginning in about 2010.

  7. Sea-level records at ~80 ka from tectonically stable platforms: Florida and Bermuda

    USGS Publications Warehouse

    Ludwig, K. R.; Muhs, D.R.; Simmons, K.R.; Halley, R.B.; Shinn, E.A.

    1996-01-01

    Studies from technically active coasts on New Guinea and Barbados have suggested that sea level at ???80 ka was significantly lower than present, whereas data from the Atlantic and Pacific coasts of North America indicate an ???80 ka sea level close to that of the present. We determined ages of corals from a shallow submerged reef off the Florida Keys and an emergent marine deposit on Bermuda. Both localities are on tectonically stable platforms distant from plate boundaries. Uranium-series ages show that corals at both localities grew during the ???80 ka sea-level highstand, and geologic data show that sea level at that time was no lower than 7-9 m below present (Florida) and may have been 1-2 m above present (Bermuda). The ice-volume discrepancy of the 80 ka sea-level estimates is greater than the volume of the Greenland or West Antarctic ice sheets. Comparison of our ages with high-latitude insolation values indicates that the sea-level stand near the present at ???80 ka could have been orbitally forced.

  8. 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

  9. 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.

  10. 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.

  11. [One amino acid mutation in an anti-CD20 antibody fragment that affects the yield bacterial secretion and the affinity].

    PubMed

    Liu, Yin-Xing; Xiong, Dong-Sheng; Fan, Dong-Mei; Shao, Xiao-Feng; Xu, Yuan-Fu; Zhu, Zhen-Ping; Yang, Chun-Zheng

    2003-05-01

    Monoclonal antibodies (mAb) directed against CD20, either unmodified or in radiolabeled forms, have been successfully exploited in clinic as effective therapeutic agents in the management of non-Hodgkin's B-cell lymphoma. The antibody fragment is a potential agent in image and therapy of tumor. To further improve the soluble expression of anti-CD20 antibody Fab' fragment, PCR was used to mutate the anti-CD20 VL and VH genes and its biological activity was identified. The expression vector of chimeric antibody Fab' was constructed and expressed in E. coli. The data of mutant clone DNA sequence showed that the amino acid of light chain gene of the parent anti-CD20 antibody (H47) was successful mutated as Ser (GAG)-Asn (CAG). The soluble expression of mutated anti-CD20 Fab' (CD20-7) was 3.8 mg/g dry cell weight, while the parent (CD20-2) was 1.3 mg/g dry cell weight. The affinity constant Ka of CD20-7 was 2.2 x 10(9) L/mol. The primary results of competitive assays by FACS showed that CD20-7 could partially block the sites through which parent antibody (HI47) bind to Raji cells. There was difference in the Raji cells (CD20+)-binding activity between the mutant CD20-7 and parent CD20-2. The site mutation of anti-CD20 Fab' gene make it possible that the anti-CD20 antibody fragment was succeeded to obtain higher expression. In this thesis, we succeeded in completing mutation and expression of anti-CD20 Fab' genes, distinguishing its biological activity, and obtaining its highly expression. These period results will lay a foundation for development of other kind of anti-CD20 engineering antibody (for instance: Fab' Diabody and miniantibody), and make it possible for anti-CD20 antibody to be applied to tumor therapy in civil in the future.

  12. Obesity-related known and candidate SNP markers can significantly change affinity of TATA-binding protein for human gene promoters

    PubMed Central

    2015-01-01

    empirically validated the statistical significance (α < 0.00025) of the differences in TBP affinity values between the minor and ancestral alleles of 4 out of the 22 SNPs: rs200487063, rs201381696, rs34104384, and rs183433761. We also measured half-life (t1/2), Gibbs free energy change (ΔG), and the association and dissociation rate constants, ka and kd, of the TBP-DNA complex for these SNPs. Conclusions Validation of the 22 candidate SNP markers by proper clinical protocols appears to have a strong rationale and may advance postgenomic predictive preventive personalized medicine. PMID:26694100

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Evaluating North America Paleoclimate Simulations for 6 ka and 21 ka Using a Combination of Observed Paleovegetation Data and Process-Based Vegetation Model Simulations

    NASA Astrophysics Data System (ADS)

    Shafer, S. L.; Bartlein, P. J.

    2015-12-01

    Paleoclimate model simulations are often evaluated using observed paleovegetation data (e.g., pollen and plant macrofossils) that record vegetation responses to past climate changes. These observed vegetation data can be combined with mechanistic vegetation model simulations to develop process-based evaluations of paleoclimate model simulations. The use of mechanistic vegetation model simulations allows us to identify the particular spatial and temporal features of individual paleoclimate simulations that may be producing agreement or disagreement between the observed and simulated vegetation data. We used this approach to evaluate a set of eight PMIP3 (Paleoclimate Modelling Intercomparison Project phase 3) paleoclimate simulations for 6 ka and 21 ka from the CMIP5 (Coupled Model Intercomparison Project phase 5) database. Climate data were regridded onto a 10-km grid of North America using the PMIP3 vegetation simulation protocol. The regridded climate data were used as input to BIOME4, an equilibrium vegetation model, to simulate 6 ka and 21 ka biomes across the study area. The simulated biome data were compared with observed paleovegetation data from the BIOME 6000 (version 4.2) dataset. In general, agreement between simulated and observed biomes was greater for forest biomes than for non-forest biomes. We evaluated specific instances of disagreement between the simulated and observed biomes to determine whether the biome disagreement was produced by the climate model simulation (e.g., temperature bias), the vegetation model simulation (e.g., inability to simulate important disturbance regimes), the observed paleovegetation data (e.g., limits in the biomization method), or a combination of these factors. The results are summarized and we describe some of the strengths and limitations of this data-model comparison approach for evaluating paleoclimate simulations.

  20. Synthesis of sulfonamide- and sulfonyl-phenylboronic acid-modified silica phases for boronate affinity chromatography at physiological pH.

    PubMed

    Li, Xiaobao; Pennington, Justin; Stobaugh, John F; Schöneich, Christian

    2008-01-15

    Two new types of boronate affinity solid phases were synthesized and characterized. The materials were prepared by silylation of porous silica gel with monochlorosilane derivatives containing synthetic sulfonyl- and sulfonamide-substituted phenylboronic acids. The new solid phases were evaluated for boronate affinity chromatography with aryl and alkyl cis-diol compounds and were found to be suitable for the retention of cis-diols under acidic conditions. Significant correlations between the retention factor (K) and the pH of the mobile phase demonstrate that the binding of cis-diols to the solid phases is best rationalized by chelation. Based on the lower pKa, caused by the electron-withdrawing effects of the sulfonyl and sulfonamide groups, these media display an enhanced affinity for cis-diols as compared with unsubstituted phenylboronic acid. Using isocratic elution, a mixture of various biologically relevant l-tyrosines, l-DOPA, and several catecholamines were resolved with a mobile phase composed of 0.05M phosphate buffer (pH 5.5). Mono-, di-, and triphosphates of adenosine were also separated at pH 6.0. Hence, the new boronate solid phase offers efficient affinity separation and purification of cis-diol-containing molecules under rather mild pH conditions.

  1. NASA's K/Ka-Band Broadband Aeronautical Terminal for Duplex Satellite Video Communications

    NASA Technical Reports Server (NTRS)

    Densmore, A.; Agan, M.

    1994-01-01

    JPL has recently begun the development of a Broadband Aeronautical Terminal (BAT) for duplex video satellite communications on commercial or business class aircraft. The BAT is designed for use with NASA's K/Ka-band Advanced Communications Technology Satellite (ACTS). The BAT system will provide the systems and technology groundwork for an eventual commercial K/Ka-band aeronautical satellite communication system. With industry/government partnerships, three main goals will be addressed by the BAT task: 1) develop, characterize and demonstrate the performance of an ACTS based high data rate aeronautical communications system; 2) assess the performance of current video compression algorithms in an aeronautical satellite communication link; and 3) characterize the propagation effects of the K/Ka-band channel for aeronautical communications.

  2. Validation of SARAL/AltiKa data in the Amazon basin

    NASA Astrophysics Data System (ADS)

    Santos da Silva, Joecila; Calmant, Stephane; Medeiros Moreira, Daniel; Oliveira, Robson; Conchy, Taina; Gennero, Marie-Claude; Seyler, Frederique

    2015-04-01

    SARAL/AltiKa is a link between past missions (since it flies on the ERS-ENVISAT orbit with Ku band nadir altimeters in LRM) and future missions such as SWOT's Ka band interferometry swaths. In the present study, we compare the capability of its altimeter AltiKa to that of previous missions working in the Ku band such as ENVISAT and Jason-2 in retrieving water levels over the Amazon basin. Same as for the aforementioned preceding missions, the best results were obtained with the ICE-1 retracking algorithm. We qualitatively analyze the impact of rainfalls in the loss of measurements. Since making long -multi mission- time series is of major importance either for hydro-climatic studies or for basin management, we also present an estimate of the altimeter bias in order that the SARAL series of water level can be appended to those of these previous missions.

  3. Radar altimetry backscattering signatures at Ka, Ku, C, and S bands over West Africa

    NASA Astrophysics Data System (ADS)

    Frappart, F.; Fatras, C.; Mougin, E.; Marieu, V.; Diepkilé, A. T.; Blarel, F.; Borderies, P.

    This study presents a comprehensive comparison of radar altimetry signatures at Ka-, Ku-, C-, and S-bands using SARAL, ENVISAT and Jason-2 data over the major bioclimatic zones, soil and vegetation types encountered in West-Africa, with an emphasis on the new information at Ka-band provided by the recently launched SARAL-Altika mission. Spatio-temporal variations of the radar altimetry responses were related to changes in surface roughness, land cover and soil wetness. Analysis of time series of backscattering coefficients along the West African bioclimatic gradient shows that radar echoes at nadir incidence are well correlated to soil moisture in semi-arid savannah environments. Radar altimeters are able to detect the presence of water even under a dense canopy cover at all frequencies. But only measurements at Ka-band are able to penetrate underneath the canopy of non-inundated tropical evergreen forests.

  4. The Celestial Reference Frame at X/Ka-band (8.4/32 GHz)

    NASA Technical Reports Server (NTRS)

    Jacobs, C. S.; Clark, J. E.; Heflin, M. B.; Skjerve, L. J.; Sovers, O. J.; Garcia-Miro, C.; Moll, V. E.; Horiuchi, S.

    2011-01-01

    A celestial reference frame at X/Ka-band (8.4/32 GHz) has been constructed using fifty-one 24-hour sessions with the Deep Space Network. We report on observations which have detected 436 sources covering the full 24 hours of right ascension and declinations down to -45 deg. Comparison of this X/Ka-band frame to the S/X-band (2.3/8.4 GHz) ICRF2 shows wRMS agreement of 200 micro-arcsec in a cos delta and 290 micro-arcsec in delta. There is evidence for zonal errors at the 100 micro-arcsec level. Known errors include limited SNR, lack of phase calibration, troposphere mismodelling, and limited southern geometry. The motivations for extending the ICRF to frequencies above 8 GHz are to access more compact source morphology for improved frame stability, to provide calibrators for phase referencing, and to support spacecraft navigation at Ka-band.

  5. 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

  6. 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.

  7. [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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Location of high-affinity metal binding sites in the profile structure of the Ca+2-ATPase in the sarcoplasmic reticulum by resonance x-ray diffraction.

    PubMed Central

    Asturias, F J; Blasie, J K

    1991-01-01

    Resonance x-ray diffraction measurements on the lamellar diffraction from oriented multilayers of isolated sarcoplasmic reticulum (SR) membranes containing a small concentration of lanthanide (III) ions (lanthanide/protein molar ratio approximately 4) have allowed us to calculate both the electron density profile of the SR membrane and the separate electron density profile of the resonant lanthanide atoms bound to the membrane to a relatively low spatial resolution of approximately 40 A. Analysis of the membrane electron density profile and modeling of the separate low resolution lanthanide atom profile, using step-function electron density models based on the assumption that metal binding sites in the membrane profile are discrete and localized, resulted in the identification of a minimum of three such binding sites in the membrane profile. Two of these sites are low-affinity, low-occupancy sites identified with the two phospholipid polar headgroup regions of the lipid bilayer within the membrane profile. Up to 20% of the total lanthanide (III) ions bind to these low-affinity sites. The third site has relatively high affinity for lanthanide ion binding; its Ka is roughly an order of magnitude larger than that for the lower affinity polar headgroup sites. Approximately 80% of the total lanthanide ions present in the sample are bound to this high-affinity site, which is located in the "stalk" portion of the "headpiece" within the profile structure of the Ca+2 ATPase protein, approximately 12 A outside of the phospholipid polar headgroups on the extravesicular side of the membrane profile. Based on the nature of our results and on previous reports in the literature concerning the ability of lanthanide (III) ions to function as Ca+2 analogues for the Ca+2 ATPase we suggest that we have located a high-affinity metal binding site in the membrane profile which is involved in the active transport of Ca+2 ions across the SR membrane by the Ca+2 ATPase. PMID:1826221

  18. Complementary combining site contact residue mutations of the anti-digoxin Fab 26-10 permit high affinity wild-type binding.

    PubMed

    Short, Mary K; Krykbaev, Rustem A; Jeffrey, Philip D; Margolies, Michael N

    2002-05-10

    Antibody 26-10, obtained in a secondary immune response, binds digoxin with high affinity (K(a) = 1.3 x 10(10) M(-1)) because of extensive shape complementarity. We demonstrated previously that mutations of the hapten contact residue HTrp-100 to Arg (where H refers to the heavy chain) resulted in increased specificity for digoxin analogs substituted at the cardenolide 16 position. However, mutagenesis of H:CDR1 did not result in such a specificity change despite the proximity of the H:CDR1 hapten contact residue Asn-35 to the cardenolide 16 position. Here we constructed a bacteriophage-displayed library containing randomized mutations at H chain residues 30-35 in a 26-10 mutant containing Arg-100 (26-10-RRALD). Phage were selected by panning against digoxin, gitoxin (16-OH), and 16-acetylgitoxin coupled to bovine serum albumin. Clones that retained wild-type Asn at position 35 showed preferred binding to gitoxin, like the 26-10-RRALD parent. In contrast, clones containing Val-35 selected mainly on digoxin-bovine serum albumin demonstrated a shift back to wild-type specificity. Several clones containing Val-35 bound digoxin with increased affinity, approaching that of the wild type in a few instances, in contrast to the mutation Val-35 in the wild-type 26-10 background, which reduces affinity for digoxin 90-fold. It has therefore proven possible to reorder the 26-10 binding site by mutations including two major contact residues on opposite sides of the site and yet to retain high affinity for binding for digoxin. Thus, even among antibodies that have undergone affinity maturation in vivo, different structural solutions to high affinity binding may be revealed.

  19. Simulated Changes in Extreme Temperature and Precipitation Events at 6 ka

    NASA Astrophysics Data System (ADS)

    Diffenbaugh, N. S.; Bell, J. L.; Sloan, L. C.

    2003-12-01

    Paleoenviromental archives record a range of information about past environments. Three key influences shaping paleoclimate records at a given time plane are the mean state of the climate system, interannual variability, and the frequency and seasonality of extreme climate events. We have employed a high resolution regional climate model (RCM) to test the sensitivity of extreme climate events to 6 ka orbital forcing, using western North America as a case study. Extreme precipitation and temperature events were defined by the distribution of daily precipitation and temperature values in the control simulation. Simulated anomalies (6 ka - control) in the number of extreme precipitation events per year were positive throughout the RCM domain, as were anomalies in the percent of annual precipitation delivered by extreme precipitation events. These annual-scale positive anomalies in extreme precipitation were driven by changes in the seasonality of extreme precipitation events at 6 ka, with January, October and November showing the greatest positive anomalies in percent of monthly precipitation delivered by extreme precipitation events. The frequency and length of extreme temperature events in the western United States was also sensitive to 6 ka orbital forcing. Positive anomalies in the frequency of extreme maximum daily temperature values occurred inland in the RCM domain, with peak anomalies of 24 days/year centered over the Great Basin. Likewise, the number of days/year in which the maximum daily temperature exceeded 32° C increased over land by 24%, with the average heat-wave up to 12 days longer in the 6 ka simulation than in the control simulation. Finally, mean first and last freeze dates were later inland in the 6 ka simulation than in the control simulation.

  20. Systematic Behavior of the Non-dipole Magnetic Field during the 32 ka Mono Lake Excursion

    NASA Astrophysics Data System (ADS)

    Negrini, R. M.; McCuan, D.; Cassata, W. S.; Channell, J. E.; Verosub, K. L.; Liddicoat, J. C.; Knott, J. R.; Coe, R. S.; Benson, L. V.; Sarna-Wojcicki, A.; Lund, S.; Horton, R.; Lopez, J.

    2012-12-01

    Paleomagnetic excursions are enigmatic phenomena that reveal geodynamo behavior in its transitional state and provide important refinements in age control for the late Pleistocene, a critical time period for the study of paleoclimate and human evolution. We report here on two widely separated, unusually detailed records of the Mono Lake excursion (MLE) from sedimentary sequences dated at 32 ka. One of the records is from Summer Lake, Oregon. The vector components of this new record faithfully reproduce the principle features of the MLE as recorded at the type localities around Mono Lake, CA, though with greater detail and higher amplitude. Radiocarbon dates on bulk organics in the Summer Lake record confirm the 32 ka age of the MLE. The other record is from the marine Irminger Basin off of eastern Greenland and is based on the measurement of discrete samples rather than u-channels. The associated VGP paths of the two records strongly suggest systematic field behavior that includes three loci of nondipole flux whose relative dominance oscillates through time. The staggered sequence followed by the two paths through each flux locus further suggests that both the demise and return of the main field floods zonally during the excursion. The composite path is also compatible with the VGPs of a 32 ka set of lavas from New Zealand and, notably, it does not include VGPs associated with the 40 ka Laschamp excursion. This confirms that these two excursions are distinct events and, more specifically, shows that it is the 32 ka Mono Lake excursion that is recorded in the sediments surrounding Mono Lake rather than the ~40 ka Laschamp excursion.