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Sample records for strong binding ability

  1. Stability and Sugar Recognition Ability of Ricin-Like Carbohydrate Binding Domains

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Jianzhuang [ORNL; Nellas, Ricky B [ORNL; Glover, Mary M [ORNL; Shen, Tongye [ORNL

    2011-01-01

    Lectins are a class of proteins known for their novel binding to saccharides. Understanding this sugar recognition process can be crucial in creating structure-based designs of proteins with various biological roles. We focus on the sugar binding of a particular lectin, ricin, which has two -trefoil carbohydrate-binding domains (CRDs) found in several plant protein toxins. The binding ability of possible sites of ricin-like CRD has been puzzling. The apo and various (multiple) ligand-bound forms of the sugar-binding domains of ricin were studied by molecular dynamics simulations. By evaluating structural stability, hydrogen bond dynamics, flexibility, and binding energy, we obtained a detailed picture of the sugar recognition of the ricin-like CRD. Unlike what was previously believed, we found that the binding abilities of the two known sites are not independent of each other. The binding ability of one site is positively affected by the other site. While the mean positions of different binding scenarios are not altered significantly, the flexibility of the binding pockets visibly decreases upon multiple ligand binding. This change in flexibility seems to be the origin of the binding cooperativity. All the hydrogen bonds that are strong in the monoligand state are also strong in the double-ligand complex, although the stability is much higher in the latter form due to cooperativity. These strong hydrogen bonds in a monoligand state are deemed to be the essential hydrogen bonds. Furthermore, by examining the structural correlation matrix, the two domains are structurally one entity. Galactose hydroxyl groups, OH4 and OH3, are the most critical parts in both site 1 and site 2 recognition.

  2. Structural and Histone Binding Ability Characterizations of Human PWWP Domains

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Hong; Zeng, Hong; Lam, Robert; Tempel, Wolfram; Amaya, Maria F.; Xu, Chao; Dombrovski, Ludmila; Qiu, Wei; Wang, Yanming; Min, Jinrong (Toronto); (Penn)

    2013-09-25

    The PWWP domain was first identified as a structural motif of 100-130 amino acids in the WHSC1 protein and predicted to be a protein-protein interaction domain. It belongs to the Tudor domain 'Royal Family', which consists of Tudor, chromodomain, MBT and PWWP domains. While Tudor, chromodomain and MBT domains have long been known to bind methylated histones, PWWP was shown to exhibit histone binding ability only until recently. The PWWP domain has been shown to be a DNA binding domain, but sequence analysis and previous structural studies show that the PWWP domain exhibits significant similarity to other 'Royal Family' members, implying that the PWWP domain has the potential to bind histones. In order to further explore the function of the PWWP domain, we used the protein family approach to determine the crystal structures of the PWWP domains from seven different human proteins. Our fluorescence polarization binding studies show that PWWP domains have weak histone binding ability, which is also confirmed by our NMR titration experiments. Furthermore, we determined the crystal structures of the BRPF1 PWWP domain in complex with H3K36me3, and HDGF2 PWWP domain in complex with H3K79me3 and H4K20me3. PWWP proteins constitute a new family of methyl lysine histone binders. The PWWP domain consists of three motifs: a canonical {beta}-barrel core, an insertion motif between the second and third {beta}-strands and a C-terminal {alpha}-helix bundle. Both the canonical {beta}-barrel core and the insertion motif are directly involved in histone binding. The PWWP domain has been previously shown to be a DNA binding domain. Therefore, the PWWP domain exhibits dual functions: binding both DNA and methyllysine histones.

  3. Mutations at the Qo-Site of the Cytochrome bc1 Complex Strongly Affect Oxygen Binding

    DEFF Research Database (Denmark)

    Husen, Peter; Solov'yov, Ilia A

    2017-01-01

    The homodimeric bc1 protein complex is embedded in membranes of mitochondria and photosynthetic bacteria, where it transports protons across the membrane to maintain an electrostatic potential used to drive ATP synthesis as part of the respiratory or photosynthetic pathways. The reaction cycle...... of the bc1 complex is driven by series of redox processes involving substrate molecules from the membrane, but occasional side reactions between an intermediate semiquinone substrate and molecular oxygen are suspected to be a source of toxic superoxide, which is believed to be a factor in aging. The present...... investigation employs molecular dynamics simulations to study the effect of mutations in the Qo binding sites of the bc1 complex on the ability of oxygen molecules to migrate to and bind at various locations within the complex. It is found that the mutations strongly affect the ability of oxygen to bind...

  4. Synthesis and Binding Ability of Molecular Probes Based on a Phenanthroline Derivative: Theory and Experiment

    Directory of Open Access Journals (Sweden)

    Xuefang Shang

    2013-12-01

    Full Text Available A fluorescent and colorimetric molecular probe containing phenol groups has been designed and synthesized. The anion binding ability was evaluated for biolgically important anions (F−, Cl−, Br−, I−, AcO− and H2PO4− by theoretical investigation, UV-Vis and fluorescence spectroscopy and 1H-NMR titration experiments. Results indicated the probe showed strong binding ability for H2PO4− without the interference of other anions tested and the interaction process was accompanied by color changes. Theoretical investigation analysis revealed that intramolecular hydrogen bonds existed in the structure of the probe and the roles of molecular frontier orbitals in molecular interplay were determined.

  5. Structural and histone binding ability characterizations of human PWWP domains.

    Directory of Open Access Journals (Sweden)

    Hong Wu

    Full Text Available The PWWP domain was first identified as a structural motif of 100-130 amino acids in the WHSC1 protein and predicted to be a protein-protein interaction domain. It belongs to the Tudor domain 'Royal Family', which consists of Tudor, chromodomain, MBT and PWWP domains. While Tudor, chromodomain and MBT domains have long been known to bind methylated histones, PWWP was shown to exhibit histone binding ability only until recently.The PWWP domain has been shown to be a DNA binding domain, but sequence analysis and previous structural studies show that the PWWP domain exhibits significant similarity to other 'Royal Family' members, implying that the PWWP domain has the potential to bind histones. In order to further explore the function of the PWWP domain, we used the protein family approach to determine the crystal structures of the PWWP domains from seven different human proteins. Our fluorescence polarization binding studies show that PWWP domains have weak histone binding ability, which is also confirmed by our NMR titration experiments. Furthermore, we determined the crystal structures of the BRPF1 PWWP domain in complex with H3K36me3, and HDGF2 PWWP domain in complex with H3K79me3 and H4K20me3.PWWP proteins constitute a new family of methyl lysine histone binders. The PWWP domain consists of three motifs: a canonical β-barrel core, an insertion motif between the second and third β-strands and a C-terminal α-helix bundle. Both the canonical β-barrel core and the insertion motif are directly involved in histone binding. The PWWP domain has been previously shown to be a DNA binding domain. Therefore, the PWWP domain exhibits dual functions: binding both DNA and methyllysine histones.This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the

  6. Thermodynamics of nucleotide binding to actomyosin V and VI: a positive heat capacity change accompanies strong ADP binding.

    Science.gov (United States)

    Robblee, James P; Cao, Wenxiang; Henn, Arnon; Hannemann, Diane E; De La Cruz, Enrique M

    2005-08-02

    We have measured the energetics of ATP and ADP binding to single-headed actomyosin V and VI from the temperature dependence of the rate and equilibrium binding constants. Nucleotide binding to actomyosin V and VI can be modeled as two-step binding mechanisms involving the formation of collision complexes followed by isomerization to states with high nucleotide affinity. Formation of the actomyosin VI-ATP collision complex is much weaker and slower than for actomyosin V. A three-step binding mechanism where actomyosin VI isomerizes between two conformations, one competent to bind ATP and one not, followed by rapid ATP binding best accounts for the data. ADP binds to actomyosin V more tightly than actomyosin VI. At 25 degrees C, the strong ADP-binding equilibria are comparable for actomyosin V and VI, and the different overall ADP affinities arise from differences in the ADP collision complex affinity. The actomyosin-ADP isomerization leading to strong ADP binding is entropy driven at >15 degrees C and occurs with a large, positive change in heat capacity (DeltaC(P) degrees ) for both actomyosin V and VI. Sucrose slows ADP binding and dissociation from actomyosin V and VI but not the overall equilibrium constants for strong ADP binding, indicating that solvent viscosity dampens ADP-dependent kinetic transitions, presumably a tail swing that occurs with ADP binding and release. We favor a mechanism where strong ADP binding increases the dynamics and flexibility of the actomyosin complex. The heat capacity (DeltaC(P) degrees ) and entropy (DeltaS degrees ) changes are greater for actomyosin VI than actomyosin V, suggesting different extents of ADP-induced structural rearrangement.

  7. Much ado about aha!: Insight problem solving is strongly related to working memory capacity and reasoning ability.

    Science.gov (United States)

    Chuderski, Adam; Jastrzębski, Jan

    2018-02-01

    A battery comprising 4 fluid reasoning tests as well as 13 working memory (WM) tasks that involved storage, recall, updating, binding, and executive control, was applied to 318 adults in order to evaluate the true relationship of reasoning ability and WM capacity (WMC) to insight problem solving, measured using 40 verbal, spatial, math, matchstick, and remote associates problems (insight problems). WMC predicted 51.8% of variance in insight problem solving and virtually explained its almost isomorphic link to reasoning ability (84.6% of shared variance). The strong link between WMC and insight pertained generally to most WM tasks and insight problems, was identical for problems solved with and without reported insight, was linear throughout the ability levels, and was not mediated by age, motivation, anxiety, psychoticism, and openness to experience. In contrast to popular views on the sudden and holistic nature of insight, the solving of insight problems results primarily from typical operations carried out by the basic WM mechanisms that are responsible for the maintenance, retrieval, transformation, and control of information in the broad range of intellectual tasks (including fluid reasoning). Little above and beyond WM is unique about insight. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  8. Effect of dipole polarizability on positron binding by strongly polar molecules

    International Nuclear Information System (INIS)

    Gribakin, G F; Swann, A R

    2015-01-01

    A model for positron binding to polar molecules is considered by combining the dipole potential outside the molecule with a strongly repulsive core of a given radius. Using existing experimental data on binding energies leads to unphysically small core radii for all of the molecules studied. This suggests that electron–positron correlations neglected in the simple model play a large role in determining the binding energy. We account for these by including the polarization potential via perturbation theory and non-perturbatively. The perturbative model makes reliable predictions of binding energies for a range of polar organic molecules and hydrogen cyanide. The model also agrees with the linear dependence of the binding energies on the polarizability inferred from the experimental data (Danielson et al 2009 J. Phys. B: At. Mol. Opt. Phys. 42 235203). The effective core radii, however, remain unphysically small for most molecules. Treating molecular polarization non-perturbatively leads to physically meaningful core radii for all of the molecules studied and enables even more accurate predictions of binding energies to be made for nearly all of the molecules considered. (paper)

  9. Predictions of RNA-binding ability and aggregation propensity of proteins

    OpenAIRE

    Agostini, Federico, 1985-

    2014-01-01

    RNA-binding proteins (RBPs) control the fate of a multitude of coding and non-coding transcripts. Formation of ribonucleoprotein (RNP) complexes fine-tunes regulation of post-transcriptional events and influences gene expression. Recently, it has been observed that non-canonical proteins with RNA-binding ability are enriched in structurally disordered and low-complexity regions that are generally involved in functional and dysfunctional associations. Therefore, it is possible that interaction...

  10. Ability to bind salivary alpha-amylase discriminates certain viridans group streptococcal species.

    OpenAIRE

    Kilian, M; Nyvad, B

    1990-01-01

    A collection of 144 viridans group streptococcal strains recently characterized as part of a taxonomic study was examined for the ability to bind salivary alpha-amylase. This property was found in most strains of Streptococcus gordonii and Streptococcus mitis and in occasional strains of Streptococcus anginosus and Streptococcus salivarius. In contrast, all strains of Streptococcus sanguis, Streptococcus oralis, Streptococcus vestibularis, and Streptococcus mutans lacked alpha-amylase-binding...

  11. Effects of heat treatment on oil-binding ability of rice flour.

    Science.gov (United States)

    Tabara, Aya; Nakagawa, Mariko; Ushijima, Yuki; Matsunaga, Kotaro; Seguchi, Masaharu

    2015-01-01

    Heat-treated (120 °C for 120 min) rice flour showed high affinity to oil (oil-binding ability). This oil-binding ability could be observed by shaking the heat-treated rice flour (2.0 g), oil (4.0 mL), and water (20 mL) vigorously in a test tube, and the oil bound to the rice flour sank into the water. To examine the time-dependent levels of the oil-binding ability, rice flour was heat-treated at 120 °C for 10, 20, 40, 60, and 120 min, and the precipitated volume of oil/rice flour complex increased with an increase of the heating time. The oil-binding ability of the rice flour was not affected by the treatments with diethyl ether or boiled chloroform/methanol (2:1) solutions, which suggested no relationship to the oil in the rice flour, but was lost upon alkali (0.2% NaOH solution) or pepsin treatment, which suggested its relationship to the rice proteins.

  12. Visual binding abilities in the initial and advanced stages of schizophrenia

    DEFF Research Database (Denmark)

    Parnas, J; Vianin, P; Saebye, D

    2001-01-01

    patients believed to be suffering from a pre-schizophrenic prodrome) and a group of normal control subjects were tested on three tasks targeting visual 'binding' abilities (Muller-Lyer's illusion and two figure detection tasks) in addition to control parameters such as reaction time, visual selective...

  13. Kinetics of fatty acid binding ability of glycated human serum albumin

    Indian Academy of Sciences (India)

    Unknown

    ). One of the most striking functions of HSA is its ability to bind reversibly with many kinds of compounds in blood plasma and show particularly high affinity to variety of saturated and un- saturated fatty acids of various chain lengths (Lee and.

  14. Investigation of ability of serum albumin to bind the tritium labeled drotaverine hydrochloride at virus hepatitis

    International Nuclear Information System (INIS)

    Kim, A.A.; Mavlyanov, I.R.; Shukurov, B.V.; Djuraeva, G.T.

    2005-01-01

    The most of pathological conditions, and especially liver pathologies, proceeds on the background of intoxication syndromes. One of universal mechanisms of reaction of an organism on increase of concentration of toxic metabolites is removing of metabolites with the help of one of the basic protein of blood plasma - serum albumin. The purpose of the present research was studying of serum albumin ability to bind drotaverine hydrochloride at virus hepatitis in dynamics of traditional therapy. This parameter is rather important for therapy as it is known, that serum albumin is a carrier of pharmaceutical preparations. At intoxication of organism the toxic metabolites can reduce the binding capacity of serum albumin due to competitive binding and by that to reduce efficiency of carry of pharmaceutical preparations. Application of a radiochemical method with use of tritium labeled drotaverine hydrochloride in the given research it is represented to the most effective. The method of tritium labeling of pharmacological preparation of drotaverine hydrochloride was developed. Drotaverine hydrochloride was labeled by thermally activated tritium. The system of purification of tritium labeled drotaverine hydrochloride by thin layer chromatography (TLC) has been developed. Tritium labeled preparation of drotaverine hydrochloride was purified by TLC on silica gel in system isopropanol : ammonia : water (8:1:1). The output of purified tritium labeled preparation of drotaverine hydrochloride was about 25 %. The received preparation had specific radioactivity - 3,2 MBq/mg (37,4 mCi/mmol), radiochemical purity of a preparation was 95 %. We had been developed a micromethod of definition of binding ability of albumin, allowing analyze 20 microliters of blood serum. The method consists in incubation of tritium labeled drotaverine hydrochloride with blood serum in vitro, the following fractionation of serum proteins by gel - filtration on a microcolumn with Sephadex G-25, and direct

  15. Calf thymus DNA-binding ability study of anthocyanins from purple sweet potatoes ( Ipomoea batatas L.).

    Science.gov (United States)

    Wang, Dan; Wang, Xirui; Zhang, Chao; Ma, Yue; Zhao, Xiaoyan

    2011-07-13

    A total of 10 anthocyanin compounds were identified from five purple sweet potato ( Ipomoea batatas L.) varieties, Qunzi, Zishu038, Ji18, Jingshu6, and Ziluolan, by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to assess their calf thymus DNA-binding ability in vitro. The interaction between anthocyanins and calf thymus DNA in Tris-HCl buffer solution (pH 6.9) was evaluated by fluorescence spectroscopy. Using ethidium bromide (EB) as a fluorescence probe, fluorescence quenching of the emission peak was seen in the DNA-EB system when anthocyanins were added, indicating that the anthocyanins bound with DNA. The acylated groups influenced the ability of the interaction with DNA. Anthocyanins from purple sweet potato with more acylated groups in sorphorose have a stronger binding ability with DNA.

  16. Interactions among motility, fertilizing ability, and testosterone binding on spermatozoa of bonnet monkey (Macaca radiata).

    Science.gov (United States)

    Warikoo, P K; Majumdar, S S; Allag, I S; Das, R P; Roy, S

    1986-01-01

    Fresh ejaculates of bonnet monkeys were separated into fractions rich with highly motile and sluggishly motile spermatozoa. The motility, ability to fertilize zona-free hamster eggs, and distribution of testosterone-binding sites on spermatozoa were assessed to determine the relation between these sperm functions. Two parameters of objective assessment of motility--velocity and degree of flagellar bending--were significantly correlated with the ability to form pronuclei in zona-free hamster eggs. Only spermatozoa with good motility could form pronuclei, which might be important for assessment of the fertilizing ability. The motility was directly related to the distribution of testosterone-binding sites; the fraction having mostly motile spermatozoa was distributed over the sperm surface. The technique is simple and may be used to evaluate semen of nonhuman primates.

  17. Visual binding abilities in the initial and advanced stages of schizophrenia

    DEFF Research Database (Denmark)

    Parnas, J; Vianin, P; Saebye, D

    2001-01-01

    patients believed to be suffering from a pre-schizophrenic prodrome) and a group of normal control subjects were tested on three tasks targeting visual 'binding' abilities (Muller-Lyer's illusion and two figure detection tasks) in addition to control parameters such as reaction time, visual selective...... attention, Raven's test and two conventional cortical tasks of spatial working memory (SWM) and a global local test. RESULTS: Chronic patients had a decreased performance on the binding tests. Unexpectedly, the prodromal group exhibited an enhanced Gestalt extraction on these tests compared both...

  18. Ability to bind salivary alpha-amylase discriminates certain viridans group streptococcal species.

    Science.gov (United States)

    Kilian, M; Nyvad, B

    1990-01-01

    A collection of 144 viridans group streptococcal strains recently characterized as part of a taxonomic study was examined for the ability to bind salivary alpha-amylase. This property was found in most strains of Streptococcus gordonii and Streptococcus mitis and in occasional strains of Streptococcus anginosus and Streptococcus salivarius. In contrast, all strains of Streptococcus sanguis, Streptococcus oralis, Streptococcus vestibularis, and Streptococcus mutans lacked alpha-amylase-binding capacity. A rapid and easy assay described in this paper may be an important supplementary test for identification of oral streptococci. PMID:2254435

  19. Visual binding abilities in the initial and advanced stages of schizophrenia

    DEFF Research Database (Denmark)

    Parnas, Josef; Vianin, P; Saebye, D

    2001-01-01

    OBJECTIVE: The study tests the hypothesis that intramodal visual binding is disturbed in schizophrenia and should be detectable in all illness stages as a stable trait marker. METHOD: Three groups of patients (rehospitalized chronic schizophrenic, first admitted schizophrenic and schizotypal...... patients believed to be suffering from a pre-schizophrenic prodrome) and a group of normal control subjects were tested on three tasks targeting visual 'binding' abilities (Muller-Lyer's illusion and two figure detection tasks) in addition to control parameters such as reaction time, visual selective...... attention, Raven's test and two conventional cortical tasks of spatial working memory (SWM) and a global local test. RESULTS: Chronic patients had a decreased performance on the binding tests. Unexpectedly, the prodromal group exhibited an enhanced Gestalt extraction on these tests compared both...

  20. Using Regression to Measure Holistic Face Processing Reveals a Strong Link with Face Recognition Ability

    Science.gov (United States)

    DeGutis, Joseph; Wilmer, Jeremy; Mercado, Rogelio J.; Cohan, Sarah

    2013-01-01

    Although holistic processing is thought to underlie normal face recognition ability, widely discrepant reports have recently emerged about this link in an individual differences context. Progress in this domain may have been impeded by the widespread use of subtraction scores, which lack validity due to their contamination with control condition…

  1. Visual binding abilities in the initial and advanced stages of schizophrenia

    DEFF Research Database (Denmark)

    Parnas, Josef; Vianin, P; Saebye, D

    2001-01-01

    patients believed to be suffering from a pre-schizophrenic prodrome) and a group of normal control subjects were tested on three tasks targeting visual 'binding' abilities (Muller-Lyer's illusion and two figure detection tasks) in addition to control parameters such as reaction time, visual selective......OBJECTIVE: The study tests the hypothesis that intramodal visual binding is disturbed in schizophrenia and should be detectable in all illness stages as a stable trait marker. METHOD: Three groups of patients (rehospitalized chronic schizophrenic, first admitted schizophrenic and schizotypal...... of neurocognitive deficits in schizophrenia which, however, in this sample seem to be linked to chronicity of illness. However, certain aspects of visual processing concerned with Gestalt extraction deserve attention as potential vulnerability- or prodrome- indicators. The initial hypothesis of the study...

  2. Screening of Auricularia auricula strains for strong production ability of melanin pigments

    Directory of Open Access Journals (Sweden)

    Yu ZOU

    Full Text Available Abstract Melanin pigments have great application value and development potential in food industry to use as nature functional food colorants. In initial study, twenty-two Auricularia auricula strains were screened for stronger production ability of melanin pigments by solid culture. Three A. auricula strains (RF201, QD2 and QD6 with higher pigment production capacity were selected for further study through submerged culture supplementing 1 g/L l-tyrosine. The maximal pigment yields of A. auricula RF201, QD2 and QD6 were 493.9, 367.6 and 318.5 mg/L, respectively. Among three strains, A. auricula RF201 possessed the strongest production ability of melanin pigments. The present study indicated that A. auricula RF201 could be used as potential excellent producer of melanin pigments.

  3. Screening of Auricularia auricula strains for strong production ability of melanin pigments

    OpenAIRE

    ZOU, Yu; MA, Kun

    2017-01-01

    Abstract Melanin pigments have great application value and development potential in food industry to use as nature functional food colorants. In initial study, twenty-two Auricularia auricula strains were screened for stronger production ability of melanin pigments by solid culture. Three A. auricula strains (RF201, QD2 and QD6) with higher pigment production capacity were selected for further study through submerged culture supplementing 1 g/L l-tyrosine. The maximal pigment yields of A. aur...

  4. Antibiotic modulation of the plasminogen binding ability of viridans group streptococci.

    Science.gov (United States)

    Teles, Cristina; Smith, Andrew; Lang, Sue

    2012-01-01

    The ability of viridans group streptococci to bind human plasminogen and its subsequent activation into plasmin may contribute to the pathogenesis of infective endocarditis (IE) by leading to a decreased stability of the streptococcal vegetation and facilitating dehiscence of emboli. At levels greater than or equal to their MICs, penicillin, vancomycin, and linezolid are efficacious in the treatment of streptococcal endocarditis. However, at sub-MICs, antibiotics can modulate the expression of bacterial genes, including virulence-associated genes, which can have counterproductive effects on the treatment of endocarditis. The effects of 1/8× and 1/4× MICs of penicillin, vancomycin, and linezolid on the plasminogen binding ability of IE isolates Streptococcus mitis 881/956, Streptococcus oralis 12601, and Streptococcus sanguinis 12403 were assessed phenotypically and the expression of plasminogen receptors α-enolase and glyceraldehyde 3-phosphate dehydrogenase of S. oralis 12601 when exposed to 1/4× MIC of penicillin, was analyzed through quantitative reverse transcription (qRT)-PCR. The plasminogen binding ability of S. mitis 881/956 and S. sanguinis 12403 remained unaffected by exposure to sub-MICs of all of the antibiotics tested, while that of S. oralis 12601 was significantly enhanced by all of the antibiotics tested at sub-MICs. qRT-PCR analysis of S. oralis 12601 demonstrated an upregulation of the eno and gapdh genes, indicating an overexpression of plasminogen receptors. These findings suggest that for some endocarditis isolates, the effect of antibiotic sub-MICs, in addition to a reduced antibacterial effect, may influence the clinical response to nonsurgical therapy. It remains difficult to accurately predict isolate responses to sub-MIC antimicrobials since there appears to be interspecies variation.

  5. Bovine epididymal spermatozoa: Resistance to cryopreservation and binding ability to oviductal cells.

    Science.gov (United States)

    Cunha, A T M; Carvalho, J O; Kussano, N R; Martins, C F; Mourão, G B; Dode, M A N

    2016-12-01

    In this study we examined quality, longevity and ability of epididymal sperm (EP) to bind to oviduct explants (OE) after cooling and cryopreservation. Ejaculated (EJ) and EP sperm from seven bulls were evaluated before, during and after cryopreservation for total (TM), progressive motility (PM), sperm morphology, plasma membrane integrity (PMI) and acrosome integrity (ACI). For longevity, cryopreserved EP, EJ and a third group of cells in which EP spermatozoa were incubated with seminal plasm (SP) for 10 min after thawing (EPP group), were compared, and the groups were analyzed at 0, 3, 6, and 24 h for all parameters. Sperm from each group were co-incubated with OE for 30 min, 6 h, and 24 h for binding evaluation. Data were analyzed by the generalized linear models SAS 9.1 (P sperm. However, a reduction in motility occurred in the EJ sperm after cooling, while in EP group such reduction occurred only after cryopreservation. At 6 h of incubation EP and EPP had higher PMI and ACI than EJ (P  0.05) for all groups either at 30 min or 24 h. We conclude that EP are more resistant to cooling than EJ, and can bind to OE similarly to EJ. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Enzymatic hydrolysis of heated whey: iron-binding ability of peptides and antigenic protein fractions.

    Science.gov (United States)

    Kim, S B; Seo, I S; Khan, M A; Ki, K S; Lee, W S; Lee, H J; Shin, H S; Kim, H S

    2007-09-01

    This study evaluated the influence of various enzymes on the hydrolysis of whey protein concentrate (WPC) to reduce its antigenic fractions and to quantify the peptides having iron-binding ability in its hydrolysates. Heated (for 10 min at 100 degrees C) WPC (2% protein solution) was incubated with 2% each of Alcalase, Flavourzyme, papain, and trypsin for 30, 60, 90, 120, 150, 180, and 240 min at 50 degrees C. The highest hydrolysis of WPC was observed after 240 min of incubation with Alcalase (12.4%), followed by Flavourzyme (12.0%), trypsin (10.4%), and papain (8.53%). The nonprotein nitrogen contents of WPC hydrolysate followed the hydrolytic pattern of whey. The major antigenic fractions (beta-lactoglobulin) in WPC were degraded within 60 min of its incubation with Alcalase, Flavourzyme, or papain. Chromatograms of enzymatic hydrolysates of heated WPC also indicated complete degradation of beta-lactoglobulin, alpha-lactalbumin, and BSA. The highest iron solubility was noticed in hydrolysates derived with Alcalase (95%), followed by those produced with trypsin (90%), papain (87%), and Flavourzyme (81%). Eluted fraction 1 (F-1) and fraction 2 (F-2) were the respective peaks for the 0.25 and 0.5 M NaCl chromatographic step gradient for analysis of hydrolysates. Iron-binding ability was noticeably higher in F-1 than in F-2 of all hydrolysates of WPC. The highest iron contents in F-1 were observed in WPC hydrolysates derived with Alcalase (0.2 mg/kg), followed by hydrolysates derived with Flavourzyme (0.14 mg/kg), trypsin (0.14 mg/kg), and papain (0.08 mg/kg). Iron concentrations in the F-2 fraction of all enzymatic hydrolysates of WPC were low and ranged from 0.03 to 0.05 mg/kg. Fraction 1 may describe a new class of iron chelates based on the reaction of FeSO4 x 7 H2O with a mixture of peptides obtained by the enzymatic hydrolysis of WPC. The chromatogram of Alcalase F-1 indicated numerous small peaks of shorter wavelengths, which probably indicated a variety of

  7. The gambler's fallacy is associated with weak affective decision making but strong cognitive ability.

    Directory of Open Access Journals (Sweden)

    Gui Xue

    Full Text Available Humans demonstrate an inherent bias towards making maladaptive decisions, as shown by a phenomenon known as the gambler's fallacy (GF. The GF has been traditionally considered as a heuristic bias supported by the fast and automatic intuition system, which can be overcome by the reasoning system. The present study examined an intriguing hypothesis, based on emerging evidence from neuroscience research, that the GF might be attributed to a weak affective but strong cognitive decision making mechanism. With data from a large sample of college students, we found that individuals' use of the GF strategy was positively correlated with their general intelligence and executive function, such as working memory and conflict resolution, but negatively correlated with their affective decision making capacities, as measured by the Iowa Gambling Task. Our result provides a novel insight into the mechanisms underlying the GF, which highlights the significant role of affective mechanisms in adaptive decision-making.

  8. The Gambler’s Fallacy Is Associated with Weak Affective Decision Making but Strong Cognitive Ability

    Science.gov (United States)

    Xue, Gui; He, Qinghua; Lei, Xuemei; Chen, Chunhui; Liu, Yuyun; Chen, Chuansheng; Lu, Zhong-Lin; Dong, Qi; Bechara, Antoine

    2012-01-01

    Humans demonstrate an inherent bias towards making maladaptive decisions, as shown by a phenomenon known as the gambler’s fallacy (GF). The GF has been traditionally considered as a heuristic bias supported by the fast and automatic intuition system, which can be overcome by the reasoning system. The present study examined an intriguing hypothesis, based on emerging evidence from neuroscience research, that the GF might be attributed to a weak affective but strong cognitive decision making mechanism. With data from a large sample of college students, we found that individuals’ use of the GF strategy was positively correlated with their general intelligence and executive function, such as working memory and conflict resolution, but negatively correlated with their affective decision making capacities, as measured by the Iowa Gambling Task. Our result provides a novel insight into the mechanisms underlying the GF, which highlights the significant role of affective mechanisms in adaptive decision-making. PMID:23071701

  9. Mature habitats associated with genetic divergence despite strong dispersal ability in an arthropod

    Directory of Open Access Journals (Sweden)

    Taylor Derek J

    2007-04-01

    Full Text Available Abstract Background Populations may be bound by contemporary gene flow, selective sweeps, and extinction-recolonization processes. Indeed, existing molecular estimates indicate that species with low levels of gene flow are rare. However, strong priority effects and local selective regimes may hinder gene flow (despite dispersal sending populations on independent evolutionary trajectories. In this scenario (the monopolization hypothesis, population differentiation will increase with time and genealogical evidence should yield ample private haplotypes. Cyclical parthenogens (e.g. rotifers and cladocerans such as Daphnia have an increased capacity for rapid local adaptation and priority effects because sexual reproduction is followed by multiple generations of clonal selection and massive egg bank formation. We aimed to better understand the history of population differentiation and ongoing gene flow in Daphnia rosea s.l., by comparing population and regional divergences in mature unglaciated areas and younger previously glaciated areas. We also examined the timing and paths of colonization of previously-glaciated areas to assess the dispersal limitations of D. rosea s.l. We used DNA sequence variation (84 populations and >400 individuals at the mitochondrial ND2 and nuclear HSP90 loci from Holarctic populations for our genetic analyses. Results The genetic evidence indicated pronounced historical structure. Holarctic mtDNA phylogenies of D. rosea s.l. revealed three geographically restricted and divergent clades: European, Siberian and Japanese/American. The Japanese/American clade showed marked population genetic structure (FST > 0.8 that was weakly associated with geographic distance, and a high proportion of private haplotypes. Populations from older unglaciated habitats (i.e., Japan showed higher DNA sequence divergences than populations from presumed younger habitats (i.e. non-Beringian North America with nDNA and with mtDNA. Mismatch

  10. An improved method for the diatom test utilizing DNA binding ability of silica.

    Science.gov (United States)

    Seo, Yasuhisa; Ichida, Daisuke; Sato, Shingo; Kuroki, Kohji; Kishida, Tetsuko

    2014-05-01

    In order to devise a better forensic test for diatoms, the DNA binding ability of the diatom frustule constructing by silica, in the presence of chaotropic ions were utilized. It was proved that the diatoms were able to be captured via λDNA using silica-coated magnetic beads (Mag beads), followed by isolation and purification from the Mag beads as a solid phase by substituting the chaotropic agent with ultrapure water. Five cases of drowning, three in freshwater and two in seawater, were applied to the present method and similar results as the usual diatom test were obtained. Specimens of lung and other organs were rendered clearly visible, with elimination of foreign impurities. The present method appears applicable for detection of diatoms indirectly using PCR amplification of bound DNA or directly staining of the DNA. © 2014 American Academy of Forensic Sciences.

  11. Functional studies of ssDNA binding ability of MarR family protein TcaR from Staphylococcus epidermidis.

    Directory of Open Access Journals (Sweden)

    Yu-Ming Chang

    Full Text Available The negative transcription regulator of the ica locus, TcaR, regulates proteins involved in the biosynthesis of poly-N-acetylglucosamine (PNAG. Absence of TcaR increases PNAG production and promotes biofilm formation in Staphylococci. Previously, the 3D structure of TcaR in its apo form and its complex structure with several antibiotics have been analyzed. However, the detailed mechanism of multiple antibiotic resistance regulator (MarR family proteins such as TcaR is unclear and only restricted on the binding ability of double-strand DNA (dsDNA. Here we show by electrophoretic mobility shift assay (EMSA, electron microscopy (EM, circular dichroism (CD, and Biacore analysis that TcaR can interact strongly with single-stranded DNA (ssDNA, thereby identifying a new role in MarR family proteins. Moreover, we show that TcaR preferentially binds 33-mer ssDNA over double-stranded DNA and inhibits viral ssDNA replication. In contrast, such ssDNA binding properties were not observed for other MarR family protein and TetR family protein, suggesting that the results from our studies are not an artifact due to simple charge interactions between TcaR and ssDNA. Overall, these results suggest a novel role for TcaR in regulation of DNA replication. We anticipate that the results of this work will extend our understanding of MarR family protein and broaden the development of new therapeutic strategies for Staphylococci.

  12. Screening of Lactobacillus strains for their ability to bind benzo(a)pyrene and the mechanism of the process.

    Science.gov (United States)

    Zhao, Hongfei; Zhou, Fang; Qi, Yeqiong; Dziugan, Piotr; Bai, Fengling; Walczak, Piotr; Zhang, Bolin

    2013-09-01

    In order to investigate the binding ability of Lactobacillus strains to Benzo(a)pyrene (BaP), 15 strains were analysed. L. plantarum CICC 22135 and L. pentosus CICC 23163 exhibited high efficiency in removing BaP from aqueous medium; the binding rates were 66.76% and 64.31%, respectively. This process was affected by temperature, incubation time and pH, and cell viability was not necessary for the binding ability. Additionally, both strains, especially strain CICC 23163 showed high specificity in binding BaP. The cell-BaP complexes were stable in aqueous medium. The mechanism of binding was investigated by examining the binding ability of different components of the microorganism cells. The results revealed that peptidoglycans played an important role in binding BaP and its structural integrity was required. Consequently, we proposed that the mechanism of this process was a physisorption and peptidoglycan was the main binding site. These two strains may be used for dietary detoxification in human diet and animal feed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. The ability of haemolysins expressed by atypical enteropathogenic Escherichia coli to bind to extracellular matrix components

    Directory of Open Access Journals (Sweden)

    Caroline A Magalhães

    2011-03-01

    Full Text Available Typical and atypical enteropathogenic Escherichia coli (EPEC are considered important bacterial causes of diarrhoea. Considering the repertoire of virulence genes, atypical EPEC (aEPEC is a heterogeneous group, harbouring genes that are found in other diarrheagenic E. coli pathotypes, such as those encoding haemolysins. Haemolysins are cytolytic toxins that lyse host cells disrupting the function of the plasma membrane. In addition, these cytolysins mediate a connection to vascular tissue and/or blood components, such as plasma and cellular fibronectin. Therefore, we investigated the haemolytic activity of 72 aEPEC isolates and determined the correlation of this phenotype with the presence of genes encoding enterohaemolysins (Ehly and cytolysin A (ClyA. In addition, the correlation between the expression of haemolysins and the ability of these secreted proteins to adhere to extracellular matrix (ECM components was also assessed in this study. Our findings demonstrate that a subset of aEPEC presents haemolytic activity due to the expression of Ehlys and/or ClyA and that this activity is closely related to the ability of these isolates to bind to ECM components.

  14. O2 Binding to Heme is Strongly Facilitated by Near‐Degeneracy of Electronic States

    DEFF Research Database (Denmark)

    Kepp, Kasper P.

    2013-01-01

    This paper reports the computed O2 binding to heme, which for the first time explains experimental enthalpies for this process of central importance to bioinorganic chemistry. All four spin states along the relaxed FeO2‐binding curves were optimized using the full heme system with dispersion......, thermodynamic, and scalar‐relativistic corrections, applying several density functionals. When including all these physical terms, the experimental enthalpy of O2 binding (−59 kJ mol−1) is closely reproduced by TPSSh‐D3 (−66 kJ mol−1). Dispersion changes the potential energy surfaces and leads to the correct...

  15. Technetium-99m labeling and fibronectin binding ability of Corynebacterium diphtheriae

    International Nuclear Information System (INIS)

    Souza, S.M.S.; Nagao, P.E.; Bernardo-Filho, M.; Pereira, G.A.; Napoleao, F.; Andrade, A.F.B.; Hirata Junior, R.; Mattos-Guaraldi, A.L.

    2004-01-01

    The use of radionuclides has permitted advances in areas of clinical and scientific knowledge. Several molecules and cells have been labelled with Technetium-99m ( 99m Tc). The stannous chloride (SnCl 2 ) has a significant influence on the labeling and stability of 99m Tc radiotracers. The frequent risk of diphtheria epidemics has intensified interest in the virulence factors of Corynebacterium diphtheriae. Although studies have looked at potential adhesins including haemagglutinins and exposed sugar residues, the molecular basis of mechanisms of adherence remains unclear. Adherence of pathogens to mammalian tissues may be mediated by fibronectin (FN) found in body fluids, matrix of connective tissues, and cell surfaces. In the present study we evaluated the binding ability to human plasma FN by 99m Tc labeled-C.diphtheriae. Due to adverse effects of stannous ions, microorganisms were submitted to survival and filamentation induction assays. Data showed a dose dependent susceptibility to SnCl 2 bactericidal effects. Cell filamentation was observed for concentrations of SnCl 2 > 110 μg/ml. Adherence levels of 99m Tc labelled 241strain to coverslips coated with 20 μg/ml FN were higher (P = 0.0037) than coated with bovine serum albumin. FN binding by the sucrose fermenting 241 C. diphtheriae strain (8.9% + 2.6) was significantly lower (P=0.0139) than Staphylococcus aureus Cowan I strain (34.1% ± 1.2). Therefore, bacterial 99m Tc labeling represents an additional tool that may contribute to the comprehension of C. diphtheriae interactions with host receptors such as FN that act as biological organizers by holding bacterial cells in position and guiding their migration. (author)

  16. Ability of Intestinal Lactic Acid Bacteria to Bind and/or Metabolise Indole

    Directory of Open Access Journals (Sweden)

    Zdzisława Libudzisz

    2008-01-01

    Full Text Available Intestinal microbiota can contribute to the development of colon cancer by the production of many substances playing a role in carcinogenesis. Metabolites of protein fermentation in the colon, such as ammonia, amines, indole, phenol, skatole and their derivatives are toxic. On the other hand, lactic acid bacteria (LAB existing in the colon may exert an anticarcinogenic action, but the mechanism is still poorly understood. In the present study, the aim is to determine the ability of intestinal lactobacilli to adsorb or metabolise indole in vitro. Lactobacillus strains were cultivated in MRS and a modified MRS broth with reduced concentrations of nitrogen and carbon. Indole concentration in the media was from 2 to 20 μg/mL. The decrease in indole concentration was from 1 to 10 μg/mL after cultivation in MRS broth, and from 4.3 to 6.7 μg/mL after cultivation in a modified MRS broth. It was shown that the higher concentration of indole in the medium, the higher reduction of its level. Killed bacteria displayed slight binding capacity. After the interaction of alive lactobacilli with 10 μg/mL of indole, it displayed a lower genotoxicity, as evaluated by the alkaline comet assay. The phenomenon did not depend on the decrease of indole concentration, but on the culture medium and the strain of LAB and ranged from 7 to 96 %.

  17. Chemical Affinity between Tannin Size and Salivary Protein Binding Abilities: Implications for Wine Astringency.

    Directory of Open Access Journals (Sweden)

    Wen Ma

    Full Text Available Astringency perception, as an essential parameter for high-quality red wine, is principally elicited by condensed tannins in diversified chemical structures. Condensed tannins, which are also known as proanthocyanidins (PAs, belong to the flavonoid class of polyphenols and are incorporated by multiple flavan-3-ols units according to their degree of polymerization (DP. However, the influence of DP size of PAs on astringency perception remains unclear for decades. This controversy was mainly attributed to the lack of efficient strategies to isolate the PAs in non-galloylated forms and with individual degree size from grape/wine. In the present study, the astringency intensity of purified and identified grape oligomeric tannins (DP ranged from 1 to 5 was firstly explored. A novel non-solid phase strategy was used to rapidly exclude the galloylated PAs from the non-galloylated PAs and fractionate the latter according to their DP size. Then, a series of PAs with individual DP size and galloylation were purified by an approach of preparative hydrophilic interaction chromatography. Furthermore, purified compounds were identified by both normal phase HPLC-FLD and reverse phase UHPLC-ESI-Q-TOF. Finally, the contribution of the astringency perception of the individual purified tannins was examined with a salivary protein binding ability test. The results were observed by HPLC-FLD and quantified by changes in PA concentration remaining in the filtrate. In summary, a new approach without a solid stationary phase was developed to isolate PAs according to their DP size. And a positive relationship between the DP of PAs and salivary protein affinity was revealed.

  18. Chemical Affinity between Tannin Size and Salivary Protein Binding Abilities: Implications for Wine Astringency.

    Science.gov (United States)

    Ma, Wen; Waffo-Teguo, Pierre; Jourdes, Michael; Li, Hua; Teissedre, Pierre-Louis

    2016-01-01

    Astringency perception, as an essential parameter for high-quality red wine, is principally elicited by condensed tannins in diversified chemical structures. Condensed tannins, which are also known as proanthocyanidins (PAs), belong to the flavonoid class of polyphenols and are incorporated by multiple flavan-3-ols units according to their degree of polymerization (DP). However, the influence of DP size of PAs on astringency perception remains unclear for decades. This controversy was mainly attributed to the lack of efficient strategies to isolate the PAs in non-galloylated forms and with individual degree size from grape/wine. In the present study, the astringency intensity of purified and identified grape oligomeric tannins (DP ranged from 1 to 5) was firstly explored. A novel non-solid phase strategy was used to rapidly exclude the galloylated PAs from the non-galloylated PAs and fractionate the latter according to their DP size. Then, a series of PAs with individual DP size and galloylation were purified by an approach of preparative hydrophilic interaction chromatography. Furthermore, purified compounds were identified by both normal phase HPLC-FLD and reverse phase UHPLC-ESI-Q-TOF. Finally, the contribution of the astringency perception of the individual purified tannins was examined with a salivary protein binding ability test. The results were observed by HPLC-FLD and quantified by changes in PA concentration remaining in the filtrate. In summary, a new approach without a solid stationary phase was developed to isolate PAs according to their DP size. And a positive relationship between the DP of PAs and salivary protein affinity was revealed.

  19. The 5-HT2A receptor binding pattern in the human brain is strongly genetically determined

    DEFF Research Database (Denmark)

    Pinborg, Lars H; Arfan, Haroon; Haugbol, Steven

    2007-01-01

    With the appropriate radiolabeled tracers, positron emission tomography (PET) enables in vivo human brain imaging of markers for neurotransmission, including neurotransmitter synthesis, receptors, and transporters. Whereas structural imaging studies have provided compelling evidence that the human...... variability in cortical 5-HT(2A) receptor binding as measured with [(18)F]altanserin PET imaging. The intraclass correlation coefficients were 0.67 for dizygotic and 0.87 for monozygotic twin pairs. For comparison, the intraclass correlation coefficient was 0.93 in a group of six male healthy subjects...

  20. Organic-inorganic hybrid optical foils with strong visible reflection, excellent near infrared-shielding ability and high transparency.

    Science.gov (United States)

    Zhou, Yijie; Huang, Aibin; Zhou, Huaijuan; Ji, Shidong; Jin, Ping

    2018-03-02

    Research on functional flexible films has recently been attracting widespread attention especially with regards to foils, which can be designed artificially on the basis of the practical requirements. In this work, a foil with high visible reflection and a strong near infrared shielding efficiency was prepared by a simple wet chemical method. In the process of making this kind of optical foil, emulsion polymerization was first introduced to synthesize polymer opals, which were further compressed between two pieces of polyethylene terephthalate (PET) foil under polymer melting temperature to obtain a photonic crystal film with a strong reflection in the visible region to block blue rays. The following step was to coat a layer of the inorganic nano paint, which was synthesized by dispersing Cs-doped WO 3 (CWO) nanoparticles homogenously into organic resin on the surface of the PET to achieve a high near infrared shielding ability. The final composite foil exhibited unique optical properties such as high visible reflectance (23.9%) to block blue rays, and excellent near infrared shielding efficiency (98.0%), meanwhile it still maintained a high transparency meaning that this foil could potentially be applied in energy-saving window films. To sum up, this study provides new insight into devising flexible hybrid films with novel optical properties, which could be further extended to prepare other optical films for potential use in automobile, architectural and other decorative fields.

  1. Organic-inorganic hybrid optical foils with strong visible reflection, excellent near infrared-shielding ability and high transparency

    Science.gov (United States)

    Zhou, Yijie; Huang, Aibin; Zhou, Huaijuan; Ji, Shidong; Jin, Ping

    2018-03-01

    Research on functional flexible films has recently been attracting widespread attention especially with regards to foils, which can be designed artificially on the basis of the practical requirements. In this work, a foil with high visible reflection and a strong near infrared shielding efficiency was prepared by a simple wet chemical method. In the process of making this kind of optical foil, emulsion polymerization was first introduced to synthesize polymer opals, which were further compressed between two pieces of polyethylene terephthalate (PET) foil under polymer melting temperature to obtain a photonic crystal film with a strong reflection in the visible region to block blue rays. The following step was to coat a layer of the inorganic nano paint, which was synthesized by dispersing Cs-doped WO3 (CWO) nanoparticles homogenously into organic resin on the surface of the PET to achieve a high near infrared shielding ability. The final composite foil exhibited unique optical properties such as high visible reflectance (23.9%) to block blue rays, and excellent near infrared shielding efficiency (98.0%), meanwhile it still maintained a high transparency meaning that this foil could potentially be applied in energy-saving window films. To sum up, this study provides new insight into devising flexible hybrid films with novel optical properties, which could be further extended to prepare other optical films for potential use in automobile, architectural and other decorative fields.

  2. Failed fertilization with conventional oocyte insemination can be overcome with the ability of ICSI according to binding or failing to bind to the zona pellucida.

    Science.gov (United States)

    Check, J H; Bollendorf, A; Wilson, C

    2016-01-01

    To determine the frequency of failed fertilization with conventional oocyte insemination and to determine the ability of intracytoplasmic sperm injection (ICSI) to overcome the failed fertilization according to binding or failing to bind to the zona pellucida. Retrospective review of 12,448 in vitro fertilization (IVF) cycle to identify cycles where failed fertilization occurred following conventional oocyte insemination with seemingly normal sperm. A number of three oocytes retrieved was required. There were only 12 cases of failed fertilization (0.1%). Six were related to failure of any or few sperm attaching to the zona pellucida These six had high fertilization rates with ICSI. Six had normal attachment and five attempted another cycle, this time with ICSI. Only 60% had good fertilization. When there is failed fertilization with normal sperm oocyte binding following conventional oocyte insemination, ICSI may still be effective in 60% of the cases, but it would be probably recommended to combine ICSI with artificial oocyte activation by calcium ionophore.

  3. A ChIP-Seq benchmark shows that sequence conservation mainly improves detection of strong transcription factor binding sites.

    Directory of Open Access Journals (Sweden)

    Tony Håndstad

    Full Text Available BACKGROUND: Transcription factors are important controllers of gene expression and mapping transcription factor binding sites (TFBS is key to inferring transcription factor regulatory networks. Several methods for predicting TFBS exist, but there are no standard genome-wide datasets on which to assess the performance of these prediction methods. Also, it is believed that information about sequence conservation across different genomes can generally improve accuracy of motif-based predictors, but it is not clear under what circumstances use of conservation is most beneficial. RESULTS: Here we use published ChIP-seq data and an improved peak detection method to create comprehensive benchmark datasets for prediction methods which use known descriptors or binding motifs to detect TFBS in genomic sequences. We use this benchmark to assess the performance of five different prediction methods and find that the methods that use information about sequence conservation generally perform better than simpler motif-scanning methods. The difference is greater on high-affinity peaks and when using short and information-poor motifs. However, if the motifs are specific and information-rich, we find that simple motif-scanning methods can perform better than conservation-based methods. CONCLUSIONS: Our benchmark provides a comprehensive test that can be used to rank the relative performance of transcription factor binding site prediction methods. Moreover, our results show that, contrary to previous reports, sequence conservation is better suited for predicting strong than weak transcription factor binding sites.

  4. Lysozyme binding ability toward psychoactive stimulant drugs: Modulatory effect of colloidal metal nanoparticles.

    Science.gov (United States)

    Sonu, Vikash K; Islam, Mullah Muhaiminul; Rohman, Mostofa Ataur; Mitra, Sivaprasad

    2016-10-01

    The interaction and binding behavior of the well-known psychoactive stimulant drugs theophylline (THP) and theobromine (THB) with lysozyme (LYS) was monitored by in-vitro fluorescence titration and molecular docking calculations under physiological condition. The quenching of protein fluorescence on addition of the drugs is due to the formation of protein-drug complex in the ground state in both the cases. However, the binding interaction is almost three orders of magnitude stronger in THP, which involves mostly hydrogen bonding interaction in comparison with THB where hydrophobic binding plays the predominant role. The mechanism of fluorescence quenching (static type) remains same also in presence of gold and silver nanoparticles (NPs); however, the binding capacity of LYS with the drugs changes drastically in comparison with that in aqueous buffer medium. While the binding affinity of LYS to THB increases ca. 100 times in presence of both the NPs, it is seen to decrease drastically (by almost 1000 fold) for THP. This significant modulation in binding behavior indicates that the drug transportation capacity of LYS can be controlled significantly with the formation protein-NP noncovalent assembly system as an efficient delivery channel. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Silicene on Monolayer PtSe2: From Strong to Weak Binding via NH3 Intercalation

    KAUST Repository

    Sattar, Shahid

    2018-01-16

    We study the properties of silicene on monolayer PtSe2 by first-principles calculations and demonstrate a much stronger interlayer interaction than previously reported for silicene on other semiconducting substrates. This fact opens the possibility of a direct growth. A band gap of 165 meV results from inversion symmetry breaking and large spin-splittings in the valence and conduction bands from proximity to monolayer PtSe2 and its strong spin–orbit coupling. It is also shown that the interlayer interaction can be effectively reduced by intercalating NH3 molecules between silicene and monolayer PtSe2 without inducing charge transfer or defect states near the Fermi energy. A small NH3 diffusion barrier makes intercalation a viable experimental approach to control the interlayer interaction.

  6. An approach to the construction of tailor-made amphiphilic peptides that strongly and selectively bind to hairpin RNA targets.

    Science.gov (United States)

    Lee, Su Jin; Hyun, Soonsil; Kieft, Jeffrey S; Yu, Jaehoon

    2009-02-18

    The hairpin RNA motif is one of the most frequently observed secondary structures and is often targeted by therapeutic agents. An amphiphilic peptide with seven lysine and eight leucine residues and its derivatives were designed for use as ligands against RNA hairpin motifs. We hypothesized that variations in both the hydrophobic leucine-rich and hydrophilic lysine-rich spheres of these amphiphilic peptides would create extra attractive interactions with hairpin RNA targets. A series of alanine-scanned peptides were probed to identify the most influential lysine residues in the hydrophilic sphere. The binding affinities of these modified peptides with several hairpins, such as RRE, TAR from HIV, a short hairpin from IRES of HCV, and a hairpin from the 16S A-site stem from rRNA, were determined. Since the hairpin from IRES of HCV was the most susceptible to the initial series of alanine-scanned peptides, studies investigating how further variations in the peptides effect binding employed the IRES hairpin. Next, the important Lys residues were substituted by shorter chain amines, such as ornithine, to place the peptide deeper into the hairpin groove. In a few cases, a 70-fold improved binding was observed for peptides that contained the specifically located shorter amine side chains. To further explore changes in binding affinities brought about by alterations in the hydrophobic sphere, tryptophan residues were introduced in place of leucine. A few peptides with tryptophan in specific positions also displayed 70-fold improved binding affinities. Finally, double mutant peptides incorporating both specifically located shorter amine side chains in the hydrophilic region and tryptophan residues in the hydrophobic region were synthesized. The binding affinities of peptides containing the simple double modification were observed to be 80 times lower, and their binding specificities were increased 40-fold. The results of this effort provide important information about

  7. Reduction of the IgE-binding ability and maintenance of immunogenicity of gamma-irradiated Dermatophagoides farinae

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ju-Woon; Seo, Ji-Hyun; Kim, Jae-Hun [Radiation Application Research Division, Advanced Radiation Technology Institute, Jeongeup 580 185 (Korea, Republic of); Lee, Soo-Young [Department of Pediatrics, Ajou University School of medicine, Suwon 442 749 (Korea, Republic of); Park, Joong-Won [Department of Allergy and Immunology, Severance Hospital, Yonsei University, Seoul 120 752 (Korea, Republic of); Byun, Myung-Woo [Radiation Application Research Division, Advanced Radiation Technology Institute, Jeongeup 580 185 (Korea, Republic of)], E-mail: mwbyun@kaeri.re.kr

    2007-11-15

    House dust mites, Dermatophagoides farinae (DF) and Dermatophagoides pteronyssinus, are major allergens in the most common indoor allergen and are important risk factor for asthma. The modified antigen has been studied to treat allergic disorder. This study was carried out to measure possibility of modified allergen using gamma irradiation to treat allergy such as asthma. DF solutions (2 mg/ml) as target allergen were irradiated with Co-60 at 50 and 100 kGy. Conformational alternation of irradiated DF was observed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Levels of anti-irradiated DF mouse IgGs (sub-isotypes) against intact DF were measured similar to that of anti-intact DF IgGs. The binding abilities of house dust mite-allergic patients' IgE were reduced depending on radiation dose, and irradiation could inhibit the binding ability of patients' IgE more than 40%. This study has shown that the binding ability of IgE was reduced by conformational alteration by irradiation and the irradiated DF had epitopes capable to induce immunogeniciy.

  8. Oviduct binding ability of porcine spermatozoa develops in the epididymis and can be advanced by incubation with caudal fluid.

    Science.gov (United States)

    Peña, Santiago; Summers, Phillip; Gummow, Bruce; Paris, Damien B B P

    2015-06-01

    The sperm reservoir is formed when spermatozoa bind to the epithelium of the uterotubal junction and caudal isthmus of the oviduct. It is an important mechanism that helps synchronize the meeting of gametes by regulating untimely capacitation and polyspermic fertilization. This study investigated the influence of epididymal maturation and caudal fluid on the ability of spermatozoa to bind to oviduct epithelium using a model porcine oviduct explant assay. Spermatozoa from the rete testis, middle caput (E2-E3), middle corpus (E6), and cauda (E8) of Large White or Large White × Landrace boars aged 10 to 14 months were diluted in modified Androhep solution and incubated with porcine oviduct explants. Results reported in this study support our hypothesis that testicular spermatozoa need to pass through the regions of the epididymis to acquire the ability to bind to the oviduct. There was a sequential increase in the number of spermatozoa that bound to oviduct explants from the rete testis to caudal epididymis. Binding of caudal spermatozoa to isthmic explants was the highest (15.0 ± 1.2 spermatozoa per 1.25 mm(2), mean ± standard error of the mean; P ≤ 0.05) and lowest by spermatozoa from the rete testis (2.0 ± 0.3 per 1.25 mm(2)), and higher to isthmus from sows compared to gilts (35.8 ± 6.7 per 1.25 mm(2) vs. 14.8 ± 3.0 per 1.25 mm(2); P ≤ 0.05). Binding of ejaculated spermatozoa to porcine isthmus was higher than that for caudal spermatozoa (26.3 ± 1.4 per 1.25 mm(2) vs. 15.0 ± 0.8 per 1.25 mm(2); P ≤ 0.05) and higher to porcine than to bovine isthmus (26.3 ± 2.3 per 1.25 mm(2) vs. 18.8 ± 1.9 per 1.25 mm(2); P ≤ 0.05). Incubation of spermatozoa from the caput and corpus in caudal fluid increased the ability of spermatozoa to bind to the oviduct epithelium (P ≤ 0.05). In conclusion, the capacity of testicular spermatozoa to bind to the oviduct epithelium increases during their maturation in the epididymis and can be advanced by components of the

  9. Toward understanding macrocycle specificity of iron on the dioxygen-binding ability: a theoretical study.

    Science.gov (United States)

    Sun, Yong; Chen, Kexian; Jia, Lu; Li, Haoran

    2011-08-14

    In an effort to examine the interaction between dioxygen and iron-macrocyclic complexes, and to understand how this interaction was affected by those different macrocyclic ligands, dioxygen binding with iron-porphyrin, iron-phthalocyanine, iron-dibenzotetraaza[14]annulene, and iron-salen complexes is investigated by means of quantum chemical calculations utilizing Density Functional Theory (DFT). Based on the analysis of factors influencing the corresponding dioxygen binding process, it showed that different macrocyclic ligands possess different O-O bond distances, and different electronic configurations for the bound O(2) and non-aromatic macrocyclic ligands favor dioxygen activation. Furthermore, the smaller the energy gap between the HOMO of iron-macrocyclic complexes and the LUMO of dioxygen, the more active the bound O(2) becomes, with a longer O-O bond distance and a shorter Fe-O bond length.

  10. Investigating the DNA-binding ability of GATA-1-N-terminal zinc finger

    International Nuclear Information System (INIS)

    Wong, R.; Newton, A.; Crossley, M.; Mackay, J.

    2001-01-01

    Erythroid transcription factor GATA-1 interacts with both DNA and other proteins through its zinc finger domains (ZnFs). While it has been known for me time that the C-terminal ZnF binds DNA at GATA sites, only recently has it been observed that the N-terminal finger (NF) is capable of interacting with GATC sites. Further, a number of naturally occurring mutations in NF (V205M, G208S, R216Q, D218G) that lead to anaemia and thrombocytopenia have been identified. We are interested in characterising the NF-DNA interaction and determining the effects of mutation upon this interaction. Using nuclear magnetic resonance (NMR) spectroscopy, we have observed an interaction between recombinant NF and a 16-mer DNA duplex containing a core GATC sequence. This result forms the basis from which residues in NF involved in DNA binding can be identified, and work is being carried out to improve the quality of the NMR data with the aim of determining the solution structure of the NF-DNA complex. The DNA-binding affinity of both wild-type and mutant NFs mentioned above is also being investigated using isothermal titration calorimetry. These data suggest that the strength of the interaction between NF and the 16-mer DNA duplex is in the sub-micromolar range, and comparisons between the DNA-binding affinities of the NF mutants are being made. Together, these studies will help us to understand how GATA-1 acts as a transcriptional regulator and how mutations in NF domain of GATA-1 may lead to blood disorders

  11. Phosphorylation of nitrogen regulator I of Escherichia coli induces strong cooperative binding to DNA essential for activation of transcription.

    OpenAIRE

    Weiss, V; Claverie-Martin, F; Magasanik, B

    1992-01-01

    We studied the effect of phosphorylation of nitrogen regulator I (NRI) on its binding properties. Both phosphorylated and unphosphorylated NRI bind linearly to a single binding site but cooperatively to two adjacent binding sites. Cooperative binding of NRI is severely affected by phosphorylation: half-maximal binding of NRI-phosphate is at 20-fold lower concentrations than that of unphosphorylated NRI. This is more due to a huge increase in the cooperativity constant--which is the strength o...

  12. High cadmium-binding ability of a novel Colocasia esculenta metallothionein increases cadmium tolerance in Escherichia coli and tobacco.

    Science.gov (United States)

    Kim, Yeon-Ok; Patel, Darshan H; Lee, Dae-Seok; Song, Younho; Bae, Hyeun-Jong

    2011-01-01

    Experimental evidence in vivo as to the functional roles and binding properties to cadmium (Cd) of type-2 plants metallothionein (MT) has been limited thus far. We investigated the biological role of metallothionein from Colocasia esculenta (CeMT2b) in Escherichia coli and tobacco, and developed a new model for the relationship between Cd tolerance and Cd-binding ability. Heterologous expression of CeMT2b in Escherichia coli greatly enhanced Cd tolerance and accumulated Cd content as compared to control cells. The molecular weight of CeMT2b increased with Cd, and CeMT2b bound up to 5.96±1 molar ratio (Cd/protein). Under Cd stress, transgenic tobacco plants displayed much better seedling growth and high Cd accumulation than the wild type. The presence of an extra CXC motif in CeMT2b contributed to the enhanced Cd-tolerance. The present study provides the first insight into the ability of type-2 plant MT to bind physiological Cd.

  13. The C-terminal domain of the Arabidopsis AtMBD7 protein confers strong chromatin binding activity

    International Nuclear Information System (INIS)

    Zemach, Assaf; Paul, Laju K.; Stambolsky, Perry; Efroni, Idan; Rotter, Varda; Grafi, Gideon

    2009-01-01

    The Arabidopsis MBD7 (AtMBD7) - a naturally occurring poly MBD protein - was previously found to be functional in binding methylated-CpG dinucleotides in vitro and localized to highly methylated chromocenters in vivo. Furthermore, AtMBD7 has significantly lower mobility within the nucleus conferred by cooperative activity of its three MBD motifs. Here we show that besides the MBD motifs, AtMBD7 possesses a strong chromatin binding domain located at its C-terminus designated sticky-C (StkC). Mutational analysis showed that a glutamic acid residue near the C-terminus is essential though not sufficient for the StkC function. Further analysis demonstrated that this motif can render nuclear proteins highly immobile both in plant and animal cells, without affecting their native subnuclear localization. Thus, the C-terminal, StkC motif plays an important role in fastening AtMBD7 to its chromosomal, CpG-methylated sites. It may be possible to utilize this motif for fastening nuclear proteins to their chromosomal sites both in plant and animal cells for research and gene therapy applications.

  14. Loss of Hoogsteen Pairing Ability upon N1 Adenine Platinum Binding

    Czech Academy of Sciences Publication Activity Database

    Schmidt, K. S.; Reedijk, J.; Weisz, K.; Janke, E. M. B.; Šponer, Judit E.; Šponer, Jiří; Lippert, B.

    2002-01-01

    Roč. 41, č. 11 (2002), s. 2855-2863 ISSN 0020-1669 R&D Projects: GA MŠk LN00A016; GA AV ČR IAA4040903 Institutional research plan: CEZ:AV0Z4040901 Keywords : adenine * thymine * Hoogsteen pairing ability Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.950, year: 2002

  15. Visual binding abilities in the initial and advanced stages of schizophrenia

    DEFF Research Database (Denmark)

    Parnas, Josef; Vianin, P; Saebye, D

    2001-01-01

    attention, Raven's test and two conventional cortical tasks of spatial working memory (SWM) and a global local test. RESULTS: Chronic patients had a decreased performance on the binding tests. Unexpectedly, the prodromal group exhibited an enhanced Gestalt extraction on these tests compared both...... of neurocognitive deficits in schizophrenia which, however, in this sample seem to be linked to chronicity of illness. However, certain aspects of visual processing concerned with Gestalt extraction deserve attention as potential vulnerability- or prodrome- indicators. The initial hypothesis of the study...

  16. TGFβ/BMP inhibits the bone marrow transformation capability of Hoxa9 by repressing its DNA-binding ability

    Science.gov (United States)

    Wang, Ning; Kim, Hyung-Gyoong; Cotta, Claudiu V; Wan, Mei; Tang, Yi; Klug, Christopher A; Cao, Xu

    2006-01-01

    Homeobox (Hox) gene mutations and their altered expressions are frequently linked to human leukemia. Here, we report that transforming growth factor β (TGFβ)/bone morphogenetic protein (BMP) inhibits the bone marrow transformation capability of Hoxa9 and Nup98-Hoxa9, the chimeric fusion form of Hoxa9 identified in human acute myeloid leukemia (AML), through Smad4, the common Smad (Co-Smad) in the TGFβ/BMP signaling pathway. Smad4 interacts directly with the homeodomain of Hoxa9 and blocks the ability of Nup98-Hoxa9 to bind DNA, thereby suppressing its ability to regulate downstream gene transcription. Mapping data revealed that the amino-terminus of Smad4 mediates this interaction and overexpression of the Hoxa9 interaction domain of Smad4 was sufficient to inhibit the enhanced serial replating ability of primary bone marrow cells induced by Nup98-Hoxa9. These studies establish a novel mechanism by which TGFβ/BMP regulates hematopoiesis and suggest that modification of Hox DNA-binding activity may serve as a novel therapeutic intervention for those leukemias that involve deregulation of Hox. PMID:16525506

  17. Human papillomavirus E5 oncoproteins bind the A4 endoplasmic reticulum protein to regulate proliferative ability upon differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Kotnik Halavaty, Katarina; Regan, Jennifer; Mehta, Kavi; Laimins, Laimonis, E-mail: l-laimins@northwestern.edu

    2014-03-15

    Human papillomaviruses (HPV) infect stratified epithelia and link their life cycles to epithelial differentiation. The HPV E5 protein plays a role in the productive phase of the HPV life cycle but its mechanism of action is still unclear. We identify a new binding partner of E5, A4, using a membrane-associated yeast-two hybrid system. The A4 protein co-localizes with HPV 31 E5 in perinuclear regions and forms complexes with E5 and Bap31. In normal keratinocytes, A4 is found primarily in basal cells while in HPV positive cells high levels of A4 are seen in both undifferentiated and differentiated cells. Reduction of A4 expression by shRNAs, enhanced HPV genome amplification and increased cell proliferation ability following differentiation but this was not seen in cells lacking E5. Our studies suggest that the A4 protein is an important E5 binding partner that plays a role in regulating cell proliferation ability upon differentiation. - Highlights: • A4 associates with HPV 31 E5 proteins. • A4 is localized to endoplasmic reticulum. • HPV proteins induce A4 expression in suprabasal layers of stratified epithelium. • E5 is important for proliferation ability of differentiating HPV positive cells.

  18. Protein Engineered Triblock Polymers Comprised of Two SADs: Enhanced Mechanical Properties and Binding Abilities.

    Science.gov (United States)

    Olsen, Andrew J; Katyal, Priya; Haghpanah, Jennifer S; Kubilius, Matthew B; Li, Ruipeng; Schnabel, Nicole L; O'Neill, Sean C; Wang, Yao; Dai, Min; Singh, Navjot; Tu, Raymond S; Montclare, Jin Kim

    2018-03-15

    Recombinant methods have been used to engineer artificial protein triblock polymers comprised of two different self-assembling domains (SADs) bearing one elastin (E) flanked by two cartilage oligomeric matrix protein coiled-coil (C) domains to generate CEC. To understand how the two C domains improve small molecule recognition and the mechanical integrity of CEC, we have constructed CL44AECL44A, which bears an impaired CL44A domain that is unstructured as a negative control. The CEC triblock polymer demonstrates increased small molecule binding and ideal elastic behavior for hydrogel formation. The negative control CL44AECL44A does not exhibit binding to small molecule and is inelastic at lower temperatures, affirming the favorable role of C domain and its helical conformation. While both CEC and CL44AECL44A assemble into micelles, CEC is more densely packed with C domains on the surface enabling the development of networks leading to hydrogel formation. Such protein engineered triblock copolymers capable of forming robust hydrogels hold tremendous promise for biomedical applications in drug delivery and tissue engineering.

  19. In vitro phosphate-binding ability of calcium-based agents is augmented by co-administration of activated charcoal.

    Science.gov (United States)

    Jia, Meng; Cheng, Xu-Yang; Zuo, Li

    2013-06-01

    Calcium carbonate is widely used as a phosphate binder in patients on maintenance hemodialysis. An unwanted side effect of calcium carbonate is hypercalcemia and vascular calcification. Oral activated charcoal (AC) is a non-selective and highly effective adsorbent. We hypothesized that AC augments the phosphate binding capacity of calcium-based agents. We performed an in vitro study to test this hypothesis. Simulated gastric fluid and intestinal fluid were prepared with a phosphate concentration of 10 mmol/l. Different dosages of calcium chloride (0.083 g, 0.167 g, and 0.250 g), AC (0.15 g, 0.30 g, and 0.45 g) or a combination of both were added to either gastric or intestinal fluid for phosphate binding. After a reaction time of 2 hours, phosphate concentrations in the supernatant were measured, and absolute reduction and percent reduction of phosphate were calculated. The phosphate-binding abilities of calcium chloride, AC, and a combination of both were compared. In simulated intestinal fluid there was no significant difference in the percent reduction of phosphate concentrations among the different calcium chloride concentration groups (28.90 ± 2.04 vs. 33.33 ± 3.90 vs. 31.86 ± 5.23) and there was still no significant difference in phosphate concentrations among the different AC groups (3.33 ± 0.08 vs. 3.26 ± 0.01 vs. 3.36 ± 0.11). In simulated gastric fluid phosphate concentrations at each of the time points (before the reaction, 1 hour after calcium chloride was added, and 2 hours after AC was added) were not significantly different. In simulated intestinal fluid the percent decrease in phosphate concentration in the calcium chloride + AC group was significantly higher than that in the calcium chloride group (48.23 ± 5.55 vs. 30.72 ± 6.11). AC alone had no phosphate-binding ability in either gastric or intestinal fluid. The phosphate-binding ability of calcium chloride was improved by AC in intestinal fluid.

  20. Metal-Binding Ability of Leu-Enkephalin, Related Glycoconjugates and Peptidomimetics

    Directory of Open Access Journals (Sweden)

    Zsuzsa Majer

    2015-12-01

    Full Text Available Both the chemistry and consequences of the nonenzymatic reaction between reducing sugars and reactive amino groups of amino acids, peptides and proteins (known as the Maillard reaction, have received considerable attention in food and health science fields. This initial reaction results in Amadori and similar products formation, followed by degradation to advanced glycation end products (AGEs. It is well established that AGEs are associated with color and odor of thermally processed or stored food, as well as with pathogen products in a number of diseases. The model systems of early stage Maillard reaction products (MRP were prepared between endogenous opioid peptide leucine enkephalin (1 and D-glucose / D-glucuronic acid. The complexation ability of prepared MRP with metal ions (Ca2+, Zn2+, Al3+, Pb2+ and Cu2+ was investigated and compared to the complexation ability of parent peptide using ECD and FTIR spectroscopic measurements.

  1. Current approach to male infertility treatment: sperm selection procedure based on hyaluronic acid binding ability

    Directory of Open Access Journals (Sweden)

    A. V. Zobova

    2015-01-01

    Full Text Available Intracytoplasmic sperm injection into an oocyte is widely used throughout the world in assisted reproductive technologies programs in the presence of male infertility factor. However, this approach can allow selection of a single sperm, which is carrying different types of pathologies. Minimizing of any potential risks, entailing the occurrence of abnormalities in the embryos development (apoptosis, fragmentation of embryos, alterations in gene expression, aneuploidies is a very important condition for reducing the potential negative consequences resulting the manipulation with gametes. Processes that could be influenced by the embryologist must be fulfilled in safe and physiological way as much as it is possible. Data of numerous publications reporting about the positive effects of using the technology of sperm selection by hyaluronic acid binding, let make a conclusion about the high prospects of this approach in the treatment of male infertility by methods of in vitro fertilization. The selection of sperm with improved characteristics, which determine the maturity and genetic integrity, provides an opportunity to improve the parameters of pre-implantation embryogenesis, having thus a positive effect on clinical outcomes of assisted reproductive technologies programs.

  2. Increased Hyaluronan Acid Binding Ability of Spermatozoa Indicating a Better Maturity, Morphology, and Higher DNA Integrity After Micronutrient Supplementation

    Directory of Open Access Journals (Sweden)

    Markus Lipovac

    2014-05-01

    Full Text Available Measuring the hyaluronan-binding ability of spermatozoa is useful in predicting the ability of spermatozoa to fertilise oocytes during in vitro fertilisation (IVF. Recent publications discuss an influence of micronutrients on sperm quality. The objective of this paper was to evaluate the effect of a non-prescription nutraceutical containing eight micronutrients on sperm-hyaluronan binding assay (SHBA values among males with idiopathic sub-/infertility, using an open comparative pilot study. The study took place at the Outpatient Fertility Centre IMI, Vienna, Austria, and involved 67 sub-/infertile males. Sub-/infertile males were invited to participate and take two daily capsules of the active compound for a 3-month period between the first and the follow-up semen analysis. Each capsule contained L-carnitine, L-arginine, zinc, vitamin E, glutathione, selenium, coenzyme Q10 (CoQ10, and folic acid (Profertil®. 40 sub-/infertile men receiving no active treatment served as controls; this was measured by change in SHBA after 3 months. It was found that SHBA values significantly increased after 3 months of treatment with the active compound, from a median baseline value of 56.0% to 74% (p<0.05. This represented a 19.7% increase compared to baseline, which was significantly higher than the 2.1% decrease observed in the control group. The rate of subjects displaying an increase in SHBA values after 3 months was significantly higher in the active group (74.6% versus 30.0%, p=0.0001, which showed that sub-/infertile men treated with the active micronutrient compound displayed increased SHBA ability. However, more research is necessary to get detailed information on this specific subject.

  3. Binding abilities of a chiral calix[4]resorcinarene: a polarimetric investigation on a complex case of study

    Directory of Open Access Journals (Sweden)

    Marco Russo

    2017-12-01

    Full Text Available Polarimetry was used to investigate the binding abilities of a chiral calix[4]resorcinarene derivative, bearing L-proline subunits, towards a set of suitably selected organic guests. The simultaneous formation of 1:1 and 2:1 host–guest inclusion complexes was observed in several cases, depending on both the charge status of the host and the structure of the guest. Thus, the use of the polarimetric method was thoroughly revisited, in order to keep into account the occurrence of multiple equilibria. Our data indicate that the stability of the host–guest complexes is affected by an interplay between Coulomb interactions, π–π interactions, desolvation effects and entropy-unfavorable conformational dynamic restraints. Polarimetry is confirmed as a very useful and versatile tool for the investigation of supramolecular interactions with chiral hosts, even in complex systems involving multiple equilibria.

  4. An assessment tumor targeting ability of 177Lu labeled cyclic CCK analogue peptide by binding with cholecystokinin receptor

    Directory of Open Access Journals (Sweden)

    Eun-Ha Cho

    2016-07-01

    Full Text Available The cholecystokinin (CCK receptor is known as a receptor that is overexpressed in many human tumors. The present study was designed to investigate the targeting ability of cyclic CCK analogue in AR42J pancreatic cells. The CCK analogues, DOTA-K(glucose-Gly-Trp-Nle-Asp-Phe (DOTA-glucose-CCK and DOTA-Nle-cyclo(Glu-Trp-Nle-Asp-Phe-Lys-NH2 (DOTA-[Nle]-cCCK, were synthesized and radiolabeled with 177Lu, and competitive binding was evaluated. The binding appearance of synthesized peptide with AR42J cells was evaluated by confocal microscopy. And bio-distribution was performed in AR42J xenografted mice. Synthesized peptides were prepared by a solid phase synthesis method, and their purity was over 98%. DOTA is the chelating agent for 177Lu-labeling, in which the peptides were radiolabeled with 177Lu by a high radiolabeling yield. A competitive displacement of 125I-CCK8 on the AR42J cells revealed that the 50% inhibitory concentration value (IC50 was 12.3 nM of DOTA-glucose-CCK and 1.7 nM of DOTA-[Nle]-cCCK. Radio-labeled peptides were accumulated in AR42J tumor in vivo, and %ID/g of the tumor was 0.4 and 0.9 at 2 h p.i. It was concluded that 177Lu-DOTA-[Nle]-cCCK has higher binding affinity than 177Lu-DOTA-glucose-CCK and can be a potential candidate as a targeting modality for a CCK receptor over-expressing tumors.

  5. Adaptability of the Saccharomyces cerevisiae yeasts to wine fermentation conditions relies on their strong ability to consume nitrogen.

    Science.gov (United States)

    Brice, Claire; Cubillos, Francisco A; Dequin, Sylvie; Camarasa, Carole; Martínez, Claudio

    2018-01-01

    Saccharomyces cerevisiae strains are genetically diverse, largely as a result of human efforts to develop strains specifically adapted to various fermentation processes. These adaptive pressures from various ecological niches have generated behavioral differences among these strains, particularly in terms of their nitrogen consumption capacities. In this work, we characterize this phenotype by the specific quantity of nitrogen consumed under oenological fermentation conditions using a new approach. Indeed, unlike previous studies, our experiments were conducted in an environment containing excess nitrogen, eliminating the nitrogen limitation/starvation factor that is generally observed in fermentation processes. Using these conditions, we evaluated differences in the nitrogen consumption capacities for a set of five strains from diverse origins. The strains presented extremely different phenotypes and variations in their capacities to take up nitrogen from a wine fermentation environment. These variations reflect the differences in the nitrogen uptake capacities between wine and non-wine strains. Finally, the strains differed in their ability to adapt to the nitrogen composition of the environment, leading to variations in the cellular stress states, fermentation performances and the activity of the nitrogen sensing signaling pathway.

  6. Astrocytic CCAAT/Enhancer Binding Protein δ Regulates Neuronal Viability and Spatial Learning Ability via miR-135a.

    Science.gov (United States)

    Chu, Yu-Yi; Ko, Chiung-Yuan; Wang, Wei-Jan; Wang, Shao-Ming; Gean, Po-Wu; Kuo, Yu-Min; Wang, Ju-Ming

    2016-08-01

    The progression of Alzheimer's disease (AD) has been associated with astrocytes-induced neuroinflammation. However, the detailed mechanism of astrocytes associated with learning impairments and neuronal loss in AD is poorly defined. Here, we provide novel evidences that astrocytic miR-135a is critical for neuronal viability and spatial learning ability in vivo. The AppTg/Cebpd (-/-) mice showed a spatial learning improvement compared with the APPswe/PS1/E9 bigenic (AppTg) mice. miR-135a was found to be a CCAAT/enhancer binding protein δ (CEBPD) responsive miRNA and can repress the transcription of thrombospondin 1 (THBS1) / Thbs1 (mouse) via its 3'-untranslated region (3'UTR). We used different experimental approaches to attenuate the expression of CEBPD/Cebpd (mouse) or miR-135a in astrocytes and found the following results: increase in THBS1/Thbs1 expression, decrease in neuronal apoptosis, and increase in growth of neurites. Importantly, injection of miR-135a antagonist (AM135a) into the brain of AppTg mice was found to prevent neuronal apoptosis and improved the spatial learning ability. Together, our findings demonstrate a critical function for the astrocytic CEBPD, and point to miR-135a antagonist as an attractive therapeutic target for the treatment of Alzheimer's disease.

  7. White-rot fungus Ganoderma sp.En3 had a strong ability to decolorize and tolerate the anthraquinone, indigo and triphenylmethane dye with high concentrations.

    Science.gov (United States)

    Lu, Ruoying; Ma, Li; He, Feng; Yu, Dong; Fan, Ruozhi; Zhang, Yangming; Long, Zheping; Zhang, Xiaoyu; Yang, Yang

    2016-03-01

    The ability of the white-rot fungus Ganoderma sp.En3 to decolorize different kinds of dyes widely applied in the textile and dyeing industry, including the anthraquinone dye Remazol Brilliant Blue R (RBBR), indigo dye indigo carmine and triphenylmethane dye methyl green, was evaluated in this study. Ganoderma sp.En3 had a strong capability of decolorizing high concentrations of RBBR, indigo carmine and methyl green. Obvious reduction of Chemical Oxygen Demand was observed after decolorization of different dyes. Ganoderma sp.En3 had a strong ability to tolerate RBBR, indigo carmine and methyl green with high concentrations. High concentrations of RBBR, indigo carmine and methyl green could also be efficiently decolorized by the crude enzyme of Ganoderma sp.En3. Different redox mediators such as syringaldehyde, acetosyringone and acetovanillone could enhance the decolorization capability for higher concentration of indigo carmine and methyl green. Different metal ions had little effect on the ability of the crude enzyme to decolorize indigo carmine and methyl green. Our study suggested that Ganoderma sp.En3 had a strong capability for decolorizing and tolerating high concentrations of different types of dyes such as RBBR, indigo carmine and methyl green.

  8. Two SusD-like proteins encoded within a polysaccharide utilization locus of an uncultured ruminant Bacteroidetes phylotype bind strongly to cellulose

    DEFF Research Database (Denmark)

    Mackenzie, A.K.; Pope, P.B.; Pedersen, Henriette Lodberg

    2012-01-01

    We demonstrate that two characteristic Sus-like proteins encoded within a polysaccharide utilization locus (PUL) bind strongly to cellulosic substrates and interact with plant primary cell walls. This shows associations between uncultured Bacteroidetes-affiliated lineages and cellulose in the rumen...

  9. Role of ICAM-1 polymorphisms (G241R, K469E) in mediating its single-molecule binding ability: Atomic force microscopy measurements on living cells

    Energy Technology Data Exchange (ETDEWEB)

    Bai, Rui [Chinese (301) General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853 (China); Yi, Shaoqiong [Beijing Institute of Biotechnology, 20 Dongdajie, Fengtai, Beijing 100071 (China); Zhang, Xuejie [Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry Chinese Academy of Sciences, 2 Zhongguancun North 1st Street, Beijing 100190 (China); Liu, Huiliang, E-mail: lhl518@vip.sina.com [Department of Cardiology, The General Hospital of Chinese People’s Armed Police Forces, Beijing 100039 (China); Fang, Xiaohong, E-mail: xfang@iccas.ac.cn [Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry Chinese Academy of Sciences, 2 Zhongguancun North 1st Street, Beijing 100190 (China)

    2014-06-13

    Highlights: • We evaluated both single molecule binding ability and expression level of 4 ICAM-1 mutations. • AFM was used to measure single-molecule binding ability on living cells. • The SNP of ICAM-1 may induce changes in expressions rather than single-molecule binding ability. - Abstract: Atherosclerosis (As) is characterized by chronic inflammation and is a major cause of human mortality. ICAM-1-mediated adhesion of leukocytes in vessel walls plays an important role in the pathogenesis of atherosclerosis. Two single nucleotide polymorphisms (SNPs) of human intercellular adhesion molecule-1 (ICAM-1), G241R and K469E, are associated with a number of inflammatory diseases. SNP induced changes in ICAM-1 function rely not only on the expression level but also on the single-molecule binding ability which may be affected by single molecule conformation variations such as protein splicing and folding. Previous studies have shown associations between G241R/K469E polymorphisms and ICAM-1 gene expression. Nevertheless, few studies have been done that focus on the single-molecule forces of the above SNPs and their ligands. In the current study, we evaluated both single molecule binding ability and expression level of 4 ICAM-1 mutations – GK (G241/K469), GE (G241/E469), RK (R241/K469) and RE (R241/E469). No difference in adhesion ability was observed via cell adhesion assay or atomic force microscopy (AFM) measurement when comparing the GK, GE, RK, or RE genotypes of ICAM-1 to each other. On the other hand, flow cytometry suggested that there was significantly higher expression of GE genotype of ICAM-1 on transfected CHO cells. Thus, we concluded that genetic susceptibility to diseases related to ICAM-1 polymorphisms, G241R or K469E, might be due to the different expressions of ICAM-1 variants rather than to the single-molecule binding ability of ICAM-1.

  10. Bile acid-binding ability of kaki-tannin from young fruits of persimmon (Diospyros kaki) in vitro and in vivo.

    Science.gov (United States)

    Matsumoto, Kenji; Kadowaki, Akio; Ozaki, Natsumi; Takenaka, Makiko; Ono, Hiroshi; Yokoyama, Shin-ichiro; Gato, Nobuki

    2011-04-01

    The bile acid-binding ability of a highly polymerized tannin (kaki-tannin) extracted from dried-young fruits of persimmon (Diospyros kaki) was examined. The kaki-tannin was composed mainly of epicatechin, epigallocatechin, epicatechin-3-O-gallate and epigallocatechin-3-O-gallate. Bile acid-binding ability of kaki-tannin was examined against cholic acid, glycocholic acid, taurocholic acid and deoxycholic acid in vitro, and its effect on fecal bile acid excretion in mice was also examined. Although the bile acid-binding ability of kaki-tannin was weaker than that of cholestyramine, kaki-tannin adsorbed all the bile acids tested and significantly promoted fecal bile acid excretion in mice when supplied at 1% (w/w) in the diet. Copyright © 2010 John Wiley & Sons, Ltd.

  11. Slow Off-rates and Strong Product Binding Are Required for Processivity and Efficient Degradation of Recalcitrant Chitin by Family 18 Chitinases*

    Science.gov (United States)

    Kurašin, Mihhail; Kuusk, Silja; Kuusk, Piret; Sørlie, Morten; Väljamäe, Priit

    2015-01-01

    Processive glycoside hydrolases are the key components of enzymatic machineries that decompose recalcitrant polysaccharides, such as chitin and cellulose. The intrinsic processivity (PIntr) of cellulases has been shown to be governed by the rate constant of dissociation from polymer chain (koff). However, the reported koff values of cellulases are strongly dependent on the method used for their measurement. Here, we developed a new method for determining koff, based on measuring the exchange rate of the enzyme between a non-labeled and a 14C-labeled polymeric substrate. The method was applied to the study of the processive chitinase ChiA from Serratia marcescens. In parallel, ChiA variants with weaker binding of the N-acetylglucosamine unit either in substrate-binding site −3 (ChiA-W167A) or the product-binding site +1 (ChiA-W275A) were studied. Both ChiA variants showed increased off-rates and lower apparent processivity on α-chitin. The rate of the production of insoluble reducing groups on the reduced α-chitin was an order of magnitude higher than koff, suggesting that the enzyme can initiate several processive runs without leaving the substrate. On crystalline chitin, the general activity of the wild type enzyme was higher, and the difference was magnifying with hydrolysis time. On amorphous chitin, the variants clearly outperformed the wild type. A model is proposed whereby strong interactions with polymer in the substrate-binding sites (low off-rates) and strong binding of the product in the product-binding sites (high pushing potential) are required for the removal of obstacles, like disintegration of chitin microfibrils. PMID:26468285

  12. Slow Off-rates and Strong Product Binding Are Required for Processivity and Efficient Degradation of Recalcitrant Chitin by Family 18 Chitinases.

    Science.gov (United States)

    Kurašin, Mihhail; Kuusk, Silja; Kuusk, Piret; Sørlie, Morten; Väljamäe, Priit

    2015-11-27

    Processive glycoside hydrolases are the key components of enzymatic machineries that decompose recalcitrant polysaccharides, such as chitin and cellulose. The intrinsic processivity (P(Intr)) of cellulases has been shown to be governed by the rate constant of dissociation from polymer chain (koff). However, the reported koff values of cellulases are strongly dependent on the method used for their measurement. Here, we developed a new method for determining koff, based on measuring the exchange rate of the enzyme between a non-labeled and a (14)C-labeled polymeric substrate. The method was applied to the study of the processive chitinase ChiA from Serratia marcescens. In parallel, ChiA variants with weaker binding of the N-acetylglucosamine unit either in substrate-binding site -3 (ChiA-W167A) or the product-binding site +1 (ChiA-W275A) were studied. Both ChiA variants showed increased off-rates and lower apparent processivity on α-chitin. The rate of the production of insoluble reducing groups on the reduced α-chitin was an order of magnitude higher than koff, suggesting that the enzyme can initiate several processive runs without leaving the substrate. On crystalline chitin, the general activity of the wild type enzyme was higher, and the difference was magnifying with hydrolysis time. On amorphous chitin, the variants clearly outperformed the wild type. A model is proposed whereby strong interactions with polymer in the substrate-binding sites (low off-rates) and strong binding of the product in the product-binding sites (high pushing potential) are required for the removal of obstacles, like disintegration of chitin microfibrils. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Salt bridge interactions within the β2integrin α7helix mediate force-induced binding and shear resistance ability.

    Science.gov (United States)

    Zhang, Xiao; Li, Linda; Li, Ning; Shu, Xinyu; Zhou, Lüwen; Lü, Shouqin; Chen, Shenbao; Mao, Debin; Long, Mian

    2018-01-01

    The functional performance of the αI domain α 7 helix in β 2 integrin activation depends on the allostery of the α 7 helix, which axially slides down; therefore, it is critical to elucidate what factors regulate the allostery. In this study, we determined that there were two conservative salt bridge interaction pairs that constrain both the upper and bottom ends of the α 7 helix. Molecular dynamics (MD) simulations for three β 2 integrin members, lymphocyte function-associated antigen-1 (LFA-1; α L β 2 ), macrophage-1 antigen (Mac-1; α M β 2 ) and α x β 2 , indicated that the magnitude of the salt bridge interaction is related to the stability of the αI domain and the strength of the corresponding force-induced allostery. The disruption of the salt bridge interaction, especially with double mutations in both salt bridges, significantly reduced the force-induced allostery time for all three members. The effects of salt bridge interactions of the αI domain α 7 helix on β 2 integrin conformational stability and allostery were experimentally validated using Mac-1 constructs. The results demonstrated that salt bridge mutations did not alter the conformational state of Mac-1, but they did increase the force-induced ligand binding and shear resistance ability, which was consistent with MD simulations. This study offers new insight into the importance of salt bridge interaction constraints of the αI domain α 7 helix and external force for β 2 integrin function. © 2017 Federation of European Biochemical Societies.

  14. Disruption of key NADH-binding pocket residues of the Mycobacterium tuberculosis InhA affects DD-CoA binding ability.

    Science.gov (United States)

    Shaw, Daniel J; Robb, Kirsty; Vetter, Beatrice V; Tong, Madeline; Molle, Virginie; Hunt, Neil T; Hoskisson, Paul A

    2017-07-05

    Tuberculosis (TB) is a global health problem that affects over 10 million people. There is an urgent need to develop novel antimicrobial therapies to combat TB. To achieve this, a thorough understanding of key validated drug targets is required. The enoyl reductase InhA, responsible for synthesis of essential mycolic acids in the mycobacterial cell wall, is the target for the frontline anti-TB drug isoniazid. To better understand the activity of this protein a series of mutants, targeted to the NADH co-factor binding pocket were created. Residues P193 and W222 comprise a series of hydrophobic residues surrounding the cofactor binding site and mutation of both residues negatively affect InhA function. Construction of an M155A mutant of InhA results in increased affinity for NADH and DD-CoA turnover but with a reduction in V max for DD-CoA, impairing overall activity. This suggests that NADH-binding geometry of InhA likely permits long-range interactions between residues in the NADH-binding pocket to facilitate substrate turnover in the DD-CoA binding region of the protein. Understanding the precise details of substrate binding and turnover in InhA and how this may affect protein-protein interactions may facilitate the development of improved inhibitors enabling the development of novel anti-TB drugs.

  15. Metal binding ability of glutathione transferases conserved between two animal species, the vanadium-rich ascidian Ascidia sydneiensis samea and the schistosome Schistosoma japonicum.

    Science.gov (United States)

    Yoshinaga, Masafumi; Ueki, Tatsuya; Michibata, Hitoshi

    2007-09-01

    Glutathione transferases (GSTs) are multifunctional enzymes found in many organisms. We recently identified vanadium-binding GSTs, designated AsGSTs, from the vanadium-rich ascidian, Ascidia sydneiensis samea. In this study, the metal-selectivity of AsGST-I was investigated. Immobilized metal ion affinity chromatography (IMAC) analysis revealed that AsGST-I binds to V(IV), Fe(III), and Cu(II) with high affinity in the following order Cu(II)>V(IV)>Fe(III), and to Co(II), Ni(II), and Zn(II) with low affinity. The GST activity of AsGST-I was inhibited dose-dependently by not V(IV) but Cu(II). A competition experiment demonstrated that the binding of V(IV) to AsGST-I was not inhibited by Cu(II). These results suggest that AsGST-I has high V(IV)-selectivity, which can confer the specific vanadium accumulation of ascidians. Because there are few reports on the metal-binding ability of GSTs, we performed the same analysis on SjGST (GST from the schistosome, Schistosoma japonicum). SjGST also demonstrated metal-binding ability although the binding pattern differed from that of AsGST-I. The GST activity of SjGST was inhibited by Cu(II) only, as that of AsGST-I. Our results indicate a possibility that metal-binding abilities of GSTs are conserved among organisms, at least animals, which is suggestive of a new role for these enzymes in metal homeostasis or detoxification.

  16. Multiple mechanisms responsible for strong Congo-red-binding variants of Escherichia coli O157:H7 strains.

    Science.gov (United States)

    Chen, Chin-Yi; Nguyen, Ly-Huong T; Cottrell, Bryan J; Irwin, Peter L; Uhlich, Gaylen A

    2016-03-01

    High variability in the expression of csgD-dependent, biofilm-forming and adhesive properties is common among Shiga toxin-producing Escherichia coli. Although many strains of serotype O157:H7 form little biofilm, conversion to stronger biofilm phenotypes has been observed. In this study, we screened different strains of serotype O157:H7 for the emergence of strong Congo-red (CR) affinity/biofilm-forming properties and investigated the underlying genetic mechanisms. Two major mechanisms which conferred stronger biofilm phenotypes were identified: mutations (insertion, deletion, single nucleotide change) in rcsB region and stx-prophage excision from the mlrA site. Restoration of the native mlrA gene (due to prophage excision) resulted in strong biofilm properties to all variants. Whereas RcsB mutants showed weaker CR affinity and biofilm properties, it provided more possibilities for phenotypic presentations through heterogenic sequence mutations. Published by Oxford University Press on behalf of FEMS 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  17. The cytotoxic effect of spiroflavanone derivatives, their binding ability to human serum albumin (HSA) and a DFT study on the mechanism of their synthesis

    Science.gov (United States)

    Budzisz, Elzbieta; Paneth, Piotr; Geromino, Inacrist; Muzioł, Tadeusz; Rozalski, Marek; Krajewska, Urszula; Pipiak, Paulina; Ponczek, Michał B.; Małecka, Magdalena; Kupcewicz, Bogumiła

    2017-06-01

    This paper examines the cytotoxic effect of nine compounds with spiropyrazoline structures, and determines the reaction mechanism between diazomethane and selected benzylideneflavanones, their lipophilicity, and their binding ability to human serum albumin. The cytotoxic effect was determined on two human leukaemia cell lines (HL-60 and NALM-6) and melanoma WM-115 cells, as well as on normal human umbilical vein endothelial cells (HUVEC). The highest cytotoxicity was exhibited by compound B7: it was found to have an IC50 of less than 10 μM for all three cancer cell lines, with five to 12-fold lower sensitivity against normal cells (HUVEC). All the compounds exhibit comparable affinity energy in human serum albumin binding (from -8.1 to -8.6 kcal mol-1) but vary in their binding sites depending on the substituent. X-ray crystallography of two derivatives confirmed their synthetic pathway, and their structures were carefully examined.

  18. More recent swine vesicular disease virus isolates retain binding to coxsackie-adenovirus receptor, but have lost the ability to bind human decay-accelerating factor (CD55).

    Science.gov (United States)

    Jimenez-Clavero, Miguel A; Escribano-Romero, Estela; Ley, Victoria; Spiller, O Brad

    2005-05-01

    Swine vesicular disease virus (SVDV) evolved from coxsackie B virus serotype 5 (CVB5) in the recent past, crossing the species barrier from humans to pigs. Here, SVDV isolates from early and recent outbreaks have been compared for their capacity to utilize the progenitor virus receptors coxsackie-adenovirus receptor (CAR) and decay-accelerating factor (DAF; CD55). Virus titre of CVB5 and SVDV isolates It'66 and UK'72 on human HeLa cells was reduced by pre-incubation with either anti-DAF or anti-CAR antibodies; however, recent SVDV isolates R1072, R1120 and SPA'93 did not infect HeLa cells lytically. CVB5 and SVDV infection of the pig cell line IB-RS-2 was inhibited completely by anti-CAR antibodies for all isolates, and no reduction was observed following pre-incubation of cells with anti-pig DAF antibodies. Expression of human DAF in the pig cell line IB-RS-2 enhanced the virus titre of early SVDV isolates by 25-fold, but had no effect on recent SVDV isolate titre. Binding of radiolabelled CVB5 to IB-RS-2 cells was increased seven- to eightfold by expression of human DAF and binding of early SVDV isolates was increased 1.2-1.3-fold, whereas no increase in binding by recent SVDV isolates was mediated by human DAF expression. Addition of soluble hDAF-Fc inhibited CVB5, but not SVDV, infection of pig cells. Pre-incubation of all viruses with soluble hCAR-Fc blocked infection of IB-RS-2 pig cells completely; titration of the amount of soluble hCAR-Fc required to block infection revealed that early isolate UK'72 was the least susceptible to inhibition, and the most recent isolate, SPA'93, was the most susceptible.

  19. role of gamma rays and carbohydrate sources on the ability of exopolysaccharides of lactic acid bacteria to bind malathion and seliton insecticides

    International Nuclear Information System (INIS)

    Hussien, H.H.; El-Shatoury, E.H.

    2010-01-01

    six lactic acid bacterial strains were isolated from yoghurt and cottage (unfatted cheese) cheese. only three strains namely lactococcus lactis, lactobacillus helveticus and streptococcus thermophilus were able to produce exopolysaccharides (EPS) when cultured in de Man-Rogosa-Sharpe broth (MRS) medium. MRS containing sucrose, instead of the original media containing glucose was found to be the best media for EPS production . lactococcus lactis, lactobacillus helveticus and streptococcus thermophilus produced 650, 644 and 649 mg/L EPS when grown on MRS containing sucrose compared with 567, 584 and 293 mg/L when they grown on MRS containing glucose, respectively. by increasing the concentration of sucrose in the medium, significant increases in EPS production was observed. maximum EPS was produced at 15 g/L sucrose for both lactococcus lactis and streptococcus thermophilus (900 mg/L). 800 mg/L EPS was produced by lactobacillus helveticus at 20 g/L sucrose. exposing the bacterial isolates to 1 kGy increased their ability to bind malathion. malathion binding of irradiated lactococcus lactis, lactobacillus helveticus and streptococcus thermophilus cells were 30 %, 19.8 % and 13 % more than non-irradiated controls. also exposing lactococcus lactis to 1 kGy increased their binding capacity to seliton by 33.8 % on the other land irradiating lactobacillus helveticus cells caused a decrease in the binding capacity of seliton by 5 % . irradiated and non-irradiated cells of streptococcus thermophilus failed to bind the seliton.

  20. Jun and Fos related gene products bind to and modulate the GPE I, a strong enhancer element of the rat glutathione transferase P gene.

    Science.gov (United States)

    Oridate, N; Nishi, S; Inuyama, Y; Sakai, M

    1994-10-18

    The rat glutathione transferase P gene has a strong enhancer element, termed GPE I, which is composed of a dyad of palindromicly oriented TPA (phorbol 12-O-tetradecanoate 13-acetate) responsive element (TRE)-like sequences. TRE is a binding sequence of the transcription factor AP-1, which consists of several closely related proteins belonging to the Jun and Fos family. The gel retardation experiments show that all the heterodimers formed between the Jun and Fos related gene products bind to the GPE I as well as to the TRE. In spite of the fact that the GPE I has a stronger activity than the TRE, the binding affinities of these heterodimers to the GPE I are much lower than to the TRE. Co-transfection studies of the reporter construct containing the GPE I and expression constructs of each of the Jun and Fos family cDNAs indicate that FosB and delta FosB repress transcription through the GPE I enhancer. These results suggests that some of Jun/Fos family may regulate the rat GST-P gene expression through the GPE I in vivo.

  1. Hyaluronic acid binding ability of human sperm reflects cellular maturity and fertilizing potential: selection of sperm for intracytoplasmic sperm injection.

    Science.gov (United States)

    Huszar, Gabor; Ozkavukcu, Sinan; Jakab, Attila; Celik-Ozenci, Ciler; Sati, G Leyla; Cayli, Sevil

    2006-06-01

    The current concepts of sperm biochemical markers and the central role of the HspA2 chaperone protein, a measure of sperm cellular maturity and fertilizing potential, are reviewed. Because HspA2 is a component of the synaptonemal complex, low HspA2 levels and increased frequency of chromosomal aneuploidies are related in diminished maturity sperm. We also suggest a relationship between HspA2 expression in elongating spermatids and events of late spermiogenesis, such as cytoplasmic extrusion and plasma membrane remodeling that aid the formation of the zona pellucida binding and hyaluronic acid binding sites. The presence of hyaluronic acid receptor on the plasma membrane of mature sperm, coupled with hyaluronic acid coated glass or plastic surfaces, facilitates testing of sperm function and selection of single mature sperm for intracytoplasmic sperm injection. The frequencies of sperm with chromosomal disomy are reduced approximately fourfold to fivefold in hyaluronic acid selected sperm compared with semen sperm, comparable to the increase in such abnormalities in intracytoplasmic sperm injection offspring. Hyaluronic acid binding also excludes immature sperm with cytoplasmic extrusion, persistent histones, and DNA chain breaks. Hyaluronic acid mediated sperm selection is a novel technique that is comparable to sperm zona pellucida binding. Hyaluronic acid selected sperm will also alleviate the risks related to intracytoplasmic sperm injection fertilization with sperm of diminished maturity that currently cause worldwide concern.

  2. Binding ability of a HHP-tagged protein towards Ni{sup 2+} studied by paramagnetic NMR relaxation: The possibility of obtaining long-range structure information

    Energy Technology Data Exchange (ETDEWEB)

    Jensen, Malene Ringkjo bing [University of Copenhagen, H.C. Orsted Institute, Department of Chemistry (Denmark); Lauritzen, Conni; Dahl, Soren Weis; Pedersen, John [Unizyme Laboratories A/S (Denmark); Led, Jens J. [University of Copenhagen, H.C. Orsted Institute, Department of Chemistry (Denmark)

    2004-06-15

    The binding ability of a protein with a metal binding tag towards Ni{sup 2+} was investigated by longitudinal paramagnetic NMR relaxation, and the possibility of obtaining long-range structure information from the paramagnetic relaxation was explored. A protein with a well-defined solution structure (Escherichia coli thioredoxin) was used as the model system, and the peptide His-His-Pro (HHP) fused to the N-terminus of the protein was used as the metal binding tag. It was found that the tag forms a stable dimer complex with the paramagnetic Ni{sup 2+} ion, where each metal ion binds two HHP-tagged protein molecules. However, it was also found that additional sites in the protein compete with the HHP-tag for the binding of the metal ion. These binding sites were identified as the side chain carboxylate groups of the aspartic and glutamic acid residues. Yet, the carboxylate groups bind the Ni{sup 2+} ions considerably weaker than the HHP-tag, and only protons spatially close to the carboxylate sites are affected by the Ni{sup 2+} ions bound to these groups. As for the protons that are unaffected by the carboxylate-bound Nisupb2+bsup> ions, it was found that the long-range distances derived from the paramagnetic relaxation enhancements are in good agreement with the solution structure of thioredoxin. Specifically, the obtained long-range paramagnetic distance constraints revealed that the dimer complex is asymmetric with different orientations of the two protein molecules relative to the Ni{sup 2+} ion. Abbreviations: NOE - nuclear Overhauser enhancement; E. coli - Escherichia coli; Trx - thioredoxin; IMAC - immobilized metal ion affinity chromatography; HT-DPPI - Polyhistidine-tagged dipeptidyl peptidase I; IPTG - isopropyl-1-thio-galactopyranoside; IR - inversion recovery; RMSD - root mean square deviation.

  3. Distinct Structural Features of G Protein-Coupled Receptor Kinase 5 (GRK5) Regulate Its Nuclear Localization and DNA-Binding Ability

    Science.gov (United States)

    Johnson, Laura R.; Robinson, James D.; Lester, Katrina N.; Pitcher, Julie A.

    2013-01-01

    G protein-coupled receptor kinases (GRKs) act to desensitize G protein-coupled receptors (GPCRs). In addition to this role at the plasma membrane, a nuclear function for GRK5, a member of the GRK4 subfamily of GRKs, has been reported. GRK5 phosphorylates and promotes the nuclear export of the histone deacetylase, HDAC5. Here we demonstrate that the possession of a nuclear localization sequence (NLS) is a common feature of GRK4 subfamily members (GRKs 4, 5 and 6). However, the location of the NLS and the ability of these GRKs to bind DNA in vitro are different. The NLSs of GRK5 and 6 bind DNA in vitro, whilst the NLS of GRK4 does not. Using mutants of GRK5 we identify the regions of GRK5 required for DNA-binding in vitro and nuclear localization in cells. The DNA-binding ability of GRK5 requires both the NLS and an N-terminal calmodulin (CaM)-binding site. A functional nuclear export sequence (NES), required for CaM-dependent nuclear export of the kinase, is also identified. Based on our observations we propose a model to explain how nuclear localization of GRK5 may be regulated. Notably, the nuclear localization of GRK5 and 6 is differentially regulated. These results suggest subfamily specific nuclear functions for the GRK4 subfamily members. Identification of GRK specific small molecule inhibitors of nuclear localization and/or function for the GRK4 subfamily may thus be an achievable goal. PMID:23658733

  4. Effect of amino acid ligands on the structure of iron porphyrins and their ability to bind oxygen.

    Science.gov (United States)

    Berryman, Victoria E J; Baker, Matthew G; Boyd, Russell J

    2014-06-26

    Density functional theory is used to study a series of model iron porphyrins in the gas phase. In the first part of this study, three range-separated hybrid density functionals developed by Chai and Head-Gordon were assessed; ωB97, ωB97X, and ωB97XD. The effects of including full Hartree-Fock exchange at long-range and dispersion corrections are reported with respect to the geometries and binding energies of oxygen to the iron porphyrin systems. The functionals all correctly predict the quintet ground state for the deoxy-iron porphyrins, where typically hybrid functionals fail and predict a triplet ground state. Including dispersion in ωB97XD is shown to give the best results for the O2 binding energy and geometrical parameters. The second part of the study employs ωB97XD to study iron porphine systems with different amino acids in the axial position. Geometrical parameters are reported and compared to experimental data, where available. Binding energies of the systems with oxygen are also reported and discussed.

  5. LGN blocks the ability of NuMA to bind and stabilize microtubules. A mechanism for mitotic spindle assembly regulation.

    Science.gov (United States)

    Du, Quansheng; Taylor, Laura; Compton, Duane A; Macara, Ian G

    2002-11-19

    LGN is closely related to a Drosophila protein, Partner of inscuteable (Pins), which is required for polarity establishment and asymmetric cell divisions during embryonic development. In mammalian cells, LGN binds with high affinity to the C-terminal tail of NuMA, a large nuclear protein that is required for spindle organization, and accumulates at the spindle poles during mitosis. LGN also regulates spindle organization, possibly through inhibition of NuMA function, but the mechanism of this effect has not yet been understood. Using mammalian cells, frog egg extracts, and in vitro assays, we now show that a small domain within the C terminus of NuMA stabilizes microtubules (MTs), and that LGN blocks stabilization. The nuclear localization signal adjacent to this domain is not involved in stabilization. NuMA can interact directly with MTs, and the MT binding domain on NuMA overlaps by ten amino acid residues with the LGN binding domain. We therefore propose that a simple steric exclusion model can explain the inhibitory effect of LGN on NuMA-dependent mitotic spindle organization.

  6. Repeated Vaccination of Cows with HIV Env gp140 during Subsequent Pregnancies Elicits and Sustains an Enduring Strong Env-Binding and Neutralising Antibody Response.

    Science.gov (United States)

    Heydarchi, Behnaz; Center, Rob J; Gonelli, Christopher; Muller, Brian; Mackenzie, Charlene; Khoury, Georges; Lichtfuss, Marit; Rawlin, Grant; Purcell, Damian F J

    2016-01-01

    An important feature of a potential vaccine against HIV is the production of broadly neutralising antibodies (BrNAbs) capable of potentially blocking infectivity of a diverse array of HIV strains. BrNAbs naturally arise in some HIV infected individuals after several years of infection and their serum IgG can neutralise various HIV strains across different subtypes. We previously showed that vaccination of cows with HIV gp140 AD8 trimers resulted in a high titre of serum IgG against HIV envelope (Env) that had strong BrNAb activity. These polyclonal BrNAbs concentrated into the colostrum during the late stage of pregnancy and can be harvested in vast quantities immediately after calving. In this study, we investigated the effect of prolonged HIV gp140 vaccination on bovine colostrum IgG HIV Env-binding and BrNAb activity over subsequent pregnancies. Repeated immunisation led to a maintained high titre of HIV Env specific IgG in the colostrum batches, but this did not increase through repeated cycles. Colostrum IgG from all batches also strongly competed with sCD4 binding to gp140 Env trimer and with human-derived monoclonal VRC01 and b12 BrNAbs that bind the CD4 binding site (CD4bs). Furthermore, competition neutralisation assays using RSC3 Env gp120 protein core and a derivative CD4bs mutant, RSC3 Δ371I/P363N, showed that CD4bs neutralising antibodies contribute to the neutralising activity of all batches of purified bovine colostrum IgG. This result indicates that the high IgG titre/avidity of anti-CD4bs antibodies with BrNAb activity was achieved during the first year of vaccination and was sustained throughout the years of repeated vaccinations in the cow tested. Although IgG of subsequent colostrum batches may have a higher avidity towards the CD4bs, the overall breadth in neutralisation was not enhanced. This implies that the boosting vaccinations over 4 years elicited a polyclonal antibody response that maintained the proportion of both neutralising and non

  7. Repeated Vaccination of Cows with HIV Env gp140 during Subsequent Pregnancies Elicits and Sustains an Enduring Strong Env-Binding and Neutralising Antibody Response.

    Directory of Open Access Journals (Sweden)

    Behnaz Heydarchi

    Full Text Available An important feature of a potential vaccine against HIV is the production of broadly neutralising antibodies (BrNAbs capable of potentially blocking infectivity of a diverse array of HIV strains. BrNAbs naturally arise in some HIV infected individuals after several years of infection and their serum IgG can neutralise various HIV strains across different subtypes. We previously showed that vaccination of cows with HIV gp140 AD8 trimers resulted in a high titre of serum IgG against HIV envelope (Env that had strong BrNAb activity. These polyclonal BrNAbs concentrated into the colostrum during the late stage of pregnancy and can be harvested in vast quantities immediately after calving. In this study, we investigated the effect of prolonged HIV gp140 vaccination on bovine colostrum IgG HIV Env-binding and BrNAb activity over subsequent pregnancies. Repeated immunisation led to a maintained high titre of HIV Env specific IgG in the colostrum batches, but this did not increase through repeated cycles. Colostrum IgG from all batches also strongly competed with sCD4 binding to gp140 Env trimer and with human-derived monoclonal VRC01 and b12 BrNAbs that bind the CD4 binding site (CD4bs. Furthermore, competition neutralisation assays using RSC3 Env gp120 protein core and a derivative CD4bs mutant, RSC3 Δ371I/P363N, showed that CD4bs neutralising antibodies contribute to the neutralising activity of all batches of purified bovine colostrum IgG. This result indicates that the high IgG titre/avidity of anti-CD4bs antibodies with BrNAb activity was achieved during the first year of vaccination and was sustained throughout the years of repeated vaccinations in the cow tested. Although IgG of subsequent colostrum batches may have a higher avidity towards the CD4bs, the overall breadth in neutralisation was not enhanced. This implies that the boosting vaccinations over 4 years elicited a polyclonal antibody response that maintained the proportion of both

  8. TRH receptor mobility in the plasma membrane is strongly affected by agonist binding and by interaction with some cognate signaling proteins.

    Science.gov (United States)

    Moravcova, Radka; Melkes, Barbora; Novotny, Jiri

    2018-02-01

    Extensive research has been dedicated to elucidating the mechanisms of signal transduction through different G protein-coupled receptors (GPCRs). However, relatively little is known about the regulation of receptor movement within the cell membrane upon ligand binding. In this study we focused our attention on the thyrotropin-releasing hormone (TRH) receptor that typically couples to G q/11 proteins. We monitored receptor diffusion in the plasma membrane of HEK293 cells stably expressing yellow fluorescent protein (YFP)-tagged TRH receptor (TRHR-YFP) by fluorescence recovery after photobleaching (FRAP). FRAP analysis indicated that the lateral movement of the TRH receptor was markedly reduced upon TRH binding as the value of its diffusion coefficient fell down by 55%. This effect was prevented by the addition of the TRH receptor antagonist midazolam. We also found that siRNA-mediated knockdown of G q/11 α, Gβ, β-arrestin2 and phospholipase Cβ1, but not of G i α1, β-arrestin1 or G protein-coupled receptor kinase 2, resulted in a significant decrease in the rate of TRHR-YFP diffusion, indicating the involvement of the former proteins in the regulation of TRH receptor behavior. The observed partial reduction of the TRHR-YFP mobile fraction caused by down-regulation of G i α1 and β-arrestin1 suggests that these proteins may also play distinct roles in THR receptor-mediated signaling. These results demonstrate for the first time that not only agonist binding but also abundance of some signaling proteins may strongly affect TRH receptor dynamics in the plasma membrane.

  9. Altered levels of laminin receptor mRNA in various human carcinoma cells that have different abilities to bind laminin

    DEFF Research Database (Denmark)

    Wewer, U M; Liotta, L A; Jaye, M

    1986-01-01

    The human laminin receptor was purified and molecularly cloned to investigate its biosynthetic regulation. Laminin receptor from normal and neoplastic tissue was preparatively affinity purified to homogeneity based on the high affinity of the receptor for laminin. The apparent molecular weight...... of the receptor from different carcinoma sources and from normal placental tissue is in the range of 68-72 kDa. Isoelectric focusing and two-dimensional gel electrophoresis indicated that the receptor protein consists of one major polypeptide chain with a pI value of 6.4 +/- 0.2. Laminin receptor cDNA clones were...... isolated after screening a human endothelial lambda gt11 cDNA library with a monoclonal antibody directed against a domain of the laminin receptor involved in ligand binding. Definitive identification of the cDNA clones was based on comparison of cDNA sequence with the amino acid sequence of a cyanogen...

  10. Ability of a Lactobacillus rhamnosus strain cultured in milk whey based medium to bind aflatoxin B1

    Directory of Open Access Journals (Sweden)

    Fernanda Bovo

    2014-09-01

    Full Text Available This study aimed to compare Lactobacillus rhamnosus growth in MRS (de Man, Rogosa and Sharpe broth and a culture medium containing milk whey (MMW and to evaluate aflatoxin B1 (AFB1 adsorption capacity by bacterial cells produced in both culture media. L. rhamnosus cells were cultivated in MRS broth and MMW (37 °C, 24 hours, and bacterial cell concentration was determined spectrophotometrically at 600 nm. AFB1 (1 µg/ml adsorption assays were conducted using 1 x 10(10 non-viable L. rhamnosus cells (121 °C, 15 minutes at pHs 3.0 and 6.0 and contact time of 60 minutes. AFB1 quantification was performed by High Performance Liquid Chromatography. Bacterial cell concentration in MMW was higher (9.84 log CFU/ml than that in MRS broth (9.63 log CFU/ml. There were no significant differences between AFB1 binding results at the same pH value (3.0 or 6.0 for the cells cultivated in MRS broth (46.0% and 35.8%, respectively and in MMW (43.7% and 25.8%, respectively, showing that MMW can adequately replace the MRS broth. Therefore, it can be concluded that the use of L. rhamnosus cells cultivated in MMW offers advantages such as reduction in large scale production costs, improvement of environmental sustainability, and being a practicable alternative for decontamination of food products susceptible to aflatoxin contamination.

  11. Catalytic and glycan-binding abilities of ppGalNAc-T2 are regulated by acetylation

    DEFF Research Database (Denmark)

    Zlocowski, Natacha; Sendra, Victor G; Lorenz, Virginia

    2011-01-01

    Post-translational acetylation is an important molecular regulatory mechanism affecting the biological activity of proteins. Polypeptide GalNAc transferases (ppGalNAc-Ts) are a family of enzymes that catalyze initiation of mucin-type O-glycosylation. All ppGalNAc-Ts in mammals are type II...... transmembrane proteins having a Golgi lumenal region that contains a catalytic domain with glycosyltransferase activity, and a C-terminal R-type ("ricin-like") lectin domain. We investigated the effect of acetylation on catalytic activity of glycosyltransferase, and on fine carbohydrate-binding specificity...... of the R-type lectin domain of ppGalNAc-T2. Acetylation effect on ppGalNAc-T2 biological activity in vitro was studied using a purified human recombinant ppGalNAc-T2. Mass spectrometric analysis of acetylated ppGalNAc-T2 revealed seven acetylated amino acids (K103, S109, K111, K363, S373, K521, and S529...

  12. An investigation of drug binding ability of a surface active ionic liquid: micellization, electrochemical, and spectroscopic studies.

    Science.gov (United States)

    Mahajan, Suruchi; Sharma, Rabia; Mahajan, Rakesh Kumar

    2012-12-18

    Keeping in view the use of surfactants in drug delivery, the interactions of surface active ionic liquids, such as 1-tetradecyl-3-methylimidazolium bromide (C(14)mimBr), with drugs, viz., dopamine hydrochloride (DH) and acetylcholine chloride (AC), have been studied, and the results are further compared with that of the structurally similar conventional cationic surfactant tetradecyltrimethylammonium bromide (TTAB). The micellization and interfacial behavior of C(14)mimBr and TTAB, in the presence of DH and AC, has been investigated from conductivity and surface tension measurements. Various micellar and adsorption characteristics for these drug-surfactant systems (DH/AC + C(14)mimBr/TTAB) have been investigated, indicating favorable interactions between them. The more detailed information regarding the nature of interactions between C(14)mimBr/TTAB and DH/AC is obtained from cyclic voltammetry (CV) and (1)H NMR measurements. CV measurements have been employed to evaluate the binding constant (K) and the Gibbs free energy change (ΔG) for these drug-surfactant complexes. These measurements indicate the existence of cation-π as well as π-π interactions between drugs and surfactants. A detailed analysis of chemical shifts of protons of drug molecules (DH and AC) in the presence of C(14)mimBr and TTAB has been done by (1)H NMR. The results obtained from (1)H NMR are in agreement with those of CV measurements. (1)H NMR studies along with the conductivity and surface tension measurements help in predicting the possible location of adsorption of these drug molecules in C(14)mimBr and TTAB micelles.

  13. A study on antigenicity and receptor-binding ability of fragment 450-650 of the spike protein of SARS coronavirus

    International Nuclear Information System (INIS)

    Zhao Jincun; Wang Wei; Yuan Zhihong; Jia Rujing; Zhao Zhendong; Xu Xiaojun; Lv Ping; Zhang Yan; Jiang Chengyu; Gao Xiaoming

    2007-01-01

    The spike (S) protein of SARS coronavirus (SARS-CoV) is responsible for viral binding with ACE2 molecules. Its receptor-binding motif (S-RBM) is located between residues 424 and 494, which folds into 2 anti-parallel β-sheets, β5 and β6. We have previously demonstrated that fragment 450-650 of the S protein (S450-650) is predominantly recognized by convalescent sera of SARS patients. The N-terminal 60 residues (450-510) of the S450-650 fragment covers the entire β6 strand of S-RBM. In the present study, we demonstrate that patient sera predominantly recognized 2 linear epitopes outside the β6 fragment, while the mouse antisera, induced by immunization of BALB/c mice with recombinant S450-650, mainly recognized the β6 strand-containing region. Unlike patient sera, however, the mouse antisera were unable to inhibit the infectivity of S protein-expressing (SARS-CoV-S) pseudovirus. Fusion protein between green fluorescence protein (GFP) and S450-650 (S450-650-GFP) was able to stain Vero E6 cells and deletion of the β6 fragment rendered the fusion product (S511-650-GFP) unable to do so. Similarly, recombinant S450-650, but not S511-650, was able to block the infection of Vero E6 cells by the SARS-CoV-S pseudovirus. Co-precipitation experiments confirmed that S450-650 was able to specifically bind with ACE2 molecules in lysate of Vero E6 cells. However, the ability of S450-510, either alone or in fusion with GFP, to bind with ACE2 was significantly poorer compared with S450-650. Our data suggest a possibility that, although the β6 strand alone is able to bind with ACE2 with relatively high affinity, residues outside the S-RBM could also assist the receptor binding of SARS-CoV-S protein

  14. In vitro ability of beer fermentation residue and yeast-based products to bind aflatoxin B1

    Directory of Open Access Journals (Sweden)

    Fernanda Bovo

    2015-06-01

    Full Text Available This study aimed to verify the in vitro ability of beer fermentation residue (BFR containing Saccharomyces cerevisiae cells and five commercial products that differed in the viability and integrity of S. cerevisiae cells to remove aflatoxin B1 (AFB1 from a citrate-phosphate buffer solution (CPBS. BFR was collected at a microbrewery and prepared by drying and milling. The commercial yeast-based products were as follows: inactive intact yeast cells from beer alcoholic fermentation, inactive intact yeast cells from sugarcane alcoholic fermentation, hydrolyzed yeast cells, yeast cell walls and active yeast cells. Adsorption assays were performed in CPBS spiked with 1.0 μg AFB1/mL at pH 3.0 and 6.0 for a contact time of 60 min at room temperature. Analysis of AFB1 in the samples was performed by high performance liquid chromatography. AFB1 adsorption by the products ranged from 45.5% to 69.4% at pH 3.0 and from 24.0% to 63.8% at pH 6.0. The higher percentages (p 0.05 from commercial products containing inactive intact yeast cells. The results of this trial indicate that the yeast-based products tested, especially the BFR, have potential applications in animal feeds as a suitable biological method for reducing the adverse effects of aflatoxins.

  15. In vitro ability of beer fermentation residue and yeast-based products to bind aflatoxin B1.

    Science.gov (United States)

    Bovo, Fernanda; Franco, Larissa Tuanny; Rosim, Roice Eliana; Barbalho, Ricardo; de Oliveira, Carlos Augusto Fernandes

    2015-06-01

    This study aimed to verify the in vitro ability of beer fermentation residue (BFR) containing Saccharomyces cerevisiae cells and five commercial products that differed in the viability and integrity of S. cerevisiae cells to remove aflatoxin B1 (AFB1) from a citrate-phosphate buffer solution (CPBS). BFR was collected at a microbrewery and prepared by drying and milling. The commercial yeast-based products were as follows: inactive intact yeast cells from beer alcoholic fermentation, inactive intact yeast cells from sugarcane alcoholic fermentation, hydrolyzed yeast cells, yeast cell walls and active yeast cells. Adsorption assays were performed in CPBS spiked with 1.0 μg AFB1/mL at pH 3.0 and 6.0 for a contact time of 60 min at room temperature. Analysis of AFB1 in the samples was performed by high performance liquid chromatography. AFB1 adsorption by the products ranged from 45.5% to 69.4% at pH 3.0 and from 24.0% to 63.8% at pH 6.0. The higher percentages (p 0.05) from commercial products containing inactive intact yeast cells. The results of this trial indicate that the yeast-based products tested, especially the BFR, have potential applications in animal feeds as a suitable biological method for reducing the adverse effects of aflatoxins.

  16. Novel Structure and Unexpected RNA-Binding Ability of the C-Terminal Domain of Herpes Simplex Virus 1 Tegument Protein UL21

    Energy Technology Data Exchange (ETDEWEB)

    Metrick, Claire M.; Heldwein, Ekaterina E. (Tufts-MED)

    2016-04-06

    Proteins forming the tegument layers of herpesviral virions mediate many essential processes in the viral replication cycle, yet few have been characterized in detail. UL21 is one such multifunctional tegument protein and is conserved among alphaherpesviruses. While UL21 has been implicated in many processes in viral replication, ranging from nuclear egress to virion morphogenesis to cell-cell spread, its precise roles remain unclear. Here we report the 2.7-Å crystal structure of the C-terminal domain of herpes simplex virus 1 (HSV-1) UL21 (UL21C), which has a unique α-helical fold resembling a dragonfly. Analysis of evolutionary conservation patterns and surface electrostatics pinpointed four regions of potential functional importance on the surface of UL21C to be pursued by mutagenesis. In combination with the previously determined structure of the N-terminal domain of UL21, the structure of UL21C provides a 3-dimensional framework for targeted exploration of the multiple roles of UL21 in the replication and pathogenesis of alphaherpesviruses. Additionally, we describe an unanticipated ability of UL21 to bind RNA, which may hint at a yet unexplored function.

    IMPORTANCEDue to the limited genomic coding capacity of viruses, viral proteins are often multifunctional, which makes them attractive antiviral targets. Such multifunctionality, however, complicates their study, which often involves constructing and characterizing null mutant viruses. Systematic exploration of these multifunctional proteins requires detailed road maps in the form of 3-dimensional structures. In this work, we determined the crystal structure of the C-terminal domain of UL21, a multifunctional tegument protein that is conserved among alphaherpesviruses. Structural analysis pinpointed surface areas of potential functional importance that provide a starting point for mutagenesis. In addition, the unexpected RNA-binding ability of UL21 may expand its functional repertoire

  17. Melatonin improves the fertilization ability of post-ovulatory aged mouse oocytes by stabilizing ovastacin and Juno to promote sperm binding and fusion.

    Science.gov (United States)

    Dai, Xiaoxin; Lu, Yajuan; Zhang, Mianqun; Miao, Yilong; Zhou, Changyin; Cui, Zhaokang; Xiong, Bo

    2017-03-01

    What are the underlying mechanisms of the decline in the fertilization ability of post-ovulatory aged oocytes? Melatonin improves the fertilization ability of post-ovulatory aged oocytes by reducing aging-induced reactive oxygen species (ROS) levels and inhibiting apoptosis and by maintaining the levels and localization of the fertilization proteins, ovastacin and Juno. Following ovulation, the quality of mammalian metaphase II oocytes irreversibly deteriorates over time with a concomitant loss of fertilization ability. Melatonin has been found to prevent post-ovulatory oocyte aging and extend the window for optimal fertilization in mice. Mouse oocytes were randomly assigned to three groups and aged in vitro for 0, 6, 12 and 24 h, respectively. Increasing concentrations of melatonin (10-9 M, 10-7 M, 10-5 M and 10-3 M) were added to the 24 h aging group. Sperm binding assays, in-vitro fertilization, immunofluorescent staining and western blotting were performed to investigate key regulators and events during fertilization of post-ovulatory aged mouse oocytes. We found that the actin cap which promotes a cortical granule (CG) free domain is disrupted with a re-distribution of CGs in the subcortex of aged oocytes. Ovastacin, a CG metalloendoprotease, is mis-located and prematurely exocytosed in aged oocytes with subsequent cleavage of the zona pellucida protein ZP2. This disrupts the sperm recognition domain and dramatically reduces the number of sperm binding to the zona pellucida. The abundance of Juno, the sperm receptor on the oocyte membrane, also is reduced in aged oocytes. Exposure of aged oocytes to melatonin significantly elevates in-vitro fertilization rates potentially by rescuing the above age-associated defects of fertilization, and reducing ROS and inhibiting apoptosis. N/A. We explored the mechanisms of the decline in fertilization ability decline in aged mouse oocytes, in vitro but not in vivo. Our findings may contribute to the development a more

  18. Evidence on How a Conserved Glycine in the Hinge Region of HapR Regulates Its DNA Binding Ability: LESSONS FROM A NATURAL VARIANT.

    Energy Technology Data Exchange (ETDEWEB)

    M Dongre; N Singh; C Dureja; N Peddada; A Solanki; F Ashish; S Raychaudhuri

    2011-12-31

    HapR has been recognized as a quorum-sensing master regulator in Vibrio cholerae. Because it controls a plethora of disparate cellular events, the absence of a functional HapR affects the physiology of V. cholerae to a great extent. In the current study, we pursued an understanding of an observation of a natural protease-deficient non-O1, non-O139 variant V. cholerae strain V2. Intriguingly, a nonfunctional HapR (henceforth designated as HapRV2) harboring a substitution of glycine to aspartate at position 39 of the N-terminal hinge region has been identified. An in vitro gel shift assay clearly suggested the inability of HapRV2 to interact with various cognate promoters. Reinstatement of glycine at position 39 restores DNA binding ability of HapRV2 (HapRV2G), thereby rescuing the protease-negative phenotype of this strain. The elution profile of HapRV2 and HapRV2G proteins in size-exclusion chromatography and their circular dichroism spectra did not reflect any significant differences to explain the functional discrepancies between the two proteins. To gain insight into the structure-function relationship of these two proteins, we acquired small/wide angle x-ray scattering data from samples of the native and G39D mutant. Although Guinier analysis and indirect Fourier transformation of scattering indicated only a slight difference in the shape parameters, structure reconstruction using dummy amino acids concluded that although HapR adopts a 'Y' shape similar to its crystal structure, the G39D mutation in hinge drastically altered the DNA binding domains by bringing them in close proximity. This altered spatial orientation of the helix-turn-helix domains in this natural variant provides the first structural evidence on the functional role of the hinge region in quorum sensing-related DNA-binding regulatory proteins of Vibrio spp.

  19. Construction of iron-polymer-graphene nanocomposites with low nonspecific adsorption and strong quenching ability for competitive immunofluorescent detection of biomarkers in GM crops.

    Science.gov (United States)

    Yin, Kaifei; Liu, Anran; Shangguan, Li; Mi, Li; Liu, Xu; Liu, Yuanjian; Zhao, Yuewu; Li, Ying; Wei, Wei; Zhang, Yuanjian; Liu, Songqin

    2017-04-15

    We developed a new immunofluorescent biosensor by utilizing a novel nanobody (Nb) and iron-polymer-graphene nanocomposites for sensitive detection of 5-enolpyruvylshikimate-3-phosphate synthase from Agrobacdterium tumefaciens strain CP4 (CP4-EPSPS), which considered as biomarkers of genetically modified (GM) crops. Specifically, we prepared iron doped polyacrylic hydrazide modified reduced graphene nanocomposites (Fe@RGO/PAH) by in-situ polymerization approach and subsequent a one-pot reaction with hydrazine. The resulting Fe@RGO/PAH nanocomposites displayed low nonspecific adsorption to analytes (11% quenching caused by nonspecific adsorption) due to electrostatic, energetic and steric effect of the nanocomposites. After Nb immobilizing, the as-prepared Fe@RGO/PAH/Nbs showed good selectivity and high quenching ability (92% quenching) in the presence of antigen (Ag) and polyethylene glycol (PEG) modified CdTe QDs (Ag/QDs@PEG), which is a nearly 4 fold than that of the unmodified GO in same condition. The high quenching ability of Fe@RGO/PAH/Nbs can be used for detection of CP4-EPSPS based on competitive immunoassay with a linearly proportional concentration range of 5-100ng/mL and a detection limit of 0.34ng/mL. The good stability, reproducibility and specificity of the resulting immunofluorescent biosensor are demonstrated and might open a new window for investigation of fluorescent sensing with numerous multifunctional graphene based materials. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Copper complexes based on chiral Schiff-base ligands: DNA/BSA binding ability, DNA cleavage activity, cytotoxicity and mechanism of apoptosis.

    Science.gov (United States)

    Zhou, Xue-Quan; Li, Yang; Zhang, Dong-Yan; Nie, Yan; Li, Zong-Jin; Gu, Wen; Liu, Xin; Tian, Jin-Lei; Yan, Shi-Ping

    2016-05-23

    Four copper(II) complexes with chiral Schiff-base ligands, [Cu(R-L(1))2]·EtOAc (1) and [Cu(S-L(1))2]·EtOAc (2), [Cu(R-L(2))2]·EtOAc (3) and [Cu(S-L(2))2]·EtOAc (4), (R/S-HL(1) = (R/S)-(1-naththyl)-salicylaldimine, R/S-HL(2) = (R/S)-(1-naththyl)-3-methoxysalicylaldimine, EtOAc = ethyl acetate) were synthesized to serve as artificial nucleases and anticancer drugs. All complexes and R/S-HL(1) ligands were structurally characterized by X-ray crystallography. The interaction of these complexes with CT-DNA was researched via several spectroscopy methods, which indicates that complexes bind to CT-DNA by moderate intercalation binding mode. Moreover, DNA cleavage experiments revealed that the complexes exhibited remarkable DNA cleavage activities in the presence of H2O2via the generation of hydroxyl radical. Particularly, complex 4 also could nick DNA with the production of (1)O2. And all complexes exhibited excellent cytotoxicity to MDA-MB-231, A549 and Hela human cancer cells in micromole magnitude. Furthermore, complex 4 exhibited comparable cytotoxic effect to cisplatin against the proliferation of MDA-MB-231 and A549 cancer cells, as well as showed better anticancer ability to the three cancer cells than the other complexes. The results of cell cycle analysis indicated that complexes 3-4 could induce G2/M phase cell cycle arrest. Furthermore, MDA-MB-231 cells treated with 3 and 4 were subjected to apoptosis and death by generation of ROS and the activation of caspase-3. Interestingly, the chiral complexes 3 and 4 may induce cell apoptosis through extrinsic and mitochondrial intrinsic pathway, respectively. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  1. Melanin protects melanocytes and keratinocytes against H2O2-induced DNA strand breaks through its ability to bind Ca2+.

    Science.gov (United States)

    Hoogduijn, M J; Cemeli, E; Ross, K; Anderson, D; Thody, A J; Wood, J M

    2004-03-10

    Reactive oxygen species (ROS) such as hydrogen peroxide (H(2)O(2)) are produced in the skin under the influence of UV radiation. These compounds are highly reactive and can induce DNA lesions in epidermal cells. Melanin is considered to protect human skin against DNA damage by absorbing UV radiation. We have investigated whether melanin can, in addition, offer protection against the effects of H(2)O(2) in human melanocytes and HaCaT keratinocytes. In the present study, it was shown that 40 and 100 microM H(2)O(2) increased the number of DNA strand breaks as measured using the comet assay, in melanocytes of Caucasian origin. In melanocytes of the same origin in which melanin levels were increased by culturing in presence of 10 mM NH(4)Cl and elevated l-tyrosine, H(2)O(2)-induced DNA damage was reduced compared to that in control melanocytes. Similarly, HaCaT cells that were loaded with melanin were better protected against H(2)O(2)-induced DNA strand breaks than control HaCaT cells. These protective effects of melanin were mimicked by the intracellular Ca(2+)-chelator BAPTA. Thus, BAPTA reduced the level of H(2)O(2)-induced DNA strand breaks in melanocytes. Like BAPTA, melanin is known to be a potent chelator of Ca(2+) and this was confirmed in the present study. It was shown that melanin levels in melanocytic cells correlated directly with intracellular Ca(2+) binding capacity and, in addition, correlated inversely with H(2)O(2)-induced increases in intracellular Ca(2+). Our results show that melanin may have an important role in regulating intracellular Ca(2+) homeostasis and it is suggested that melanin protects against H(2)O(2)-induced DNA strand breaks in both melanocytes and keratinocytes and through its ability to bind Ca(2+).

  2. The ability of AIF-1 to activate human vascular smooth muscle cells is lost by mutations in the EF-hand calcium-binding region

    International Nuclear Information System (INIS)

    Autieri, Michael V.; Chen Xing

    2005-01-01

    Allograft Inflammatory Factor-1 (AIF-1) is a cytoplasmic calcium-binding protein expressed in vascular smooth muscle cells (VSMC) in response to injury or cytokine stimulation. AIF-1 contains a partially conserved EF-hand calcium-binding domain, and participates in VSMC activation by activation of Rac1 and induction of Granulocyte-Colony Stimulating Factor (G-CSF) expression; however, the mechanism whereby AIF-1 mediates these effects is presently uncharacterized. To determine if calcium binding plays a functional role in AIF-1 activity, a single site-specific mutation was made in the EF-hand calcium-binding domain to abrogate binding of calcium (AIF-1ΔA), which was confirmed by calcium overlay. Functionally, similar to wild-type AIF-1, AIF-1ΔA was able to polymerize F-actin in vitro. However, in contrast to wild-type AIF-1, over-expression of AIF-1ΔA was unable to increase migration or proliferation of primary human VSMC. Further, it was unable to activate Rac1, or induce G-CSF expression to the degree as wild-type AIF-1. Taken together, modification of the wild-type EF-hand domain and native calcium-binding activity results in a loss of AIF-1 function. We conclude that appropriate calcium-binding potential is critical in AIF-1-mediated effects on VSMC pathophysiology, and that AIF-1 activity is mediated by Rac1 activation and G-CSF expression

  3. Silencing the Odorant Binding Protein RferOBP1768 Reduces the Strong Preference of Palm Weevil for the Major Aggregation Pheromone Compound Ferrugineol

    Directory of Open Access Journals (Sweden)

    Binu Antony

    2018-03-01

    Full Text Available In insects, perception of the environment—food, mates, and prey—is mainly guided by chemical signals. The dynamic process of signal perception involves transport to odorant receptors (ORs by soluble secretory proteins, odorant binding proteins (OBPs, which form the first stage in the process of olfactory recognition and are analogous to lipocalin family proteins in vertebrates. Although OBPs involved in the transport of pheromones to ORs have been functionally identified in insects, there is to date no report for Coleoptera. Furthermore, there is a lack of information on olfactory perception and the molecular mechanism by which OBPs participate in the transport of aggregation pheromones. We focus on the red palm weevil (RPW Rhynchophorus ferrugineus, the most devastating quarantine pest of palm trees worldwide. In this work, we constructed libraries of all OBPs and selected antenna-specific and highly expressed OBPs for silencing through RNA interference. Aggregation pheromone compounds, 4-methyl-5-nonanol (ferrugineol and 4-methyl-5-nonanone (ferruginone, and a kairomone, ethyl acetate, were then sequentially presented to individual RPWs. The results showed that antenna-specific RferOBP1768 aids in the capture and transport of ferrugineol to ORs. Silencing of RferOBP1768, which is responsible for pheromone binding, significantly disrupted pheromone communication. Study of odorant perception in palm weevil is important because the availability of literature regarding the nature and role of olfactory signaling in this insect may reveal likely candidates representative of animal olfaction and, more generally, of molecular recognition. Knowledge of OBPs recognizing the specific pheromone ferrugineol will allow for designing biosensors for the detection of this key compound in weevil monitoring in date palm fields.

  4. Silencing the Odorant Binding ProteinRferOBP1768Reduces the Strong Preference of Palm Weevil for the Major Aggregation Pheromone Compound Ferrugineol.

    Science.gov (United States)

    Antony, Binu; Johny, Jibin; Aldosari, Saleh A

    2018-01-01

    In insects, perception of the environment-food, mates, and prey-is mainly guided by chemical signals. The dynamic process of signal perception involves transport to odorant receptors (ORs) by soluble secretory proteins, odorant binding proteins (OBPs), which form the first stage in the process of olfactory recognition and are analogous to lipocalin family proteins in vertebrates. Although OBPs involved in the transport of pheromones to ORs have been functionally identified in insects, there is to date no report for Coleoptera. Furthermore, there is a lack of information on olfactory perception and the molecular mechanism by which OBPs participate in the transport of aggregation pheromones. We focus on the red palm weevil (RPW) Rhynchophorus ferrugineus , the most devastating quarantine pest of palm trees worldwide. In this work, we constructed libraries of all OBPs and selected antenna-specific and highly expressed OBPs for silencing through RNA interference. Aggregation pheromone compounds, 4-methyl-5-nonanol (ferrugineol) and 4-methyl-5-nonanone (ferruginone), and a kairomone, ethyl acetate, were then sequentially presented to individual RPWs. The results showed that antenna-specific RferOBP1768 aids in the capture and transport of ferrugineol to ORs. Silencing of RferOBP1768 , which is responsible for pheromone binding, significantly disrupted pheromone communication. Study of odorant perception in palm weevil is important because the availability of literature regarding the nature and role of olfactory signaling in this insect may reveal likely candidates representative of animal olfaction and, more generally, of molecular recognition. Knowledge of OBPs recognizing the specific pheromone ferrugineol will allow for designing biosensors for the detection of this key compound in weevil monitoring in date palm fields.

  5. Polyester monomers lack ability to bind and activate both androgenic and estrogenic receptors as determined by in vitro and in silico methods.

    Science.gov (United States)

    Osimitz, Thomas G; Welsh, William J; Ai, Ni; Toole, Colleen

    2015-01-01

    The paper presents results from the screening of seven monomers used by Eastman Chemical to make various polymers. Ethylene glycol, diethylene glycol, polytetramethylene glycol, isophthalic acid, monosodium-5-sulfoisophthalic acid, 1,4-cyclohexanedicarboxylic acid, and dimethylcyclohexanedicarboxylate were screened for potential androgenicity or estrogenicity. The following studies were conducted: QSAR for binding to the AR and ER, in vitro Androgen Receptor Binding Assay, in vitro Estrogen Receptor Binding Assays (alpha and beta isoforms), in vitro Androgen Receptor Transactivation Assay in human cells, and in vitro Estrogen Receptor Transactivation Assay in human cells. None of the QSAR models predicted that any of the monomers possessed appreciable binding affinity for either AR or ER. Binding assays showed no evidence of interaction with either the AR or the alpha or beta ER receptors. Similarly, the AR and ER transactivation assays were negative. Moreover, six of the seven monomers have been subjected to 13-week and developmental toxicity studies in rats with no androgen- or estrogen-related effects being noted. Given the negative results of the in vitro screening assays (except PMG which demonstrated cytotoxicity) as well as available repeated dose and developmental and reproductive studies, the data suggest that none of the monomers tested exhibit androgenic or estrogenic hazards. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Vacuolar ATPases, like F1,F0-ATPases, show a strong dependence of the reaction velocity on the binding of more than one ATP per enzyme

    International Nuclear Information System (INIS)

    Kasho, V.N.; Boyer, P.D.

    1989-01-01

    Recent studies with vacuolar ATPases have shown that multiple copies catalytic subunits are present and that these have definite sequence homology with catalytic subunits of the F 1 , F 0 -ATPases. Experiments are reported that assess whether the vacuolar ATPases may have the unusual catalytic cooperativity with sequential catalytic site participation as in the binding change mechanism for the F 1 ,F 0 -ATPases. The extent of reversal of bound ATP hydrolysis to bound ADP and P i as medium ATP concentration was lowered was determined by 18 O-exchange measurements for yeast and neurospora vacuolar ATPases. The results show a pronounced increase in the extent of water oxygen incorporation into the P i formed as ATP concentration is decreased to the micromolar range. The F 1 ,F 0 -ATPase from neurospora mitochondria showed an event more pronounced modulation, similar to that of other F 1 -type ATPases. The vacuolar ATPases thus appear to have a catalytic mechanism quite analogous to that of the F 1 ,F 0 -ATPases

  7. Host-Guest Complexes of Cyclodextrins and Nanodiamonds as a Strong Non-Covalent Binding Motif for Self-Assembled Nanomaterials.

    Science.gov (United States)

    Schibilla, Frauke; Voskuhl, Jens; Fokina, Natalie A; Dahl, Jeremy E P; Schreiner, Peter R; Ravoo, Bart Jan

    2017-11-13

    We report the inclusion of carboxy- and amine-substituted molecular nanodiamonds (NDs) adamantane, diamantane, and triamantane by β-cyclodextrin and γ-cyclodextrin (β-CD and γ-CD), which have particularly well-suited hydrophobicity and symmetry for an optimal fit of the host and guest molecules. We studied the host-guest interactions in detail and generally observed 1:1 association of the NDs with the larger γ-CD cavity, but observed 1:2 association for the largest ND in the series (triamantane) with β-CD. We found higher binding affinities for carboxy-substituted NDs than for amine-substituted NDs. Additionally, cyclodextrin vesicles (CDVs) were decorated with d-mannose by using adamantane, diamantane, and triamantane as non-covalent anchors, and the resulting vesicles were compared with the lectin concanavalin A in agglutination experiments. Agglutination was directly correlated to the host-guest association: adamantane showed lower agglutination than di- or triamantane with β-CDV and almost no agglutination with γ-CDV, whereas high agglutination was observed for di- and triamantane with γ-CDV. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Synthesis, characterization, crystal structure, DNA/BSA binding ability and antibacterial activity of asymmetric europium complex based on 1,10- phenanthroline

    Science.gov (United States)

    Alfi, Nafiseh; Khorasani-Motlagh, Mozhgan; Rezvani, Ali Reza; Noroozifar, Meissam; Molčanov, Krešimir

    2017-06-01

    A heteroleptic europium coordination compound formulated as [Eu(phen)2(OH2)2(Cl)2](Cl)(H2O) (phen = 1,10-phenanthroline), has been synthesized and characterized by elemental analysis, FT-IR spectroscopy, and single-crystal X-ray diffractometer. Crystal structure analysis reveals the complex is crystallized in orthorhombic system with Pca21 space group. Electronic absorption and various emission methods for investigation of the binding system of europium(III) complex to Fish Salmon deoxyribonucleic acid (FS-DNA) and Bovamin Serum Albumin (BSA) have been explored. Furthermore, the binding constants, binding sites and the corresponding thermodynamic parameters of the interaction system based on the van't Hoff equation for FS-DNA and BSA were calculated. The thermodynamic parameters reflect the exothermic nature of emission process (ΔH°<0 and ΔS°<0). The experimental results seem to indicate that the [Eu(phen)2(OH2)2(Cl)2](Cl)(H2O) bound to FS-DNA by non-intercalative mode which the groove binding is preferable mode. Also, the complex exhibits a brilliant antimicrobial activity in vitro against standard bacterial strains.

  9. Frataxin directly stimulates mitochondrial cysteine desulfurase by exposing substrate-binding sites, and a mutant Fe-S cluster scaffold protein with frataxin-bypassing ability acts similarly.

    Science.gov (United States)

    Pandey, Alok; Gordon, Donna M; Pain, Jayashree; Stemmler, Timothy L; Dancis, Andrew; Pain, Debkumar

    2013-12-27

    For iron-sulfur (Fe-S) cluster synthesis in mitochondria, the sulfur is derived from the amino acid cysteine by the cysteine desulfurase activity of Nfs1. The enzyme binds the substrate cysteine in the pyridoxal phosphate-containing site, and a persulfide is formed on the active site cysteine in a manner depending on the accessory protein Isd11. The persulfide is then transferred to the scaffold Isu, where it combines with iron to form the Fe-S cluster intermediate. Frataxin is implicated in the process, although it is unclear where and how, and deficiency causes Friedreich ataxia. Using purified proteins and isolated mitochondria, we show here that the yeast frataxin homolog (Yfh1) directly and specifically stimulates cysteine binding to Nfs1 by exposing substrate-binding sites. This novel function of frataxin does not require iron, Isu1, or Isd11. Once bound to Nfs1, the substrate cysteine is the source of the Nfs1 persulfide, but this step is independent of frataxin and strictly dependent on Isd11. Recently, a point mutation in Isu1 was found to bypass many frataxin functions. The data presented here show that the Isu1 suppressor mimics the frataxin effects on Nfs1, explaining the bypassing activity. We propose a regulatory mechanism for the Nfs1 persulfide-forming activity. Specifically, at least two separate conformational changes must occur in the enzyme for optimum activity as follows: one is mediated by frataxin interaction that exposes the "buried" substrate-binding sites, and the other is mediated by Isd11 interaction that brings the bound substrate cysteine and the active site cysteine in proximity for persulfide formation.

  10. Effect of single physical exercise at 35% VO2 max. intensity on secretion activity of pancreas β-cells and 125J-insulin binding and degradation ability by erythrocyte receptors in children with diabetes mellitus

    International Nuclear Information System (INIS)

    Szczesniak, L.; Rychlewski, T.; Banaszak, F.; Kasprzak, Z.; Walczak, M.

    1994-01-01

    In this report we showed research results of effect of single physical exercise on cycloergometer at 35% VO 2 max. intensity on 125 J-insulin binding and degradation ability by erythrocyte receptors in children with diabetes mellitus, secreting and non-secreting endogenous insulin. Insulin secretion was evaluated by measurement of C-peptide by Biodet test (Serono) of sensitivity threshold at 0.3 μg/ml. We indicated in children non-secreting endogenous insulin (n=32) there is statistically essential lower 125 J-insulin binding with erythrocyte receptor in comparison to children group with C-peptide. Physical exercise on cycloergometer at 35% VO 2 max. intensity caused different reaction in range of physiological indices, like acid-base parameters, level of glucose and 125 J-insulin binding and degradation. In children devoid of endogenous insulin we indicated statistically nonessential changes in 125 J-insulin degradation by non-impaired erythrocytes and by hemolizate, as well. 125 J-insulin binding after physical exercise increased in both groups, though change amplitude was different. Obtained research results allowed us to conclude, in children with I-type diabetes, that in dependence of impairment degree of pancreas βcells sensitivity of insulin receptor and/or number of receptors on erythrocyte surface is different

  11. Activation of the DNA-binding ability of latent p53 protein by protein kinase C is abolished by protein kinase CK2

    Czech Academy of Sciences Publication Activity Database

    Pospíšilová, Š.; Brázda, Václav; Kuchaříková, Kateřina; Luciani, M. G.; Hupp, T. R.; Skládal, P.; Paleček, Emil; Vojtěšek, B.

    2004-01-01

    Roč. 378, č. 3 (2004), s. 939-947 ISSN 0264-6021 R&D Projects: GA ČR GA301/00/P094; GA ČR GA301/02/0831; GA ČR GA301/00/D001; GA AV ČR IAB5004203; GA MŠk OC 518.30 Institutional research plan: CEZ:AV0Z5004920 Keywords : activation * cdk2/ cyclin A * DNA binding Subject RIV: BO - Biophysics Impact factor: 4.278, year: 2004

  12. Diarctigenin, a lignan constituent from Arctium lappa, down-regulated zymosan-induced transcription of inflammatory genes through suppression of DNA binding ability of nuclear factor-kappaB in macrophages.

    Science.gov (United States)

    Kim, Byung Hak; Hong, Seong Su; Kwon, Soon Woo; Lee, Hwa Young; Sung, Hyeran; Lee, In-Jeong; Hwang, Bang Yeon; Song, Sukgil; Lee, Chong-Kil; Chung, Daehyun; Ahn, Byeongwoo; Nam, Sang-Yoon; Han, Sang-Bae; Kim, Youngsoo

    2008-11-01

    Diarctigenin was previously isolated as an inhibitor of nitric oxide (NO) production in macrophages from the seeds of Arctium lappa used as an alternative medicine for the treatment of inflammatory disorders. However, little is known about the molecular basis of these effects. Here, we demonstrated that diarctigenin inhibited the production of NO, prostaglandin E(2), tumor necrosis factor-alpha, and interleukin (IL)-1beta and IL-6 with IC(50) values of 6 to 12 miciroM in zymosan- or lipopolysaccharide-(LPS) activated macrophages. Diarctigenin attenuated zymosan-induced mRNA synthesis of inducible NO synthase (iNOS) and also inhibited promoter activities of iNOS and cytokine genes in the cells. Because nuclear factor (NF)-kappaB plays a pivotal role in inflammatory gene transcription, we next investigated the effect of diarctigenin on NF-kappaB activation. Diarctigenin inhibited the transcriptional activity and DNA binding ability of NF-kappaB in zymosan-activated macrophages but did not affect the degradation and phosphorylation of inhibitory kappaB (IkappaB) proteins. Moreover, diarctigenin suppressed expression vector NF-kappaB p65-elicited NF-kappaB activation and also iNOS promoter activity, indicating that the compound could directly target an NF-kappa-activating signal cascade downstream of IkappaB degradation and inhibit NF-kappaB-regulated iNOS expression. Diarctigenin also inhibited the in vitro DNA binding ability of NF-kappaB but did not affect the nuclear import of NF-kappaB p65 in the cells. Taken together, diarctigenin down-regulated zymosan- or LPS-induced inflammatory gene transcription in macrophages, which was due to direct inhibition of the DNA binding ability of NF-kappaB. Finally, this study provides a pharmacological potential of diarctigenin in the NF-kappaB-associated inflammatory disorders.

  13. A sugar beet chlorophyll a/b binding protein promoter void of G-box like elements confers strong and leaf specific reporter gene expression in transgenic sugar beet

    Directory of Open Access Journals (Sweden)

    Kloos Dorothee U

    2004-12-01

    Full Text Available Abstract Background Modification of leaf traits in sugar beet requires a strong leaf specific promoter. With such a promoter, expression in taproots can be avoided which may otherwise take away available energy resources for sugar accumulation. Results Suppression Subtractive Hybridization (SSH was utilized to generate an enriched and equalized cDNA library for leaf expressed genes from sugar beet. Fourteen cDNA fragments corresponding to thirteen different genes were isolated. Northern blot analysis indicates the desired tissue specificity of these genes. The promoters for two chlorophyll a/b binding protein genes (Bvcab11 and Bvcab12 were isolated, linked to reporter genes, and transformed into sugar beet using promoter reporter gene fusions. Transient and transgenic analysis indicate that both promoters direct leaf specific gene expression. A bioinformatic analysis revealed that the Bvcab11 promoter is void of G-box like regulatory elements with a palindromic ACGT core sequence. The data indicate that the presence of a G-box element is not a prerequisite for leaf specific and light induced gene expression in sugar beet. Conclusions This work shows that SSH can be successfully employed for the identification and subsequent isolation of tissue specific sugar beet promoters. These promoters are shown to drive strong leaf specific gene expression in transgenic sugar beet. The application of these promoters for expressing resistance improving genes against foliar diseases is discussed.

  14. Combination of size selective binding ability of 18-crown-6 dissolved in aqueous phase and extractive properties of an amic acid; toward enhancement of rare earths separation

    International Nuclear Information System (INIS)

    Safarbali, Reyhaneh; Yaftian, Mohammad Reza; Ghorbanloo, Massomeh; Zamani, Abbasali

    2016-01-01

    The separation of La(III), Eu(III) and Er(III) ions by an amic acid, N,N-dioctyldiglycolamic acid (HL), dissolved in carbon tetrachloride has been improved in the presence of 18-crown-6 (18C6) in aqueous phase as a selective masking agent. The interaction between the studied metal ions and 18C6 resulted a shift in the extraction curve of the studied metal ions versus pH toward higher pH region. The displacement of the extraction curves was more pronounced for lanthanum ions and was varied as La(III) > Eu(III) > Er(III). This order of complexing ability of 18C6 toward the studied ions was attributed to the size adaptation of the ions and that of the crown ether cavity. The stability constants of the lanthanide-crown ether complexes in aqueous phase were evaluated. The influence of temperature on the extraction of studied metal ions from aqueous phase in the absence and the presence of 18C6 was tested in the range 298-308 K. This investigation allowed evaluating the thermodynamic parameters associated with the extraction process and those of the complexation of cations by 18C6 in the aqueous phase.

  15. The role of the class A scavenger receptors, SR-A and MARCO, in the immune system. Part 1. The structure of receptors, their ligand binding repertoires and ability to initiate intracellular signaling

    Directory of Open Access Journals (Sweden)

    Szczepan Józefowski

    2012-02-01

    Full Text Available  Recognition of pathogens by innate immune cells is mediated by pattern recognition receptors (PRR, which include scavenger receptors (SR. The class A SR, SR-A/CD204 and MARCO, are characterized by the presence of collagenous and SR cysteine-rich domains in their extracellular portions. Both receptors are expressed mainly on macrophages and dendritic cells. Thanks to their ability to bind to a wide range of polyanionic ligands, the class A SR may participate in numerous functions of these cells, such as endocytosis, and adhesion to extracellular matrix and to other cells. Among SR-A ligands are oxidized lipoproteins and β-amyloid fibrils, which link SR-A to the pathogenesis of arteriosclerosis and Alzheimer’s disease. Despite the demonstration of class A SR involvement in so many processes, the lack of selective ligands precluded reaching definite conclusions concerning their signaling abilities. Using specific receptor ligation with antibodies, we showed that SR-A and MARCO trigger intracellular signaling, modulating pro-inflammatory and microbicidal activities of macrophages. Surprisingly, despite similarities in structure and ligand binding repertoires, SR-A and MARCO exert opposite effects on interleukin-12 (IL-12 production in macrophages. SR-A ligation also stimulated H2O2 and IL-10 production, but had no effect on the release of several other cytokines. These limited effects of specific SR-A ligation contrast with generalized enhancement of immune responses observed in SR-A-deficient mice. Recent studies have revealed that many of these effects of SR-A deficiency may be caused by compensatory changes in the expression of other receptors and/or disinhibition of signal transduction from receptors belonging to the Toll/IL-1R family, rather than by the loss of the receptor function of SR-A.

  16. Technetium-99m labeling and fibronectin binding ability of Corynebacterium diphtheriae; Marcacao de Corynebacterium diphtheriae com Tecnecio-99m e avaliacao da capacidade de ligacao a fibronectina de plasma humano

    Energy Technology Data Exchange (ETDEWEB)

    Souza, S.M.S.; Nagao, P.E.; Bernardo-Filho, M. [Universidade do Estado do Rio de Janeiro, RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes; Pereira, G.A.; Napoleao, F.; Andrade, A.F.B.; Hirata Junior, R.; Mattos-Guaraldi, A.L. [Universidade do Estado do Rio de Janeiro, RJ (Brazil). Faculdade de Ciencias Medicas

    2004-04-15

    The use of radionuclides has permitted advances in areas of clinical and scientific knowledge. Several molecules and cells have been labelled with Technetium-99m ({sup 99m}Tc). The stannous chloride (SnCl{sub 2}) has a significant influence on the labeling and stability of {sup 99m}Tc radiotracers. The frequent risk of diphtheria epidemics has intensified interest in the virulence factors of Corynebacterium diphtheriae. Although studies have looked at potential adhesins including haemagglutinins and exposed sugar residues, the molecular basis of mechanisms of adherence remains unclear. Adherence of pathogens to mammalian tissues may be mediated by fibronectin (FN) found in body fluids, matrix of connective tissues, and cell surfaces. In the present study we evaluated the binding ability to human plasma FN by {sup 99m}Tc labeled-C.diphtheriae. Due to adverse effects of stannous ions, microorganisms were submitted to survival and filamentation induction assays. Data showed a dose dependent susceptibility to SnCl{sub 2} bactericidal effects. Cell filamentation was observed for concentrations of SnCl{sub 2} > 110 {mu}g/ml. Adherence levels of {sup 99m}Tc labelled 241strain to coverslips coated with 20 {mu}g/ml FN were higher (P = 0.0037) than coated with bovine serum albumin. FN binding by the sucrose fermenting 241 C. diphtheriae strain (8.9% + 2.6) was significantly lower (P=0.0139) than Staphylococcus aureus Cowan I strain (34.1% {+-} 1.2). Therefore, bacterial {sup 99m}Tc labeling represents an additional tool that may contribute to the comprehension of C. diphtheriae interactions with host receptors such as FN that act as biological organizers by holding bacterial cells in position and guiding their migration. (author)

  17. Behavior of solvent-exposed hydrophobic groove in the anti-apoptotic Bcl-XL protein: clues for its ability to bind diverse BH3 ligands from MD simulations.

    Directory of Open Access Journals (Sweden)

    Dilraj Lama

    Full Text Available Bcl-XL is a member of Bcl-2 family of proteins involved in the regulation of intrinsic pathway of apoptosis. Its overexpression in many human cancers makes it an important target for anti-cancer drugs. Bcl-XL interacts with the BH3 domain of several pro-apoptotic Bcl-2 partners. This helical bundle protein has a pronounced hydrophobic groove which acts as a binding region for the BH3 domains. Eight independent molecular dynamics simulations of the apo/holo forms of Bcl-XL were carried out to investigate the behavior of solvent-exposed hydrophobic groove. The simulations used either a twin-range cut-off or particle mesh Ewald (PME scheme to treat long-range interactions. Destabilization of the BH3 domain-containing helix H2 was observed in all four twin-range cut-off simulations. Most of the other major helices remained stable. The unwinding of H2 can be related to the ability of Bcl-XL to bind diverse BH3 ligands. The loss of helical character can also be linked to the formation of homo- or hetero-dimers in Bcl-2 proteins. Several experimental studies have suggested that exposure of BH3 domain is a crucial event before they form dimers. Thus unwinding of H2 seems to be functionally very important. The four PME simulations, however, revealed a stable helix H2. It is possible that the H2 unfolding might occur in PME simulations at longer time scales. Hydrophobic residues in the hydrophobic groove are involved in stable interactions among themselves. The solvent accessible surface areas of bulky hydrophobic residues in the groove are significantly buried by the loop LB connecting the helix H2 and subsequent helix. These observations help to understand how the hydrophobic patch in Bcl-XL remains stable in the solvent-exposed state. We suggest that both the destabilization of helix H2 and the conformational heterogeneity of loop LB are important factors for binding of diverse ligands in the hydrophobic groove of Bcl-XL.

  18. Radiation damage to DNA-binding proteins

    International Nuclear Information System (INIS)

    Culard, G.; Eon, S.; DeVuyst, G.; Charlier, M.; Spotheim-Maurizot, M.

    2003-01-01

    The DNA-binding properties of proteins are strongly affected upon irradiation. The tetrameric lactose repressor (a dimer of dimers) losses its ability to bind operator DNA as soon as at least two damages per protomer of each dimer occur. The monomeric MC1 protein losses its ability to bind DNA in two steps : i) at low doses only the specific binding is abolished, whereas the non-specific one is still possible; ii) at high doses all binding vanishes. Moreover, the DNA bending induced by MC1 binding is less pronounced for a protein that underwent the low dose irradiation. When the entire DNA-protein complexes are irradiated, the observed disruption of the complexes is mainly due to the damage of the proteins and not to that of DNA. The doses necessary for complex disruption are higher than those inactivating the free protein. This difference, larger for MC1 than for lactose repressor, is due to the protection of the protein by the bound DNA. The oxidation of the protein side chains that are accessible to the radiation-induced hydroxyl radicals seems to represent the inactivating damage

  19. Mutated Leguminous Lectin Containing a Heparin-Binding like Motif in a Carbohydrate-Binding Loop Specifically Binds to Heparin.

    Directory of Open Access Journals (Sweden)

    Hirohito Abo

    Full Text Available We previously introduced random mutations in the sugar-binding loops of a leguminous lectin and screened the resulting mutated lectins for novel specificities using cell surface display. Screening of a mutated peanut agglutinin (PNA, revealed a mutated PNA with a distinct preference for heparin. Glycan microarray analyses using the mutated lectin fused to the Fc region of human immunoglobulin, revealed that a particular sulfated glycosaminoglycan (GAG, heparin, had the highest binding affinity for mutated PNA among 97 glycans tested, although wild-type PNA showed affinity towards Galβ1-3GalNAc and similar galactosylated glycans. Further analyses of binding specificity using an enzyme-linked immunoadsorbent assay demonstrated that the mutated PNA specifically binds to heparin, and weakly to de-2-O-sulfated heparin, but not to other GAG chains including de-6-O-sulfated and de-N-sulfated heparins. The mutated PNA had six amino acid substitutions within the eight amino acid-long sugar-binding loop. In this loop, the heparin-binding like motif comprised three arginine residues at positions 124, 128, and 129, and a histidine at position 125 was present. Substitution of each arginine or histidine residue to alanine reduced heparin-binding ability, indicating that all of these basic amino acid residues contributed to heparin binding. Inhibition assay demonstrated that heparin and dextran sulfate strongly inhibited mutated PNA binding to heparin in dose-dependent manner. The mutated PNA could distinguish between CHO cells and proteoglycan-deficient mutant cells. This is the first report establishing a novel leguminous lectin that preferentially binds to highly sulfated heparin and may provide novel GAG-binding probes to distinguish between heterogeneous GAG repeating units.

  20. Mutated Leguminous Lectin Containing a Heparin-Binding like Motif in a Carbohydrate-Binding Loop Specifically Binds to Heparin.

    Science.gov (United States)

    Abo, Hirohito; Soga, Keisuke; Tanaka, Atsuhiro; Tateno, Hiroaki; Hirabayashi, Jun; Yamamoto, Kazuo

    2015-01-01

    We previously introduced random mutations in the sugar-binding loops of a leguminous lectin and screened the resulting mutated lectins for novel specificities using cell surface display. Screening of a mutated peanut agglutinin (PNA), revealed a mutated PNA with a distinct preference for heparin. Glycan microarray analyses using the mutated lectin fused to the Fc region of human immunoglobulin, revealed that a particular sulfated glycosaminoglycan (GAG), heparin, had the highest binding affinity for mutated PNA among 97 glycans tested, although wild-type PNA showed affinity towards Galβ1-3GalNAc and similar galactosylated glycans. Further analyses of binding specificity using an enzyme-linked immunoadsorbent assay demonstrated that the mutated PNA specifically binds to heparin, and weakly to de-2-O-sulfated heparin, but not to other GAG chains including de-6-O-sulfated and de-N-sulfated heparins. The mutated PNA had six amino acid substitutions within the eight amino acid-long sugar-binding loop. In this loop, the heparin-binding like motif comprised three arginine residues at positions 124, 128, and 129, and a histidine at position 125 was present. Substitution of each arginine or histidine residue to alanine reduced heparin-binding ability, indicating that all of these basic amino acid residues contributed to heparin binding. Inhibition assay demonstrated that heparin and dextran sulfate strongly inhibited mutated PNA binding to heparin in dose-dependent manner. The mutated PNA could distinguish between CHO cells and proteoglycan-deficient mutant cells. This is the first report establishing a novel leguminous lectin that preferentially binds to highly sulfated heparin and may provide novel GAG-binding probes to distinguish between heterogeneous GAG repeating units.

  1. Thermodynamic prediction of glass formation tendency, cluster-in-jellium model for metallic glasses, ab initio tight-binding calculations, and new density functional theory development for systems with strong electron correlation

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Yongxin [Iowa State Univ., Ames, IA (United States)

    2009-01-01

    also plays an important role, as it may directly track the movement of every atom. Simulation time is a major limit for molecular dynamics, not only because of “slow” computer speed, but also because of the accumulation error in the numerical treatment of the motion equations. There is also a great concern about the reliability of the emperical potentials if using classical molecular dynamics. Ab initio methods based on density functional theory(DFT) do not have this problem, however, it suffers from small simulation cells and is more demanding computationally. When crystal phase is involved, size effect of the simulation cell is more pronounced since long-range elastic energy would be established. Simulation methods which are more efficient in computation but yet have similar reliability as the ab initio methods, like tight-binding method, are highly desirable. While the complexity of metallic glasses comes from the atomistic level, there is also a large field which deals with the complexity from electronic level. The only “ab initio” method applicable to solid state systems is density functional theory with local density approximation( LDA) or generalized gradient approximation(GGA) for the exchange-correlation energy. It is very successful for simple sp element, where it reaches an high accuracy for determining the surface reconstruction. However, there is a large class of materials with strong electron correlation, where DFT based on LDA or GGA fails in a fundamental way. An “ab initio” method which can generally apply to correlated materials, as LDA for simple sp element, is still to be developed. The thesis is prepared to address some of the above problems.

  2. Zinc Binding by Lactic Acid Bacteria

    Directory of Open Access Journals (Sweden)

    Jasna Mrvčić

    2009-01-01

    Full Text Available Zinc is an essential trace element in all organisms. A common method for the prevention of zinc deficiency is pharmacological supplementation, especially in a highly available form of a metalloprotein complex. The potential of different microbes to bind essential and toxic heavy metals has recently been recognized. In this work, biosorption of zinc by lactic acid bacteria (LAB has been investigated. Specific LAB were assessed for their ability to bind zinc from a water solution. Significant amount of zinc ions was bound, and this binding was found to be LAB species-specific. Differences among the species in binding performance at a concentration range between 10–90 mg/L were evaluated with Langmuir model for biosorption. Binding of zinc was a fast process, strongly influenced by ionic strength, pH, biomass concentration, and temperature. The most effective metal-binding LAB species was Leuconostoc mesenteroides (27.10 mg of Zn2+ per gram of dry mass bound at pH=5 and 32 °C, during 24 h. FT-IR spectroscopy analysis and electron microscopy demonstrated that passive adsorption and active uptake of the zinc ions were involved.

  3. Titanium: light, strong, and white

    Science.gov (United States)

    Woodruff, Laurel; Bedinger, George

    2013-01-01

    Titanium (Ti) is a strong silver-gray metal that is highly resistant to corrosion and is chemically inert. It is as strong as steel but 45 percent lighter, and it is twice as strong as aluminum but only 60 percent heavier. Titanium dioxide (TiO2) has a very high refractive index, which means that it has high light-scattering ability. As a result, TiO2 imparts whiteness, opacity, and brightness to many products. ...Because of the unique physical properties of titanium metal and the whiteness provided by TiO2, titanium is now used widely in modern industrial societies.

  4. Complement factor H binds malondialdehyde epitopes and protects from oxidative stress

    DEFF Research Database (Denmark)

    Weismann, David; Hartvigsen, Karsten; Lauer, Nadine

    2011-01-01

    polymorphism H402, which is strongly associated with AMD, markedly reduces the ability of CFH to bind MDA, indicating a causal link to disease aetiology. Our findings provide important mechanistic insights into innate immune responses to oxidative stress, which may be exploited in the prevention of and therapy...

  5. The interaction of beta 2-microglobulin (beta 2m) with mouse class I major histocompatibility antigens and its ability to support peptide binding. A comparison of human and mouse beta 2m

    DEFF Research Database (Denmark)

    Pedersen, L O; Stryhn, A; Holter, T L

    1995-01-01

    The function of major histocompatibility complex (MHC) class I molecules is to sample peptides derived from intracellular proteins and to present these peptides to CD8+ cytotoxic T lymphocytes. In this paper, biochemical assays addressing MHC class I binding of both peptide and beta 2-microglobul...

  6. Frataxin Directly Stimulates Mitochondrial Cysteine Desulfurase by Exposing Substrate-binding Sites, and a Mutant Fe-S Cluster Scaffold Protein with Frataxin-bypassing Ability Acts Similarly*♦

    Science.gov (United States)

    Pandey, Alok; Gordon, Donna M.; Pain, Jayashree; Stemmler, Timothy L.; Dancis, Andrew; Pain, Debkumar

    2013-01-01

    For iron-sulfur (Fe-S) cluster synthesis in mitochondria, the sulfur is derived from the amino acid cysteine by the cysteine desulfurase activity of Nfs1. The enzyme binds the substrate cysteine in the pyridoxal phosphate-containing site, and a persulfide is formed on the active site cysteine in a manner depending on the accessory protein Isd11. The persulfide is then transferred to the scaffold Isu, where it combines with iron to form the Fe-S cluster intermediate. Frataxin is implicated in the process, although it is unclear where and how, and deficiency causes Friedreich ataxia. Using purified proteins and isolated mitochondria, we show here that the yeast frataxin homolog (Yfh1) directly and specifically stimulates cysteine binding to Nfs1 by exposing substrate-binding sites. This novel function of frataxin does not require iron, Isu1, or Isd11. Once bound to Nfs1, the substrate cysteine is the source of the Nfs1 persulfide, but this step is independent of frataxin and strictly dependent on Isd11. Recently, a point mutation in Isu1 was found to bypass many frataxin functions. The data presented here show that the Isu1 suppressor mimics the frataxin effects on Nfs1, explaining the bypassing activity. We propose a regulatory mechanism for the Nfs1 persulfide-forming activity. Specifically, at least two separate conformational changes must occur in the enzyme for optimum activity as follows: one is mediated by frataxin interaction that exposes the “buried” substrate-binding sites, and the other is mediated by Isd11 interaction that brings the bound substrate cysteine and the active site cysteine in proximity for persulfide formation. PMID:24217246

  7. Binding mechanism and electrochemical properties of M13 phage-sulfur composite.

    Science.gov (United States)

    Dong, Dexian; Zhang, Yongguang; Sutaria, Sanjana; Konarov, Aishuak; Chen, Pu

    2013-01-01

    Self-assembly of nanostructured materials has been proven a powerful technique in material design and synthesis. By phage display screening, M13 phage was found to strongly bind sulfur particles. Fourier transform infrared and X-ray photoelectron spectroscopy measurements indicated that the strong sulfur-binding ability of M13 phage derives from newly generated S-O and C-S bonds. Using this phage assembled sulfur composite in a lithium battery, the first discharge capacity reached 1117 mAh g(-1), which is more than twice that of the sulfur only cathode. Besides, the negative polysulfide shuttle effect in a lithium-sulfur battery was significantly suppressed.

  8. Quarkeosynthesis Binding Energy

    Science.gov (United States)

    Webb, Bill

    2009-05-01

    Quarkeosynthesis shows that the binding energy of a nucleus is the difference between the relativistic kinetic energies of its threesome of Jumbo Quarks and that of its building block quarks from neutrons and protons. There is no involvement of a nuclear strong force or gluon material.

  9. Testing strong interaction theories

    International Nuclear Information System (INIS)

    Ellis, J.

    1979-01-01

    The author discusses possible tests of the current theories of the strong interaction, in particular, quantum chromodynamics. High energy e + e - interactions should provide an excellent means of studying the strong force. (W.D.L.)

  10. Functional consequences of piceatannol binding to glyceraldehyde-3-phosphate dehydrogenase.

    Science.gov (United States)

    Gerszon, Joanna; Serafin, Eligiusz; Buczkowski, Adam; Michlewska, Sylwia; Bielnicki, Jakub Antoni; Rodacka, Aleksandra

    2018-01-01

    Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is one of the key redox-sensitive proteins whose activity is largely affected by oxidative modifications at its highly reactive cysteine residue in the enzyme's active site (Cys149). Prolonged exposure to oxidative stress may cause, inter alia, the formation of intermolecular disulfide bonds leading to accumulation of GAPDH aggregates and ultimately to cell death. Recently these anomalies have been linked with the pathogenesis of Alzheimer's disease. Novel evidences indicate that low molecular compounds may be effective inhibitors potentially preventing the GAPDH translocation to the nucleus, and inhibiting or slowing down its aggregation and oligomerization. Therefore, we decided to establish the ability of naturally occurring compound, piceatannol, to interact with GAPDH and to reveal its effect on functional properties and selected parameters of the dehydrogenase structure. The obtained data revealed that piceatannol binds to GAPDH. The ITC analysis indicated that one molecule of the tetrameric enzyme may bind up to 8 molecules of polyphenol (7.3 ± 0.9). Potential binding sites of piceatannol to the GAPDH molecule were analyzed using the Ligand Fit algorithm. Conducted analysis detected 11 ligand binding positions. We indicated that piceatannol decreases GAPDH activity. Detailed analysis allowed us to presume that this effect is due to piceatannol ability to assemble a covalent binding with nucleophilic cysteine residue (Cys149) which is directly involved in the catalytic reaction. Consequently, our studies strongly indicate that piceatannol would be an exceptional inhibitor thanks to its ability to break the aforementioned pathologic disulfide linkage, and therefore to inhibit GAPDH aggregation. We demonstrated that by binding with GAPDH piceatannol blocks cysteine residue and counteracts its oxidative modifications, that induce oligomerization and GAPDH aggregation.

  11. Functional consequences of piceatannol binding to glyceraldehyde-3-phosphate dehydrogenase.

    Directory of Open Access Journals (Sweden)

    Joanna Gerszon

    Full Text Available Glyceraldehyde-3-phosphate dehydrogenase (GAPDH is one of the key redox-sensitive proteins whose activity is largely affected by oxidative modifications at its highly reactive cysteine residue in the enzyme's active site (Cys149. Prolonged exposure to oxidative stress may cause, inter alia, the formation of intermolecular disulfide bonds leading to accumulation of GAPDH aggregates and ultimately to cell death. Recently these anomalies have been linked with the pathogenesis of Alzheimer's disease. Novel evidences indicate that low molecular compounds may be effective inhibitors potentially preventing the GAPDH translocation to the nucleus, and inhibiting or slowing down its aggregation and oligomerization. Therefore, we decided to establish the ability of naturally occurring compound, piceatannol, to interact with GAPDH and to reveal its effect on functional properties and selected parameters of the dehydrogenase structure. The obtained data revealed that piceatannol binds to GAPDH. The ITC analysis indicated that one molecule of the tetrameric enzyme may bind up to 8 molecules of polyphenol (7.3 ± 0.9. Potential binding sites of piceatannol to the GAPDH molecule were analyzed using the Ligand Fit algorithm. Conducted analysis detected 11 ligand binding positions. We indicated that piceatannol decreases GAPDH activity. Detailed analysis allowed us to presume that this effect is due to piceatannol ability to assemble a covalent binding with nucleophilic cysteine residue (Cys149 which is directly involved in the catalytic reaction. Consequently, our studies strongly indicate that piceatannol would be an exceptional inhibitor thanks to its ability to break the aforementioned pathologic disulfide linkage, and therefore to inhibit GAPDH aggregation. We demonstrated that by binding with GAPDH piceatannol blocks cysteine residue and counteracts its oxidative modifications, that induce oligomerization and GAPDH aggregation.

  12. Development of the Adverse Outcome Pathway (AOP): Chronic binding of antagonist to N-methyl-d-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities of children.

    Science.gov (United States)

    Sachana, Magdalini; Rolaki, Alexandra; Bal-Price, Anna

    2018-03-07

    The Adverse Outcome Pathways (AOPs) are designed to provide mechanistic understanding of complex biological systems and pathways of toxicity that result in adverse outcomes (AOs) relevant to regulatory endpoints. AOP concept captures in a structured way the causal relationships resulting from initial chemical interaction with biological target(s) (molecular initiating event) to an AO manifested in individual organisms and/or populations through a sequential series of key events (KEs), which are cellular, anatomical and/or functional changes in biological processes. An AOP provides the mechanistic detail required to support chemical safety assessment, the development of alternative methods and the implementation of an integrated testing strategy. An example of the AOP relevant to developmental neurotoxicity (DNT) is described here following the requirements of information defined by the OECD Users' Handbook Supplement to the Guidance Document for developing and assessing AOPs. In this AOP, the binding of an antagonist to glutamate receptor N-methyl-d-aspartate (NMDAR) receptor is defined as MIE. This MIE triggers a cascade of cellular KEs including reduction of intracellular calcium levels, reduction of brain derived neurotrophic factor release, neuronal cell death, decreased glutamate presynaptic release and aberrant dendritic morphology. At organ level, the above mentioned KEs lead to decreased synaptogenesis and decreased neuronal network formation and function causing learning and memory deficit at organism level, which is defined as the AO. There are in vitro, in vivo and epidemiological data that support the described KEs and their causative relationships rendering this AOP relevant to DNT evaluation in the context of regulatory purposes. Copyright © 2018. Published by Elsevier Inc.

  13. Synthesis and structure elucidation of a copper(II) Schiff-base complex: in vitro DNA binding, pBR322 plasmid cleavage and HSA binding studies.

    Science.gov (United States)

    Tabassum, Sartaj; Ahmad, Musheer; Afzal, Mohd; Zaki, Mehvash; Bharadwaj, Parimal K

    2014-11-01

    New copper(II) complex with Schiff base ligand 4-[(2-Hydroxy-3-methoxy-benzylidene)-amino]-benzoic acid (H₂L) was synthesized and characterized by spectroscopic and analytical and single crystal X-ray diffraction studies which revealed that the complex 1 exist in a distorted octahedral environment. In vitro CT-DNA binding studies were performed by employing different biophysical technique which indicated that the 1 strongly binds to DNA in comparison to ligand via electrostatic binding mode. Complex 1 cleaves pBR322 DNA via hydrolytic pathway and recognizes minor groove of DNA double helix. The HSA binding results showed that ligand and complex 1 has ability to quench the fluorescence emission intensity of Trp 214 residue available in the subdomain IIA of HSA. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Specific binding of an immunoreactive and biologically active 125I-labeled substance P derivative to mouse mesencephalic cells in primary culture

    International Nuclear Information System (INIS)

    Beaujouan, J.C.; Torrens, Y.; Herbet, A.; Daguet, M.C.; Glowinski, J.; Prochiantz, A.

    1982-01-01

    Binding characteristics of 125 I-labeled Bolton-Hunter substance P ([ 125 I]BHSP), a radioactive analogue of substance P, were studied with mesencephalic primary cultures prepared from embryonic mouse brain. Nonspecific binding represented no more than 20% of the total binding observed on the cells. In contrast, significant specific binding--saturable, reversible, and temperature-dependent--was demonstrated. Scatchard analysis of concentration-dependent binding saturation indicates a single population of noninteracting sites with a high affinity (Kd . 169 pM). Substance P and different substance P analogues were tested for their competitive potencies with regard to [ 125 I]BHSP binding. BHSP itself, substance P, (Tyr8)-substance P, and (nor-Leu11)-substance P strongly inhibited the binding. Good inhibition was also obtained with physalaemin and eledoisin, two peptides structurally related to substance P. When substance P C-terminal fragments were tested for their ability to compete with [ 125 I]BHSP binding, a good relationship was found between competitive activity and peptide length. Regional distribution of [ 125 I]BHSP binding sites was found using primary cultures obtained from different regions of embryonic mouse brain. Mesencephalic, hypothalamic, and striatal cultures had the highest [ 125 I]BHSP binding capacities, whereas cortical, hippocampal, and cerebellar cells shared only little binding activity. Finally, when mesencephalic cells were grown under conditions impairing glial development, [ 125 I]BHSP binding was not affected, demonstrating that binding sites are located on neuronal cells

  15. A dipeptide with enhanced anion binding affinity enables cell uptake and protein delivery.

    Science.gov (United States)

    Li, Mao; Mosel, Stefanie; Knauer, Shirley K; Schmuck, Carsten

    2018-03-14

    Herein, we report a rather simple strategy to enhance the anion binding ability of a dipeptide to achieve cell uptake and also protein delivery. Peptide 1, composed of only two synthetic amino acids with an artificial anion binding site in the side chains, has an overall molecular weight of only 630 Da and demonstrated strong binding affinity (10 7 M -1 ) and clustering ability with heparin as a model for cell surface sugars. Furthermore, peptide 1 is also efficiently taken up by cells most likely via endocytosis. The uptake efficiency is dependent on the amount of glycosaminoglycans on the cell surface. Cells with reduced amounts of surface bound glycosaminoglycans show significantly less uptake of peptide 1. Moreover, 1 induced the uptake of a model protein (avidin, around 67 kDa) into cells, which makes 1 a highly attractive candidate for drug and protein delivery, especially as 1 has negligible cytotoxicity.

  16. Strongly Correlated Topological Insulators

    Science.gov (United States)

    2016-02-03

    Strongly Correlated Topological Insulators In the past year, the grant was used for work in the field of topological phases, with emphasis on finding...surface of topological insulators. In the past 3 years, we have started a new direction, that of fractional topological insulators. These are materials...in which a topologically nontrivial quasi-flat band is fractionally filled and then subject to strong interactions. The views, opinions and/or

  17. Strong Cosmic Censorship

    Science.gov (United States)

    Isenberg, James

    2017-01-01

    The Hawking-Penrose theorems tell us that solutions of Einstein's equations are generally singular, in the sense of the incompleteness of causal geodesics (the paths of physical observers). These singularities might be marked by the blowup of curvature and therefore crushing tidal forces, or by the breakdown of physical determinism. Penrose has conjectured (in his `Strong Cosmic Censorship Conjecture`) that it is generically unbounded curvature that causes singularities, rather than causal breakdown. The verification that ``AVTD behavior'' (marked by the domination of time derivatives over space derivatives) is generically present in a family of solutions has proven to be a useful tool for studying model versions of Strong Cosmic Censorship in that family. I discuss some of the history of Strong Cosmic Censorship, and then discuss what is known about AVTD behavior and Strong Cosmic Censorship in families of solutions defined by varying degrees of isometry, and discuss recent results which we believe will extend this knowledge and provide new support for Strong Cosmic Censorship. I also comment on some of the recent work on ``Weak Null Singularities'', and how this relates to Strong Cosmic Censorship.

  18. Solute-vacancy binding in aluminum

    International Nuclear Information System (INIS)

    Wolverton, C.

    2007-01-01

    Previous efforts to understand solute-vacancy binding in aluminum alloys have been hampered by a scarcity of reliable, quantitative experimental measurements. Here, we report a large database of solute-vacancy binding energies determined from first-principles density functional calculations. The calculated binding energies agree well with accurate measurements where available, and provide an accurate predictor of solute-vacancy binding in other systems. We find: (i) some common solutes in commercial Al alloys (e.g., Cu and Mg) possess either very weak (Cu), or even repulsive (Mg), binding energies. Hence, we assert that some previously reported large binding energies for these solutes are erroneous. (ii) Large binding energies are found for Sn, Cd and In, confirming the proposed mechanism for the reduced natural aging in Al-Cu alloys containing microalloying additions of these solutes. (iii) In addition, we predict that similar reduction in natural aging should occur with additions of Si, Ge and Au. (iv) Even larger binding energies are found for other solutes (e.g., Pb, Bi, Sr, Ba), but these solutes possess essentially no solubility in Al. (v) We have explored the physical effects controlling solute-vacancy binding in Al. We find that there is a strong correlation between binding energy and solute size, with larger solute atoms possessing a stronger binding with vacancies. (vi) Most transition-metal 3d solutes do not bind strongly with vacancies, and some are even energetically strongly repelled from vacancies, particularly for the early 3d solutes, Ti and V

  19. Cross-Modal Binding in Developmental Dyslexia

    Science.gov (United States)

    Jones, Manon W.; Branigan, Holly P.; Parra, Mario A.; Logie, Robert H.

    2013-01-01

    The ability to learn visual-phonological associations is a unique predictor of word reading, and individuals with developmental dyslexia show impaired ability in learning these associations. In this study, we compared developmentally dyslexic and nondyslexic adults on their ability to form cross-modal associations (or "bindings") based…

  20. A Heparin Binding Motif Rich in Arginine and Lysine is the Functional Domain of YKL-40

    Directory of Open Access Journals (Sweden)

    Nipaporn Ngernyuang

    2018-02-01

    Full Text Available The heparin-binding glycoprotein YKL-40 (CHI3L1 is intimately associated with microvascularization in multiple human diseases including cancer and inflammation. However, the heparin-binding domain(s pertinent to the angiogenic activity have yet been identified. YKL-40 harbors a consensus heparin-binding motif that consists of positively charged arginine (R and lysine (K (RRDK; residues 144–147; but they don't bind to heparin. Intriguingly, we identified a separate KR-rich domain (residues 334–345 that does display strong heparin binding affinity. A short synthetic peptide spanning this KR-rich domain successfully competed with YKL-40 and blocked its ability to bind heparin. Three individual point mutations, where alanine (A substituted for K or R (K337A, K342A, R344A, led to remarkable decreases in heparin-binding ability and angiogenic activity. In addition, a neutralizing anti-YKL-40 antibody that targets these residues and prevents heparin binding impeded angiogenesis in vitro. MDA-MB-231 breast cancer cells engineered to express ectopic K337A, K342A or R344A mutants displayed reduced tumor development and compromised tumor vessel formation in mice relative to control cells expressing wild-type YKL-40. These data reveal that the KR-rich heparin-binding motif is the functional heparin-binding domain of YKL-40. Our findings shed light on novel molecular mechanisms underlying endothelial cell angiogenesis promoted by YKL-40 in a variety of diseases.

  1. A Heparin Binding Motif Rich in Arginine and Lysine is the Functional Domain of YKL-40.

    Science.gov (United States)

    Ngernyuang, Nipaporn; Yan, Wei; Schwartz, Lawrence M; Oh, Dennis; Liu, Ying-Bin; Chen, Hongzhuan; Shao, Rong

    2018-02-01

    The heparin-binding glycoprotein YKL-40 (CHI3L1) is intimately associated with microvascularization in multiple human diseases including cancer and inflammation. However, the heparin-binding domain(s) pertinent to the angiogenic activity have yet been identified. YKL-40 harbors a consensus heparin-binding motif that consists of positively charged arginine (R) and lysine (K) (RRDK; residues 144-147); but they don't bind to heparin. Intriguingly, we identified a separate KR-rich domain (residues 334-345) that does display strong heparin binding affinity. A short synthetic peptide spanning this KR-rich domain successfully competed with YKL-40 and blocked its ability to bind heparin. Three individual point mutations, where alanine (A) substituted for K or R (K337A, K342A, R344A), led to remarkable decreases in heparin-binding ability and angiogenic activity. In addition, a neutralizing anti-YKL-40 antibody that targets these residues and prevents heparin binding impeded angiogenesis in vitro. MDA-MB-231 breast cancer cells engineered to express ectopic K337A, K342A or R344A mutants displayed reduced tumor development and compromised tumor vessel formation in mice relative to control cells expressing wild-type YKL-40. These data reveal that the KR-rich heparin-binding motif is the functional heparin-binding domain of YKL-40. Our findings shed light on novel molecular mechanisms underlying endothelial cell angiogenesis promoted by YKL-40 in a variety of diseases. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Atoms in strong laser fields

    International Nuclear Information System (INIS)

    L'Huillier, A.

    2002-01-01

    When a high-power laser focuses into a gas of atoms, the electromagnetic field becomes of the same magnitude as the Coulomb field which binds a 1s electron in a hydrogen atom. 3 highly non-linear phenomena can happen: 1) ATI (above threshold ionization): electrons initially in the ground state absorb a large number of photons, many more than the minimum number required for ionization; 2) multiple ionization: many electrons can be emitted one at a time, in a sequential process, or simultaneously in a mechanism called direct or non-sequential; and 3) high order harmonic generation (HHG): efficient photon emission in the extreme ultraviolet range, in the form of high-order harmonics of the fundamental laser field can occur. The theoretical problem consists in solving the time dependent Schroedinger equation (TDSE) that describes the interaction of a many-electron atom with a laser field. A number of methods have been proposed to solve this problem in the case of a hydrogen atom or a single-active electron atom in a strong laser field. A large effort is presently being devoted to go beyond the single-active approximation. The understanding of the physics of the interaction between atoms and strong laser fields has been provided by a very simple model called ''simple man's theory''. A unified view of HHG, ATI, and non-sequential ionization, originating from the simple man's model and the strong field approximation, expressed in terms of electrons trajectories or quantum paths is slowly emerging. (A.C.)

  3. Strong Arcwise Connectedness

    OpenAIRE

    Espinoza, Benjamin; Gartside, Paul; Kovan-Bakan, Merve; Mamatelashvili, Ana

    2012-01-01

    A space is `n-strong arc connected' (n-sac) if for any n points in the space there is an arc in the space visiting them in order. A space is omega-strong arc connected (omega-sac) if it is n-sac for all n. We study these properties in finite graphs, regular continua, and rational continua. There are no 4-sac graphs, but there are 3-sac graphs and graphs which are 2-sac but not 3-sac. For every n there is an n-sac regular continuum, but no regular continuum is omega-sac. There is an omega-sac ...

  4. Abortion: Strong's counterexamples fail

    DEFF Research Database (Denmark)

    Di Nucci, Ezio

    2009-01-01

    This paper shows that the counterexamples proposed by Strong in 2008 in the Journal of Medical Ethics to Marquis's argument against abortion fail. Strong's basic idea is that there are cases--for example, terminally ill patients--where killing an adult human being is prima facie seriously morally......'s scenarios have some valuable future or admitted that killing them is not seriously morally wrong. Finally, if "valuable future" is interpreted as referring to objective standards, one ends up with implausible and unpalatable moral claims....

  5. A strong comeback

    International Nuclear Information System (INIS)

    Marier, D.

    1992-01-01

    This article presents the results of a financial rankings survey which show a strong economic activity in the independent energy industry. The topics of the article include advisor turnover, overseas banks, and the increase in public offerings. The article identifies the top project finance investors for new projects and restructurings and rankings for lenders

  6. Thermodynamics of Ligand Binding to Acyl-Coenzyme A Binding Protein Studied by Titration Calorimetry

    DEFF Research Database (Denmark)

    Færgeman, Nils Joakim; Sigurskjold, Bent Walther; Kragelund, Birthe B.

    1996-01-01

    Ligand binding to recombinant bovine acyl-CoA binding protein (ACBP) was examined using isothermal microcalorimetry. Microcalorimetric measurements confirm that the binding affinity of acyl-CoA esters for ACBP is strongly dependent on the length of the acyl chain with a clear preference for acyl-...

  7. Thermodynamics of ligand binding to acyl-coenzyme A binding protein studied by titration calorimetry

    DEFF Research Database (Denmark)

    Færgeman, Nils J.; Sigurskjold, B W; Kragelund, B B

    1996-01-01

    Ligand binding to recombinant bovine acyl-CoA binding protein (ACBP) was examined using isothermal microcalorimetry. Microcalorimetric measurements confirm that the binding affinity of acyl-CoA esters for ACBP is strongly dependent on the length of the acyl chain with a clear preference for acyl-...

  8. Strong Electroweak Symmetry Breaking

    CERN Document Server

    Grinstein, Benjamin

    2011-01-01

    Models of spontaneous breaking of electroweak symmetry by a strong interaction do not have fine tuning/hierarchy problem. They are conceptually elegant and use the only mechanism of spontaneous breaking of a gauge symmetry that is known to occur in nature. The simplest model, minimal technicolor with extended technicolor interactions, is appealing because one can calculate by scaling up from QCD. But it is ruled out on many counts: inappropriately low quark and lepton masses (or excessive FCNC), bad electroweak data fits, light scalar and vector states, etc. However, nature may not choose the minimal model and then we are stuck: except possibly through lattice simulations, we are unable to compute and test the models. In the LHC era it therefore makes sense to abandon specific models (of strong EW breaking) and concentrate on generic features that may indicate discovery. The Technicolor Straw Man is not a model but a parametrized search strategy inspired by a remarkable generic feature of walking technicolor,...

  9. Binding abilities of copper to phospholipids and transport of oxalate

    Czech Academy of Sciences Publication Activity Database

    Jaklová Dytrtová, Jana; Jakl, M.; Nováková, Kateřina; Navrátil, Tomáš; Šádek, Vojtěch

    2015-01-01

    Roč. 146, č. 5 (2015), s. 831-837 ISSN 0026-9247 R&D Projects: GA ČR GP13-21409P; GA ČR(CZ) GAP208/12/1645 Institutional support: RVO:61388963 ; RVO:61388955 Keywords : copper cations * dipalmitoylphosphatidylcholine (lecithin) * ESI-MS * impedance spectroscopy * oxalic acid * voltammetry * membrane Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.131, year: 2015

  10. [Role of histidine in ligand binding ability of hemoglobin gene].

    Science.gov (United States)

    Romanova, T A; Krasnov, P O; Kuzubov, A A; Avramov, P V

    2004-01-01

    The atomic and electronic structures of heme complexes with His, Gly, and Cys residues (Heme-His, Heme-Gly, and Heme-Cys) in the fifth coordination position of the Fe atom and with oxygen and nitrogen oxide molecules in the sixth Fe position were studied by the semiempirical quantum-chemical method PM3. A comparative analysis of internuclear distances showed that the strength of chemical bonding between the ligand molecules (oxygen and nitrogen oxide) is greater for Heme-Cys than for Heme-His and Heme-Gly complexes. Consequently, the strengthening of the chemical bond of the oxygen (or nitrogen oxide) molecule with Heme-Cys substantially weakens the chemical bond in the ligand molecule. The Mulliken population analysis showed that the electronic density of ligand (oxygen or nitrogen oxide) p-orbitals is transferred to the d-orbitals of the Fe atom, whose charge, calculated according to the Mulliken analysis, formally becomes negative. In the Heme-His complex with oxygen, this charge is substantially greater than in the complex with NO, and the oxygen molecule becomes polarized. No oxygen polarization is observed in the Heme-Cys complex, and the electron density (judging from the change in the Fe charge) is transferred to the coordinated sulfur atom. This is also characteristic of Heme-Cys complexes with nitrogen oxide. An analysis of charges on the atoms indicates that the character of chemical bonding of the oxygen molecule in Heme-Cys and Heme-Gly complexes is similar and basically differs from that in the case of the Heme-His complex. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 2; see also http://www.maik.ru.

  11. Plasmons in strong superconductors

    International Nuclear Information System (INIS)

    Baldo, M.; Ducoin, C.

    2011-01-01

    We present a study of the possible plasmon excitations that can occur in systems where strong superconductivity is present. In these systems the plasmon energy is comparable to or smaller than the pairing gap. As a prototype of these systems we consider the proton component of Neutron Star matter just below the crust when electron screening is not taken into account. For the realistic case we consider in detail the different aspects of the elementary excitations when the proton, electron components are considered within the Random-Phase Approximation generalized to the superfluid case, while the influence of the neutron component is considered only at qualitative level. Electron screening plays a major role in modifying the proton spectrum and spectral function. At the same time the electron plasmon is strongly modified and damped by the indirect coupling with the superfluid proton component, even at moderately low values of the gap. The excitation spectrum shows the interplay of the different components and their relevance for each excitation modes. The results are relevant for neutrino physics and thermodynamical processes in neutron stars. If electron screening is neglected, the spectral properties of the proton component show some resemblance with the physical situation in high-T c superconductors, and we briefly discuss similarities and differences in this connection. In a general prospect, the results of the study emphasize the role of Coulomb interaction in strong superconductors.

  12. Roles of the human Rad51 L1 and L2 loops in DNA binding.

    Science.gov (United States)

    Matsuo, Yusuke; Sakane, Isao; Takizawa, Yoshimasa; Takahashi, Masayuki; Kurumizaka, Hitoshi

    2006-07-01

    The human Rad51 protein, a eukaryotic ortholog of the bacterial RecA protein, is a key enzyme that functions in homologous recombination and recombinational repair of double strand breaks. The Rad51 protein contains two flexible loops, L1 and L2, which are proposed to be sites for DNA binding, based on a structural comparison with RecA. In the present study, we performed mutational and fluorescent spectroscopic analyses on the L1 and L2 loops to examine their role in DNA binding. Gel retardation and DNA-dependent ATP hydrolysis measurements revealed that the substitution of the tyrosine residue at position 232 (Tyr232) within the L1 loop with alanine, a short side chain amino acid, significantly decreased the DNA-binding ability of human Rad51, without affecting the protein folding or the salt-induced, DNA-independent ATP hydrolysis. Even the conservative replacement with tryptophan affected the DNA binding, indicating that Tyr232 is involved in DNA binding. The importance of the L1 loop was confirmed by the fluorescence change of a tryptophan residue, replacing the Asp231, Ser233, or Gly236 residue, upon DNA binding. The alanine replacement of phenylalanine at position 279 (Phe279) within the L2 loop did not affect the DNA-binding ability of human Rad51, unlike the Phe203 mutation of the RecA L2 loop. The Phe279 side chain may not be directly involved in the interaction with DNA. However, the fluorescence intensity of the tryptophan replacing the Rad51-Phe279 residue was strongly reduced upon DNA binding, indicating that the L2 loop is also close to the DNA-binding site.

  13. Strong-coupling approximations

    International Nuclear Information System (INIS)

    Abbott, R.B.

    1984-03-01

    Standard path-integral techniques such as instanton calculations give good answers for weak-coupling problems, but become unreliable for strong-coupling. Here we consider a method of replacing the original potential by a suitably chosen harmonic oscillator potential. Physically this is motivated by the fact that potential barriers below the level of the ground-state energy of a quantum-mechanical system have little effect. Numerically, results are good, both for quantum-mechanical problems and for massive phi 4 field theory in 1 + 1 dimensions. 9 references, 6 figures

  14. Strong interaction and QFD

    International Nuclear Information System (INIS)

    Ebata, T.

    1981-01-01

    With an assumed weak multiplet structure for bosonic hadrons, which is consistent with the ΔI = 1/2 rule, it is shown that the strong interaction effective hamiltonian is compatible with the weak SU(2) x U(1) gauge transformation. Especially the rho-meson transforms as a triplet under SU(2)sub(w), and this is the origin of the rho-photon analogy. It is also shown that the existence of the non-vanishing Cabibbo angle is a necessary condition for the absence of the exotic hadrons. (orig.)

  15. Very Strong Binding for a Neutral Calix[4]pyrrole Receptor Displaying Positive Allosteric Binding

    DEFF Research Database (Denmark)

    Duedal, Troels; Nielsen, Kent; Olsen, Gunnar

    2017-01-01

    The dual-analyte responsive behavior of tetraTTF-calix[4]pyrrole receptor 1 has shown to complex electron-deficient planar guests in a 2:1 fashion in the so-called 1,3-alternate conformation. However, stronger 1:1 complexes have been demonstrated with tetraalkylammonium halide salts that defer...... receptor 1 to its so-called cone conformation. Herein, we report the complexation of an electron-deficient planar guest, namely 1,4,5,8-naphthalene-tetracarboxylic dianhydride (NTCDA, 2), that champions the complexation with 1 resulting in a very high association constant Ka = 3 × 1010 M−2...

  16. Strong Coupling Holography

    CERN Document Server

    Dvali, Gia

    2009-01-01

    We show that whenever a 4-dimensional theory with N particle species emerges as a consistent low energy description of a 3-brane embedded in an asymptotically-flat (4+d)-dimensional space, the holographic scale of high-dimensional gravity sets the strong coupling scale of the 4D theory. This connection persists in the limit in which gravity can be consistently decoupled. We demonstrate this effect for orbifold planes, as well as for the solitonic branes and string theoretic D-branes. In all cases the emergence of a 4D strong coupling scale from bulk holography is a persistent phenomenon. The effect turns out to be insensitive even to such extreme deformations of the brane action that seemingly shield 4D theory from the bulk gravity effects. A well understood example of such deformation is given by large 4D Einstein term in the 3-brane action, which is known to suppress the strength of 5D gravity at short distances and change the 5D Newton's law into the four-dimensional one. Nevertheless, we observe that the ...

  17. LIGO: The strong belief

    CERN Multimedia

    Antonella Del Rosso

    2016-01-01

    Twenty years of designing, building and testing a number of innovative technologies, with the strong belief that the endeavour would lead to a historic breakthrough. The Bulletin publishes an abstract of the Courier’s interview with Barry Barish, one of the founding fathers of LIGO.   The plots show the signals of gravitational waves detected by the twin LIGO observatories at Livingston, Louisiana, and Hanford, Washington. (Image: Caltech/MIT/LIGO Lab) On 11 February, the Laser Interferometer Gravitational-Wave Observatory (LIGO) and Virgo collaborations published a historic paper in which they showed a gravitational signal emitted by the merger of two black holes. These results come after 20 years of hard work by a large collaboration of scientists operating the two LIGO observatories in the US. Barry Barish, Linde Professor of Physics, Emeritus at the California Institute of Technology and former Director of the Global Design Effort for the Internat...

  18. A Unitary Anesthetic Binding Site at High Resolution

    Energy Technology Data Exchange (ETDEWEB)

    L Vedula; G Brannigan; N Economou; J Xi; M Hall; R Liu; M Rossi; W Dailey; K Grasty; et. al.

    2011-12-31

    Propofol is the most widely used injectable general anesthetic. Its targets include ligand-gated ion channels such as the GABA{sub A} receptor, but such receptor-channel complexes remain challenging to study at atomic resolution. Until structural biology methods advance to the point of being able to deal with systems such as the GABA{sub A} receptor, it will be necessary to use more tractable surrogates to probe the molecular details of anesthetic recognition. We have previously shown that recognition of inhalational general anesthetics by the model protein apoferritin closely mirrors recognition by more complex and clinically relevant protein targets; here we show that apoferritin also binds propofol and related GABAergic anesthetics, and that the same binding site mediates recognition of both inhalational and injectable anesthetics. Apoferritin binding affinities for a series of propofol analogs were found to be strongly correlated with the ability to potentiate GABA responses at GABA{sub A} receptors, validating this model system for injectable anesthetics. High resolution x-ray crystal structures reveal that, despite the presence of hydrogen bond donors and acceptors, anesthetic recognition is mediated largely by van der Waals forces and the hydrophobic effect. Molecular dynamics simulations indicate that the ligands undergo considerable fluctuations about their equilibrium positions. Finally, apoferritin displays both structural and dynamic responses to anesthetic binding, which may mimic changes elicited by anesthetics in physiologic targets like ion channels.

  19. John Strong (1941 - 2006)

    CERN Multimedia

    Wickens, F

    Our friend and colleague John Strong was cruelly taken from us by a brain tumour on Monday 31st July, a few days before his 65th birthday John started his career working with a group from Westfield College, under the leadership of Ted Bellamy. He obtained his PhD and spent the early part of his career on experiments at Rutherford Appleton Laboratory (RAL), but after the early 1970s his research was focussed on experiments in CERN. Over the years he made a number of notable contributions to experiments in CERN: The Omega spectrometer adopted a system John had originally developed for experiments at RAL using vidicon cameras to record the sparks in the spark chambers; He contributed to the success of NA1 and NA7, where he became heavily involved in the electronic trigger systems; He was responsible for the second level trigger system for the ALEPH detector and spent five years leading a team that designed and built the system, which ran for twelve years with only minor interventions. Following ALEPH he tur...

  20. Stirring Strongly Coupled Plasma

    CERN Document Server

    Fadafan, Kazem Bitaghsir; Rajagopal, Krishna; Wiedemann, Urs Achim

    2009-01-01

    We determine the energy it takes to move a test quark along a circle of radius L with angular frequency w through the strongly coupled plasma of N=4 supersymmetric Yang-Mills (SYM) theory. We find that for most values of L and w the energy deposited by stirring the plasma in this way is governed either by the drag force acting on a test quark moving through the plasma in a straight line with speed v=Lw or by the energy radiated by a quark in circular motion in the absence of any plasma, whichever is larger. There is a continuous crossover from the drag-dominated regime to the radiation-dominated regime. In the crossover regime we find evidence for significant destructive interference between energy loss due to drag and that due to radiation as if in vacuum. The rotating quark thus serves as a model system in which the relative strength of, and interplay between, two different mechanisms of parton energy loss is accessible via a controlled classical gravity calculation. We close by speculating on the implicati...

  1. Strong-interaction nonuniversality

    International Nuclear Information System (INIS)

    Volkas, R.R.; Foot, R.; He, X.; Joshi, G.C.

    1989-01-01

    The universal QCD color theory is extended to an SU(3) 1 direct product SU(3) 2 direct product SU(3) 3 gauge theory, where quarks of the ith generation transform as triplets under SU(3)/sub i/ and singlets under the other two factors. The usual color group is then identified with the diagonal subgroup, which remains exact after symmetry breaking. The gauge bosons associated with the 16 broken generators then form two massive octets under ordinary color. The interactions between quarks and these heavy gluonlike particles are explicitly nonuniversal and thus an exploration of their physical implications allows us to shed light on the fundamental issue of strong-interaction universality. Nonuniversality and weak flavor mixing are shown to generate heavy-gluon-induced flavor-changing neutral currents. The phenomenology of these processes is studied, as they provide the major experimental constraint on the extended theory. Three symmetry-breaking scenarios are presented. The first has color breaking occurring at the weak scale, while the second and third divorce the two scales. The third model has the interesting feature of radiatively induced off-diagonal Kobayashi-Maskawa matrix elements

  2. Scientific Ability and Creativity

    Science.gov (United States)

    Heller, Kurt A.

    2007-01-01

    Following an introductory definition of "scientific ability and creativity", product-oriented, personality and social psychological approaches to studying scientific ability are examined with reference to competence and performance. Studies in the psychometric versus cognitive psychological paradigms are dealt with in more detail. These two…

  3. Identification and Structural Basis of Binding to Host Lung Glycogen by Streptococcal Virulence Factors

    Energy Technology Data Exchange (ETDEWEB)

    Lammerts van Bueren,A.; Higgins, M.; Wang, D.; Burke, R.; Boraston, A.

    2007-01-01

    The ability of pathogenic bacteria to recognize host glycans is often essential to their virulence. Here we report structure-function studies of previously uncharacterized glycogen-binding modules in the surface-anchored pullulanases from Streptococcus pneumoniae (SpuA) and Streptococcus pyogenes (PulA). Multivalent binding to glycogen leads to a strong interaction with alveolar type II cells in mouse lung tissue. X-ray crystal structures of the binding modules reveal a novel fusion of tandem modules into single, bivalent functional domains. In addition to indicating a structural basis for multivalent attachment, the structure of the SpuA modules in complex with carbohydrate provides insight into the molecular basis for glycogen specificity. This report provides the first evidence that intracellular lung glycogen may be a novel target of pathogenic streptococci and thus provides a rationale for the identification of the streptococcal {alpha}-glucan-metabolizing machinery as virulence factors.

  4. Interaction of bacteriophage T4 and T7 single-stranded DNA-binding proteins with DNA

    International Nuclear Information System (INIS)

    Shokri, Leila; Williams, Mark C; Rouzina, Ioulia

    2009-01-01

    Bacteriophages T4 and T7 are well-studied model replication systems, which have allowed researchers to determine the roles of many proteins central to DNA replication, recombination and repair. Here we summarize and discuss the results from two recently developed single-molecule methods to determine the salt-dependent DNA-binding kinetics and thermodynamics of the single-stranded DNA (ssDNA)-binding proteins (SSBs) from these systems. We use these methods to characterize both the equilibrium double-stranded DNA (dsDNA) and ssDNA binding of the SSBs T4 gene 32 protein (gp32) and T7 gene 2.5 protein (gp2.5). Despite the overall two-orders-of-magnitude weaker binding of gp2.5 to both forms of DNA, we find that both proteins exhibit four-orders-of-magnitude preferential binding to ssDNA relative to dsDNA. This strong preferential ssDNA binding as well as the weak dsDNA binding is essential for the ability of both proteins to search dsDNA in one dimension to find available ssDNA-binding sites at the replication fork

  5. Thallium-201: Autoradiography in pigmented mice and melanin-binding in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Tjaelve, H.; Nilsson, M.; Larsson, B. (Uppsala Univ. (Sweden))

    1982-01-01

    Autoradiography with /sup 201/Tl/sup +/ in C57Bl mice showed a strong labelling of the eye melanin and of pigmented hair follicles. An analysis of the affinity of thallium for pigment from cow eyes indicated a binding to three groups of sites and showed a marked sensitivity to the addition of H/sup +/-ions. The results are consistent with the conception that a binding of thallium occurs to the free carboxyl groups of the melanin and that the structure of the polymer has a marked influence on the affinity. Similar results have previously been obtained with other cations. There was no indication that the strong in vivo affinity of thallium to melanin is due to a more firm binding than for other cations which do not localize on melanin in vivo. Instead, the ability of cations to pass the melanocyte membranes and reach the melanin granules is probably decisive for whether a melanin-binding will take place in vivo. Toxic effects on the eye and epilation are symptoms of thallium intoxication which may be related to its melanin-binding. The fate of /sup 201/Tl/sup +/ in some other tissues is also described and discussed.

  6. Measuring Creative Imagery Abilities

    Directory of Open Access Journals (Sweden)

    Dorota M. Jankowska

    2015-10-01

    Full Text Available Over the decades, creativity and imagination research developed in parallel, but they surprisingly rarely intersected. This paper introduces a new theoretical model of creative imagination, which bridges creativity and imagination research, as well as presents a new psychometric instrument, called the Test of Creative Imagery Abilities (TCIA, developed to measure creative imagery abilities understood in accordance with this model. Creative imagination is understood as constituted by three interrelated components: vividness (the ability to create images characterized by a high level of complexity and detail, originality (the ability to produce unique imagery, and transformativeness (the ability to control imagery. TCIA enables valid and reliable measurement of these three groups of abilities, yielding the general score of imagery abilities and at the same time making profile analysis possible. We present the results of eight studies on a total sample of more than 1,700 participants, showing the factor structure of TCIA using confirmatory factor analysis, as well as provide data confirming this instrument’s validity and reliability. The availability of TCIA for interested researchers may result in new insights and possibilities of integrating the fields of creativity and imagination science.

  7. Phase diagram of strongly correlated Fermi systems

    International Nuclear Information System (INIS)

    Zverev, M.V.; Khodel', V.A.; Baldo, M.

    2000-01-01

    Phase transitions in uniform Fermi systems with repulsive forces between the particles caused by restructuring of quasiparticle filling n(p) are analyzed. It is found that in terms of variables, i.e. density ρ, nondimensional binding constant η, phase diagram of a strongly correlated Fermi system for rather a wide class of interactions reminds of a puff-pastry pie. Its upper part is filled with fermion condensate, the lower one - with normal Fermi-liquid. They are separated by a narrow interlayer - the Lifshits phase, characterized by the Fermi multibound surface [ru

  8. Girls underestimate maths ability

    Science.gov (United States)

    2017-05-01

    A study by psychologists in the US has found that high-school girls rate their competence in mathematics lower than boys, even for those with similar abilities (Front. Psychol. 10.3389/fpsyg.2017.00386).

  9. DNA binding affinity of a macrocyclic copper(II) complex: Spectroscopic and molecular docking studies.

    Science.gov (United States)

    Shahabadi, Nahid; Hakimi, Mohammad; Morovati, Teimoor; Fatahi, Navid

    2017-08-03

    The interaction of a novel macrocyclic copper(II) complex, ([CuL(ClO 4 ) 2 ] that L is 1,3,6,10,12,15-hexaazatricyclo[13.3.1.1 6,10 ]eicosane) with calf thymus DNA (ct-DNA) was investigated by various physicochemical techniques and molecular docking at simulated physiological conditions (pH = 7.4). The absorption spectra of the Cu(II) complex with ct-DNA showed a marked hyperchroism with 10 nm blue shift. The intrinsic binding constant (K b ) was determined as 1.25 × 10 4 M -1 , which is more in keeping with the groove binding with DNA. Furthermore, competitive fluorimetric studies with Hoechst33258 have shown that Cu(II) complex exhibits the ability to displace the ct-DNA-bound Hoechst33258 indicating that it binds to ct-DNA in strong competition with Hoechst33258 for the groove binding. Also, no change in the relative viscosity of ct-DNA and fluorescence intensity of ct-DNA-MB complex in the present of Cu(II) complex is another evidence to groove binding. The thermodynamic parameters are calculated by van't Hoff equation, which demonstrated that hydrogen bonds and van der Waals interactions played major roles in the binding reaction. The experimental results were in agreement with the results obtained via molecular docking study.

  10. Linear and circular dichroism characterization of thionine binding mode with DNA polynucleotides

    Science.gov (United States)

    Tuite, Eimer Mary; Nordén, Bengt

    2018-01-01

    The binding mode of thionine (3,7-diamino-5-phenothiazinium) with alternating and non-alternating DNA polynucleotides at low binding ratios was conclusively determined using linear and circular dichroism spectroscopies. The binding to [poly(dG-dC)]2 and poly(dG)·poly(dC) was purely intercalative and was insensitive to ionic strength. Intercalative binding to [poly(dA-dT)]2 is observed at low ionic strength, but a shift of some dye to an non-intercalative mode is observed as the background salt concentration increases. With poly(dA)·poly(dT), intercalative binding is unfavourable, although some dye molecules may intercalate at low ionic strength, and groove binding is strongly promoted with increasing concentration of background salt. However, stacking with bases is observed with single-stranded poly(dA) and with triplex poly(dT)*poly(dA)·poly(dT) which suggests that the unusual structure of poly(dA)·poly(dT) precludes intercalation. Thionine behaves similarly to the related dye methylene blue, and small differences may be attributed either to the ability of thionine to form H-bonds that stabilize intercalation or to its improved stacking interactions in the basepair pocket on steric grounds.

  11. Calcium binding by dietary fibre

    International Nuclear Information System (INIS)

    James, W.P.T.; Branch, W.J.; Southgate, D.A.T.

    1978-01-01

    Dietary fibre from plants low in phytate bound calcium in proportion to its uronic-acid content. This binding by the non-cellulosic fraction of fibre reduces the availability of calcium for small-intestinal absorption, but the colonic microbial digestion of uronic acids liberates the calcium. Thus the ability to maintain calcium balance on high-fibre diets may depend on the adaptive capacity on the colon for calcium. (author)

  12. Quantum Transport in Strongly Correlated Systems

    DEFF Research Database (Denmark)

    Bohr, Dan

    2007-01-01

    the density matrix renormalization group (DMRG) method. We present two DMRG setups for calculating the linear conductance of strongly correlated nanostructures in the infinitesimal source-drain voltage regime. The first setup describes the leads by modified real-space tight-binding chains, whereas the second...... screening plays a much less significant role than in bulk systems due to the reduced size of the objects, therefore making it necessary to consider the importance of correlations between electrons. The work presented in this thesis deals with quantum transport through strongly correlated systems using....... Thus both coherence and correlation effects are important in this model, and the methods applied should be able to handle both these effects rigorously. We present the DMRG setup for this model and benchmark against existing Greens function results for the model. Then we present initial DMRG results...

  13. Development of arithmetical abilities

    Directory of Open Access Journals (Sweden)

    Tatjana Levstek

    2014-02-01

    Full Text Available Arithmetic (from the word 'arithmos' which means 'numbers' is an elementary branch of mathematics. Numeracy is essential for understanding mathematics, so the development of arithmetic abilities has been an area of scientific research for a long time. Recent research has shown that the development of arithmetic abilities is not based only on gaining experience and learning. Some arithmetic abilities, especially the sense of quantity, are innate. Even babies are able to distinguish between groups with different number of elements and they perceive numeracy amodally. Six-month-olds distinguish between two groups with the numeracy ratio of 1 : 2. With age this ratio improves rapidly. Five-year-old children already distinguish between groups with the number ratio 7 : 8. The ability to compare two quantities begins to develop after 15 months of age and children learn how to count spontaneously, together with the acquisition of language. Speech enables children to understand number in its abstract, symbolic sense, thus opening the way to symbolic arithmetic. During the preschool period children use intuition when doing calculations, but in school the arithmetic is based on the knowledge of arithmetical algorithms. So, in order to acquire mathematical knowledge, it is necessary to incorporate memory and automate arithmetical processes, without the use of intuition. However, research has shown that intuition is very important and is even a predictive factor for the development of mathematical abilities throughout the schooling process.

  14. Peptide Nucleic Acids Having Enhanced Binding Affinity and Sequence Specificity

    DEFF Research Database (Denmark)

    1998-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than a corresponding DNA strand, and exhibit increased sequence specificity and binding affinity. Methods of increasing binding affinity and sequence specificity of peptide nucleic acids...

  15. Binding of corroded ions to human saliva.

    Science.gov (United States)

    Mueller, H J

    1985-05-01

    Employing equilibrium dialysis, the binding abilities of Cu, Al, Co and Cr ions from corroded Cu-Al and Co-Cr dental casting alloys towards human saliva and two of its gel chromatographic fractions were determined. Results indicate that both Cu and Co bind to human saliva i.e. 0.045 and 0.027 mg/mg protein, respectively. Besides possessing the largest binding ability, Cu also possessed the largest binding capacity. The saturation of Cu binding was not reached up to the limit of 0.35 mg protein/ml employed in the tests, while Co reached full saturation at about 0.2 mg protein/ml. Chromium showed absolutely no binding to human saliva while Al ions did not pass through the dialysis membranes. Compared to the binding with solutions that were synthetically made up to contain added salivary-type proteins, it is shown that the binding to human saliva is about 1 order of magnitude larger, at least for Cu ions.

  16. Fast gradient HPLC method to determine compounds binding to human serum albumin. Relationships with octanol/water and immobilized artificial membrane lipophilicity.

    Science.gov (United States)

    Valko, Klara; Nunhuck, Shenaz; Bevan, Chris; Abraham, Michael H; Reynolds, Derek P

    2003-11-01

    A fast gradient HPLC method (cycle time 15 min) has been developed to determine Human Serum Albumin (HSA) binding of discovery compounds using chemically bonded protein stationary phases. The HSA binding values were derived from the gradient retention times that were converted to the logarithm of the equilibrium constants (logK HSA) using data from a calibration set of molecules. The method has been validated using literature plasma protein binding data of 68 known drug molecules. The method is fully automated, and has been used for lead optimization in more than 20 company projects. The HSA binding data obtained for more than 4000 compounds were suitable to set up global and project specific quantitative structure binding relationships that helped compound design in early drug discovery. The obtained HSA binding of known drug molecules were compared to the Immobilized Artificial Membrane binding data (CHI IAM) obtained by our previously described HPLC-based method. The solvation equation approach has been used to characterize the normal binding ability of HSA, and this relationship shows that compound lipophilicity is a significant factor. It was found that the selectivity of the "baseline" lipophilicity governing HSA binding, membrane interaction, and octanol/water partition are very similar. However, the effect of the presence of positive or negative charges have very different effects. It was found that negatively charged compounds bind more strongly to HSA than it would be expected from the lipophilicity of the ionized species at pH 7.4. Several compounds showed stronger HSA binding than can be expected from their lipophilicity alone, and comparison between predicted and experimental binding affinity allows the identification of compounds that have good complementarities with any of the known binding sites. Copyright 2003 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:2236-2248, 2003

  17. Priming Ability Emotional Intelligence

    Science.gov (United States)

    Schutte, Nicola S.; Malouff, John M.

    2012-01-01

    Two studies examined whether priming self-schemas relating to successful emotional competency results in better emotional intelligence performance. In the first study participants were randomly assigned to a successful emotional competency self-schema prime condition or a control condition and then completed an ability measure of emotional…

  18. Polynomial fitting of tight-binding method in carbon

    Science.gov (United States)

    Haa, Wai Kang; Yeak, Su Hoe

    2017-04-01

    Carbon is very unique in among the elements and its ability to form strong chemical bonds with a variety number such as two carbons (graphene) and four carbons (diamond). This combination of strong bonds with tight mass and high melting point makes them technologically and scientifically important in nanoscience development. Tight-binding model (TB) is one of the semi-empirical approximations used in quantum mechanical world which is restricted to the Linear Combinations of Localized Atomic Orbitals (LCAO). Currently, there are many approaches in tight-binding calculation. In this paper, we have reproduced a polynomial scaling function by fitting to the TB model. The model is then applied into carbon molecules and obtained the energy bands of the system. The elements of the overlap Hamiltonian matrix in the model will be depending on the parameter of the polynomials. Our purpose is to find out a set of parameters in the polynomial which were commonly fit to an independently calculated band structure. We used minimization approach to calculate the polynomial coefficients which involves differentiation of eigenvalues in the eigensystem. The algorithm of fitting the parameters is carried out in FORTRAN.

  19. Music and nonmusical abilities.

    Science.gov (United States)

    Schellenberg, E G

    2001-06-01

    Reports that exposure to music causes benefits in nonmusical domains have received widespread attention in the mainstream media. Such reports have also influenced public policy. The so-called "Mozart effect" actually refers to two relatively distinct phenomena. One concerns short-term increases in spatial abilities that are said to occur from listening to music composed by Mozart. The other refers to the possibility that formal training in music yields nonmusical benefits. A review of the relevant findings indicates that the short-term effect is small and unreliable. Moreover, when it is evident, it can be explained by between-condition differences in the listener's mood or levels of cognitive arousal. By contrast, the effect of music lessons on nonmusical aspects of cognitive development is still an open question. Several studies have reported positive associations between formal music lessons and abilities in nonmusical (e.g., linguistic, mathematical, and spatial) domains. Nonetheless, compelling evidence for a causal link remains elusive.

  20. Quantum electrodynamics of strong fields

    International Nuclear Information System (INIS)

    Greiner, W.

    1983-01-01

    Quantum Electrodynamics of Strong Fields provides a broad survey of the theoretical and experimental work accomplished, presenting papers by a group of international researchers who have made significant contributions to this developing area. Exploring the quantum theory of strong fields, the volume focuses on the phase transition to a charged vacuum in strong electric fields. The contributors also discuss such related topics as QED at short distances, precision tests of QED, nonperturbative QCD and confinement, pion condensation, and strong gravitational fields In addition, the volume features a historical paper on the roots of quantum field theory in the history of quantum physics by noted researcher Friedrich Hund

  1. Probing the binding of coumarins and cyclothialidines to DNA gyrase

    DEFF Research Database (Denmark)

    Kampranis, S C; Gormley, N A; Tranter, R

    1999-01-01

    B and coumarin and cyclothialidine drugs and made mutations by site-directed mutagenesis. We used proteolysis as a probe of drug binding to wild-type and mutant proteins. Limited proteolysis of gyrase revealed that binding of these antibiotics is associated with a characteristic proteolytic fingerprint......, suggesting a drug-induced conformational change. The ability of the mutants to bind the drugs was studied by testing their ability to induce the coumarin-associated proteolytic signature and to bind to a novobiocin-affinity column. To analyze further the interaction of the drugs with gyrase, we studied...

  2. Characterization of feline serum-cobalt binding.

    Science.gov (United States)

    Schnelle, Amy N; Barger, Anne M; MacNeill, Amy L; Mitchell, Mark M; Solter, Philip

    2015-06-01

    Oxidative stress inhibits albumin's ability to complex with cobalt. Feline serum-cobalt binding has not been described. The objective was to develop a cobalt binding test for use with feline serum, and correlate the results with other biochemical and cellular constituents in blood, and with clinical diseases of cats. A colorimetric test of cobalt binding, based on the oxidation-reduction reaction of Co(+2) and dithiothreitol, was developed using feline serum. The test was used to measure cobalt binding in stored serum from 176 cats presented to the University of Illinois Veterinary Teaching Hospital for a variety of disease conditions. Time-matched hematology and biochemical data, and clinical information, were obtained from the medical record of each cat and correlated with the serum-cobalt binding results. Serial dilution of feline serum with phosphate-buffered saline resulted in a highly linear decrease in serum-cobalt binding (r(2)  = .9984). Serum-cobalt binding of the clinical samples also correlated with albumin concentrations in a stepwise linear regression model (r(2)  = .425), and both cobalt binding and albumin were significantly decreased in cases of inflammation. Albumin and cobalt binding also shared significant correlations with several erythron variables, and serum concentration of total calcium and bilirubin. The correlation of cobalt binding measured by a colorimetric test with albumin concentration in the clinical samples and with serum dilution is consistent with feline albumin-cobalt complex formation. Hypoalbuminemia is the likely cause of reduced serum-cobalt binding in inflammation and the correlations observed between cobalt binding and other variables. © 2015 American Society for Veterinary Clinical Pathology.

  3. Cognitive Ability, Principled Reasoning and Political Tolerance

    DEFF Research Database (Denmark)

    Hebbelstrup Rye Rasmussen, Stig; Nørgaard, Asbjørn Sonne

    Individuals are not equally politically tolerant. To explain why, individual differences in emotions and threat have received much scholarly attention in recent years. However, extant research also shows that psychological dispositions, habitual cognitive styles, ideological orientation...... and ‘principled reasoning’ influence political tolerance judgments. The extent to which cognitive ability plays a role has not been entertained even if the capacity to think abstractly, comprehend complex ideas and apply abstract ideas to concrete situations is inherent to both principled tolerance judgment...... and cognitive ability. Cognitive ability, we argue and show, adds to the etiology of political tolerance. In Danish and American samples cognitive ability strongly predicts political tolerance after taking habitual cognitive styles (as measured by personality traits), education, social ideology, and feelings...

  4. Investigation of proton pump inhibitors binding with bovine serum albumin and their relationship to molecular structure

    International Nuclear Information System (INIS)

    Zhang Yuping; Shi Shuyun; Peng Mijun

    2012-01-01

    The interactions of three proton pump inhibitors (PPIs), omeprazole, pantoprazole and ilaprazole with bovine serum albumin (BSA) have been investigated by fluorescence, synchronous fluorescence, ultraviolet–visible (UV–vis) and circular dichroism (CD). Various binding parameters have been calculated at various temperatures. The results indicated that omeprazole, pantoprazole and ilaprazole had a strong ability to quench the intrinsic fluorescence of BSA with static quenching mechanism, and the binding affinities were significantly affected by different substituents and polarities as the order ilaprazole>pantoprazole>omeprazole. The site marker competitive experiments indicated that the binding of omeprazole, pantoprazole and ilaprazole to BSA primarily took place in subdomain IIA. The results of thermodynamic parameters ΔG, ΔH and ΔS indicated that electrostatic interaction played a major role for PPIs–BSA association. The distance r between PPIs and BSA was evaluated according to the theory of Förster's energy transfer. The quantitative analysis of synchronous fluorescence and CD spectra showed the change in secondary structure of the BSA upon interaction with PPIs by a reduction of α-helix. All the above results many have relevant insight into the PPIs' availability and distribution. - Highlights: ► The interactions of three PPIs with BSA have been investigated. ► The fluorescence quenching mechanism is static quenching. ► Binding affinities were greatly affected by the substituents and polarities. ► The binding of three PPIs to BSA primarily took place in subdomain IIA.

  5. Isothermal titration calorimetry and surface plasmon resonance allow quantifying substrate binding to different binding sites of Bacillus subtilis xylanase

    DEFF Research Database (Denmark)

    Cuyvers, Sven; Dornez, Emmie; Abou Hachem, Maher

    2012-01-01

    Isothermal titration calorimetry and surface plasmon resonance were tested for their ability to study substrate binding to the active site (AS) and to the secondary binding site (SBS) of Bacillus subtilis xylanase A separately. To this end, three enzyme variants were compared. The first was a cat......Isothermal titration calorimetry and surface plasmon resonance were tested for their ability to study substrate binding to the active site (AS) and to the secondary binding site (SBS) of Bacillus subtilis xylanase A separately. To this end, three enzyme variants were compared. The first...

  6. Strong WW Interaction at LHC

    Energy Technology Data Exchange (ETDEWEB)

    Pelaez, Jose R

    1998-12-14

    We present a brief pedagogical introduction to the Effective Electroweak Chiral Lagrangians, which provide a model independent description of the WW interactions in the strong regime. When it is complemented with some unitarization or a dispersive approach, this formalism allows the study of the general strong scenario expected at the LHC, including resonances.

  7. (TH) diazepam binding to human granulocytes

    Energy Technology Data Exchange (ETDEWEB)

    Bond, P.A.; Cundall, R.L.; Rolfe, B.

    1985-07-08

    (TH)-diazepam binds to sites on human granulocyte membranes, with little or no binding to platelets or lymphocytes. These (TH)-diazepam binding sites are of the peripheral type, being strongly inhibited by R05-4864 (Ki=6.23nM) but only weakly by clonazepam (Ki=14 M). Binding of (TH) diazepam at 0 is saturable, specific and stereoselective. Scatchard analysis indicates a single class of sites with Bmax of 109 +/- 17f moles per mg of protein and K/sub D/ of 3.07 +/- 0.53nM. Hill plots of saturation experiments gave straight lines with a mean Hill coefficient of 1.03 +/- 0.014. Binding is time dependent and reversible and it varies linearly with granulocyte protein concentration over the range 0.025-0.300 mg of protein. 11 references, 3 figures, 1 table.

  8. Managing tight-binding receptors for new separations technologies. 1998 annual progress report

    International Nuclear Information System (INIS)

    Busch, D.H.; Givens, R.S.

    1998-01-01

    'Whereas such traditional separation methodologies as ion exchange and solvent extraction require rapid interaction between ligands and metal ions, the most strongly binding ligands invariably bind slowly; e.g., cryptates bind and dissociate more slowly than macrocycles, which are slower than open-chain chelating ligands. This project seeks to maximize the binding and dissociation rates for tight-binding receptors in order to make them more useful to separations science. An alternative slow-binding technology is also under exploration.'

  9. Strong-back safety latch

    International Nuclear Information System (INIS)

    DeSantis, G.N.

    1995-01-01

    The calculation decides the integrity of the safety latch that will hold the strong-back to the pump during lifting. The safety latch will be welded to the strong-back and will latch to a 1.5-in. dia cantilever rod welded to the pump baseplate. The static and dynamic analysis shows that the safety latch will hold the strong-back to the pump if the friction clamps fail and the pump become free from the strong-back. Thus, the safety latch will meet the requirements of the Lifting and Rigging Manual for under the hook lifting for static loading; it can withstand shock loads from the strong-back falling 0.25 inch

  10. Strong-back safety latch

    Energy Technology Data Exchange (ETDEWEB)

    DeSantis, G.N.

    1995-03-06

    The calculation decides the integrity of the safety latch that will hold the strong-back to the pump during lifting. The safety latch will be welded to the strong-back and will latch to a 1.5-in. dia cantilever rod welded to the pump baseplate. The static and dynamic analysis shows that the safety latch will hold the strong-back to the pump if the friction clamps fail and the pump become free from the strong-back. Thus, the safety latch will meet the requirements of the Lifting and Rigging Manual for under the hook lifting for static loading; it can withstand shock loads from the strong-back falling 0.25 inch.

  11. Former for ability

    DEFF Research Database (Denmark)

    Andersen, Maja Lundemark

    Resume FORMER FOR ABILITY Hvilke betydninger tillægges en ADHD-diagnose i forhold til selvforståelse,intersubjektive og institutionelle positioner? Med denne afhandling har jeg ønsket at synliggøre, hvordan voksne med ADHD selv skaber mening med diagnosen, og hvilke betydninger og anvendelsesmuli......Resume FORMER FOR ABILITY Hvilke betydninger tillægges en ADHD-diagnose i forhold til selvforståelse,intersubjektive og institutionelle positioner? Med denne afhandling har jeg ønsket at synliggøre, hvordan voksne med ADHD selv skaber mening med diagnosen, og hvilke betydninger og......, de kan. ADHD anvendes som kategori, men i en kompleks betydning, hvor ADHD som diagnose anvendes som overskrift, men indholdet defineres og beskrives af respondenterne selv. ADHD anvendes subjektivt med forskellig betydning i komplekse mønstre, der inddrager såvel alder, køn som social forankring...... adfærdsregulering og skaber basis for indlæring af ritualer, der fungerer som sociale dørtrin i enhver social samhandling. Samtidig fastholder respondenterne dog krav til omgivelserne om hensyn og særlige kommunikationsformer. Jeg konkluderer, at medicin ikke fjerner symptomerne, men til en vis grad dæmper dem, og...

  12. Synthetic LPS-Binding Polymer Nanoparticles

    Science.gov (United States)

    Jiang, Tian

    Lipopolysaccharide (LPS), one of the principal components of most gram-negative bacteria's outer membrane, is a type of contaminant that can be frequently found in recombinant DNA products. Because of its strong and even lethal biological effects, selective LPS removal from bioproducts solution is of particular importance in the pharmaceutical and health care industries. In this thesis, for the first time, a proof-of-concept study on preparing LPS-binding hydrogel-like NPs through facile one-step free-radical polymerization was presented. With the incorporation of various hydrophobic (TBAm), cationic (APM, GUA) monomers and cross-linkers (BIS, PEG), a small library of NPs was constructed. Their FITC-LPS binding behaviors were investigated and compared with those of commercially available LPS-binding products. Moreover, the LPS binding selectivity of the NPs was also explored by studying the NPs-BSA interactions. The results showed that all NPs obtained generally presented higher FITC-LPS binding capacity in lower ionic strength buffer than higher ionic strength. However, unlike commercial poly-lysine cellulose and polymyxin B agarose beads' nearly linear increase of FITC-LPS binding with particle concentration, NPs exhibited serious aggregation and the binding quickly saturated or even decreased at high particle concentration. Among various types of NPs, higher FITC-LPS binding capacity was observed for those containing more hydrophobic monomers (TBAm). However, surprisingly, more cationic NPs with higher content of APM exhibited decreased FITC-LPS binding in high ionic strength conditions. Additionally, when new cationic monomer and cross-linker, GUA and PEG, were applied to replace APM and BIS, the obtained NPs showed improved FITC-LPS binding capacity at low NP concentration. But compared with APM- and BIS-containing NPs, the FITC-LPS binding capacity of GUA- and PEG-containing NPs saturated earlier. To investigate the NPs' binding to proteins, we tested the NPs

  13. Total iron binding capacity

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003489.htm Total iron binding capacity To use the sharing features on this page, please enable JavaScript. Total iron binding capacity (TIBC) is a blood test to ...

  14. Stimulation of translation by human Unr requires cold shock domains 2 and 4, and correlates with poly(A) binding protein interaction.

    Science.gov (United States)

    Ray, Swagat; Anderson, Emma C

    2016-03-03

    The RNA binding protein Unr, which contains five cold shock domains, has several specific roles in post-transcriptional control of gene expression. It can act as an activator or inhibitor of translation initiation, promote mRNA turnover, or stabilise mRNA. Its role depends on the mRNA and other proteins to which it binds, which includes cytoplasmic poly(A) binding protein 1 (PABP1). Since PABP1 binds to all polyadenylated mRNAs, and is involved in translation initiation by interaction with eukaryotic translation initiation factor 4G (eIF4G), we investigated whether Unr has a general role in translational control. We found that Unr strongly stimulates translation in vitro, and mutation of cold shock domains 2 or 4 inhibited its translation activity. The ability of Unr and its mutants to stimulate translation correlated with its ability to bind RNA, and to interact with PABP1. We found that Unr stimulated the binding of PABP1 to mRNA, and that Unr was required for the stable interaction of PABP1 and eIF4G in cells. siRNA-mediated knockdown of Unr reduced the overall level of cellular translation in cells, as well as that of cap-dependent and IRES-dependent reporters. These data describe a novel role for Unr in regulating cellular gene expression.

  15. High Ability and Learner Characteristics

    Directory of Open Access Journals (Sweden)

    Huda Hindal

    2013-01-01

    Full Text Available The outstandingly able learner has been conceptualised, in terms of test and examination performance, as the learner showing superior academic performance which is markedly better than that of peers and in ways regarded as of value by wider society. In Kuwait, such superior examination performance leads to a classification regarded as being ‘gifted’. This study looks at the inter-correlations between performance in various subjects in examinations and then considers how examination performance correlates with measures of working memory capacity, extent of field dependency, extent of divergency and visual-spatial abilities. A very large sample of grade 7 Kuwaiti students (aged ~13 was involved, the sample being selected in such a way that it contained a high proportion of those regarded as ‘gifted’ under the procedures used in Kuwait. While specific learner characteristics have been related to examination performance, this study brings four different characteristics together to gain a picture of the way these characteristics may be seen in those who perform extremely well in examinations. Principal components analysis using varimax rotation, was used to look at the examination data and one factor accounted for 87% of the variance. A consideration of the examination papers led to the conclusion that the national examinations tested only recall-recognition. It was also found that those who performed best in all six subjects tended to be those who are highly divergent and strongly visual-spatial as well as those tending to have higher working memory capacities and being more field independent. The inter-correlations between the various learner characteristics are explained in terms of the way the brain is known to process information. The implications of the findings for assessment and for the way high ability is considered are discussed.

  16. Mapping the signal peptide binding and oligomer contact sites of the core subunit of the pea twin arginine protein translocase.

    Science.gov (United States)

    Ma, Xianyue; Cline, Kenneth

    2013-03-01

    Twin arginine translocation (Tat) systems of thylakoid and bacterial membranes transport folded proteins using the proton gradient as the sole energy source. Tat substrates have hydrophobic signal peptides with an essential twin arginine (RR) recognition motif. The multispanning cpTatC plays a central role in Tat operation: It binds the signal peptide, directs translocase assembly, and may facilitate translocation. An in vitro assay with pea (Pisum sativum) chloroplasts was developed to conduct mutagenesis and analysis of cpTatC functions. Ala scanning mutagenesis identified mutants defective in substrate binding and receptor complex assembly. Mutations in the N terminus (S1) and first stromal loop (S2) caused specific defects in signal peptide recognition. Cys matching between substrate and imported cpTatC confirmed that S1 and S2 directly and specifically bind the RR proximal region of the signal peptide. Mutations in four lumen-proximal regions of cpTatC were defective in receptor complex assembly. Copurification and Cys matching analyses suggest that several of the lumen proximal regions may be important for cpTatC-cpTatC interactions. Surprisingly, RR binding domains of adjacent cpTatCs directed strong cpTatC-cpTatC cross-linking. This suggests clustering of binding sites on the multivalent receptor complex and explains the ability of Tat to transport cross-linked multimers. Transport of substrate proteins cross-linked to the signal peptide binding site tentatively identified mutants impaired in the translocation step.

  17. Ability Grouping in Social Studies.

    Science.gov (United States)

    Social Education, 1992

    1992-01-01

    Presents a position statement of the National Council for the Social Studies (NCSS). Reports that the NCSS objects to ability grouping in social studies. Argues that ability grouping disadvantages minority, handicapped, and low ability students. Suggests that ability grouping undermines the democratic ideals that should be the basis of the social…

  18. DNA-binding by oncoprotein E2a-Pbx1 is important for blocking differentiation but dispensable for fibroblast transformation.

    Science.gov (United States)

    Kamps, M P; Wright, D D; Lu, Q

    1996-01-04

    The t(1;19) chromosomal translocation of pediatric pre-B cell lymphoblastic leukemia produces the E2A-PBX1 oncogene, which can transform fibroblasts, induce acute myeloid leukemia and T cell lymphomas in mice, and immortalize factor-dependent myeloid progenitors in cultured marrow. The homeodomain of Pbx1 binds ATCAATCAA, and while Pbx1 does not activate transcription through this motif, E2A-Pbx1 induces constitutive transactivation. Here, we investigate whether DNA-binding by Pbx1 or transcriptional activation by E2A are essential for the transforming abilities of E2A-Pbx1. Elimination of DNA-binding in E2A-Pbx1 by point mutations in the Pbx1 homeodomain or by large deletions that removed the Pbx1 homeodomain and carboxyl terminus did not alter ability of E2A-Pbx1 to induce focus-formation in fibroblast, even though these mutations completely eliminated its ability to activate transcription through the PRS. These same DNA-binding mutations, however, severely impaired or eliminated the ability of E2A-Pbx1 to immortalize factor-dependent myeloid progenitors in marrow cultures. Elimination of the first transcriptional activation domain of E2A abolished both fibroblast and myeloid transforming activities while elimination of the second altered neither of these activities. We conclude that DNA-binding is important for the ability of E2A-Pbx1 to disrupt differentiation, as evidenced in myeloblast immortalization, but dispensable for its ability to induce focus-formation, and that the aminoterminal domain of E2A, which strongly activates transcription, is essential for both transforming activities.

  19. ALG-2, a multifunctional calcium binding protein?

    DEFF Research Database (Denmark)

    Tarabykina, Svetlana; Mollerup, Jens; Winding Gojkovic, P.

    2004-01-01

    ALG-2 was originally discovered as a pro-apoptotic protein in a genetic screen. Due to its ability to bind calcium with high affinity it was postulated to provide a link between the known effect of calcium in programmed cell death and the molecular death execution machinery. This review article d...

  20. Extracts of Edible Plants Inhibit Pancreatic Lipase, Cholesterol Esterase and Cholesterol Micellization, and Bind Bile Acids

    Directory of Open Access Journals (Sweden)

    Julnaryn Intrawangso

    2012-01-01

    Full Text Available The application of edible plants with more effective ability to inhibit fat digestion and absorption has recently been explored for possible treatment of hyperlipidaemia. The aim of the present study is to investigate the effect of nine edible plants on the inhibition of pancreatic lipase and pancreatic cholesterol esterase activities, as well as the inhibition of cholesterol micelle formation, and bile acid binding. Our findings have shown strong pancreatic lipase inhibitory activity and the inhibition of cholesterol micellization by mulberry leaf extract. Safflower extract was the most potent inhibitor of pancreatic cholesterol esterase. In addition, cat’s whiskers and safflower extracts had a potent bile acid binding activity. It is suggested that a daily intake of these edible plants may delay postprandial hypertriacylglycerolaemia and hypercholesterolaemia, and therefore may be applied for the prevention and treatment of hyperlipidaemia.

  1. Quantifying the Tendency of Therapeutic Target Proteins to Bind Promiscuous or Selective Compounds

    Science.gov (United States)

    Hu, Ye; Bajorath, Jürgen

    2015-01-01

    The ability of target proteins to bind structurally diverse compounds and compounds with different degrees of promiscuity (multi-target activity) was systematically assessed on the basis of currently available activity data and target annotations. Intuitive first- and second-order target promiscuity indices were introduced to quantify these binding characteristics and relate them to each other. For compounds and targets, opposite promiscuity trends were observed. Furthermore, the analysis detected many targets that interacted with compounds representing a similar degree of structural diversity but displayed strong tendencies to recognize either promiscuous or selective compounds. Moreover, target families were identified that preferentially interacted with promiscuous compounds. Taken together, these findings further extend our understanding of the molecular basis of polypharmacology. PMID:26000736

  2. Preliminary screening and identification of the hepatocarcinoma cell-binding peptide

    International Nuclear Information System (INIS)

    Zhu Xiaohua; Wu Hua

    2004-01-01

    Objective: To explore the feasibility of screening and isolating homing peptides that bind specifically, or preferentially, to hepatocarcinoma cells using phage display random peptide library and to develop a new peptide which may be potentially used as targeting delivery carrier in the biological targeted diagnosis or therapy for liver cancer. Methods: A 12-mer peptide phage display library was used to screen and isolate peptides that bind to human hepatocarcinoma cells, and four rounds of subtractive panning were carried out with the human hepatocarcinoma cell line HepG2 as the target. The affinities of selected phage clones for human hepatocarcinoma cells were determined with enzyme-linked immunosorbent assay (ELISA) and compared with that to human liver cell and other tumor cells of different tissue origins, respectively. In addition, the binding site in the tumor cells was observed with immunofluorescence analysis under confocal light microscopy. The amino acid sequences of phages that bind HepG2 specifically were deduced through DNA sequencing. Based on the results of DNA sequence, a 16-mer peptide (WH16) was designed and synthesized. Binding ability of the new peptide, WH16, was determined with competitive inhibition test. Results: After four rounds of panning, the phages that were bound to and internalized in human hepatocarcinoma cells were isolated. ELISA and immunofluorescence analysis confirmed the affinity of these phages for hepatocarcinoma cells. 56.67%(17/30) of the isolated phages displayed repeated sequence FLLEPHLMDTSM, and FLEP was defined as conservative motif . Binding of the selected phage to HepG2 cells was inhibited by synthesized peptide WH16, that strongly support that cellular binding of the phage is mediated through its displayed peptide, and WH16 can also bind to HepG2. Conclusions: It is feasible to screen and isolate homing peptides that bind specifically, or preferentially, to hepatocarcinoma cells using phage display random peptide

  3. Preliminary screening and identification of the peptide binding to hepatocarcinoma cell

    International Nuclear Information System (INIS)

    Zhu Xiaohua; Wu Ha

    2004-01-01

    Objective: The present study was performed to screen and isolate homing peptides that bind specifically, or preferentially, to hepatocarcinoma cells using phage display of random peptide library with the purpose of developing a new peptide which may be potentially used as target delivery carrier in the biological target diagnosis or therapy for liver cancer. Methods: A peptide 12-mer phage display library was used to screen and isolate peptide that bind to human hepatocarcinoma cell, and four rounds subtractive panning were carried out with the human hepatocarcinoma cell line HepG2 as the target. The affinities of selected phage clones to human hepatocarcinoma cell were determined with ELISA and compared with human liver cell and other tumor cells of different tissue origins respectively. In addition, the binding site in the tumor cells was observed with immunofluorescence analysis under confocal light microscopy. The amino acid sequences of phages that bind HepG2 specifically were deduced though DNA sequencing. Based on the results of DNA sequence, a 16-mer peptide (WH16) was designed and synthesized. Binding ability of the new peptide WH16 was determined with competitive inhibition test. Results: After four rounds panning, the phages that bound to and internalized in human hepatocarcinoma cell were isolated. ELISA and immunofluorescence analysis confirmed the affinity of these phages to hepatpcarcinoma cells 56.57%(17/30) of the isolated phages displayed repeated sequence FLLEPHLMDTSM, and FLEP was defined as conservative motif. Binding of the selected phage to HepG2 cells was inhibited by synthesized peptide WH16, which strongly support that cellular binding of phage is mediated though its displayed peptide and WH16 can also bind to HepG2. Conclusion: It is feasible to screen and isolate homing peptides that bind specifically, or preferentially, to hepatocarcinoma cells using phage display of random peptide libraries. The sequence of peptide that can bind to

  4. A twin study of auditory processing indicates that dichotic listening ability is a strongly heritable trait

    NARCIS (Netherlands)

    Morell, Robert J.; Brewer, Carmen C.; Ge, Dongliang; Snieder, Harold; Zalewski, Christopher K.; King, Kelly A.; Drayna, Dennis; Friedman, Thomas B.

    We administered tests commonly used in the diagnosis of auditory processing disorders (APDs) to twins recruited from the general population. We observed significant correlations in test scores between co-twins. Our analyses of test score correlations among 106 MZ and 33 DZ twin pairs indicate that

  5. Agrobacterium rhizogenes mutants that fail to bind to plant cells.

    OpenAIRE

    Crews, J L; Colby, S; Matthysse, A G

    1990-01-01

    Transposon insertion mutants of Agrobacterium rhizogenes were screened to obtain mutant bacteria that failed to bind to carrot suspension culture cells. A light microscope binding assay was used. The bacterial isolates that were reduced in binding to carrot cells were all avirulent on Bryophyllum diagremontiana leaves and on carrot root disks. The mutants did not appear to be altered in cellulose production. The composition of the medium affected the ability of the parent and mutant bacteria ...

  6. Role of exposed aromatic residues in substrate-binding of CBM family 5 chitin-binding domain of alkaline chitinase.

    Science.gov (United States)

    Uni, Fumiya; Lee, Sunmi; Yatsunami, Rie; Fukui, Toshiaki; Nakamura, Satoshi

    2009-01-01

    Chitinase J (ChiJ) from alkaliphilic Bacillus sp. strain J813 has a multidomain structure containing a catalytic domain (CatD), a fibronectin type III like domain (FnIIID) and a chitin-binding domain (ChBD). It has been shown that the ChBD binds to an insoluble chitin and enhances its degradation by the CatD. Further binding study of the ChBD was performed with a glutathione-S-transferase fusion protein. This fusion protein showed binding abilities to insoluble chitin and chitosan. Two surface-exposed aromatic residues (Trp541 and Trp542) were found in the tertiary-structure model of ChBD and targeted for mutational analysis. Single and double mutations of the two aromatic residues decreased the chitin- and chitosan-binding abilities. It was revealed that these residues would be important for substrate-binding of the ChBD.

  7. Binding of reactive organophosphate by oximes via hydrogen bond

    Indian Academy of Sciences (India)

    In this contribution, the ability of simple oximes to bind a well-known nerve agent simulant (dimethylmethylphosphonate, DMMP) via hydrogen bond is reported. UV/Vis measurements indicate the formation of 1:1 complexes. 1H-, 31P-NMR titrations and T-ROESY experiments confirm that oximes bind the organophosphate ...

  8. Polypeptide binding properties of the chaperone calreticulin

    DEFF Research Database (Denmark)

    Jørgensen, C S; Heegaard, N H; Holm, A

    2000-01-01

    to be elucidated. We have investigated the interactions of human calreticulin with denatured ovalbumin, proteolytic digests of ovalbumin, and different available peptides by solid phase assays, size-exclusion chromatography, capillary electrophoresis, and MS. The results show that calreticulin interacts better...... with unfolded ovalbumin than with native ovalbumin, that calreticulin strongly binds components in proteolytic digests of denatured ovalbumin, and that calreticulin interacts strongly with certain synthetic peptides....

  9. The SNAP Strong Lens Survey

    Energy Technology Data Exchange (ETDEWEB)

    Marshall, P.

    2005-01-03

    Basic considerations of lens detection and identification indicate that a wide field survey of the types planned for weak lensing and Type Ia SNe with SNAP are close to optimal for the optical detection of strong lenses. Such a ''piggy-back'' survey might be expected even pessimistically to provide a catalogue of a few thousand new strong lenses, with the numbers dominated by systems of faint blue galaxies lensed by foreground ellipticals. After sketching out our strategy for detecting and measuring these galaxy lenses using the SNAP images, we discuss some of the scientific applications of such a large sample of gravitational lenses: in particular we comment on the partition of information between lens structure, the source population properties and cosmology. Understanding this partitioning is key to assessing strong lens cosmography's value as a cosmological probe.

  10. Strong coupling phase in QED

    International Nuclear Information System (INIS)

    Aoki, Ken-ichi

    1988-01-01

    Existence of a strong coupling phase in QED has been suggested in solutions of the Schwinger-Dyson equation and in Monte Carlo simulation of lattice QED. In this article we recapitulate the previous arguments, and formulate the problem in the modern framework of the renormalization theory, Wilsonian renormalization. This scheme of renormalization gives the best understanding of the basic structure of a field theory especially when it has a multi-phase structure. We resolve some misleading arguments in the previous literature. Then we set up a strategy to attack the strong phase, if any. We describe a trial; a coupled Schwinger-Dyson equation. Possible picture of the strong coupling phase QED is presented. (author)

  11. Strong Decomposition of Random Variables

    DEFF Research Database (Denmark)

    Hoffmann-Jørgensen, Jørgen; Kagan, Abram M.; Pitt, Loren D.

    2007-01-01

    A random variable X is stongly decomposable if X=Y+Z where Y=Φ(X) and Z=X-Φ(X) are independent non-degenerated random variables (called the components). It is shown that at least one of the components is singular, and we derive a necessary and sufficient condition for strong decomposability...

  12. Strong interaction at finite temperature

    Indian Academy of Sciences (India)

    Abstract. We review two methods discussed in the literature to determine the effective parameters of strongly interacting particles as they move through a heat bath. The first one is the general method of chiral perturbation theory, which may be readily applied to this problem. The other is the method of thermal QCD sum rules ...

  13. Strong-strong beam-beam simulation on parallel computer

    Energy Technology Data Exchange (ETDEWEB)

    Qiang, Ji

    2004-08-02

    The beam-beam interaction puts a strong limit on the luminosity of the high energy storage ring colliders. At the interaction points, the electromagnetic fields generated by one beam focus or defocus the opposite beam. This can cause beam blowup and a reduction of luminosity. An accurate simulation of the beam-beam interaction is needed to help optimize the luminosity in high energy colliders.

  14. Strong-strong beam-beam simulation on parallel computer

    International Nuclear Information System (INIS)

    Qiang, Ji

    2004-01-01

    The beam-beam interaction puts a strong limit on the luminosity of the high energy storage ring colliders. At the interaction points, the electromagnetic fields generated by one beam focus or defocus the opposite beam. This can cause beam blowup and a reduction of luminosity. An accurate simulation of the beam-beam interaction is needed to help optimize the luminosity in high energy colliders

  15. Feature Binding in Zebrafish

    Directory of Open Access Journals (Sweden)

    P Neri

    2012-07-01

    Full Text Available Binding operations are primarily ascribed to cortex or similarly complex avian structures. My experiments show that the zebrafish, a lower vertebrate lacking cortex, supports visual feature binding of form and motion for the purpose of social behavior. These results challenge the notion that feature binding may require highly evolved neural structures and demonstrate that the nervous system of lower vertebrates can afford unexpectedly complex computations.

  16. DNS & Bind Cookbook

    CERN Document Server

    Liu, Cricket

    2011-01-01

    The DNS & BIND Cookbook presents solutions to the many problems faced by network administrators responsible for a name server. Following O'Reilly's popular problem-and-solution cookbook format, this title is an indispensable companion to DNS & BIND, 4th Edition, the definitive guide to the critical task of name server administration. The cookbook contains dozens of code recipes showing solutions to everyday problems, ranging from simple questions, like, "How do I get BIND?" to more advanced topics like providing name service for IPv6 addresses. It's full of BIND configuration files that yo

  17. PREFACE: Strongly correlated electron systems Strongly correlated electron systems

    Science.gov (United States)

    Saxena, Siddharth S.; Littlewood, P. B.

    2012-07-01

    This special section is dedicated to the Strongly Correlated Electron Systems Conference (SCES) 2011, which was held from 29 August-3 September 2011, in Cambridge, UK. SCES'2011 is dedicated to 100 years of superconductivity and covers a range of topics in the area of strongly correlated systems. The correlated electronic and magnetic materials featured include f-electron based heavy fermion intermetallics and d-electron based transition metal compounds. The selected papers derived from invited presentations seek to deepen our understanding of the rich physical phenomena that arise from correlation effects. The focus is on quantum phase transitions, non-Fermi liquid phenomena, quantum magnetism, unconventional superconductivity and metal-insulator transitions. Both experimental and theoretical work is presented. Based on fundamental advances in the understanding of electronic materials, much of 20th century materials physics was driven by miniaturisation and integration in the electronics industry to the current generation of nanometre scale devices. The achievements of this industry have brought unprecedented advances to society and well-being, and no doubt there is much further to go—note that this progress is founded on investments and studies in the fundamentals of condensed matter physics from more than 50 years ago. Nevertheless, the defining challenges for the 21st century will lie in the discovery in science, and deployment through engineering, of technologies that can deliver the scale needed to have an impact on the sustainability agenda. Thus the big developments in nanotechnology may lie not in the pursuit of yet smaller transistors, but in the design of new structures that can revolutionise the performance of solar cells, batteries, fuel cells, light-weight structural materials, refrigeration, water purification, etc. The science presented in the papers of this special section also highlights the underlying interest in energy-dense materials, which

  18. Anion binding in biological systems

    Energy Technology Data Exchange (ETDEWEB)

    Feiters, Martin C [Department of Organic Chemistry, Institute for Molecules and Materials, Faculty of Science, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen (Netherlands); Meyer-Klaucke, Wolfram [EMBL Hamburg Outstation at DESY, Notkestrasse 85, D-22607 Hamburg (Germany); Kostenko, Alexander V; Soldatov, Alexander V [Faculty of Physics, Southern Federal University, Sorge 5, Rostov-na-Donu, 344090 (Russian Federation); Leblanc, Catherine; Michel, Gurvan; Potin, Philippe [Centre National de la Recherche Scientifique and Universite Pierre et Marie Curie Paris-VI, Station Biologique de Roscoff, Place Georges Teissier, BP 74, F-29682 Roscoff cedex, Bretagne (France); Kuepper, Frithjof C [Scottish Association for Marine Science, Dunstaffnage Marine Laboratory, Oban, Argyll PA37 1QA, Scotland (United Kingdom); Hollenstein, Kaspar; Locher, Kaspar P [Institute of Molecular Biology and Biophysics, ETH Zuerich, Schafmattstrasse 20, Zuerich, 8093 (Switzerland); Bevers, Loes E; Hagedoorn, Peter-Leon; Hagen, Wilfred R, E-mail: m.feiters@science.ru.n [Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC Delft (Netherlands)

    2009-11-15

    We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L{sub 3} (2p{sub 3/2}) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

  19. Anion binding in biological systems

    International Nuclear Information System (INIS)

    Feiters, Martin C; Meyer-Klaucke, Wolfram; Kostenko, Alexander V; Soldatov, Alexander V; Leblanc, Catherine; Michel, Gurvan; Potin, Philippe; Kuepper, Frithjof C; Hollenstein, Kaspar; Locher, Kaspar P; Bevers, Loes E; Hagedoorn, Peter-Leon; Hagen, Wilfred R

    2009-01-01

    We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L 3 (2p 3/2 ) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

  20. Anion binding in biological systems

    Science.gov (United States)

    Feiters, Martin C.; Meyer-Klaucke, Wolfram; Kostenko, Alexander V.; Soldatov, Alexander V.; Leblanc, Catherine; Michel, Gurvan; Potin, Philippe; Küpper, Frithjof C.; Hollenstein, Kaspar; Locher, Kaspar P.; Bevers, Loes E.; Hagedoorn, Peter-Leon; Hagen, Wilfred R.

    2009-11-01

    We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L3 (2p3/2) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

  1. Cigarette smoke-induced reduction in binding of the salivary translocator protein is not mediated by free radicals.

    Science.gov (United States)

    Nagler, R; Savulescu, D; Gavish, M

    2016-02-01

    Oral cancer is the most common malignancy of the head and neck and its main inducer is exposure to cigarette smoke (CS) in the presence of saliva. It is commonly accepted that CS contributes to the pathogenesis of oral cancer via reactive free radicals and volatile aldehydes. The 18 kDa translocator protein (TSPO) is an intracellular receptor involved in proliferation and apoptosis, and has been linked to various types of cancer. The presence of TSPO in human saliva has been linked to oral cancer, and its binding affinity to its ligand is reduced following exposure to CS. In the present study we wished to further investigate the mechanism behind the CS-induced reduction of TSPO binding by exploring the possible mediatory role of reactive oxygen species (ROS) and volatile aldehydes in this process. We first analyzed TSPO binding in control saliva and in saliva exposed to CS in the presence and absence of various antioxidants. These experiments found that TSPO binding ability was not reversed by any of the antioxidants added, suggesting that CS exerts its effect on TSPO via mechanisms that do not involve volatile aldehydes and free radicals tested. Next, we analyzed TSPO binding in saliva following addition of exogenous ROS in the form of H2O2. These experiments found that TSPO binding was enhanced due to the treatment, once again showing that the CS-induced TSPO binding reduction is not mediated by this common form of ROS. However, the previously reported CS-induced reduction in salivary TSPO binding together with the role of TSPO in cells and its link to cancer strongly suggest that TSPO has a critical role in the pathogenesis of CS-induced oral cancer. The importance of further elucidating the mechanisms behind it should be emphasized. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  2. Application of phenol red as a marker ligand for bilirubin binding site at subdomain IIA on human serum albumin.

    Science.gov (United States)

    Sochacka, Jolanta

    2015-10-01

    The drug-bilirubin interaction for all drugs administered especially to infants with hyperbilirubinemia should be evaluated for their ability to displace bilirubin and vice versa. In order to examine whether phenol red (PhRed) can be used as a marker for bilirubin binding site located in subdomain IIA the interaction between PhRed and human serum albumin (HSA) in buffer solution or in normal and pathological sera solutions with different HSA:bilirubin molar ratio was investigated using absorption/absorption difference spectroscopy and molecular docking method. Six sulfonamides representing the binding site in the subdomain IIA and known to influence the binding of bilirubin were used for the PhRed displacement studies. The absorption spectra for PhRed completely bound to HSA showed significant differences in the spectral characteristic relative to the spectral profile of free PhRed. The intensity of the peak originating from the bivalent anionic form of dye was strongly reduced and the maximum peak position was red-shifted by 12 nm. The binding constant (K) of the bivalent anionic form of PhRed, calculated from absorbance data, was 1.61 · 10(4) L mol(-1). The variations of the absorption and absorption difference spectra of PhRed in the presence of HSA-bilirubin complex were indicative of the inhibition of PhRed binding process by bilirubin. Binding of PhRed carried out in the presence of sulfonamides showed that drugs and PhRed have a common site which also involves bilirubin. In agreement with the results of the spectroscopic analysis and molecular docking it was concluded that PhRed may be applied as a marker in the study of the binding of drugs to high-affinity bilirubin binding site. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Li+-ligand binding energies and the effect of ligand fluorination on the binding energies

    Science.gov (United States)

    Bauschlicher, Charles W.

    2018-02-01

    The Li+-ligand binding energies are computed for seven ligands and their perfluoro analogs using Density Functional Theory. The bonding is mostly electrostatic in origin. Thus the size of the binding energy tends to correlate with the ligand dipole moment, however, the charge-induced dipole contribution can be sufficiently large to affect the dipole-binding energy correlation. The perfluoro species are significantly less strongly bound than their parents, because the electron withdrawing power of the fluorine reduces the ligand dipole moment.

  4. Strongly correlated systems experimental techniques

    CERN Document Server

    Mancini, Ferdinando

    2015-01-01

    The continuous evolution and development of experimental techniques is at the basis of any fundamental achievement in modern physics. Strongly correlated systems (SCS), more than any other, need to be investigated through the greatest variety of experimental techniques in order to unveil and crosscheck the numerous and puzzling anomalous behaviors characterizing them. The study of SCS fostered the improvement of many old experimental techniques, but also the advent of many new ones just invented in order to analyze the complex behaviors of these systems. Many novel materials, with functional properties emerging from macroscopic quantum behaviors at the frontier of modern research in physics, chemistry and materials science, belong to this class of systems. The volume presents a representative collection of the modern experimental techniques specifically tailored for the analysis of strongly correlated systems. Any technique is presented in great detail by its own inventor or by one of the world-wide recognize...

  5. Strongly Correlated Systems Theoretical Methods

    CERN Document Server

    Avella, Adolfo

    2012-01-01

    The volume presents, for the very first time, an exhaustive collection of those modern theoretical methods specifically tailored for the analysis of Strongly Correlated Systems. Many novel materials, with functional properties emerging from macroscopic quantum behaviors at the frontier of modern research in physics, chemistry and materials science, belong to this class of systems. Any technique is presented in great detail by its own inventor or by one of the world-wide recognized main contributors. The exposition has a clear pedagogical cut and fully reports on the most relevant case study where the specific technique showed to be very successful in describing and enlightening the puzzling physics of a particular strongly correlated system. The book is intended for advanced graduate students and post-docs in the field as textbook and/or main reference, but also for other researchers in the field who appreciates consulting a single, but comprehensive, source or wishes to get acquainted, in a as painless as po...

  6. Strongly correlated systems numerical methods

    CERN Document Server

    Mancini, Ferdinando

    2013-01-01

    This volume presents, for the very first time, an exhaustive collection of those modern numerical methods specifically tailored for the analysis of Strongly Correlated Systems. Many novel materials, with functional properties emerging from macroscopic quantum behaviors at the frontier of modern research in physics, chemistry and material science, belong to this class of systems. Any technique is presented in great detail by its own inventor or by one of the world-wide recognized main contributors. The exposition has a clear pedagogical cut and fully reports on the most relevant case study where the specific technique showed to be very successful in describing and enlightening the puzzling physics of a particular strongly correlated system. The book is intended for advanced graduate students and post-docs in the field as textbook and/or main reference, but also for other researchers in the field who appreciate consulting a single, but comprehensive, source or wishes to get acquainted, in a as painless as possi...

  7. Strongly nonlinear oscillators analytical solutions

    CERN Document Server

    Cveticanin, Livija

    2014-01-01

    This book provides the presentation of the motion of pure nonlinear oscillatory systems and various solution procedures which give the approximate solutions of the strong nonlinear oscillator equations. The book presents the original author’s method for the analytical solution procedure of the pure nonlinear oscillator system. After an introduction, the physical explanation of the pure nonlinearity and of the pure nonlinear oscillator is given. The analytical solution for free and forced vibrations of the one-degree-of-freedom strong nonlinear system with constant and time variable parameter is considered. Special attention is given to the one and two mass oscillatory systems with two-degrees-of-freedom. The criteria for the deterministic chaos in ideal and non-ideal pure nonlinear oscillators are derived analytically. The method for suppressing chaos is developed. Important problems are discussed in didactic exercises. The book is self-consistent and suitable as a textbook for students and also for profess...

  8. Flavour Democracy in Strong Unification

    CERN Document Server

    Abel, S A; Abel, Steven; King, Steven

    1998-01-01

    We show that the fermion mass spectrum may naturally be understood in terms of flavour democratic fixed points in supersymmetric theories which have a large domain of attraction in the presence of "strong unification". Our approach provides an alternative to the approximate Yukawa texture zeroes of the Froggatt-Nielsen mechanism. We discuss a particular model based on a broken gauged $SU(3)_L\\times SU(3)_R$ family symmetry which illustrates our approach.

  9. Quantification of Cooperativity in Heterodimer-DNA Binding Improves the Accuracy of Binding Specificity Models*

    Science.gov (United States)

    Isakova, Alina; Berset, Yves; Hatzimanikatis, Vassily; Deplancke, Bart

    2016-01-01

    Many transcription factors (TFs) have the ability to cooperate on DNA elements as heterodimers. Despite the significance of TF heterodimerization for gene regulation, a quantitative understanding of cooperativity between various TF dimer partners and its impact on heterodimer DNA binding specificity models is still lacking. Here, we used a novel integrative approach, combining microfluidics-steered measurements of dimer-DNA assembly with mechanistic modeling of the implicated protein-protein-DNA interactions to quantitatively interrogate the cooperative DNA binding behavior of the adipogenic peroxisome proliferator-activated receptor γ (PPARγ):retinoid X receptor α (RXRα) heterodimer. Using the high throughput MITOMI (mechanically induced trapping of molecular interactions) platform, we derived equilibrium DNA binding data for PPARγ, RXRα, as well as the PPARγ:RXRα heterodimer to more than 300 target DNA sites and variants thereof. We then quantified cooperativity underlying heterodimer-DNA binding and derived an integrative heterodimer DNA binding constant. Using this cooperativity-inclusive constant, we were able to build a heterodimer-DNA binding specificity model that has superior predictive power than the one based on a regular one-site equilibrium. Our data further revealed that individual nucleotide substitutions within the target site affect the extent of cooperativity in PPARγ:RXRα-DNA binding. Our study therefore emphasizes the importance of assessing cooperativity when generating DNA binding specificity models for heterodimers. PMID:26912662

  10. Quantification of Cooperativity in Heterodimer-DNA Binding Improves the Accuracy of Binding Specificity Models.

    Science.gov (United States)

    Isakova, Alina; Berset, Yves; Hatzimanikatis, Vassily; Deplancke, Bart

    2016-05-06

    Many transcription factors (TFs) have the ability to cooperate on DNA elements as heterodimers. Despite the significance of TF heterodimerization for gene regulation, a quantitative understanding of cooperativity between various TF dimer partners and its impact on heterodimer DNA binding specificity models is still lacking. Here, we used a novel integrative approach, combining microfluidics-steered measurements of dimer-DNA assembly with mechanistic modeling of the implicated protein-protein-DNA interactions to quantitatively interrogate the cooperative DNA binding behavior of the adipogenic peroxisome proliferator-activated receptor γ (PPARγ):retinoid X receptor α (RXRα) heterodimer. Using the high throughput MITOMI (mechanically induced trapping of molecular interactions) platform, we derived equilibrium DNA binding data for PPARγ, RXRα, as well as the PPARγ:RXRα heterodimer to more than 300 target DNA sites and variants thereof. We then quantified cooperativity underlying heterodimer-DNA binding and derived an integrative heterodimer DNA binding constant. Using this cooperativity-inclusive constant, we were able to build a heterodimer-DNA binding specificity model that has superior predictive power than the one based on a regular one-site equilibrium. Our data further revealed that individual nucleotide substitutions within the target site affect the extent of cooperativity in PPARγ:RXRα-DNA binding. Our study therefore emphasizes the importance of assessing cooperativity when generating DNA binding specificity models for heterodimers. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Salt-mediated two-site ligand binding by the cocaine-binding aptamer.

    Science.gov (United States)

    Neves, Miguel A D; Slavkovic, Sladjana; Churcher, Zachary R; Johnson, Philip E

    2017-02-17

    Multisite ligand binding by proteins is commonly utilized in the regulation of biological systems and exploited in a range of biochemical technologies. Aptamers, although widely utilized in many rationally designed biochemical systems, are rarely capable of multisite ligand binding. The cocaine-binding aptamer is often used for studying and developing sensor and aptamer-based technologies. Here, we use isothermal titration calorimetry (ITC) and NMR spectroscopy to demonstrate that the cocaine-binding aptamer switches from one-site to two-site ligand binding, dependent on NaCl concentration. The high-affinity site functions at all buffer conditions studied, the low-affinity site only at low NaCl concentrations. ITC experiments show the two ligand-binding sites operate independently of one another with different affinities and enthalpies. NMR spectroscopy shows the second binding site is located in stem 2 near the three-way junction. This ability to control ligand binding at the second site by adjusting the concentration of NaCl is rare among aptamers and may prove a useful in biotechnology applications. This work also demonstrates that in vitro selected biomolecules can have functions as complex as those found in nature. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. Simulation and Theory of Antibody Binding to Crowded Antigen-Covered Surfaces.

    Directory of Open Access Journals (Sweden)

    Cristiano De Michele

    2016-03-01

    Full Text Available In this paper we introduce a fully flexible coarse-grained model of immunoglobulin G (IgG antibodies parametrized directly on cryo-EM data and simulate the binding dynamics of many IgGs to antigens adsorbed on a surface at increasing densities. Moreover, we work out a theoretical model that allows to explain all the features observed in the simulations. Our combined computational and theoretical framework is in excellent agreement with surface-plasmon resonance data and allows us to establish a number of important results. (i Internal flexibility is key to maximize bivalent binding, flexible IgGs being able to explore the surface with their second arm in search for an available hapten. This is made clear by the strongly reduced ability to bind with both arms displayed by artificial IgGs designed to rigidly keep a prescribed shape. (ii The large size of IgGs is instrumental to keep neighboring molecules at a certain distance (surface repulsion, which essentially makes antigens within reach of the second Fab always unoccupied on average. (iii One needs to account independently for the thermodynamic and geometric factors that regulate the binding equilibrium. The key geometrical parameters, besides excluded-volume repulsion, describe the screening of free haptens by neighboring bound antibodies. We prove that the thermodynamic parameters govern the low-antigen-concentration regime, while the surface screening and repulsion only affect the binding at high hapten densities. Importantly, we prove that screening effects are concealed in relative measures, such as the fraction of bivalently bound antibodies. Overall, our model provides a valuable, accurate theoretical paradigm beyond existing frameworks to interpret experimental profiles of antibodies binding to multi-valent surfaces of different sorts in many contexts.

  13. Metal ion binding with dehydroannulenes – Plausible two ...

    Indian Academy of Sciences (India)

    WINTEC

    Abstract. Theoretical investigations have been carried out at B3LYP/6-311++G** level of theory to study the binding interaction of various metal ions, Li+, Na+ and K+ with dehydroannulene systems. The present study reveals that alkali metal ions bind strongly to dehydroannulenes and the passage through the central.

  14. Fibrinogen binding sites P336 and Y338 of clumping factor A are crucial for Staphylococcus aureus virulence.

    Directory of Open Access Journals (Sweden)

    Elisabet Josefsson

    Full Text Available We have earlier shown that clumping factor A (ClfA, a fibrinogen binding surface protein of Staphylococcus aureus, is an important virulence factor in septic arthritis. When two amino acids in the ClfA molecule, P(336 and Y(338, were changed to serine and alanine, respectively, the fibrinogen binding property was lost. ClfAP(336Y(338 mutants have been constructed in two virulent S. aureus strains Newman and LS-1. The aim of this study was to analyze if these two amino acids which are vital for the fibrinogen binding of ClfA are of importance for the ability of S. aureus to generate disease. Septic arthritis or sepsis were induced in mice by intravenous inoculation of bacteria. The clfAP(336Y(338 mutant induced significantly less arthritis than the wild type strain, both with respect to severity and frequency. The mutant infected mice developed also a much milder systemic inflammation, measured as lower mortality, weight loss, bacterial growth in kidneys and lower IL-6 levels. The data were verified with a second mutant where clfAP(336 and Y(338 were changed to alanine and serine respectively. When sepsis was induced by a larger bacterial inoculum, the clfAP(336Y(338 mutants induced significantly less septic death. Importantly, immunization with the recombinant A domain of ClfAP(336SY(338A mutant but not with recombinant ClfA, protected against septic death. Our data strongly suggest that the fibrinogen binding activity of ClfA is crucial for the ability of S. aureus to provoke disease manifestations, and that the vaccine potential of recombinant ClfA is improved by removing its ability to bind fibrinogen.

  15. DNS BIND Server Configuration

    Directory of Open Access Journals (Sweden)

    Radu MARSANU

    2011-01-01

    Full Text Available After a brief presentation of the DNS and BIND standard for Unix platforms, the paper presents an application which has a principal objective, the configuring of the DNS BIND 9 server. The general objectives of the application are presented, follow by the description of the details of designing the program.

  16. DNS BIND Server Configuratio

    OpenAIRE

    Radu MARSANU

    2011-01-01

    After a brief presentation of the DNS and BIND standard for Unix platforms, the paper presents an application which has a principal objective, the configuring of the DNS BIND 9 server. The general objectives of the application are presented, follow by the description of the details of designing the program.

  17. DNS BIND Server Configuration

    OpenAIRE

    Radu MARSANU

    2011-01-01

    After a brief presentation of the DNS and BIND standard for Unix platforms, the paper presents an application which has a principal objective, the configuring of the DNS BIND 9 server. The general objectives of the application are presented, follow by the description of the details of designing the program.

  18. Melanin-binding radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Packer, S; Fairchild, R G; Watts, K P; Greenberg, D; Hannon, S J

    1980-01-01

    The scope of this paper is limited to an analysis of the factors that are important to the relationship of radiopharmaceuticals to melanin. While the authors do not attempt to deal with differences between melanin-binding vs. melanoma-binding, a notable variance is assumed. (PSB)

  19. Melanin-binding radiopharmaceuticals

    International Nuclear Information System (INIS)

    Packer, S.; Fairchild, R.G.; Watts, K.P.; Greenberg, D.; Hannon, S.J.

    1980-01-01

    The scope of this paper is limited to an analysis of the factors that are important to the relationship of radiopharmaceuticals to melanin. While the authors do not attempt to deal with differences between melanin-binding vs. melanoma-binding, a notable variance is assumed

  20. Experimental and theoretical studies on the DNA-binding of cationic yttrium(III) complex containing 2,2‧-bipyridine

    Science.gov (United States)

    Khorasani-Motlagh, Mozhgan; Noroozifar, Meissam; Akbari, Alireza; Mirkazehi-Rigi, Sohaila

    2015-03-01

    The interaction of DNA with [Y(bpy)(OH2)6]+3, where bpy is 2,2‧-bipyridine has been studied at physiological pH in Tris-HCl buffer. Fluorescence and absorption spectroscopy, agarose gel electrophoresis as well as EB quenching experiments are used to study DNA binding of the complex. The results reveal that DNA have the strong ability to bind with Y(III) complex. The binding constant, Kb and the Stern-Volmer quenching constant, KSV are determined. For characterization of the binding mode between the Y(III) complex and DNA various procedures such as: iodide quenching assay, salt effect and thermodynamical investigation are used. The results suggest that minor groove binding should be the interaction mode of complex to DNA. A gel electrophoresis assay demonstrates the ability of the complex to cleave the DNA via oxidative pathway. Electronic structure of [Y(bpy)(OH2)6]+3 was also carried out applying the density functional theory (DFT) method and applied to explain some obtained experimental observations.

  1. Synthesis, CMC Determination, Antimicrobial Activity and Nucleic Acid Binding of A Surfactant Copper(II) Complex Containing Phenanthroline and Alanine Schiff-Base.

    Science.gov (United States)

    Nagaraj, Karuppiah; Sakthinathan, Subramanian; Arunachalam, Sankaralingam

    2014-03-01

    A new water-soluble surfactant copper(II) complex [Cu(sal-ala)(phen)(DA)] (sal-ala = salicylalanine, phen = 1,10-phenanthroline, DA = dodecylamine), has been synthesized and characterized by physico-chemical and spectroscopic methods. The critical micelle concentration (CMC) values of this surfactant-copper(II) complex in aqueous solution were obtained from conductance measurements. Specific conductivity data (at 303, 308, 313. 318 and 323 K) served for the evaluation of the temperature-dependent CMC and the thermodynamics of micellization (ΔG(0)m, ΔH(0)m and ΔS(0)m). The interaction of this complex with nucleic acids (DNA and RNA) has been explored by using electronic absorption spectral titration, competitive binding experiment, cyclic voltammetry, circular dichroism (CD) spectra, and viscosity measurements. Electronic absorption studies have revealed that the complex can bind to nucleic acids by the intercalative binding mode which has been verified by viscosity measurements. The DNA binding constants have also been calculated (Kb = 1.2 × 10(5) M(-1) for DNA and Kb = 1.6 × 10(5) M(-1) for RNA). Competitive binding study with ethidium bromide (EB) showed that the complex exhibits the ability to displace the DNA-bound-EB indicating that the complex binds to DNA in strong competition with EB for the intercalative binding site. The presence of hydrophobic ligands, alanine Schiff-base, phenanthroline and long aliphatic chain amine in the complex were responsible for this strong intercalative binding. The surfactant-copper (II) complex was screened for its antibacterial and antifungal activities against various microorganisms. The results were compared with the standard drugs, amikacin(antibacterial) and ketokonazole(antifungal).

  2. Myeloperoxidase selectively binds and selectively kills microbes.

    Science.gov (United States)

    Allen, Robert C; Stephens, Jackson T

    2011-01-01

    Myeloperoxidase (MPO) is reported to selectively bind to bacteria. The present study provides direct evidence of MPO binding selectivity and tests the relationship of selective binding to selective killing. The microbicidal effectiveness of H(2)O(2) and of OCl(-) was compared to that of MPO plus H(2)O(2). Synergistic microbicidal action was investigated by combining Streptococcus sanguinis, a H(2)O(2)-producing microbe showing low MPO binding, with high-MPO-binding Escherichia coli, Staphylococcus aureus, or Pseudomonas aeruginosa without exogenous H(2)O(2), with and without MPO, and with and without erythrocytes (red blood cells [RBCs]). Selectivity of MPO microbicidal action was conventionally measured as the MPO MIC and minimal bactericidal concentration (MBC) for 82 bacteria including E. coli, P. aeruginosa, S. aureus, Enterococcus faecalis, Streptococcus pyogenes, Streptococcus agalactiae, and viridans streptococci. Both H(2)O(2) and OCl(-) destroyed RBCs at submicrobicidal concentrations. Nanomolar concentrations of MPO increased H(2)O(2) microbicidal action 1,000-fold. Streptococci plus MPO produced potent synergistic microbicidal action against all microbes tested, and RBCs caused only a small decrease in potency without erythrocyte damage. MPO directly killed H(2)O(2)-producing S. pyogenes but was ineffective against non-H(2)O(2)-producing E. faecalis. The MPO MICs and MBCs for E. coli, P. aeruginosa, and S. aureus were significantly lower than those for E. faecalis. The streptococcal studies showed much higher MIC/MBC results, but such testing required lysed horse blood-supplemented medium, thus preventing valid comparison of these results to those for the other microbes. E. faecalis MPO binding is reportedly weak compared to binding of E. coli, P. aeruginosa, and S. aureus but strong compared to binding of streptococci. Selective MPO binding results in selective killing.

  3. Crystal Structure of the Botulinum Neurotoxin Type G Binding Domain: Insight into Cell Surface Binding

    Energy Technology Data Exchange (ETDEWEB)

    Stenmark, Pål; Dong, Min; Dupuy, Jérôme; Chapman, Edwin R.; Stevens, Raymond C. (Scripps); (UW)

    2011-11-02

    Botulinum neurotoxins (BoNTs) typically bind the neuronal cell surface via dual interactions with both protein receptors and gangliosides. We present here the 1.9-{angstrom} X-ray structure of the BoNT serotype G (BoNT/G) receptor binding domain (residues 868-1297) and a detailed view of protein receptor and ganglioside binding regions. The ganglioside binding motif (SxWY) has a conserved structure compared to the corresponding regions in BoNT serotype A and BoNT serotype B (BoNT/B), but several features of interactions with the hydrophilic face of the ganglioside are absent at the opposite side of the motif in the BoNT/G ganglioside binding cleft. This may significantly reduce the affinity between BoNT/G and gangliosides. BoNT/G and BoNT/B share the protein receptor synaptotagmin (Syt) I/II. The Syt binding site has a conserved hydrophobic plateau located centrally in the proposed protein receptor binding interface (Tyr1189, Phe1202, Ala1204, Pro1205, and Phe1212). Interestingly, only 5 of 14 residues that are important for binding between Syt-II and BoNT/B are conserved in BoNT/G, suggesting that the means by which BoNT/G and BoNT/B bind Syt diverges more than previously appreciated. Indeed, substitution of Syt-II Phe47 and Phe55 with alanine residues had little effect on the binding of BoNT/G, but strongly reduced the binding of BoNT/B. Furthermore, an extended solvent-exposed hydrophobic loop, located between the Syt binding site and the ganglioside binding cleft, may serve as a third membrane association and binding element to contribute to high-affinity binding to the neuronal membrane. While BoNT/G and BoNT/B are homologous to each other and both utilize Syt-I/Syt-II as their protein receptor, the precise means by which these two toxin serotypes bind to Syt appears surprisingly divergent.

  4. Predicting Arithmetic Abilities: The Role of Preparatory Arithmetic Markers and Intelligence

    Science.gov (United States)

    Stock, Pieter; Desoete, Annemie; Roeyers, Herbert

    2009-01-01

    Arithmetic abilities acquired in kindergarten are found to be strong predictors for later deficient arithmetic abilities. This longitudinal study (N = 684) was designed to examine if it was possible to predict the level of children's arithmetic abilities in first and second grade from their performance on preparatory arithmetic abilities in…

  5. Strongly Interacting Light Dark Matter

    Directory of Open Access Journals (Sweden)

    Sebastian Bruggisser, Francesco Riva, Alfredo Urbano

    2017-09-01

    Full Text Available In the presence of approximate global symmetries that forbid relevant interactions, strongly coupled light Dark Matter (DM can appear weakly coupled at small energy and generate a sizable relic abundance. Fundamental principles like unitarity restrict these symmetries to a small class, where the leading interactions are captured by effective operators up to dimension-8. Chiral symmetry, spontaneously broken global symmetries and non-linearly realized supersymmetry are examples of this. Their DM candidates (composite fermions, pseudo Nambu-Goldstone Bosons and Goldstini are interesting targets for LHC missing-energy searches.

  6. Strongly interacting light dark matter

    International Nuclear Information System (INIS)

    Bruggisser, Sebastian; Riva, Francesco; Urbano, Alfredo

    2016-07-01

    In the presence of approximate global symmetries that forbid relevant interactions, strongly coupled light Dark Matter (DM) can appear weakly coupled at small-energy and generate a sizable relic abundance. Fundamental principles like unitarity restrict these symmetries to a small class, where the leading interactions are captured by effective operators up to dimension-8. Chiral symmetry, spontaneously broken global symmetries and non-linearly realized supersymmetry are examples of this. Their DM candidates (composite fermions, pseudo-Nambu-Goldstone Bosons and Goldstini) are interesting targets for LHC missing-energy searches.

  7. Rydberg atoms in strong fields

    International Nuclear Information System (INIS)

    Kleppner, D.; Tsimmerman, M.

    1985-01-01

    Experimental and theoretical achievements in studying Rydberg atoms in external fields are considered. Only static (or quasistatic) fields and ''one-electron'' atoms, i.e. atoms that are well described by one-electron states, are discussed. Mainly behaviour of alkali metal atoms in electric field is considered. The state of theoretical investigations for hydrogen atom in magnetic field is described, but experimental data for atoms of alkali metals are presented as an illustration. Results of the latest experimental and theoretical investigations into the structure of Rydberg atoms in strong fields are presented

  8. Scalar strong interaction hadron theory

    CERN Document Server

    Hoh, Fang Chao

    2015-01-01

    The scalar strong interaction hadron theory, SSI, is a first principles' and nonlocal theory at quantum mechanical level that provides an alternative to low energy QCD and Higgs related part of the standard model. The quark-quark interaction is scalar rather than color-vectorial. A set of equations of motion for mesons and another set for baryons have been constructed. This book provides an account of the present state of a theory supposedly still at its early stage of development. This work will facilitate researchers interested in entering into this field and serve as a basis for possible future development of this theory.

  9. Strong Plate, Weak Slab Dichotomy

    Science.gov (United States)

    Petersen, R. I.; Stegman, D. R.; Tackley, P.

    2015-12-01

    Models of mantle convection on Earth produce styles of convection that are not observed on Earth.Moreover non-Earth-like modes, such as two-sided downwellings, are the de facto mode of convection in such models.To recreate Earth style subduction, i.e. one-sided asymmetric recycling of the lithosphere, proper treatment of the plates and plate interface are required. Previous work has identified several model features that promote subduction. A free surface or pseudo-free surface and a layer of material with a relatively low strength material (weak crust) allow downgoing plates to bend and slide past overriding without creating undue stress at the plate interface. (Crameri, et al. 2012, GRL)A low viscosity mantle wedge, possibly a result of slab dehydration, decouples the plates in the system. (Gerya et al. 2007, Geo)Plates must be composed of material which, in the case of the overriding plate, are is strong enough to resist bending stresses imposed by the subducting plate and yet, as in the case of the subducting plate, be weak enough to bend and subduct when pulled by the already subducted slab. (Petersen et al. 2015, PEPI) Though strong surface plates are required for subduction such plates may present a problem when they encounter the lower mantle.As the subducting slab approaches the higher viscosity, lower mantle stresses are imposed on the tip.Strong slabs transmit this stress to the surface.There the stress field at the plate interface is modified and potentially modifies the style of convection. In addition to modifying the stress at the plate interface, the strength of the slab affects the morphology of the slab at the base of the upper mantle. (Stegman, et al 2010, Tectonophysics)Slabs that maintain a sufficient portion of their strength after being bent require high stresses to unbend or otherwise change their shape.On the other hand slabs that are weakened though the bending process are more amenable to changes in morphology. We present the results of

  10. Processing of space, time, and number contributes to mathematical abilities above and beyond domain-general cognitive abilities.

    Science.gov (United States)

    Skagerlund, Kenny; Träff, Ulf

    2016-03-01

    The current study investigated whether processing of number, space, and time contributes to mathematical abilities beyond previously known domain-general cognitive abilities in a sample of 8- to 10-year-old children (N=133). Multiple regression analyses revealed that executive functions and general intelligence predicted all aspects of mathematics and overall mathematical ability. Working memory capacity did not contribute significantly to our models, whereas spatial ability was a strong predictor of achievement. The study replicates earlier research showing that non-symbolic number processing seems to lose predictive power of mathematical abilities once the symbolic system is acquired. Novel findings include the fact that time discrimination ability was tied to calculation ability. Therefore, a conclusion is that magnitude processing in general contributes to mathematical achievement. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Historical Evolution of Spatial Abilities

    Directory of Open Access Journals (Sweden)

    A. Ardila

    1993-01-01

    Full Text Available Historical evolution and cross-cultural differences in spatial abilities are analyzed. Spatial abilities have been found to be significantly associated with the complexity of geographical conditions and survival demands. Although impaired spatial cognition is found in cases of, exclusively or predominantly, right hemisphere pathology, it is proposed that this asymmetry may depend on the degree of training in spatial abilities. It is further proposed that spatial cognition might have evolved in a parallel way with cultural evolution and environmental demands. Contemporary city humans might be using spatial abilities in some new, conceptual tasks that did not exist in prehistoric times: mathematics, reading, writing, mechanics, music, etc. Cross-cultural analysis of spatial abilities in different human groups, normalization of neuropsychological testing instruments, and clinical observations of spatial ability disturbances in people with different cultural backgrounds and various spatial requirements, are required to construct a neuropsychological theory of brain organization of spatial cognition.

  12. Single aromatic residue location alters nucleic acid binding and chaperone function of FIV nucleocapsid protein

    Science.gov (United States)

    Wu, Hao; Wang, Wei; Naiyer, Nada; Fichtenbaum, Eric; Qualley, Dominic F.; McCauley, Micah J.; Gorelick, Robert J.; Rouzina, Ioulia; Musier-Forsyth, Karin; Williams, Mark C.

    2014-01-01

    Feline immunodeficiency virus (FIV) is a retrovirus that infects domestic cats, and is an excellent animal model for human immunodeficiency virus type 1 (HIV-1) pathogenesis. The nucleocapsid (NC) protein is critical for replication in both retroviruses. FIV NC has several structural features that differ from HIV-1 NC. While both NC proteins have a single conserved aromatic residue in each of the two zinc fingers, the aromatic residue on the second finger of FIV NC is located on the opposite C-terminal side relative to its location in HIV-1 NC. In addition, whereas HIV-1 NC has a highly charged cationic N-terminal tail and a relatively short C-terminal extension, the opposite is true for FIV NC. To probe the impact of these differences on the nucleic acid (NA) binding and chaperone properties of FIV NC, we carried out ensemble and single-molecule assays with wild-type (WT) and mutant proteins. The ensemble studies show that FIV NC binding to DNA is strongly electrostatic, with a higher effective charge than that observed for HIV-1 NC. The C-terminal basic domain contributes significantly to the NA binding capability of FIV NC. In addition, the non-electrostatic component of DNA binding is much weaker for FIV NC than for HIV-1 NC. Mutation of both aromatic residues in the zinc fingers to Ala (F12A/W44A) further increases the effective charge of FIV NC and reduces its non-electrostatic binding affinity. Interestingly, switching the location of the C-terminal aromatic residue to mimic the HIV-1 NC sequence (N31W/W44A) reduces the effective charge of FIV NC and increases its non-electrostatic binding affinity to values similar to HIV-1 NC. Consistent with the results of these ensemble studies, single-molecule DNA stretching studies show that while WT FIV NC has reduced stacking capability relative to HIV-1 NC, the aromatic switch mutant recovers the ability to intercalate between the DNA bases. Our results demonstrate that altering the position of a single aromatic

  13. Detection of secondary binding sites in proteins using fragment screening.

    Science.gov (United States)

    Ludlow, R Frederick; Verdonk, Marcel L; Saini, Harpreet K; Tickle, Ian J; Jhoti, Harren

    2015-12-29

    Proteins need to be tightly regulated as they control biological processes in most normal cellular functions. The precise mechanisms of regulation are rarely completely understood but can involve binding of endogenous ligands and/or partner proteins at specific locations on a protein that can modulate function. Often, these additional secondary binding sites appear separate to the primary binding site, which, for example for an enzyme, may bind a substrate. In previous work, we have uncovered several examples in which secondary binding sites were discovered on proteins using fragment screening approaches. In each case, we were able to establish that the newly identified secondary binding site was biologically relevant as it was able to modulate function by the binding of a small molecule. In this study, we investigate how often secondary binding sites are located on proteins by analyzing 24 protein targets for which we have performed a fragment screen using X-ray crystallography. Our analysis shows that, surprisingly, the majority of proteins contain secondary binding sites based on their ability to bind fragments. Furthermore, sequence analysis of these previously unknown sites indicate high conservation, which suggests that they may have a biological function, perhaps via an allosteric mechanism. Comparing the physicochemical properties of the secondary sites with known primary ligand binding sites also shows broad similarities indicating that many of the secondary sites may be druggable in nature with small molecules that could provide new opportunities to modulate potential therapeutic targets.

  14. Language mastery, narrative abilities and oral expression abilities in ...

    African Journals Online (AJOL)

    The importance of language and language mastery for science learning has been the object of extensive investigation in recent decades, leading to ample recognition. However, specific focus on the role of narrative abilities is still scarce. This work focuses on the relevance of narrative abilities for chemistry learning.

  15. EDITORIAL: Strongly correlated electron systems Strongly correlated electron systems

    Science.gov (United States)

    Ronning, Filip; Batista, Cristian

    2011-03-01

    Strongly correlated electrons is an exciting and diverse field in condensed matter physics. This special issue aims to capture some of that excitement and recent developments in the field. Given that this issue was inspired by the 2010 International Conference on Strongly Correlated Electron Systems (SCES 2010), we briefly give some history in order to place this issue in context. The 2010 International Conference on Strongly Correlated Electron Systems was held in Santa Fe, New Mexico, a reunion of sorts from the 1989 International Conference on the Physics of Highly Correlated Electron Systems that also convened in Santa Fe. SCES 2010—co-chaired by John Sarrao and Joe Thompson—followed the tradition of earlier conferences, in this century, hosted by Buzios (2008), Houston (2007), Vienna (2005), Karlsruhe (2004), Krakow (2002) and Ann Arbor (2001). Every three years since 1997, SCES has joined the International Conference on Magnetism (ICM), held in Recife (2000), Rome (2003), Kyoto (2006) and Karlsruhe (2009). Like its predecessors, SCES 2010 topics included strongly correlated f- and d-electron systems, heavy-fermion behaviors, quantum-phase transitions, non-Fermi liquid phenomena, unconventional superconductivity, and emergent states that arise from electronic correlations. Recent developments from studies of quantum magnetism and cold atoms complemented the traditional subjects and were included in SCES 2010. 2010 celebrated the 400th anniversary of Santa Fe as well as the birth of astronomy. So what's the connection to SCES? The Dutch invention of the first practical telescope and its use by Galileo in 1610 and subsequent years overturned dogma that the sun revolved about the earth. This revolutionary, and at the time heretical, conclusion required innovative combinations of new instrumentation, observation and mathematics. These same combinations are just as important 400 years later and are the foundation of scientific discoveries that were discussed

  16. Cognitive and neuropsychological underpinnings of relational and conjunctive working memory binding across age

    NARCIS (Netherlands)

    Geldorp, B. van; Parra, M.A.; Kessels, R.P.C.

    2015-01-01

    The ability to form associations (i.e., binding) is critical for memory formation. Recent studies suggest that aging specifically affects relational binding (associating separate features) but not conjunctive binding (integrating features within an object). Possibly, this dissociation may be driven

  17. Binding energies of hypernuclei and hypernuclear interactions

    Energy Technology Data Exchange (ETDEWEB)

    Bodmer, A.R. [Argonne National Lab., IL (United States)]|[Univ. of Illinois, Chicago, IL (United States). Dept. of Physics; Murali, S.; Usmani, Q.N. [Jamia Millia Islamia, New Delhi (India). Dept. of Physics

    1996-05-01

    In part 1 the effect of nuclear core dynamics on the binding energies of {Lambda} hypernuclei is discussed in the framework of variational correlated wave functions. In particular, the authors discuss a new rearrangement energy contribution and its effect on the core polarization. In part 2 they consider the interpretation of the {Lambda} single-particle energy in terms of basic {Lambda}-nuclear interactions using a local density approximation based on a Fermi hypernetted chain calculation of the A binding to nuclear matter. To account for the data strongly repulsive 3-body {Lambda}NN forces are required. Also in this framework they discuss core polarization for medium and heavier hypernuclei.

  18. Binding energies of hypernuclei and hypernuclear interactions

    International Nuclear Information System (INIS)

    Bodmer, A.R.; Univ. of Illinois, Chicago, IL; Murali, S.; Usmani, Q.N.

    1996-01-01

    In part 1 the effect of nuclear core dynamics on the binding energies of Λ hypernuclei is discussed in the framework of variational correlated wave functions. In particular, the authors discuss a new rearrangement energy contribution and its effect on the core polarization. In part 2 they consider the interpretation of the Λ single-particle energy in terms of basic Λ-nuclear interactions using a local density approximation based on a Fermi hypernetted chain calculation of the A binding to nuclear matter. To account for the data strongly repulsive 3-body ΛNN forces are required. Also in this framework they discuss core polarization for medium and heavier hypernuclei

  19. Physics of Strongly Coupled Plasma

    Energy Technology Data Exchange (ETDEWEB)

    Kraeft, Wolf-Dietrich [Universitat Rostock (Germany)

    2007-07-15

    Strongly coupled plasmas (or non-ideal plasmas) are multi-component charged many-particle systems, in which the mean value of the potential energy of the system is of the same order as or even higher than the mean value of the kinetic energy. The constituents are electrons, ions, atoms and molecules. Dusty (or complex) plasmas contain still mesoscopic (multiply charged) particles. In such systems, the effects of strong coupling (non-ideality) lead to considerable deviations of physical properties from the corresponding properties of ideal plasmas, i.e., of plasmas in which the mean kinetic energy is essentially larger than the mean potential energy. For instance, bound state energies become density dependent and vanish at higher densities (Mott effect) due to the interaction of the pair with the surrounding particles. Non-ideal plasmas are of interest both for general scientific reasons (including, for example, astrophysical questions), and for technical applications such as inertially confined fusion. In spite of great efforts both experimentally and theoretically, satisfactory information on the physical properties of strongly coupled plasmas is not at hand for any temperature and density. For example, the theoretical description of non-ideal plasmas is possible only at low densities/high temperatures and at extremely high densities (high degeneracy). For intermediate degeneracy, however, numerical experiments have to fill the gap. Experiments are difficult in the region of 'warm dense matter'. The monograph tries to present the state of the art concerning both theoretical and experimental attempts. It mainly includes results of the work performed in famous Russian laboratories in recent decades. After outlining basic concepts (chapter 1), the generation of plasmas is considered (chapter 2, chapter 3). Questions of partial (chapter 4) and full ionization (chapter 5) are discussed including Mott transition and Wigner crystallization. Electrical and

  20. Strongly coupled dust coulomb clusters

    International Nuclear Information System (INIS)

    Juan Wentau; Lai Yingju; Chen Mingheng; I Lin

    1999-01-01

    The structures and motions of quasi-2-dimensional strongly coupled dust Coulomb clusters with particle number N from few to hundreds in a cylindrical rf plasma trap are studied and compared with the results from the molecular dynamic simulation using more ideal models. Shell structures with periodic packing in different shells and intershell rotational motion dominated excitations are observed at small N. As N increases, the boundary has less effect, the system recovers to the triangular lattice with isotropic vortex type cooperative excitations similar to an infinite N system except the outer shell region. The above generic behaviors are mainly determined by the system symmetry and agree with the simulation results. The detailed interaction form causes minor effect such as the fine structure of packing

  1. Probability densities in strong turbulence

    Science.gov (United States)

    Yakhot, Victor

    2006-03-01

    In this work we, using Mellin’s transform combined with the Gaussian large-scale boundary condition, calculate probability densities (PDFs) of velocity increments P(δu,r), velocity derivatives P(u,r) and the PDF of the fluctuating dissipation scales Q(η,Re), where Re is the large-scale Reynolds number. The resulting expressions strongly deviate from the Log-normal PDF P(δu,r) often quoted in the literature. It is shown that the probability density of the small-scale velocity fluctuations includes information about the large (integral) scale dynamics which is responsible for the deviation of P(δu,r) from P(δu,r). An expression for the function D(h) of the multifractal theory, free from spurious logarithms recently discussed in [U. Frisch, M. Martins Afonso, A. Mazzino, V. Yakhot, J. Fluid Mech. 542 (2005) 97] is also obtained.

  2. Sensory and cognitive factors influencing functional ability in older adults.

    Science.gov (United States)

    Wood, Kimberly M; Edwards, Jerri D; Clay, Olivio J; Wadley, Virginia G; Roenker, Daniel L; Ball, Karlene K

    2005-01-01

    Age-related sensory and cognitive impairments have been related to functional performance in older adults. With regard to cognitive abilities, processing speed in particular may be strongly related to older adults' abilities to perform everyday tasks. Identifying and comparing cognitive correlates of functional performance is particularly important in order to design interventions to promote independence and prevent functional disability. The present study examined the relative importance of cognitive (specifically, speeded and nonspeeded) and sensory factors in relation to older adults' functional abilities. Functional abilities included measures of mobility and performance of everyday activities. A cross-sectional study design was employed. Five hundred and thirty adults between the ages of 62 and 94 completed measures of sensory, cognitive (including processing speed, attention, memory, intelligence) and functional abilities. Overall, functional performance was most strongly associated with cognitive speed performance, but nonspeeded cognitive and sensory abilities also accounted for significant amounts of variance in functional performance. Age explained a small but statistically significant amount of additional variance in some functional abilities, but no additional variance in self-reported mobility measures. These findings point to the potential impact of multifaceted training programs, targeting both sensory and cognitive abilities for maintaining functional abilities. Copyright (c) 2005 S. Karger AG, Basel.

  3. Assessing Highly-Creative Ability

    Science.gov (United States)

    Cowdroy, Rob; de Graaff, Erik

    2005-01-01

    This paper presents a psychological perspective of the educational dilemma of assessing highly (high-level) creative ability (with some connections to contemporary philosophical debate). Assessment of highly-creative ability is a topic of longstanding debate involving questions of what constitutes creativity; whether the creative mental process is…

  4. Ability Dispersion and Team Performance

    DEFF Research Database (Denmark)

    Hoogendoorn, Sander; Parker, Simon C.; Van Praag, Mirjam

    increases and then decreases with ability dispersion. We seek to understand this finding by developing a model in which team members of different ability levels form sub- teams with other team members with similar ability levels to specialize in different productive tasks. Diversity spreads production over......What is the effect of dispersed levels of cognitive ability of members of a (business) team on their team's performance? This paper reports the results of a field experiment in which 573 students in 49 (student) teams start up and manage real companies under identical circumstances for one year. We...... ensured exogenous variation in otherwise random team composition by assigning students to teams based on their measured cognitive abilities. Each team performs a variety of tasks, often involving complex decision making. The key result of the experiment is that the performance of business teams first...

  5. APPLICATION OF IMMUNOGLOBULIN-BINDING PROTEINS A, G, L IN THE AFFINITY CHROMATOGRAPHY

    Directory of Open Access Journals (Sweden)

    О. V. Sviatenko

    2014-04-01

    Full Text Available Proteins A, G and L are native or recombinant proteins of microbial origin that bind to mammalian immunoglobulins. Preferably recombinant variants of proteins A, G, L are used in biotechnology for affinity sorbents production. Сomparative characteristics of proteins A, G, L and affinity sorbents on the basis of them, advantages and disadvantages of these proteins application as ligands in the affinity chromatography are done. Analysis of proteins A, G, L properties is presented. Binding specificities and affinities of these proteins differ between species and antibody subclass. Protein А has high affinity to human IgG1, IgG2, IgG4, mouse IgG2a, IgG2b, IgG3, goat and sheep IgG2, dog, cat, guinea pig, rabbit IgG. Protein G binds strongly to human, mouse, cow, goat, sheep and rabbit IgG. Protein L has ability of strong binding to immunoglobulin kappa-chains of human, mouse, rat and pig. Expediency of application of affinity chromatography with usage of sorbents on the basis of immobilized proteins A, G, L are shown for isolation and purification of antibodies different classes. Previously mentioned method is used as an alternative to conventional methods of protein purification, such as ion-exchange, hydrophobic interactions, metal affinity chromatography, ethanol precipitation due to simplicity in usage, possibility of one-step purification process, obtaining of proteins high level purity, multiuse at maintenance of proper storage and usage conditions. Affinity sorbents on the basis of immobilized proteins A, G, L are used not only for antibodies purification, but also for extraction of different antibodies fractions from blood serum.

  6. Strong Ideal Convergence in Probabilistic Metric Spaces

    Indian Academy of Sciences (India)

    In the present paper we introduce the concepts of strongly ideal convergent sequence and strong ideal Cauchy sequence in a probabilistic metric (PM) space endowed with the strong topology, and establish some basic facts. Next, we define the strong ideal limit points and the strong ideal cluster points of a sequence in this ...

  7. Strong ideal convergence in probabilistic metric spaces

    Indian Academy of Sciences (India)

    In the present paper we introduce the concepts of strongly ideal convergent sequence and strong ideal Cauchy sequence in a probabilistic metric (PM) space endowed with the strong topology, and establish some basic facts. Next, we define the strong ideal limit points and the strong ideal cluster points of a sequence in this ...

  8. Remnants of strong tidal interactions

    International Nuclear Information System (INIS)

    Mcglynn, T.A.

    1990-01-01

    This paper examines the properties of stellar systems that have recently undergone a strong tidal shock, i.e., a shock which removes a significant fraction of the particles in the system, and where the shocked system has a much smaller mass than the producer of the tidal field. N-body calculations of King models shocked in a variety of ways are performed, and the consequences of the shocks are investigated. The results confirm the prediction of Jaffe for shocked systems. Several models are also run where the tidal forces on the system are constant, simulating a circular orbit around a primary, and the development of tidal radii under these static conditions appears to be a mild process which does not dramatically affect material that is not stripped. The tidal radii are about twice as large as classical formulas would predict. Remnant density profiles are compared with a sample of elliptical galaxies, and the implications of the results for the development of stellar populations and galaxies are considered. 38 refs

  9. John Strong - 1941-2006

    CERN Document Server

    2006-01-01

    Our friend and colleague John Strong was cruelly taken from us by a brain tumour on 31 July, a few days before his 65th birthday. John started his career and obtained his PhD in a group from Westfield College, initially working on experiments at Rutherford Appleton Laboratory (RAL). From the early 1970s onwards, however, his research was focused on experiments in CERN, with several particularly notable contributions. The Omega spectrometer adopted a system John had originally developed for experiments at RAL using vidicon cameras (a type of television camera) to record the sparks in the spark chambers. This highly automated system allowed Omega to be used in a similar way to bubble chambers. He contributed to the success of NA1 and NA7, where he became heavily involved in the electronic trigger systems. In these experiments the Westfield group joined forces with Italian colleagues to measure the form factors of the pion and the kaon, and the lifetime of some of the newly discovered charm particles. Such h...

  10. Strong seismic ground motion propagation

    International Nuclear Information System (INIS)

    Seale, S.; Archuleta, R.; Pecker, A.; Bouchon, M.; Mohammadioun, G.; Murphy, A.; Mohammadioun, B.

    1988-10-01

    At the McGee Creek, California, site, 3-component strong-motion accelerometers are located at depths of 166 m, 35 m and 0 m. The surface material is glacial moraine, to a depth of 30.5 m, overlying homfels. Accelerations were recorded from two California earthquakes: Round Valley, M L 5.8, November 23, 1984, 18:08 UTC and Chalfant Valley, M L 6.4, July 21, 1986, 14:42 UTC. By separating out the SH components of acceleration, we were able to determine the orientations of the downhole instruments. By separating out the SV component of acceleration, we were able to determine the approximate angle of incidence of the signal at 166 m. A constant phase velocity Haskell-Thomson model was applied to generate synthetic SH seismograms at the surface using the accelerations recorded at 166 m. In the frequency band 0.0 - 10.0 Hz, we compared the filtered synthetic records to the filtered surface data. The onset of the SH pulse is clearly seen, as are the reflections from the interface at 30.5 m. The synthetic record closely matches the data in amplitude and phase. The fit between the synthetic accelerogram and the data shows that the seismic amplification at the surface is a result of the contrast of the impedances (shear stiffnesses) of the near surface materials

  11. Balance ability and athletic performance.

    Science.gov (United States)

    Hrysomallis, Con

    2011-03-01

    The relationship between balance ability and sport injury risk has been established in many cases, but the relationship between balance ability and athletic performance is less clear. This review compares the balance ability of athletes from different sports, determines if there is a difference in balance ability of athletes at different levels of competition within the same sport, determines the relationship of balance ability with performance measures and examines the influence of balance training on sport performance or motor skills. Based on the available data from cross-sectional studies, gymnasts tended to have the best balance ability, followed by soccer players, swimmers, active control subjects and then basketball players. Surprisingly, no studies were found that compared the balance ability of rifle shooters with other athletes. There were some sports, such as rifle shooting, soccer and golf, where elite athletes were found to have superior balance ability compared with their less proficient counterparts, but this was not found to be the case for alpine skiing, surfing and judo. Balance ability was shown to be significantly related to rifle shooting accuracy, archery shooting accuracy, ice hockey maximum skating speed and simulated luge start speed, but not for baseball pitching accuracy or snowboarding ranking points. Prospective studies have shown that the addition of a balance training component to the activities of recreationally active subjects or physical education students has resulted in improvements in vertical jump, agility, shuttle run and downhill slalom skiing. A proposed mechanism for the enhancement in motor skills from balance training is an increase in the rate of force development. There are limited data on the influence of balance training on motor skills of elite athletes. When the effectiveness of balance training was compared with resistance training, it was found that resistance training produced superior performance results for

  12. Haptenation: Chemical Reactivity and Protein Binding

    Directory of Open Access Journals (Sweden)

    Itai Chipinda

    2011-01-01

    Full Text Available Low molecular weight chemical (LMW allergens are commonly referred to as haptens. Haptens must complex with proteins to be recognized by the immune system. The majority of occupationally related haptens are reactive, electrophilic chemicals, or are metabolized to reactive metabolites that form covalent bonds with nucleophilic centers on proteins. Nonelectrophilic protein binding may occur through disulfide exchange, coordinate covalent binding onto metal ions on metalloproteins or of metal allergens, themselves, to the major histocompatibility complex. Recent chemical reactivity kinetic studies suggest that the rate of protein binding is a major determinant of allergenic potency; however, electrophilic strength does not seem to predict the ability of a hapten to skew the response between Th1 and Th2. Modern proteomic mass spectrometry methods that allow detailed delineation of potential differences in protein binding sites may be valuable in predicting if a chemical will stimulate an immediate or delayed hypersensitivity. Chemical aspects related to both reactivity and protein-specific binding are discussed.

  13. Engineered Escherichia coli silver-binding periplasmic protein that promotes silver tolerance.

    Science.gov (United States)

    Sedlak, Ruth Hall; Hnilova, Marketa; Grosh, Carolynn; Fong, Hanson; Baneyx, Francois; Schwartz, Dan; Sarikaya, Mehmet; Tamerler, Candan; Traxler, Beth

    2012-04-01

    Silver toxicity is a problem that microorganisms face in medical and environmental settings. Through exposure to silver compounds, some bacteria have adapted to growth in high concentrations of silver ions. Such adapted microbes may be dangerous as pathogens but, alternatively, could be potentially useful in nanomaterial-manufacturing applications. While naturally adapted isolates typically utilize efflux pumps to achieve metal resistance, we have engineered a silver-tolerant Escherichia coli strain by the use of a simple silver-binding peptide motif. A silver-binding peptide, AgBP2, was identified from a combinatorial display library and fused to the C terminus of the E. coli maltose-binding protein (MBP) to yield a silver-binding protein exhibiting nanomolar affinity for the metal. Growth experiments performed in the presence of silver nitrate showed that cells secreting MBP-AgBP2 into the periplasm exhibited silver tolerance in a batch culture, while those expressing a cytoplasmic version of the fusion protein or MBP alone did not. Transmission electron microscopy analysis of silver-tolerant cells revealed the presence of electron-dense silver nanoparticles. This is the first report of a specifically engineered metal-binding peptide exhibiting a strong in vivo phenotype, pointing toward a novel ability to manipulate bacterial interactions with heavy metals by the use of short and simple peptide motifs. Engineered metal-ion-tolerant microorganisms such as this E. coli strain could potentially be used in applications ranging from remediation to interrogation of biomolecule-metal interactions in vivo.

  14. Strongly interacting photons and atoms

    International Nuclear Information System (INIS)

    Alge, W.

    1999-05-01

    This thesis contains the main results of the research topics I have pursued during the my PhD studies at the University of Innsbruck and partly in collaboration with the Institut d' Optique in Orsay, France. It is divided into three parts. The first and largest part discusses the possibility of using strong standing waves as a tool to cool and trap neutral atoms in optical cavities. This is very important in the field of nonlinear optics where several successful experiments with cold atoms in cavities have been performed recently. A discussion of the optical parametric oscillator in a regime where the nonlinearity dominates the evolution is the topic of the second part. We investigated mainly the statistical properties of the cavity output of the three interactive cavity modes. Very recently a system has been proposed which promises fantastic properties. It should exhibit a giant Kerr nonlinearity with negligible absorption thus leading to a photonic turnstile device based on cold atoms in cavity. We have shown that this model suffers from overly simplistic assumptions and developed several more comprehensive approaches to study the behavior of this system. Apart from the division into three parts of different contents the thesis is divided into publications, supplements and invisible stuff. The intention of the supplements is to reach researchers which work in related areas and provide them with more detailed information about the concepts and the numerical tools we used. It is written especially for diploma and PhD students to give them a chance to use the third part of our work which is actually the largest one. They consist of a large number of computer programs we wrote to investigate the behavior of the systems in parameter regions where no hope exists to solve the equations analytically. (author)

  15. Topics in strong Langmuir turbulence

    International Nuclear Information System (INIS)

    Skoric, M.M.

    1981-01-01

    This thesis discusses certain aspects of the turbulence of a fully ionised non-isothermal plasma dominated by the Langmuir mode. Some of the basic properties of strongly turbulent plasmas are reviewed. In particular, interest is focused on the state of Langmuir turbulence, that is the turbulence of a simple externally unmagnetized plasma. The problem of the existence and dynamics of Langmuir collapse is discussed, often met as a non-linear stage of the modulational instability in the framework of the Zakharov equations (i.e. simple time-averaged dynamical equations). Possible macroscopic consequences of such dynamical turbulent models are investigated. In order to study highly non-linear collapse dynamics in its advanced stage, a set of generalized Zakharov equations are derived. Going beyond the original approximation, the author includes the effects of higher electron non-linearities and a breakdown of slow-timescale quasi-neutrality. He investigates how these corrections may influence the collapse stabilisation. Recently, it has been realised that the modulational instability in a Langmuir plasma will be accompanied by the collisionless-generation of a slow-timescale magnetic field. Accordingly, a novel physical situation has emerged which is investigated in detail. The stability of monochromatic Langmuir waves in a self-magnetized Langmuir plasma, is discussed, and the existence of a novel magneto-modulational instability shown. The wave collapse dynamics is investigated and a physical interpretation of the basic results is given. A problem of the transient analysis of an interaction of time-dependent electromagnetic pulses with linear cold plasma media is investigated. (Auth.)

  16. Promoting Strong Written Communication Skills

    Science.gov (United States)

    Narayanan, M.

    2015-12-01

    The reason that an improvement in the quality of technical writing is still needed in the classroom is due to the fact that universities are facing challenging problems not only on the technological front but also on the socio-economic front. The universities are actively responding to the changes that are taking place in the global consumer marketplace. Obviously, there are numerous benefits of promoting strong written communication skills. They can be summarized into the following six categories. First, and perhaps the most important: The University achieves learner satisfaction. The learner has documented verbally, that the necessary knowledge has been successfully acquired. This results in learner loyalty that in turn will attract more qualified learners.Second, quality communication lowers the cost per pupil, consequently resulting in increased productivity backed by a stronger economic structure and forecast. Third, quality communications help to improve the cash flow and cash reserves of the university. Fourth, having high quality communication enables the university to justify the need for high costs of tuition and fees. Fifth, better quality in written communication skills result in attracting top-quality learners. This will lead to happier and satisfied learners, not to mention greater prosperity for the university as a whole. Sixth, quality written communication skills result in reduced complaints, thus meaning fewer hours spent on answering or correcting the situation. The University faculty and staff are thus able to devote more time on scholarly activities, meaningful research and productive community service. References Boyer, Ernest L. (1990). Scholarship reconsidered: Priorities of the Professorate.Princeton, NJ: Carnegie Foundation for the Advancement of Teaching. Hawkins, P., & Winter, J. (1997). Mastering change: Learning the lessons of the enterprise.London: Department for Education and Employment. Buzzel, Robert D., and Bradley T. Gale. (1987

  17. Mannose-binding geometry of pradimicin A.

    Science.gov (United States)

    Nakagawa, Yu; Doi, Takashi; Taketani, Takara; Takegoshi, K; Igarashi, Yasuhiro; Ito, Yukishige

    2013-08-05

    Pradimicins (PRMs) and benanomicins are the only family of non-peptidic natural products with lectin-like properties, that is, they recognize D-mannopyranoside (Man) in the presence of Ca(2+) ions. Coupled with their unique Man binding ability, they exhibit antifungal and anti-HIV activities through binding to Man-containing glycans of pathogens. Notwithstanding the great potential of PRMs as the lectin mimics and therapeutic leads, their molecular basis of Man recognition has yet to be established. Their aggregate-forming propensity has impeded conventional interaction analysis in solution, and the analytical difficulty is exacerbated by the existence of two Man binding sites in PRMs. In this work, we investigated the geometry of the primary Man binding of PRM-A, an original member of PRMs, by the recently developed analytical strategy using the solid aggregate composed of the 1:1 complex of PRM-A and Man. Evaluation of intermolecular distances by solid-state NMR spectroscopy revealed that the C2-C4 region of Man is in close contact with the primary binding site of PRM-A, while the C1 and C6 positions of Man are relatively distant. The binding geometry was further validated by co-precipitation experiments using deoxy-Man derivatives, leading to the proposal that PRM-A binds not only to terminal Man residues at the non-reducing end of glycans, but also to internal 6-substituted Man residues. The present study provides new insights into the molecular basis of Man recognition and glycan specificity of PRM-A. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. CARBOHYDRATE-CONTAINING COMPOUNDS WHICH BIND TO CARBOHYDRATE BINDING RECEPTORS

    DEFF Research Database (Denmark)

    1995-01-01

    Carbohydrate-containing compounds which contain saccharides or derivatives thereof and which bind to carbohydrate binding receptors are useful in pharmaceutical products for treatment of inflammatory diseases and other diseases.......Carbohydrate-containing compounds which contain saccharides or derivatives thereof and which bind to carbohydrate binding receptors are useful in pharmaceutical products for treatment of inflammatory diseases and other diseases....

  19. DNABP: Identification of DNA-Binding Proteins Based on Feature Selection Using a Random Forest and Predicting Binding Residues.

    Science.gov (United States)

    Ma, Xin; Guo, Jing; Sun, Xiao

    2016-01-01

    DNA-binding proteins are fundamentally important in cellular processes. Several computational-based methods have been developed to improve the prediction of DNA-binding proteins in previous years. However, insufficient work has been done on the prediction of DNA-binding proteins from protein sequence information. In this paper, a novel predictor, DNABP (DNA-binding proteins), was designed to predict DNA-binding proteins using the random forest (RF) classifier with a hybrid feature. The hybrid feature contains two types of novel sequence features, which reflect information about the conservation of physicochemical properties of the amino acids, and the binding propensity of DNA-binding residues and non-binding propensities of non-binding residues. The comparisons with each feature demonstrated that these two novel features contributed most to the improvement in predictive ability. Furthermore, to improve the prediction performance of the DNABP model, feature selection using the minimum redundancy maximum relevance (mRMR) method combined with incremental feature selection (IFS) was carried out during the model construction. The results showed that the DNABP model could achieve 86.90% accuracy, 83.76% sensitivity, 90.03% specificity and a Matthews correlation coefficient of 0.727. High prediction accuracy and performance comparisons with previous research suggested that DNABP could be a useful approach to identify DNA-binding proteins from sequence information. The DNABP web server system is freely available at http://www.cbi.seu.edu.cn/DNABP/.

  20. Tension-induced binding of semiflexible biopolymers

    International Nuclear Information System (INIS)

    Benetatos, Panayotis; Heydt, Alice von der; Zippelius, Annette

    2014-01-01

    We investigate theoretically the effect of polymer tension on the collective behavior of reversibly binding cross-links. For this purpose, we employ a model of two weakly bending wormlike chains aligned in parallel by a tensile force, with a sequence of inter-chain binding sites regularly spaced along the contours. Reversible cross-links attach and detach at the sites with an affinity controlled by a chemical potential. In a mean-field approach, we calculate the free energy of the system and find the emergence of a free-energy barrier which controls the reversible (un)binding. The tension affects the conformational entropy of the chains which competes with the binding energy of the cross-links. This competition gives rise to a sudden increase in the fraction of bound sites as the tension increases. We show that this transition is related to the cross-over between weak and strong localization of a directed polymer in a pinning potential. The cross-over to the strongly bound state can be interpreted as a mechanism for force-stiffening which exceeds the capabilities of single-chain elasticity and thus available only to reversibly cross-linked polymers. (paper)

  1. Binding of diphtheria toxin to phospholipids in liposomes

    Science.gov (United States)

    Alving, Carl R.; Iglewski, Barbara H.; Urban, Katharine A.; Moss, Joel; Richards, Roberta L.; Sadoff, Jerald C.

    1980-01-01

    Diphtheria toxin bound to the phosphate portion of some, but not all, phospholipids in liposomes. Liposomes consisting of dimyristoyl phosphatidylcholine and cholesterol did not bind toxin. Addition of 20 mol% (compared to dimyristoyl phosphatidylcholine) of dipalmitoyl phosphatidic acid, dicetyl phosphate, phosphatidylinositol phosphate, cardiolipin, or phosphatidylserine in the liposomes resulted in substantial binding of toxin. Inclusion of phosphatidylinositol in dimyristol phosphatidylcholine/cholesterol liposomes did not result in toxin binding. The calcium salt of dipalmitoyl phosphatidic acid was more effective than the sodium salt, and the highest level of binding occurred with liposomes consisting only of dipalmitoyl phosphatidic acid (calcium salt) and cholesterol. Binding of toxin to liposomes was dependent on pH, and the pattern of pH dependence varied with liposomes having different compositions. Incubation of diphtheria toxin with liposomes containing dicetyl phosphate resulted in maximal binding at pH 3.6, whereas binding to liposomes containing phosphatidylinositol phosphate was maximal above pH 7. Toxin did not bind to liposomes containing 20 mol% of a free fatty acid (palmitic acid) or a sulfated lipid (3-sulfogalactosylceramide). Toxin binding to dicetyl phosphate or phosphatidylinositol phosphate was inhibited by UTP, ATP, phosphocholine, or p-nitrophenyl phosphate, but not by uracil. We conclude that (a) diphtheria toxin binds specifically to the phosphate portion of certain phospholipids, (b) binding to phospholipids in liposomes is dependent on pH, but is not due only to electrostatic interaction, and (c) binding may be strongly influenced by the composition of adjacent phospholipids that do not bind toxin. We propose that a minor membrane phospholipid (such as phosphatidylinositol phosphate or phosphatidic acid), or that some other phosphorylated membrane molecule (such as a phosphoprotein) may be important in the initial binding of

  2. Binding of Diphtheria Toxin to Phospholipids in Liposomes

    Science.gov (United States)

    Alving, Carl R.; Iglewski, Barbara H.; Urban, Katharine A.; Moss, Joel; Richards, Roberta L.; Sadoff, Jerald C.

    1980-04-01

    Diphtheria toxin bound to the phosphate portion of some, but not all, phospholipids in liposomes. Liposomes consisting of dimyristoyl phosphatidylcholine and cholesterol did not bind toxin. Addition of 20 mol% (compared to dimyristoyl phosphatidylcholine) of dipalmitoyl phosphatidic acid, dicetyl phosphate, phosphatidylinositol phosphate, cardiolipin, or phosphatidylserine in the liposomes resulted in substantial binding of toxin. Inclusion of phosphatidylinositol in dimyristol phosphatidylcholine / cholesterol liposomes did not result in toxin binding. The calcium salt of dipalmitoyl phosphatidic acid was more effective than the sodium salt, and the highest level of binding occurred with liposomes consisting only of dipalmitoyl phosphatidic acid (calcium salt) and cholesterol. Binding of toxin to liposomes was dependent on pH, and the pattern of pH dependence varied with liposomes having different compositions. Incubation of diphtheria toxin with liposomes containing dicetyl phosphate resulted in maximal binding at pH 3.6, whereas binding to liposomes containing phosphatidylinositol phosphate was maximal above pH 7. Toxin did not bind to liposomes containing 20 mol% of a free fatty acid (palmitic acid) or a sulfated lipid (3-sulfogalactosylceramide). Toxin binding to dicetyl phosphate or phosphatidylinositol phosphate was inhibited by UTP, ATP, phosphocholine, or p-nitrophenyl phosphate, but not by uracil. We conclude that (a) diphtheria toxin binds specifically to the phosphate portion of certain phospholipids, (b) binding to phospholipids in liposomes is dependent on pH, but is not due only to electrostatic interaction, and (c) binding may be strongly influenced by the composition of adjacent phospholipids that do not bind toxin. We propose that a minor membrane phospholipid (such as phosphatidylinositol phosphate or phosphatidic acid), or that some other phosphorylated membrane molecule (such as a phosphoprotein) may be important in the initial binding of

  3. Numerical ability predicts mortgage default

    Science.gov (United States)

    Gerardi, Kristopher; Goette, Lorenz; Meier, Stephan

    2013-01-01

    Unprecedented levels of US subprime mortgage defaults precipitated a severe global financial crisis in late 2008, plunging much of the industrialized world into a deep recession. However, the fundamental reasons for why US mortgages defaulted at such spectacular rates remain largely unknown. This paper presents empirical evidence showing that the ability to perform basic mathematical calculations is negatively associated with the propensity to default on one’s mortgage. We measure several aspects of financial literacy and cognitive ability in a survey of subprime mortgage borrowers who took out loans in 2006 and 2007, and match them to objective, detailed administrative data on mortgage characteristics and payment histories. The relationship between numerical ability and mortgage default is robust to controlling for a broad set of sociodemographic variables, and is not driven by other aspects of cognitive ability. We find no support for the hypothesis that numerical ability impacts mortgage outcomes through the choice of the mortgage contract. Rather, our results suggest that individuals with limited numerical ability default on their mortgage due to behavior unrelated to the initial choice of their mortgage. PMID:23798401

  4. Numerical ability predicts mortgage default.

    Science.gov (United States)

    Gerardi, Kristopher; Goette, Lorenz; Meier, Stephan

    2013-07-09

    Unprecedented levels of US subprime mortgage defaults precipitated a severe global financial crisis in late 2008, plunging much of the industrialized world into a deep recession. However, the fundamental reasons for why US mortgages defaulted at such spectacular rates remain largely unknown. This paper presents empirical evidence showing that the ability to perform basic mathematical calculations is negatively associated with the propensity to default on one's mortgage. We measure several aspects of financial literacy and cognitive ability in a survey of subprime mortgage borrowers who took out loans in 2006 and 2007, and match them to objective, detailed administrative data on mortgage characteristics and payment histories. The relationship between numerical ability and mortgage default is robust to controlling for a broad set of sociodemographic variables, and is not driven by other aspects of cognitive ability. We find no support for the hypothesis that numerical ability impacts mortgage outcomes through the choice of the mortgage contract. Rather, our results suggest that individuals with limited numerical ability default on their mortgage due to behavior unrelated to the initial choice of their mortgage.

  5. Atomic model of human Rcd-1 reveals an armadillo-like-repeat protein with in vitro nucleic acid binding properties.

    Science.gov (United States)

    Garces, Robert G; Gillon, Wanda; Pai, Emil F

    2007-02-01

    Rcd-1, a protein highly conserved across eukaryotes, was initially identified as a factor essential for nitrogen starvation-invoked differentiation in fission yeast, and its Saccharomyces cerevisiae homolog, CAF40, has been identified as part of the CCR4-NOT transcription complex, where it interacts with the NOT1 protein. Mammalian homologs are involved in various cellular differentiation processes including retinoic acid-induced differentiation and hematopoetic cell development. Here, we present the 2.2 A X-ray structure of the highly conserved region of human Rcd-1 and investigate possible functional abilities of this and the full-length protein. The monomer is made up of six armadillo repeats forming a solvent-accessible, positively-charged cleft 21-22 A wide that, in contrast to other armadillo proteins, stays fully exposed in the dimer. Prompted by this finding, we established that Rcd-1 can bind to single- and double-stranded oligonucleotides in vitro with the affinity of G/C/T > A. Mutation of an arginine residue within the cleft strongly reduced or abolished oligonucleotide binding. Rcd-1's ability to bind to nucleic acids, in addition to the previously reported protein-protein interaction with NOT1, suggests a new feature in Rcd-1's role in regulation of overall cellular differentiation processes.

  6. DNA- and BSA-binding studies and anticancer activity against human breast cancer cells (MCF-7) of the zinc(II) complex coordinated by 5,6-diphenyl-3-(2-pyridyl)-1,2,4-triazine.

    Science.gov (United States)

    Anjomshoa, Marzieh; Fatemi, Seyed Jamilaldin; Torkzadeh-Mahani, Masoud; Hadadzadeh, Hassan

    2014-06-05

    Binding studies of a mononuclear zinc(II) complex, [Zn(dppt)2Cl2] (dppt is 5,6-diphenyl-3-(2-pyridyl)-1,2,4-triazine), with DNA and bovine serum albumin (BSA) have been investigated under physiological conditions. The binding properties of the complex with fish sperm DNA (FS-DNA) have been investigated by UV-Vis absorption, thermal denaturation, competitive DNA-binding studies with ethidium bromide (EB) by fluorescence, and gel electrophoresis techniques. The competitive study with (EB) shows that the complex can displace EB from the DNA-EB system and compete for the DNA-binding sites with EB, which is usually characteristic of the intercalative interaction of compounds with DNA. The value of the fluorescence quenching constant (Ksv) was obtained as 3.1×10(4)M(-1), indicating that this complex shows a high quenching efficiency and a significant degree of binding to DNA. Moreover, the intercalative binding mode has also been verified by the results of UV-Vis absorption, thermal denaturation and gel electrophoresis. The value of Kb at room temperature was calculated to be 1.97×10(5)M(-1), indicating that the complex possesses strong tendency to bind with DNA. This value is very greater than to the values obtained for other zinc(II) complexes. The interaction of the complex with BSA has been studied by UV-Vis absorption, fluorescence and circular dichroism (CD) spectroscopic techniques. The results indicate that the complex has a quite strong ability to quench the fluorescence of BSA and the binding reaction is mainly a static quenching process. The quenching constants (KSV), the binding constants (Kb), the number of binding sites at different temperatures, the binding distance between BSA and the complex (r), and the thermodynamic parameters (ΔH(o), ΔS(o) and ΔG(o)) between BSA and the complex were calculated. The complex exhibits good binding propensity to BSA showing relatively high binding constant values. The positive ΔH(o) and ΔS(o) values indicate that

  7. Event segmentation ability uniquely predicts event memory.

    Science.gov (United States)

    Sargent, Jesse Q; Zacks, Jeffrey M; Hambrick, David Z; Zacks, Rose T; Kurby, Christopher A; Bailey, Heather R; Eisenberg, Michelle L; Beck, Taylor M

    2013-11-01

    Memory for everyday events plays a central role in tasks of daily living, autobiographical memory, and planning. Event memory depends in part on segmenting ongoing activity into meaningful units. This study examined the relationship between event segmentation and memory in a lifespan sample to answer the following question: Is the ability to segment activity into meaningful events a unique predictor of subsequent memory, or is the relationship between event perception and memory accounted for by general cognitive abilities? Two hundred and eight adults ranging from 20 to 79years old segmented movies of everyday events and attempted to remember the events afterwards. They also completed psychometric ability tests and tests measuring script knowledge for everyday events. Event segmentation and script knowledge both explained unique variance in event memory above and beyond the psychometric measures, and did so as strongly in older as in younger adults. These results suggest that event segmentation is a basic cognitive mechanism, important for memory across the lifespan. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Event Segmentation Ability Uniquely Predicts Event Memory

    Science.gov (United States)

    Sargent, Jesse Q.; Zacks, Jeffrey M.; Hambrick, David Z.; Zacks, Rose T.; Kurby, Christopher A.; Bailey, Heather R.; Eisenberg, Michelle L.; Beck, Taylor M.

    2013-01-01

    Memory for everyday events plays a central role in tasks of daily living, autobiographical memory, and planning. Event memory depends in part on segmenting ongoing activity into meaningful units. This study examined the relationship between event segmentation and memory in a lifespan sample to answer the following question: Is the ability to segment activity into meaningful events a unique predictor of subsequent memory, or is the relationship between event perception and memory accounted for by general cognitive abilities? Two hundred and eight adults ranging from 20 to 79 years old segmented movies of everyday events and attempted to remember the events afterwards. They also completed psychometric ability tests and tests measuring script knowledge for everyday events. Event segmentation and script knowledge both explained unique variance in event memory above and beyond the psychometric measures, and did so as strongly in older as in younger adults. These results suggest that event segmentation is a basic cognitive mechanism, important for memory across the lifespan. PMID:23942350

  9. Mazindol analogues as potential inhibitors of the cocaine binding site at the dopamine transporter.

    Science.gov (United States)

    Houlihan, William J; Kelly, Lawrence; Pankuch, Jessica; Koletar, Judith; Brand, Leonard; Janowsky, Aaron; Kopajtic, Theresa A

    2002-09-12

    A series of mazindol (2) and homomazindol (3) analogues with a variety of electron-donating and electron-withdrawing groups in the pendant aryl group and the benzo ring C, as well as H, methoxy, and alkyl groups replacing the hydroxyl group were synthesized, and their binding affinities at the dopamine transporter (DAT) on rat or guinea pig striatal membranes were determined. Several active analogues were also evaluated for their ability to block uptake of DA, 5-HT, and NE and inhibit binding of [(125)I] RTI-55 at HEK-hDAT, HEK-hSERT, and HEK-hNET cells. Mazindane (26) was found to be a pro-drug, oxidizing (5-H --> 5-OH) to mazindol on rat striatal membranes and HEK-hDAT cells. The 4',7,8-trichloro analogue (38) of mazindol was the most potent and selective ligand for HEK-hDAT cells (DAT K(i) = 1.1 nM; SERT/DAT = 1283 and NET/DAT = 38). Experimental results strongly favor the cyclic or ol tautomers of 2 and 3 to bind more tightly at the DAT than the corresponding keto tautomers.

  10. Human serum albumin binding of certain antimalarials

    Science.gov (United States)

    Marković, Olivera S.; Cvijetić, Ilija N.; Zlatović, Mario V.; Opsenica, Igor M.; Konstantinović, Jelena M.; Terzić Jovanović, Nataša V.; Šolaja, Bogdan A.; Verbić, Tatjana Ž.

    2018-03-01

    Interactions between eight in-house synthesized aminoquinolines, along with well-known chloroquine, and human serum albumin (HSA) have been studied by fluorescence spectroscopy. The synthesized aminoquinolines, despite being structurally diverse, were found to be very potent antimalarials. Fluorescence measurements indicate that three compounds having additional thiophene or benzothiophene substructure bind more strongly to HSA than other studied compounds. Competitive binding experiments indicate that these three compounds bind significantly stronger to warfarin compared to diazepam binding site. Fluorescence quenching at three temperatures (20, 25, and 37 °C) was analyzed using classical Stern-Volmer equation, and a static quenching mechanism was proposed. The enthalpy and entropy changes upon sulphur-containing compound-HSA interactions were calculated using Van't Hoff equation. Positive values of enthalpy and entropy changes indicate that non-specific, hydrophobic interactions are the main contributors to HSA-compound interaction. Molecular docking and calculated lipophilicity descriptors indicate the same, pointing out that the increased lipophilicity of sulphur-containing compounds might be a reason for their better binding to HSA. Obtained results might contribute to design of novel derivatives with improved pharmacokinetic properties and drug efficacy.

  11. Alpine ski bindings and injuries. Current findings.

    Science.gov (United States)

    Natri, A; Beynnon, B D; Ettlinger, C F; Johnson, R J; Shealy, J E

    1999-07-01

    In spite of the fact that the overall incidence of alpine ski injuries has decreased during the last 25 years, the incidence of serious knee sprains usually involving the anterior cruciate ligament (ACL) has risen dramatically since the late 1970s. This trend runs counter to a dramatic reduction in lower leg injuries that began in the early 1970s and to date has lowered the risk of injury below the knee by almost 90%. One of the primary design objectives of modern ski boots and bindings has been to protect the skier from tibia and ankle fractures. So, in that sense, they have done an excellent job. However, despite advances in equipment design, modern ski bindings have not protected the knee from serious ligament trauma. At the present time, we are unaware of any binding design, settings or function that can protect both the knee and lower extremities from serious ligament sprains. No innovative change in binding design appears to be on the horizon that has the potential to reduce the risk of these severe knee injuries. Indeed, only 1 study has demonstrated a means to help reduce this risk of serious knee sprains, and this study involved education of skiers, not ski equipment. Despite the inability of bindings to reduce the risk of severe knee injuries there can be no doubt that improvement in ski bindings has been the most important factor in the marked reduction in incidence of lower leg and ankle injuries during the last 25 years. The authors strongly endorse the application of present International Standards Organisation (ISO) and American Society for Testing and Materials (ASTM) standards concerning mounting, setting and maintaining modern 'state of the art' bindings.

  12. Bacillus thuringiensis Cry1Aa toxin-binding region of Bombyx mori aminopeptidase N.

    Science.gov (United States)

    Yaoi, K; Nakanishi, K; Kadotani, T; Imamura, M; Koizumi, N; Iwahana, H; Sato, R

    1999-12-17

    The Bacillus thuringiensis Cry1Aa toxin-binding region of Bombyx mori aminopeptidase N (APN) was analyzed, to better understand the molecular mechanism of susceptibility to the toxin and the development of resistance in insects. APN was digested with lysylendopeptidase and the ability of the resulting fragments to bind to Cry1Aa and 1Ac toxins was examined. The binding abilities of the two toxins to these fragments were different. The Cry1Aa toxin bound to the fragment containing 40-Asp to 313-Lys, suggesting that the Cry1Aa toxin-binding site is located in the region between 40-Asp and 313-Lys, while Cry1Ac toxin bound exclusively to mature APN. Next, recombinant APN of various lengths was expressed in Escherichia coli cells and its ability to bind to Cry1Aa toxin was examined. The results localized the Cry1Aa toxin binding to the region between 135-Ile and 198-Pro.

  13. Antibacterial activity of essential oils on the growth of Staphylococcus aureus and measurement of their binding interaction using optical biosensor.

    Science.gov (United States)

    Chung, Kyong-Hwan; Yang, Ki-Sook; Kim, Jin; Kim, Jin-Chul; Lee, Ki-Young

    2007-11-01

    Antibacterial activity of essential oils (Tea tree, Chamomile, Eucalyptus) on Staphylococcus aureus growth was evaluated as well as the essential oil-loaded alginate beads. The binding interactions between the cell and the essential oils were measured using an optical biosensor. The antibacterial activity of the essential oils to the cell was evaluated with their binding interaction and affinity. The antibacterial activity appeared in the order of Tea Tree> Chamomile>Eucalyptus, in comparison of the inhibition effects of the cell growth to the essential oils. The association rate constant and affinity of the cell binding on Tea Tree essential oil were 5.0 x 10(-13) ml/(CFU-s) and 5.0 x 10(5) ml/CFU, respectively. The affinity of the cell binding on Tea Tree was about twice higher than those on the other essential oils. It might be possible that an effective antibacterial activity of Tea Tree essential oil was derived from its strong adhesive ability to the cell, more so than those of the other essential oils.

  14. Strong tracking adaptive Kalman filters for underwater vehicle dead reckoning

    Science.gov (United States)

    Xiao, Kun; Fang, Shao-Ji; Pang, Yong-Jie

    2007-06-01

    To impove underwater vehicle dead reckoning, a developed strong tracking adaptive kalman filter is proposed. The filter is improved with an additional adaptive factor and an estimator of measurement noise covariance. Since the magnitude of fading factor is changed adaptively, the tracking ability of the filter is still enhanced in low velocity condition of underwater vehicles. The results of simulation tests prove the presented filter effective.

  15. Studies of cellulose binding by cellobiose dehydrogenase and a comparison with cellobiohydrolase 1.

    OpenAIRE

    Henriksson, G; Salumets, A; Divne, C; Pettersson, G

    1997-01-01

    The binding isotherm to cellulose of cellobiose dehydrogenase (CDH) from Phanerochaete chrysosporium has been compared with that of cellobiohydrolase 1 (CBH 1) from Trichoderma reesei. CDH binds more strongly but more sparsely to cellulose than does CBH 1. In a classical Scatchard analysis, a better fit to a one-site binding model was obtained for CDH than for CBH 1. The binding of both enzymes decreased in the presence of ethylene glycol, increased in the presence of ammonium sulphate and wa...

  16. Strong inhibition of thioredoxin reductase by highly cytotoxic gold(I) complexes. DNA binding studies.

    Science.gov (United States)

    Ortego, Lourdes; Cardoso, Fátima; Martins, Soraia; Fillat, María F; Laguna, Antonio; Meireles, Margarida; Villacampa, M Dolores; Gimeno, M Concepción

    2014-01-01

    Biological properties of a series of aminophosphine-thiolate gold(I) complexes [Au(SR)(PPh2NHpy)] [Ph2PNHpy=2-(diphenylphosphinoamino)pyridine; HSR=2-mercaptopyridine (2-HSpy) (3), 2-mercaptonicotinic acid (2-H2-mna) (4), 2-thiouracil (2-HTU) (5) or 2-thiocytosine (2-HTC) (6)] and [Au(SR){PPh2NH(Htrz)}] [Ph2PNH(Htrz)=3-(diphenylphosphinoamino)-1,2,4-triazole]; HSR=2-mercaptopyridine (2-HSpy) (7), 2-thiocytosine (2-HTC) (8) or 6-thioguanine (6-HTG) (9) have been studied. Their antitumor properties have been tested in vitro against two tumor human cell lines, HeLa (derived from cervical cancer) and MCF-7 (derived from breast cancer), using a metabolic activity test (3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide, MTT). Some of them showed excellent cytotoxic activity. With the aim to obtain more information about the mechanisms of action of these derivatives, the interactions of complexes 3, 5, 7 and 9 with thioredoxin reductase in HeLa cells were studied. They showed a potent inhibition of thioredoxin reductase activity. In order to complete this study, interactions of the complexes with calf thymus (CT-) DNA and with different bacterial DNAs, namely the plasmid pEMBL9 and the promoter region of the furA (ferric uptake regulator A) gene from Anabaena sp. PCC 7120 were investigated. Although interactions of complexes with CT-DNA have been verified, none of them cause significant changes in its structure. © 2013.

  17. Visuospatial abilities of chess players.

    Science.gov (United States)

    Waters, Andrew J; Gobet, Fernand; Leyden, Gerv

    2002-11-01

    The extent to which the acquisition of expertise in knowledge-rich domains, such as chess, can be influenced by general individual characteristics, such as intelligence, has remained unclear. Some previous studies with children have documented significant correlations between chess skill and performance on some psychometric tests, such as performance IQ. However, we found no evidence for a correlation between chess skill and visual memory ability in a group of adult chess players (N = 36, age = 28.4 years). This finding, together with other data in the literature, suggests that there is surprisingly little evidence that chess skill and visuospatial ability are associated in adults. Thus, visual memory ability, and perhaps visuospatial intelligence, may be relatively unimportant factors in the long-term acquisition of chess skill.

  18. Deafness and motor abilities level

    Directory of Open Access Journals (Sweden)

    A Zwierzchowska

    2008-09-01

    Full Text Available The audition injury hinders some motor motions and the organised coordination at the higher level and may be a cause of disturbances and disorder in some motor abilities adoption. It was assumed that deafness including its aetiology and injury mechanism may significantly influence the motor development of human being. The study aimed in checking if the deafness, as a result of various unfavourable factors, determines the motor development of children and youngsters. Consequently the dependency between qualitative features i.e.: signed motor level and aetiology, audition injury mechanism and the deafness degree was examined. The mechanism and aetiology of hearing correlated with the motor abilities displayed statistically significant dependencies in few motor trials only. Revealed correlations regarded mostly the coordination trials excluding the flexibility one. Statistically significant dependencies between the audition diminution and the motor abilities level were not found.

  19. binding protein (HABP1)

    Indian Academy of Sciences (India)

    Unknown

    adsorbed on carbon coated copper grid (400 mesh) for. 5 min at room temperature. The grids were subsequently .... and inhibition by GAGs and DMA were determined on polystyrene wells of microtitre plates (Costar, ... for binding inhibition assays was carried out by mixing equal volumes of the conjugate and the inhibitor at ...

  20. Sequential memory: Binding dynamics

    Science.gov (United States)

    Afraimovich, Valentin; Gong, Xue; Rabinovich, Mikhail

    2015-10-01

    Temporal order memories are critical for everyday animal and human functioning. Experiments and our own experience show that the binding or association of various features of an event together and the maintaining of multimodality events in sequential order are the key components of any sequential memories—episodic, semantic, working, etc. We study a robustness of binding sequential dynamics based on our previously introduced model in the form of generalized Lotka-Volterra equations. In the phase space of the model, there exists a multi-dimensional binding heteroclinic network consisting of saddle equilibrium points and heteroclinic trajectories joining them. We prove here the robustness of the binding sequential dynamics, i.e., the feasibility phenomenon for coupled heteroclinic networks: for each collection of successive heteroclinic trajectories inside the unified networks, there is an open set of initial points such that the trajectory going through each of them follows the prescribed collection staying in a small neighborhood of it. We show also that the symbolic complexity function of the system restricted to this neighborhood is a polynomial of degree L - 1, where L is the number of modalities.

  1. binding protein (HABP1)

    Indian Academy of Sciences (India)

    Unknown

    of HA in a concentration-dependent manner, suggesting its multiligand affinity amongst carbohydrates. rHABP1 shows differential affinity ... site is seen to correspond to the carbohydrate-binding site in E-selectin, which has similarity in the ... adsorbed on carbon coated copper grid (400 mesh) for. 5 min at room temperature.

  2. Control of estrogen receptor ligand binding by Hsp90.

    Science.gov (United States)

    Fliss, A E; Benzeno, S; Rao, J; Caplan, A J

    2000-04-01

    The molecular chaperone Hsp90 interacts with unliganded steroid hormone receptors and regulates their activity. We have analyzed the function of yeast and mammalian Hsp90 in regulating the ability of the human estrogen receptor (ER) to bind ligands in vivo and in vitro. Using the yeast system, we show that the ER expressed in several different hsp82 mutant strains binds reduced amounts of the synthetic estrogen diethylstilbestrol compared to the wild type. This defect in hormone binding occurs without any significant change in the steady state levels of ER protein. To analyze the role of mammalian Hsp90, we synthesized the human ER in rabbit reticulocyte lysates containing geldanamycin, an Hsp90 inhibitor. At low concentrations of geldanamycin we observed reduced levels of hormone binding by the ER. At higher concentrations, we found reduced synthesis of the receptor. These data indicate that Hsp90 functions to maintain the ER in a high affinity hormone-binding conformation.

  3. Synthesis, micellization behavior, antimicrobial and intercalative DNA binding of some novel surfactant copper(II) complexes containing modified phenanthroline ligands.

    Science.gov (United States)

    Nagaraj, Karuppiah; Ambika, Subramanian; Rajasri, Shanmugasundaram; Sakthinathan, Subramanian; Arunachalam, Sankaralingam

    2014-10-01

    The novel surfactant copper(II) complexes, [Cu(ip)2DA](ClO4)21, [Cu(dpqc)2DA](ClO4)22, [Cu(dppn)2DA](ClO4)23, where ip=imidazo[4,5-f][1,10]phenanthroline, dpqc=dipyrido[3,2-a:2',4'-c](6,7,8,9-tetrahydro)phenazine, dppn=benzo[1]dipyrido[3,2-a':2',3'-c]phenazine and DA-dodecylamine, were synthesized and characterized by physico-chemical and spectroscopic methods. In these complexes 1-3, the geometry of copper metal ions was described as square pyramidal. The critical micelle concentration (CMC) value of these surfactant copper(II) complexes in aqueous solution was found out from conductance measurements. Specific conductivity data at different temperatures served for the evaluation of the temperature-dependent CMC and the thermodynamics of micellization (ΔGm°, ΔHm° and ΔSm°). The binding interaction of these complexes with DNA (calf thymus DNA) in Tris buffer was studied by physico-chemical techniques. In the presence of the DNA UV-vis spectrum of complexes showed red shift of the absorption band along with significant hypochromicity indicating intercalation of our complexes with nucleic acids. Competitive binding study with ethidium bromide (EB) shows that the complexes exhibit the ability to displace the nucleic acid-bound EB indicating that the complexes bind to nucleic acids in strong competition with EB for the intercalative binding site. Observed changes in the circular dichoric spectra of DNA in the presence of surfactant complexes support the strong binding of complexes with DNA. CV results also confirm this mode of binding. Some significant thermodynamic parameters of the binding of the titled complexes to DNA have also been determined. The results reveal that the extent of DNA binding of 3 was greater than that of 1 and 2. The antibacterial and antifungal screening tests of these complexes have shown good results compared to its precursor chloride complexes. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. The concept of work ability.

    Science.gov (United States)

    Tengland, Per-Anders

    2011-06-01

    The concept of "work ability" is central for many sciences, especially for those related to working life and to rehabilitation. It is one of the important concepts in legislation regulating sickness insurance. How the concept is defined therefore has important normative implications. The concept is, however, often not sufficiently well defined. AIM AND METHOD The objective of this paper is to clarify, through conceptual analysis, what the concept can and should mean, and to propose a useful definition for scientific and practical work. RESULTS Several of the defining characteristics found in the literature are critically scrutinized and discussed, namely health, basic standard competence, occupational competence, occupational virtues, and motivation. These characteristics are related to the work tasks and the work environment. One conclusion is that we need two definitions of work ability, one for specific jobs that require special training or education, and one for jobs that most people can manage given a short period of practice. Having work ability, in the first sense, means having the occupational competence, the health required for the competence, and the occupational virtues that are required for managing the work tasks, assuming that the tasks are reasonable and that the work environment is acceptable. In the second sense, having work ability is having the health, the basic standard competence and the relevant occupational virtues required for managing some kind of job, assuming that the work tasks are reasonable and that the work environment is acceptable. CONCLUSION These definitions give us tools for understanding and discussing the complex, holistic and dynamic aspects of work ability, and they can lay the foundations for the creation of instruments for evaluating work ability, as well as help formulate strategies for rehabilitation.

  5. Flavonoids with M1 Muscarinic Acetylcholine Receptor Binding Activity

    Directory of Open Access Journals (Sweden)

    Meyyammai Swaminathan

    2014-06-01

    Full Text Available Muscarinic acetylcholine receptor-active compounds have potential for the treatment of Alzheimer’s disease. In this study, a series of natural and synthetic flavones and flavonols was assayed in vitro for their ability to inhibit radioligand binding at human cloned M1 muscarinic receptors. Several compounds were found to possess competitive binding affinity (Ki = 40–110 µM, comparable to that of acetylcholine (Ki = 59 µM. Despite the fact that these compounds lack a positively-charged ammonium group under physiological conditions, molecular modelling studies suggested that they bind to the orthosteric site of the receptor, mainly through non-polar interactions.

  6. Enzymes in Commercial Cellulase Preparations Bind Differently to Dioxane Extracted Lignins

    Energy Technology Data Exchange (ETDEWEB)

    Yarbrough, John M.; Mittal, Ashutosh; Katahira, Rui; Mansfield, Elisabeth; Taylor, Larry E.; Decker, Stephen R.; Himmel, Michael E.; Vinzant, Todd

    2017-04-24

    Commercial fungal cellulases used in biomass-to-biofuels processes can be grouped into three general classes: native, augmented, and engineered. To evaluate lignin binding affinities of different enzyme activities in various commercial cellulase formulations in order to determine if enzyme losses due to lignin binding can be modulated by using different enzymes of the same activity We used water:dioxane (1:9) to extract lignin from pretreated corn stover. Commercial cellulases were incubated with lignin and the unbound supernatants were evaluated for individual enzyme loss by SDS=PAGE and these were correlated with activity loss using various pNP-sugar substrates. Colorimetric assays for general glycosyl hydrolase activities showed distinct differences in enzyme binding to lignin for each enzyme activity. Native systems demonstrated low binding of endo- and exo-cellulases, high binding of xylanase, and moderate ..beta..-glucosidase binding. Engineered cellulase mixtures exhibited low binding of exo-cellulases, very strong binding of endocellulases and ..beta..- glucosidase, and mixed binding of xylanase activity. The augmented cellulase had low binding of exocellulase, high binding of endocellulase and xylanase, and moderate binding of ..beta..-glucosidase activities. Bound and unbound activities were correlated with general molecular weight ranges of proteins as measured by loss of proteins bands in bound fractions on SDS-PAGE gels. Lignin-bound high molecular weight bands correlated with binding of ..beta..-glucosidase activity. While ..beta..-glucosidases demonstrated high binding in many cases, they have been shown to remain active. Bound low molecular weight bands correlated with xylanase activity binding. Contrary to other literature, exocellulase activity did not show strong lignin binding. The variation in enzyme activity binding between the three classes of cellulases preparations indicate that it is certainly possible to alter the binding of specific

  7. Ability Dispersion and Team Performance

    DEFF Research Database (Denmark)

    Hoogendoorn, Sander; Parker, Simon C.; Van Praag, Mirjam

    What is the effect of dispersed levels of cognitive ability of members of a (business) team on their team's performance? This paper reports the results of a field experiment in which 573 students in 49 (student) teams start up and manage real companies under identical circumstances for one year. We...... ensured exogenous variation in otherwise random team composition by assigning students to teams based on their measured cognitive abilities. Each team performs a variety of tasks, often involving complex decision making. The key result of the experiment is that the performance of business teams first...

  8. Ability Dispersion and Team Performance

    DEFF Research Database (Denmark)

    Hoogendoorn, Sander; Parker, Simon C.; Van Praag, Mirjam

    What is the effect of dispersed levels of cognitive ability of members of a (business) team on their team's performance? This paper reports the results of a field experiment in which 573 students in 49 teams start up and manage real companies under identical circumstances. We ensured exogenous...... variation in - otherwise random - team composition by assigning students to teams based on their measured cognitive abilities (Raven test). Each team performs a variety of tasks, often involving complex decision making. The key result of the experiment is that the performance of business teams first...

  9. DNA-binding, spectroscopic and antimicrobial studies of palladium(II) complexes containing 2,2'-bipyridine and 1-phenylpiperazine

    Science.gov (United States)

    Shoukry, Azza A.; Mohamed, Mervat S.

    2012-10-01

    With the purpose of evaluating the ability of Pd(II) complex to interact with DNA molecule as the main biological target, two new complexes [Pd(bpy)(OH2)2] (1) and [Pd(Phenpip)(OH2)2] (2), where (bpy = 2,2'-bipyridine; Phenpip = 1-phenylpiperazine), have been synthesized and the binding properties of these complexes with CT-DNA were investigated. The intrinsic binding constants (Kb) calculated from UV-Vis absorption studies were 3.78 × 103 M-1 and 4.14 × 103 M-1 for complexes 1 and 2 respectively. Thermal denaturation has been systematically studied by spectrophotometric method and the calculated ΔTm was nearly 5 °C for each complex. All the results suggest an electrostatic and/or groove binding mode for the interaction between the complexes and CT-DNA. The redox behavior of the two complexes in the absence and in the presence of calf thymus DNA has been investigated by cyclic voltammetry. The cyclic voltammogram exhibits one quasi-reversible redox wave. The change in E1/2, ΔEp and Ipc/Ipa supports that the two complexes exhibit strong binding to calf thymus DNA. Further insight into the binding of complexes with CT-DNA has been made by gel electrophoresis, where the binding of complexes is confirmed through decreasing the intensity of DNA bands. The two complexes have been screened for their antimicrobial activities using the disc diffusion method against some selected Gram-positive and Gram-negative bacteria. The activity data showed that both complexes were more active against Gram-negative than Gram-positive bacteria. It may be concluded that the antimicrobial activity of the compounds is related to cell wall structure of bacteria.

  10. Differential binding of heavy chain variable domain 3 antigen binding fragments to protein A chromatography resins.

    Science.gov (United States)

    Bach, Julia; Lewis, Nathaniel; Maggiora, Kathy; Gillespie, Alison J; Connell-Crowley, Lisa

    2015-08-28

    This work examines the binding of 15 different VH3 IgGs and their corresponding F(ab')2 fragments to two different protein A chromatography resins: MabSelect(®), which utilizes a recombinant protein A ligand, and MabSelect SuRe(®) (SuRe), which utilizes a tetrameric Z domain ligand. The results show that VH3 F(ab')2 fragments can exhibit a variety of binding behaviours for the two resins. Contrary to previously published data, a subset of these molecules show strong interaction with the Z domain of SuRe(®). Furthermore, the results show that sequence variability of residue 57 in the VH3 heavy chain CDR2 domain correlates with binding behaviour on MabSelect(®) and SuRe(®). Site-directed mutagenesis of this residue confers gain or loss of VH3 F(ab')2 binding to these resins in 3 mAbs, demonstrating that it plays a key role in both recombinant protein A and Z domain interaction. A fourth mAb with a longer CDR2 loop was not affected by mutation of residue 57, indicating that CDR2 domain length may alter the binding interface and lead to the involvement of other residues in protein A binding. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Cognitive and neuropsychological underpinnings of relational and conjunctive working memory binding across age.

    Science.gov (United States)

    van Geldorp, Bonnie; Parra, Mario A; Kessels, Roy P C

    2015-01-01

    The ability to form associations (i.e., binding) is critical for memory formation. Recent studies suggest that aging specifically affects relational binding (associating separate features) but not conjunctive binding (integrating features within an object). Possibly, this dissociation may be driven by the spatial nature of the studies so far. Alternatively, relational binding may simply require more attentional resources. We assessed relational and conjunctive binding in three age groups and we included an interfering task (i.e., an articulatory suppression task). Binding was examined in a working memory (WM) task using non-spatial features: shape and colour. Thirty-one young adults (mean age = 22.35), 30 middle-aged adults (mean age = 54.80) and 30 older adults (mean age = 70.27) performed the task. Results show an effect of type of binding and an effect of age but no interaction between type of binding and age. The interaction between type of binding and interference was significant. These results indicate that aging affects relational binding and conjunctive binding similarly. However, relational binding is more susceptible to interference than conjunctive binding, which suggests that relational binding may require more attentional resources. We suggest that a general decline in WM resources associated with frontal dysfunction underlies age-related deficits in WM binding.

  12. Acyl-CoA-binding protein/diazepam-binding inhibitor gene and pseudogenes

    DEFF Research Database (Denmark)

    Mandrup, S; Hummel, R; Ravn, S

    1992-01-01

    modulator of the GABAA receptor in brain membranes. ACBP/DBI, or proteolytically derived polypeptides of ACBP/DBI, have also been implicated in the control of steroidogenesis in mitochondria and glucose-stimulated insulin secretion. Thus, it appears that ACBP/DBI is a remarkable, versatile protein. Now we......Acyl-CoA-binding protein (ACBP) is a 10 kDa protein isolated from bovine liver by virtue of its ability to bind and induce the synthesis of medium-chain acyl-CoA esters. Surprisingly, it turned out to be identical to a protein named diazepam-binding Inhibitor (DBI) claimed to be an endogenous....... There is a remarkable correspondence between the structural modules of ACBP/DBI as determined by 1H nuclear magnetic resonance spectroscopy and the exon-intron architecture of the ACBP/DBI gene. Detailed analyses of transcription of the ACBP/DBI gene in brain and liver were performed to map transcription initiation...

  13. Bound states in strongly correlated magnetic and electronic systems

    International Nuclear Information System (INIS)

    Trebst, S.

    2002-02-01

    A novel strong coupling expansion method to calculate two-particle spectra of quantum lattice models is developed. The technique can be used to study bosonic and fermionic models and in principle it can be applied to systems in any dimension. A number of strongly correlated magnetic and electronic systems are examined including the two-leg spin-half Heisenberg ladder, the dimerized Heisenberg chain with a frustrating next-nearest neighbor interaction, coupled Heisenberg ladders, and the one-dimensional Kondo lattice model. In the various models distinct bound states are found below the two-particle continuum. Quantitative calculations of the dispersion, coherence length and binding energy of these bound states are used to describe spectroscopic experiments on (Ca,La) 14 Cu 24 O 41 and NaV 2 O 5 . (orig.)

  14. Learning Anatomy Enhances Spatial Ability

    Science.gov (United States)

    Vorstenbosch, Marc A. T. M.; Klaassen, Tim P. F. M.; Donders, A. R. T.; Kooloos, Jan G. M.; Bolhuis, Sanneke M.; Laan, Roland F. J. M.

    2013-01-01

    Spatial ability is an important factor in learning anatomy. Students with high scores on a mental rotation test (MRT) systematically score higher on anatomy examinations. This study aims to investigate if learning anatomy also oppositely improves the MRT-score. Five hundred first year students of medicine ("n" = 242, intervention) and…

  15. Learning anatomy enhances spatial ability.

    NARCIS (Netherlands)

    Vorstenbosch, M.A.T.M.; Klaassen, T.P.; Donders, A.R.T.; Kooloos, J.G.M.; Bolhuis, S.M.; Laan, R.F.J.M.

    2013-01-01

    Spatial ability is an important factor in learning anatomy. Students with high scores on a mental rotation test (MRT) systematically score higher on anatomy examinations. This study aims to investigate if learning anatomy also oppositely improves the MRT-score. Five hundred first year students of

  16. Competence: Commodification of Human Ability

    Science.gov (United States)

    Han, Soonghee

    2008-01-01

    The purpose of this article is to analyze the meaning and presumptions of competence in the concrete context of knowledge capitalism. First, the nature of competence as a "commodification of human ability" that obtains a standardized monetary value to sell in the labor market, is elucidated by applying Karl Marx's critical theory. Second, it is…

  17. Ability Dispersion and Team Performance

    DEFF Research Database (Denmark)

    Hoogendoorn, Sander; Parker, Simon C.; Van Praag, Mirjam

    exogenous variation in -otherwise random- team composition by assigning students to teams based on their measured cognitive abilities (Raven test). Each team performs a variety of tasks, often involving complex decision making. The key result of the experiment is that the performance of business teams first...

  18. Ability Dispersion and Team Performance

    DEFF Research Database (Denmark)

    Hoogendoorn, Sander; Parker, Simon C.; Van Praag, Mirjam

    variation in - otherwise random - team composition by assigning students to teams based on their measured cognitive abilities (Raven test). Each team performs a variety of tasks, often involving complex decision making. The key result of the experiment is that the performance of business teams first...

  19. Technology and Motor Ability Development

    Science.gov (United States)

    Wang, Lin; Lang, Yong; Luo, Zhongmin

    2014-01-01

    As a new member joining the technology family, active video games have been developed to promote physical exercise. This working-in-progress paper shares an ongoing project on examining the basic motor abilities that are enhanced through participating in commercially available active video games. [For the full proceedings see ED557181.

  20. increased larval competitive ability without

    Indian Academy of Sciences (India)

    2016-06-01

    Jun 1, 2016 ... Archana Nagarajan and Sharmila Bharathi Natarajan contributed equally to this work. (MacArthur and Wilson 1967), is an important phenomenon in ecology and ... pan, fecundity, starvation resistance and dessication resis- tance, some ... competitive ability was not assayed on the CU and UU populations.

  1. Challenging high-ability students

    NARCIS (Netherlands)

    Scager, Karin; Akkerman, Sanne F.; Pilot, Albert; Wubbels, Theo

    2014-01-01

    The existing literature on indicators of an optimal learning environment for high-ability students frequently discusses the concept of challenge. It is, however, not clear what, precisely, constitutes appropriate challenge for these students. In this study, the authors examined an undergraduate

  2. The flexible loop L1 of the H3K4 demethylase JARID1B ARID domain has a crucial role in DNA-binding activity

    International Nuclear Information System (INIS)

    Yao, Wenming; Peng, Yu; Lin, Donghai

    2010-01-01

    JARID1B, a member of the JmjC demethylase family, has a crucial role in H3K4me3 demethylation. The ARID domain is a potential DNA-binding domain of JARID1B. Previous studies indicate that a GC-rich DNA motif is the specific target of the ARID domain. However, the details of the interaction between the ARID domain and duplex DNA require further study. Here, we utilized NMR spectroscopy to assign the backbone amino acids and mapped the DNA-binding sites of the human JARID1B ARID domain. Perturbations to 1 H- 15 N correlation spectra revealed that the flexible loop L1 of ARID was the main DNA-binding interface. EMSA and intrinsic fluorescence experiments demonstrated that mutations on loop L1 strongly reduced the DNA-binding activity of JARID1B ARID. Furthermore, transfection of mutant forms resulted in a distinct loss of intrinsic H3K4 demethylase activity, implying that the flexible loop L1 made a major contribution to sustaining the DNA-binding ability of JARID1B ARID domain.

  3. Resiliency and the Ability to Detect Cartoon Humor

    Science.gov (United States)

    Killlon, Jessica B.; Torres, Aurora

    2017-01-01

    The Connor Davidson Resilience Scale was developed to measure resiliency, an individual's ability to positively adapt to stressful or adverse situations. Resilient individuals have close and secure relationships, have a strong sense of purpose, know when to turn to others for help, and find humor in situations. The focus of this study was on the…

  4. Weed competitiveness and yielding ability of aerobic rice genotypes

    NARCIS (Netherlands)

    Zhao, D.L.

    2006-01-01

    Keywords:strong>    Broad-sense heritability; Crop vigour; Genetic correlation; Indirect selection index; Plant erectness; Rice germplasm; Seeding rate; Vegetative growth; Weed-suppressive ability.

  5. Differential MSC activation leads to distinct mononuclear leukocyte binding mechanisms

    Science.gov (United States)

    Kota, Daniel J.; Dicarlo, Bryan; Hetz, Robert A.; Smith, Philippa; Cox, Charles S.; Olson, Scott D.

    2014-04-01

    Advances in the field of Multipotent Mesenchymal Stromal cell (MSC) biology have demonstrated that MSCs can improve disease outcome when `activated' to exert immunomodulatory effects. However, the precise mechanisms modulating MSC-immune cells interactions remain largely elusive. In here, we activated MSC based on a recent polarization paradigm, in which MSCs can be polarized towards a pro- or anti-inflammatory phenotype depending on the Toll-like receptor stimulated, to dissect the mechanisms through which MSCs physically interact with and modulate leukocytes in this context. Our data show that MSCs activated through the Toll-like receptor (TLR) 4 pathway increased VCAM-1 and ICAM-1 dependent binding of leukocytes. On the other hand, TLR3 stimulation strongly increases leukocytes affinity to MSC comparatively, through the formation of cable-like hyaluronic acid structures. In addition, TLR4 activation elicited secretion of pro-inflammatory mediators by MSCs, whereas TLR3-activated MSCs displayed a milder pro-inflammatory phenotype, similar to inactivated MSCs. However, the differently activated MSCs maintained their ability to suppress leukocyte activation at similar levels in our in vitro model, and this immunomodulatory property was shown here to be partially mediated by prostaglandin. These results reinforce the concept that alternate activation profiles control MSC responses and may impact the therapeutic use of MSCs.

  6. Strong field approximation within a Faddeev-like formalism for laser-matter interactions

    International Nuclear Information System (INIS)

    Popov, Y.; Galstyan, A.; Piraux, B.; Mota-Furtado, F.; O'Mahony, P.F.

    2017-01-01

    We consider the interaction of atomic hydrogen with an intense laser field within the strong-field approximation (SFA). By using a Faddeev-like formalism, we introduce a new perturbative series in the binding potential of the atom. As a first test of this new approach, we calculate the electron energy spectrum in the very simple case of a photon energy higher than the ionisation potential. We show that by contrast to the standard perturbative series in the binding potential obtained within the strong field approximation, the first terms of the new series converge rapidly towards the results we get by solving the corresponding time-dependent Schroedinger equation. (authors)

  7. Atoms and clusters in strong laser fields

    NARCIS (Netherlands)

    Marchenko, T.

    2008-01-01

    This thesis describes experimental and theoretical studies on the interaction of strong infrared laser fields with atoms and atomic clusters. Part I provides an overview of the main strong-field phenomena in atoms, molecules and clusters and describes the state-of-the-art in strong-field science.

  8. Strong Bisimilarity of Simple Process Algebras

    DEFF Research Database (Denmark)

    Srba, Jirí

    2003-01-01

    We study bisimilarity and regularity problems of simple process algebras. In particular, we show PSPACE-hardness of the following problems: (i) strong bisimilarity of Basic Parallel Processes (BPP), (ii) strong bisimilarity of Basic Process Algebra (BPA), (iii) strong regularity of BPP, and (iv) ...

  9. 78 FR 15710 - Strong Sensitizer Guidance

    Science.gov (United States)

    2013-03-12

    ... definition of ``strong sensitizer'' found at 16 CFR 1500.3(c)(5). The Commission is proposing to revise the supplemental definition of ``strong sensitizer'' due to advancements in the science of sensitization that have... document is intended to clarify the ``strong sensitizer'' definition, assist manufacturers in understanding...

  10. The Relationship between Spatial Visualization Ability and Students' Ability to Model 3D Objects from Engineering Assembly Drawings

    Science.gov (United States)

    Branoff, T. J.; Dobelis, M.

    2012-01-01

    Spatial abilities have been used as a predictor of success in several engineering and technology disciplines (Strong & Smith, 2001). In engineering graphics courses, scores on spatial tests have also been used to predict success (Adanez & Velasco, 2002; Leopold, Gorska, & Sorby, 2001). Other studies have shown that some type of…

  11. Cross-modal working memory binding and word recognition skills: how specific is the link?

    Science.gov (United States)

    Wang, Shinmin; Allen, Richard J

    2018-04-01

    Recent research has suggested that the creation of temporary bound representations of information from different sources within working memory uniquely relates to word recognition abilities in school-age children. However, it is unclear to what extent this link is attributable specifically to the binding ability for cross-modal information. This study examined the performance of Grade 3 (8-9 years old) children on binding tasks requiring either temporary association formation of two visual items (i.e., within-modal binding) or pairs of visually presented abstract shapes and auditorily presented nonwords (i.e., cross-modal binding). Children's word recognition skills were related to performance on the cross-modal binding task but not on the within-modal binding task. Further regression models showed that cross-modal binding memory was a significant predictor of word recognition when memory for its constituent elements, general abilities, and crucially, within-modal binding memory were taken into account. These findings may suggest a specific link between the ability to bind information across modalities within working memory and word recognition skills.

  12. Structure-Based Inhibitor Design for an Enzyme That Binds Different Steriods

    Energy Technology Data Exchange (ETDEWEB)

    Qiu,W.; Zhou, M.; Mazumdar, M.; Azzi, A.; Ghanmi, D.; Luu-The, V.; Labrie, F.; Lin, S.

    2007-01-01

    Human type 5 17{beta}-hydroxysteroid dehydrogenase plays a crucial role in local androgen formation in prostate tissue. Several chemicals were synthesized and tested for their ability to inhibit this enzyme, and a series of estradiol derivatives bearing a lactone on the D-ring were found to inhibit its activity efficiently. The crystal structure of the type 5 enzyme in complex with NADP and such a novel inhibitor, EM1404, was determined to a resolution of 1.30 {angstrom}. Significantly more hydrogen bonding and hydrophobic interactions were defined between EM1404 and the enzyme than in the substrate ternary complex. The lactone ring of EM1404 accounts for important interactions with the enzyme, whereas the amide group at the opposite end of the inhibitor contributes to the stability of three protein loops involved in the construction of the substrate binding site. EM1404 has a strong competitive inhibition, with a K{sub i} of 6.9 {+-} 1.4 nM, demonstrating 40 times higher affinity than that of the best inhibitor previously reported. This is observed despite the fact that the inhibitor occupies only part of the binding cavity. Attempts to soak the inhibitor into crystals of the binary complex with NADP were unsuccessful, yielding a structure with a polyethylene glycol fragment occupying the substrate binding site. The relative crystal packing is discussed. Combined studies of small molecule inhibitor synthesis, x-ray crystallography, enzyme inhibition, and molecular modeling make it possible to analyze the plasticity of the substrate binding site of the enzyme, which is essential for developing more potent and specific inhibitors for hormone-dependent cancer therapy.

  13. Natural alkaloid Luotonin A and its affixed acceptor molecules: Serum albumin binding studies.

    Science.gov (United States)

    Kesavan, Mookkandi Palsamy; Kumar, Gujuluva Gangatharan Vinoth; Anitha, Kandasamy; Ravi, Lokesh; Raja, Jeyaraj Dhaveethu; Rajagopal, Gurusamy; Rajesh, Jegathalaprathaban

    2017-08-01

    Effective interaction of natural alkaloid Luotonin A (L) and its affixed acceptor molecules 1 and 2 with donor molecule as Bovine serum albumin (BSA) at various pH (4.0, 7.4 and 10.0) medium have been demonstrated using various conventional spectroscopic techniques. These analyses provide some valuable features on the interaction between BSA and acceptor molecules (L, 1 and 2). From the absorption and fluorescence spectral titration studies, the formation of ground-state complexes between the acceptor molecules (L, 1 and 2) and the BSA have been confirmed. The results of the afore titrations analysis reveal that, the strong binding of receptor 1 with BSA (K app 5.68×10 4 M -1 ; K SV 1.86×10 6 Lmol -1 ; K a 6.42×10 5 Lmol -1 ; K ass 8.09×10 6 M -1 ; ΔG -33.35kJ/mol) at physiological pH medium (7.4) than other receptor molecules 2 and L. The Förster resonance energy transfer (FRET) efficiency between the tryptophan (Trp) residues of BSA and acceptor molecules L, 1 and 2 during the interaction, are 28.85, 85.24 and 53.25 % respectively. The superior binding efficacy of acceptor 1 at physiological pH condition has been further confirmed by FT-IR and Raman spectral analysis methods. Moreover, theoretical docking studies of acceptors L, 1 and 2 towards HSA have been demonstrated to differentiate their binding behaviours. It reveals that, acceptor 1 has the strongest binding ability with HSA through two hydrogen bonding and the Atomic contact energy (ACE) value of -483.96kcal/mol. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Relating the shape of protein binding sites to binding affinity profiles: is there an association?

    Directory of Open Access Journals (Sweden)

    Bitter István

    2010-10-01

    , except for few specific cases, the shapes of the binding pockets have relatively low weights in the determination of the affinity profiles of proteins. Since the MAF profile is closely related to the target specificity of ligand binding sites we can conclude that the shape of the binding site is not a pivotal factor in selecting drug targets. Nonetheless, based on strong specific associations between certain MAF profiles and specific geometric descriptors we identified, the shapes of the binding sites do have a crucial role in virtual drug design for certain drug categories, including morphine derivatives, benzodiazepines, barbiturates and antihistamines.

  15. INDIVIDUAL ABILITIES AND LIFELONG LEARNING

    Directory of Open Access Journals (Sweden)

    Oleksandr Yu. Burov

    2016-10-01

    Full Text Available This paper describes new and emerging technologies in education, learning environments and methods that have to satisfy lifelong learning, from school age to retirement, on the basis of the psychophysiological model of the cognitive abilities formation. It covers such topics as: evaluation of a human (accounting schoolchildren, youth and adults features abilities and individual propensities, individual trajectory of learning, adaptive learning strategy and design, recommendation on curriculum design, day-to-day support for individual’s learning, assessment of a human learning environment and performance, recommendation regards vocational retraining and/or further carrier etc.. The specific goal is to facilitate a broader understanding of the promise and pitfalls of these technologies and working (learning/teaching environments in global education/development settings, with special regard to the human as subject in the system and to the collaboration of humans and technical, didactic and organizational subsystems.

  16. Modeling Shear Induced Von Willebrand Factor Binding to Collagen

    Science.gov (United States)

    Dong, Chuqiao; Wei, Wei; Morabito, Michael; Webb, Edmund; Oztekin, Alparslan; Zhang, Xiaohui; Cheng, Xuanhong

    2017-11-01

    Von Willebrand factor (vWF) is a blood glycoprotein that binds with platelets and collagen on injured vessel surfaces to form clots. VWF bioactivity is shear flow induced: at low shear, binding between VWF and other biological entities is suppressed; for high shear rate conditions - as are found near arterial injury sites - VWF elongates, activating its binding with platelets and collagen. Based on parameters derived from single molecule force spectroscopy experiments, we developed a coarse-grain molecular model to simulate bond formation probability as a function of shear rate. By introducing a binding criterion that depends on the conformation of a sub-monomer molecular feature of our model, the model predicts shear-induced binding, even for conditions where binding is highly energetically favorable. We further investigate the influence of various model parameters on the ability to predict shear-induced binding (vWF length, collagen site density and distribution, binding energy landscape, and slip/catch bond length) and demonstrate parameter ranges where the model provides good agreement with existing experimental data. Our results may be important for understanding vWF activity and also for achieving targeted drug therapy via biomimetic synthetic molecules. National Science Foundation (NSF),Division of Mathematical Sciences (DMS).

  17. Visuospatial abilities in cerebellar disorders.

    Science.gov (United States)

    Molinari, M; Petrosini, L; Misciagna, S; Leggio, M G

    2004-02-01

    Cerebellar involvement in spatial data management has been suggested on experimental and clinical grounds. To attempt a specific analysis of visuospatial abilities in a group of subjects with focal or atrophic cerebellar damage. Visuospatial performance was tested using the spatial subtests of the WAIS, the Benton line orientation test, and two tests of mental rotation of objects-the Minnesota paper form board test (MIN) and the differential aptitude test (DAT). In the Benton line orientation test, a test of sensory analysis and elementary perception, no deficits were present in subjects with cerebellar damage. In MIN, which analyses the capacity to process bidimensional complex figures mentally, and in the DAT, which is based on mental folding and manipulation of tridimensional stimuli, subjects with cerebellar damage were impaired. The results indicate that lesions of the cerebellar circuits affect visuospatial ability. The ability to rotate objects mentally is a possible functional substrate of the observed deficits. A comparison between visuospatial performance of subjects with focal right and left cerebellar lesions shows side differences in the characteristics of the visuospatial syndrome. Thus cerebellar influences on spatial cognition appear to act on multiple cognitive modules.

  18. Implicit learning as an ability.

    Science.gov (United States)

    Kaufman, Scott Barry; Deyoung, Colin G; Gray, Jeremy R; Jiménez, Luis; Brown, Jamie; Mackintosh, Nicholas

    2010-09-01

    The ability to automatically and implicitly detect complex and noisy regularities in the environment is a fundamental aspect of human cognition. Despite considerable interest in implicit processes, few researchers have conceptualized implicit learning as an ability with meaningful individual differences. Instead, various researchers (e.g., Reber, 1993; Stanovich, 2009) have suggested that individual differences in implicit learning are minimal relative to individual differences in explicit learning. In the current study of English 16-17year old students, we investigated the association of individual differences in implicit learning with a variety of cognitive and personality variables. Consistent with prior research and theorizing, implicit learning, as measured by a probabilistic sequence learning task, was more weakly related to psychometric intelligence than was explicit associative learning, and was unrelated to working memory. Structural equation modeling revealed that implicit learning was independently related to two components of psychometric intelligence: verbal analogical reasoning and processing speed. Implicit learning was also independently related to academic performance on two foreign language exams (French, German). Further, implicit learning was significantly associated with aspects of self-reported personality, including intuition, Openness to Experience, and impulsivity. We discuss the implications of implicit learning as an ability for dual-process theories of cognition, intelligence, personality, skill learning, complex cognition, and language acquisition. 2010 Elsevier B.V. All rights reserved.

  19. Functional ability of community dwelling elderly. Criterion-related validity of a new measure of functional ability

    DEFF Research Database (Denmark)

    Schultz-Larsen, K; Avlund, K; Kreiner, S

    1992-01-01

    of diagnosed chronic diseases. At the same time these outcome measures together with diagnosed diseases were considered to predict drug consumption and GP consultations. It was shown that functional ability as measured by the new index scales were strongly influenced by diagnosed diseases: arteriostenosis...... but not self-rated health was a strong predictor for drug consumption and frequent contacts with GP. It is concluded that the new measure of functional ability is suitable for health studies of community dwelling elderly, in particular as a summary statement of the individual's health status.......Criterion-related validity of a new measure of functional ability was conducted according to a causal model based on conceptual models employed in the area of rehabilitative and geriatric medicine. The criteria variables included concurrent diagnosed diseases, global self-rated health, drug...

  20. Functional ability of community dwelling elderly. Criterion-related validity of a new measure of functional ability

    DEFF Research Database (Denmark)

    Schultz-Larsen, K; Avlund, K; Kreiner, S

    1992-01-01

    consumption and general practitioner (GP) consultations. The measure of functional ability was developed with the intention of achieving a high degree of discrimination among a group of community dwelling elderly. Data were derived from a sample survey of 70-year-old men and women conducted in 1984...... of diagnosed chronic diseases. At the same time these outcome measures together with diagnosed diseases were considered to predict drug consumption and GP consultations. It was shown that functional ability as measured by the new index scales were strongly influenced by diagnosed diseases: arteriostenosis...... but not self-rated health was a strong predictor for drug consumption and frequent contacts with GP. It is concluded that the new measure of functional ability is suitable for health studies of community dwelling elderly, in particular as a summary statement of the individual's health status....

  1. Megalin binds and mediates cellular internalization of folate binding protein

    DEFF Research Database (Denmark)

    Birn, Henrik; Zhai, Xiaoyue; Holm, Jan

    2005-01-01

    to express high levels of megalin, is inhibitable by excess unlabeled FBP and by receptor associated protein, a known inhibitor of binding to megalin. Immortalized rat yolk sac cells, representing an established model for studying megalin-mediated uptake, reveal (125)I-labeled FBP uptake which is inhibited...... to bind and mediate cellular uptake of FBP. Surface plasmon resonance analysis shows binding of bovine and human milk FBP to immobilized megalin, but not to low density lipoprotein receptor related protein. Binding of (125)I-labeled folate binding protein (FBP) to sections of kidney proximal tubule, known...

  2. Binding matrix: a novel approach for binding site recognition.

    Science.gov (United States)

    Kim, Jan T; Gewehr, Jan E; Martinetz, Thomas

    2004-06-01

    Recognition of protein-DNA binding sites in genomic sequences is a crucial step for discovering biological functions of genomic sequences. Explosive growth in availability of sequence information has resulted in a demand for binding site detection methods with high specificity. The motivation of the work presented here is to address this demand by a systematic approach based on Maximum Likelihood Estimation. A general framework is developed in which a large class of binding site detection methods can be described in a uniform and consistent way. Protein-DNA binding is determined by binding energy, which is an approximately linear function within the space of sequence words. All matrix based binding word detectors can be regarded as different linear classifiers which attempt to estimate the linear separation implied by the binding energy function. The standard approaches of consensus sequences and profile matrices are described using this framework. A maximum likelihood approach for determining this linear separation leads to a novel matrix type, called the binding matrix. The binding matrix is the most specific matrix based classifier which is consistent with the input set of known binding words. It achieves significant improvements in specificity compared to other matrices. This is demonstrated using 95 sets of experimentally determined binding words provided by the TRANSFAC database.

  3. Application of strong phosphoric acid to radiochemistry

    International Nuclear Information System (INIS)

    Terada, Kikuo

    1977-01-01

    Not only inorganic and organic compounds but also natural substrances, such as accumulations in soil, are completely decomposed and distilled by heating with strong phosphoric acid for 30 to 50 minutes. As applications of strong phosphoric acid to radiochemistry, determination of uranium and boron by use of solubilization effect of this substance, titration of uranyl ion by use of sulfuric iron (II) contained in this substance, application to tracer experiment, and determination of radioactive ruthenium in environmental samples are reviewed. Strong phosphoric acid is also applied to activation analysis, for example, determination of N in pyrographite with iodate potassium-strong phosphoric acid method, separation of Os and Ru with sulfuric cerium (IV) - strong phosphoric acid method or potassium dechromate-strong phosphoric acid method, analysis of Se, As and Sb rocks and accumulations with ammonium bromide, sodium chloride and sodium bromide-strong phosphoric acid method. (Kanao, N.)

  4. Titanium Alloy Strong Back for IXO Mirror Segments

    Science.gov (United States)

    Byron, Glenn P.; Kai-Wang, Chan

    2011-01-01

    A titanium-alloy mirror-holding fixture called a strong back allows the temporary and permanent bonding of a 50 degree D263 glass x-ray mirror (IXO here stands for International X-ray Observatory). The strong back is used to hold and position a mirror segment so that mounting tabs may be bonded to the mirror with ultra-low distortion of the optical surface. Ti-15%Mo alloy was the material of choice for the strong back and tabs because the coefficient of thermal expansion closely matches that of the D263 glass and the material is relatively easy to machine. This invention has the ability to transfer bonded mounting points from a temporary location on the strong back to a permanent location on the strong back with minimal distortion. Secondly, it converts a single mirror segment into a rigid body with an acceptable amount of distortion of the mirror, and then maneuvers that rigid body into optical alignment such that the mirror segment can be bonded into a housing simulator or mirror module. Key problems are that the mirrors are 0.4-mm thick and have a very low coefficient of thermal expansion (CTE). Because the mirrors are so thin, they are very flexible and are easily distorted. When permanently bonding the mirror, the goal is to achieve a less than 1-micron distortion. Temperature deviations in the lab, which have been measured to be around 1 C, have caused significant distortions in the mirror segment.

  5. Investigation of naphthofuran moiety as potential dual inhibitor against BACE-1 and GSK-3β: molecular dynamics simulations, binding energy, and network analysis to identify first-in-class dual inhibitors against Alzheimer's disease.

    Science.gov (United States)

    Kumar, Akhil; Srivastava, Gaurava; Srivastava, Swati; Verma, Seema; Negi, Arvind S; Sharma, Ashok

    2017-08-01

    BACE-1 and GSK-3β are potential therapeutic drug targets for Alzheimer's disease. Recently, both the targets received attention for designing dual inhibitors for Alzheimer's disease. Until now, only two-scaffold triazinone and curcumin have been reported as BACE-1 and GSK-3β dual inhibitors. Docking, molecular dynamics, clustering, binding energy, and network analysis of triazinone derivatives with BACE-1 and GSK-3β was performed to get molecular insight into the first reported dual inhibitor. Further, we designed and evaluated a naphthofuran series for its ability to inhibit BACE-1 and GSK-3β with the computational approaches. Docking study of naphthofuran series showed a good binding affinity towards both the targets. Molecular dynamics, binding energy, and network analysis were performed to compare their binding with the targets and amino acids responsible for binding. Naphthofuran series derivatives showed good interaction within the active site residues of both of the targets. Hydrogen bond occupancy and binding energy suggested strong binding with the targets. Dual-inhibitor binding was mostly governed by the hydrophobic interactions for both of the targets. Per residue energy decomposition and network analysis identified the key residues involved in the binding and inhibiting BACE-1 and GSK-3β. The results indicated that naphthofuran series derivative 11 may be a promising first-in-class dual inhibitor against BACE-1 and GSK-3β. This naphthofuran series may be further explored to design better dual inhibitors. Graphical abstract Naphthofuran derivative as a dual inhibitor for BACE-1 and GSK-3β.

  6. The PDZ-binding motif of Yes-associated protein is required for its co-activation of TEAD-mediated CTGF transcription and oncogenic cell transforming activity.

    Science.gov (United States)

    Shimomura, Tadanori; Miyamura, Norio; Hata, Shoji; Miura, Ryota; Hirayama, Jun; Nishina, Hiroshi

    2014-01-17

    YAP is a transcriptional co-activator that acts downstream of the Hippo signaling pathway and regulates multiple cellular processes, including proliferation. Hippo pathway-dependent phosphorylation of YAP negatively regulates its function. Conversely, attenuation of Hippo-mediated phosphorylation of YAP increases its ability to stimulate proliferation and eventually induces oncogenic transformation. The C-terminus of YAP contains a highly conserved PDZ-binding motif that regulates YAP's functions in multiple ways. However, to date, the importance of the PDZ-binding motif to the oncogenic cell transforming activity of YAP has not been determined. In this study, we disrupted the PDZ-binding motif in the YAP (5SA) protein, in which the sites normally targeted by Hippo pathway-dependent phosphorylation are mutated. We found that loss of the PDZ-binding motif significantly inhibited the oncogenic transformation of cultured cells induced by YAP (5SA). In addition, the increased nuclear localization of YAP (5SA) and its enhanced activation of TEAD-dependent transcription of the cell proliferation gene CTGF were strongly reduced when the PDZ-binding motif was deleted. Similarly, in mouse liver, deletion of the PDZ-binding motif suppressed nuclear localization of YAP (5SA) and YAP (5SA)-induced CTGF expression. Taken together, our results indicate that the PDZ-binding motif of YAP is critical for YAP-mediated oncogenesis, and that this effect is mediated by YAP's co-activation of TEAD-mediated CTGF transcription. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Comparative studies on the human serum albumin binding of the clinically approved EGFR inhibitors gefitinib, erlotinib, afatinib, osimertinib and the investigational inhibitor KP2187.

    Science.gov (United States)

    Dömötör, Orsolya; Pelivan, Karla; Borics, Attila; Keppler, Bernhard K; Kowol, Christian R; Enyedy, Éva A

    2018-03-11

    Binding interactions between human serum albumin (HSA) and four approved epidermal growth factor receptor (EGFR) inhibitors gefitinib (GEF), erlotinib (ERL), afatinib (AFA), osimertinib (OSI), as well as the experimental drug KP2187, were investigated by means of spectrofluorometric and molecular modelling methods. Steady-state and time resolved spectrofluorometric techniques were carried out, including direct quenching of protein fluorescence and site marker displacement measurements. Proton dissociation processes and solvent dependent fluorescence properties were investigated as well. The EGFR inhibitors were predominantly presented in their single protonated form (HL + ) at physiological pH except ERL, which is charge-neutral. Significant solvent dependent fluorescence properties were found for GEF, ERL and KP2187, namely their emission spectra show strong dependence on the polarity and the hydrogen bonding ability of the solvents. The inhibitors proved to be bound at site I of HSA (in subdomain IIA) in a weak-to-moderate fashion (logK' 3.9-4.9) using spectrofluorometry. OSI (logK' 4.3) and KP2187 can additionally bind in site II (in subdomain IIIA), while GEF, ERL and AFA clearly show no interaction here. Docking methods qualitatively confirmed binding site preferences of compounds GEF and KP2187, and indicated that they probably bind to HSA in their neutral forms. Binding constants calculated on the basis of the various experimental data indicate a weak-to-moderate binding on HSA, only OSI exhibits somewhat higher affinity towards this protein. However, model calculations performed at physiological blood concentrations of HSA resulted in high (ca. 90%) bound fractions for the inhibitors, highlighting the importance of plasma protein binding. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Spectroscopic studies of the binding of Cu(II) complexes of oxicam NSAIDs to alternating G-C and homopolymeric G-C sequences.

    Science.gov (United States)

    Chakraborty, Sreeja; Bose, Madhuparna; Sarkar, Munna

    2014-03-25

    Drugs belonging to the Non-steroidal anti-inflammatory (NSAID) group are not only used as anti-inflammatory, analgesic and anti-pyretic agents, but also show anti-cancer effects. Complexing them with a bioactive metal like copper, show an enhancement in their anti-cancer effects compared to the bare drugs, whose exact mechanism of action is not yet fully understood. For the first time, it was shown by our group that Cu(II)-NSAIDs can directly bind to the DNA backbone. The ability of the copper complexes of NSAIDs namely meloxicam and piroxicam to bind to the DNA backbone could be a possible molecular mechanism behind their enhanced anticancer effects. Elucidating base sequence specific interaction of Cu(II)-NSAIDs to the DNA will provide information on their possible binding sites in the genome sequence. In this work, we present how these complexes respond to differences in structure and hydration pattern of GC rich sequences. For this, binding studies of Cu(II) complexes of piroxicam [Cu(II)-(Px)2 (L)2] and meloxicam [Cu(II)-(Mx)2 (L)] with alternating GC (polydG-dC) and homopolymeric GC (polydG-polydC) sequences were carried out using a combination of spectroscopic techniques that include UV-Vis absorption, fluorescence and circular dichroism (CD) spectroscopy. The Cu(II)-NSAIDs show strong binding affinity to both polydG-dC and polydG-polydC. The role reversal of Cu(II)-meloxicam from a strong binder of polydG-dC (Kb=11.5×10(3) M(-1)) to a weak binder of polydG-polydC (Kb=5.02×10(3) M(-1)), while Cu(II)-piroxicam changes from a strong binder of polydG-polydC (Kb=8.18×10(3) M(-1)) to a weak one of polydG-dC (Kb=2.18×10(3) M(-1)), point to the sensitivity of these complexes to changes in the backbone structures/hydration. Changes in the profiles of UV absorption band and CD difference spectra, upon complex binding to polynucleotides and the results of competitive binding assay using ethidium bromide (EtBr) fluorescence indicate different binding modes in each

  9. Spectroscopic studies of the binding of Cu(II) complexes of oxicam NSAIDs to alternating G-C and homopolymeric G-C sequences

    Science.gov (United States)

    Chakraborty, Sreeja; Bose, Madhuparna; Sarkar, Munna

    2014-03-01

    Drugs belonging to the Non-steroidal anti-inflammatory (NSAID) group are not only used as anti-inflammatory, analgesic and anti-pyretic agents, but also show anti-cancer effects. Complexing them with a bioactive metal like copper, show an enhancement in their anti-cancer effects compared to the bare drugs, whose exact mechanism of action is not yet fully understood. For the first time, it was shown by our group that Cu(II)-NSAIDs can directly bind to the DNA backbone. The ability of the copper complexes of NSAIDs namely meloxicam and piroxicam to bind to the DNA backbone could be a possible molecular mechanism behind their enhanced anticancer effects. Elucidating base sequence specific interaction of Cu(II)-NSAIDs to the DNA will provide information on their possible binding sites in the genome sequence. In this work, we present how these complexes respond to differences in structure and hydration pattern of GC rich sequences. For this, binding studies of Cu(II) complexes of piroxicam [Cu(II)-(Px)2 (L)2] and meloxicam [Cu(II)-(Mx)2 (L)] with alternating GC (polydG-dC) and homopolymeric GC (polydG-polydC) sequences were carried out using a combination of spectroscopic techniques that include UV-Vis absorption, fluorescence and circular dichroism (CD) spectroscopy. The Cu(II)-NSAIDs show strong binding affinity to both polydG-dC and polydG-polydC. The role reversal of Cu(II)-meloxicam from a strong binder of polydG-dC (Kb = 11.5 × 103 M-1) to a weak binder of polydG-polydC (Kb = 5.02 × 103 M-1), while Cu(II)-piroxicam changes from a strong binder of polydG-polydC (Kb = 8.18 × 103 M-1) to a weak one of polydG-dC (Kb = 2.18 × 103 M-1), point to the sensitivity of these complexes to changes in the backbone structures/hydration. Changes in the profiles of UV absorption band and CD difference spectra, upon complex binding to polynucleotides and the results of competitive binding assay using ethidium bromide (EtBr) fluorescence indicate different binding modes in each

  10. Auxilliary Dry Binding Properties of Some Hydrogenated Vegetable ...

    African Journals Online (AJOL)

    The ability of some hydrogenated vegetable oils to act as dry binder in direct compression tablet formulations was investigated using an instrumented rotary tablet press. The effect of these widely used tablet lubricants was compared to Avicel® PH 102, a standard, dry binding excipient in direct compression tablet ...

  11. Tritium NMR spectroscopy of ligand binding to maltose-binding protein

    Energy Technology Data Exchange (ETDEWEB)

    Gehring, K.; Williams, P.G.; Pelton, J.G.; Morimoto, H.; Wemmer, D.E. (Lawrence Berkeley Lab., CA (United States))

    1991-06-04

    Tritium-labeled {alpha}- and {beta}-maltodextrins have been used to study their complexes with maltose-binding protein (MBP), a 40-kDa bacterial protein. Five substrates, from maltose to maltohexaose, were labeled at their reducing ends and their binding studied. Tritium NMR specctroscopy of the labeled sugars showed large upfield chamical shift changes upon binding and strong anomeric specficity. At 10{degrees}C, MBP bound {alpha}-maltose with 2.7 {plus minus} 0.5-fold higher affinity than {beta}-maltose, and, for longer maltodextrins, the ratio of affinities was even larger. The maximum chemical shift change was 2.2 ppm, suggesting that the reducing end of bound {alpha}-maltodextrin makes close contact with an aromatic residue in the MBP-binding site. Experiments with maltotriose (and longer maltodextrins) also revealed the presence of two bound {beta}-maltotriose resonances in rapid exchange. The authors interpret these two resonances as arising from two distinct sugar-protein complexes. In one complex, the {beta}-maltodextrin is bound by its reducing end, and, in the other complex, the {beta}-maltodextrin is bound by the middle glucose residue(s). This interpretation also suggests how MBP is able to bind both linear and circular maltodextrins.

  12. Tritium NMR spectroscopy of ligand binding to maltose-binding protein

    International Nuclear Information System (INIS)

    Gehring, K.; Williams, P.G.; Pelton, J.G.; Morimoto, H.; Wemmer, D.E.

    1991-01-01

    Tritium-labeled α- and β-maltodextrins have been used to study their complexes with maltose-binding protein (MBP), a 40-kDa bacterial protein. Five substrates, from maltose to maltohexaose, were labeled at their reducing ends and their binding studied. Tritium NMR specctroscopy of the labeled sugars showed large upfield chamical shift changes upon binding and strong anomeric specficity. At 10 degrees C, MBP bound α-maltose with 2.7 ± 0.5-fold higher affinity than β-maltose, and, for longer maltodextrins, the ratio of affinities was even larger. The maximum chemical shift change was 2.2 ppm, suggesting that the reducing end of bound α-maltodextrin makes close contact with an aromatic residue in the MBP-binding site. Experiments with maltotriose (and longer maltodextrins) also revealed the presence of two bound β-maltotriose resonances in rapid exchange. The authors interpret these two resonances as arising from two distinct sugar-protein complexes. In one complex, the β-maltodextrin is bound by its reducing end, and, in the other complex, the β-maltodextrin is bound by the middle glucose residue(s). This interpretation also suggests how MBP is able to bind both linear and circular maltodextrins

  13. A molecular modeling based method to predict elution behavior and binding patches of proteins in multimodal chromatography.

    Science.gov (United States)

    Banerjee, Suvrajit; Parimal, Siddharth; Cramer, Steven M

    2017-08-18

    Multimodal (MM) chromatography provides a powerful means to enhance the selectivity of protein separations by taking advantage of multiple weak interactions that include electrostatic, hydrophobic and van der Waals interactions. In order to increase our understanding of such phenomena, a computationally efficient approach was developed that combines short molecular dynamics simulations and continuum solvent based coarse-grained free energy calculations in order to study the binding of proteins to Self Assembled Monolayers (SAM) presenting MM ligands. Using this method, the free energies of protein-MM SAM binding over a range of incident orientations of the protein can be determined. The resulting free energies were then examined to identify the more "strongly bound" orientations of different proteins with two multimodal surfaces. The overall free energy of protein-MM surface binding was then determined and correlated to retention factors from isocratic chromatography. This correlation, combined with analytical expressions from the literature, was then employed to predict protein gradient elution salt concentrations as well as selectivity reversals with different MM resin systems. Patches on protein surfaces that interacted strongly with MM surfaces were also identified by determining the frequency of heavy atom contacts with the atoms of the MM SAMs. A comparison of these patches to Electrostatic Potential and hydrophobicity maps indicated that while all of these patches contained significant positive charge, only the highest frequency sites also possessed hydrophobicity. The ability to identify key binding patches on proteins may have significant impact on process development for the separation of bioproduct related impurities. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Carboplatin binding to histidine

    Energy Technology Data Exchange (ETDEWEB)

    Tanley, Simon W. M. [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom); Diederichs, Kay [University of Konstanz, D-78457 Konstanz (Germany); Kroon-Batenburg, Loes M. J. [Utrecht University, Padualaan 8, 3584 CH Utrecht (Netherlands); Levy, Colin [University of Manchester, 131 Princess Street, Manchester M1 7DN (United Kingdom); Schreurs, Antoine M. M. [Utrecht University, Padualaan 8, 3584 CH Utrecht (Netherlands); Helliwell, John R., E-mail: john.helliwell@manchester.ac.uk [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom)

    2014-08-29

    An X-ray crystal structure showing the binding of purely carboplatin to histidine in a model protein has finally been obtained. This required extensive crystallization trials and various novel crystal structure analyses. Carboplatin is a second-generation platinum anticancer agent used for the treatment of a variety of cancers. Previous X-ray crystallographic studies of carboplatin binding to histidine (in hen egg-white lysozyme; HEWL) showed the partial conversion of carboplatin to cisplatin owing to the high NaCl concentration used in the crystallization conditions. HEWL co-crystallizations with carboplatin in NaBr conditions have now been carried out to confirm whether carboplatin converts to the bromine form and whether this takes place in a similar way to the partial conversion of carboplatin to cisplatin observed previously in NaCl conditions. Here, it is reported that a partial chemical transformation takes place but to a transplatin form. Thus, to attempt to resolve purely carboplatin binding at histidine, this study utilized co-crystallization of HEWL with carboplatin without NaCl to eliminate the partial chemical conversion of carboplatin. Tetragonal HEWL crystals co-crystallized with carboplatin were successfully obtained in four different conditions, each at a different pH value. The structural results obtained show carboplatin bound to either one or both of the N atoms of His15 of HEWL, and this particular variation was dependent on the concentration of anions in the crystallization mixture and the elapsed time, as well as the pH used. The structural details of the bound carboplatin molecule also differed between them. Overall, the most detailed crystal structure showed the majority of the carboplatin atoms bound to the platinum centre; however, the four-carbon ring structure of the cyclobutanedicarboxylate moiety (CBDC) remained elusive. The potential impact of the results for the administration of carboplatin as an anticancer agent are described.

  15. Optical Binding of Nanowires

    Czech Academy of Sciences Publication Activity Database

    Simpson, Stephen Hugh; Zemánek, Pavel; Marago, O.M.; Jones, P.H.; Hanna, S.

    2017-01-01

    Roč. 17, č. 6 (2017), s. 3485-3492 ISSN 1530-6984 R&D Projects: GA ČR GB14-36681G Grant - others:AV ČR(CZ) CNR-16-12 Program:Bilaterální spolupráce Institutional support: RVO:68081731 Keywords : optical binding nanowires * Brownian motion * self -organization * non-equilibrium thermodynamics * non-equilibrium steady state * spin-orbit coupling * emergent phenomena Subject RIV: BH - Optics, Masers, Lasers OBOR OECD: Optics (including laser optics and quantum optics) Impact factor: 12.712, year: 2016

  16. Convulxin binds to native, human glycoprotein Ib alpha.

    Science.gov (United States)

    Kanaji, Sachiko; Kanaji, Taisuke; Furihata, Kenichi; Kato, Kazunobu; Ware, Jerry L; Kunicki, Thomas J

    2003-10-10

    Convulxin (CVX), a C-type snake protein from Crotalus durissus terrificus venom, is the quintessential agonist for studies of the collagen receptor, glycoprotein VI (GPVI) and its role in platelet adhesion to collagens. In this study, CVX, purified from venom, behaves as expected, i.e. it binds to platelet GPVI and recombinant human GPVI, induces platelet aggregation and platelet prothrombinase activity, and binds uniquely to GPVI in ligand blots of SDS-denatured proteins. Nonetheless, we find that CVX has a dual specificity for both GPVI and native but not denatured human GPIb alpha. First, CVX binds to human GPIb alpha expressed on the surface of CHO cells. Second, CVX binds weakly to murine platelet GPIb alpha but more strongly to human platelet GPIb alpha, as evidenced by comparative binding to wild-type, GPVI(-/-), FcR gamma (-/-), and human GPIb transgenic mice. Third, the binding of CVX to human GPIb alpha is inhibited by soluble, recombinant human GPVI. Fourth, CVX binding to GPIb alpha is disrupted by phenylalanine substitutions at GPIb alpha tyrosine-276, tyrosine-278, and tyrosine-279, which also disrupts von Willebrand factor and alpha-thrombin binding to GPIb alpha. Fifth, CVX binding to GPIb alpha on Chinese hamster ovary cell transfectants is inhibited by function-blocking murine monoclonal anti-GPIb alpha antibodies. Lastly, CVX fails to bind to denatured GPIb alpha in detergent extracts of platelets. Three separate preparations of CVX (two purified by the authors; one obtained commercially) produced equivalent results. These results indicate that CVX exhibits dual specificity for both native GPIb alpha and GPVI. Furthermore, the binding site on GPIb alpha for CVX may be close to that for von Willebrand factor. Therefore, a contribution of GPIb alpha to CVX-induced platelet responses needs to be carefully re-evaluated.

  17. Teachers of high ability pupils

    Directory of Open Access Journals (Sweden)

    Cándido Genovard

    2010-04-01

    Full Text Available In this article we analyze the characteristics of gifted and talented students’ expert teachers. The subject background and the specific proprieties of the instructional process to meet gifted students’ educational needs are analyzed. The value of teacher-student interactions and of teaching and learning styles are highlighted. Also, we include different action guidelines and instructional resources to use in the classroom to teach these students. There is not an ideal teacher for high ability students. However, teachers must know what the teaching-learning processes are and how these work, and the diverse psychological, content and contextual variables involved in such processes.

  18. Binding of peptides to HLA-DQ molecules: peptide binding properties of the disease-associated HLA-DQ(alpha 1*0501, beta 1*0201) molecule

    DEFF Research Database (Denmark)

    Johansen, B H; Buus, S; Vartdal, F

    1994-01-01

    Peptide binding to DQ molecules has not previously been described. Here we report a biochemical peptide-binding assay specific for the DQ2 [i.e. DQ(alpha 1*0501, beta 1*0201)] molecule. This molecule was chosen since it shows a strong association to diseases such as celiac disease and insulin...

  19. Evaluation of a Solid Phase DNA Binding Matrix for Downstream PCR Analysis

    National Research Council Canada - National Science Library

    Bader, Douglas E; Fisher, Glen R; Stratilo, Chad W

    2005-01-01

    A commercially available solid-phase DNA binding matrix (FTA cards) was evaluated for its ability to capture and release DNA for downstream gene amplification and detection assays using polymerase chain reaction (PCR...

  20. Structure of a Viral Cap-independent Translation Element That Functions via High Affinity Binding to the eIF4E Subunit of eIF4F*S⃞

    Science.gov (United States)

    Wang, Zhaohui; Treder, Krzysztof; Miller, W. Allen

    2009-01-01

    RNAs of many positive strand RNA viruses lack a 5′ cap structure and instead rely on cap-independent translation elements (CITEs) to facilitate efficient translation initiation. The mechanisms by which these RNAs recruit ribosomes are poorly understood, and for many viruses the CITE is unknown. Here we identify the first CITE of an umbravirus in the 3′-untranslated region of pea enation mosaic virus RNA 2. Chemical and enzymatic probing of the ∼100-nucleotide PEMV RNA 2 CITE (PTE), and mutagenesis revealed that it forms a long, bulged helix that branches into two short stem-loops, with a possible pseudoknot interaction between a C-rich bulge at the branch point and a G-rich bulge in the main helix. The PTE inhibited translation in trans, and addition of eIF4F, but not eIFiso4F, restored translation. Filter binding assays revealed that the PTE binds eIF4F and its eIF4E subunit with high affinity. Tight binding required an intact cap-binding pocket in eIF4E. Among many PTE mutants, there was a strong correlation between PTE-eIF4E binding affinity and ability to stimulate cap-independent translation. We conclude that the PTE recruits eIF4F by binding eIF4E. The PTE represents a different class of translation enhancer element, as defined by its structure and ability to bind eIF4E in the absence of an m7G cap. PMID:19276085

  1. Structure of a viral cap-independent translation element that functions via high affinity binding to the eIF4E subunit of eIF4F.

    Science.gov (United States)

    Wang, Zhaohui; Treder, Krzysztof; Miller, W Allen

    2009-05-22

    RNAs of many positive strand RNA viruses lack a 5' cap structure and instead rely on cap-independent translation elements (CITEs) to facilitate efficient translation initiation. The mechanisms by which these RNAs recruit ribosomes are poorly understood, and for many viruses the CITE is unknown. Here we identify the first CITE of an umbravirus in the 3'-untranslated region of pea enation mosaic virus RNA 2. Chemical and enzymatic probing of the approximately 100-nucleotide PEMV RNA 2 CITE (PTE), and mutagenesis revealed that it forms a long, bulged helix that branches into two short stem-loops, with a possible pseudoknot interaction between a C-rich bulge at the branch point and a G-rich bulge in the main helix. The PTE inhibited translation in trans, and addition of eIF4F, but not eIFiso4F, restored translation. Filter binding assays revealed that the PTE binds eIF4F and its eIF4E subunit with high affinity. Tight binding required an intact cap-binding pocket in eIF4E. Among many PTE mutants, there was a strong correlation between PTE-eIF4E binding affinity and ability to stimulate cap-independent translation. We conclude that the PTE recruits eIF4F by binding eIF4E. The PTE represents a different class of translation enhancer element, as defined by its structure and ability to bind eIF4E in the absence of an m(7)G cap.

  2. The Data Set on the Multiple Abilities

    DEFF Research Database (Denmark)

    Klynge, Alice Heegaard

    2008-01-01

    This paper presents a data set on multiple abilities. The abilities cover the Literacy and Math Ability, the Creative and Innovative Ability, the Learning Ability, the Communication Ability, the Social Competency, the Self-Management Ability, the Environmental Awareness, the Civic Competency......, the Intercultural Awareness, and the Health Awareness. The data stems from a unique cross-sectional survey carried out for the adult population in Denmark. Several dimensions and many questions pinpoint and measure every ability. The dimensions cover areas such as the individual behavior at work, the individual...

  3. Parkinson's disease and driving ability.

    Science.gov (United States)

    Singh, Rajiv; Pentland, Brian; Hunter, John; Provan, Frances

    2007-04-01

    To explore the driving problems associated with Parkinson's disease (PD) and to ascertain whether any clinical features or tests predict driver safety. The driving ability of 154 individuals with PD referred to a driving assessment centre was determined by a combination of clinical tests, reaction times on a test rig and an in-car driving test. The majority of cases (104, 66%) were able to continue driving although 46 individuals required an automatic transmission and 10 others needed car modifications. Ability to drive was predicted by the severity of physical disease, age, presence of other associated medical conditions, particularly dementia, duration of disease, brake reaction, time on a test rig and score on a driving test (all pfeatures in distinguishing safety to drive were severe physical disease (Hoehn and Yahr stage 3), reaction time, moderate disease associated with another medical condition and high score on car testing. Most individuals with PD are safe to drive, although many benefit from car modifications or from using an automatic transmission. A combination of clinical tests and in-car driving assessment will establish safety to drive, and a number of clinical correlates can be shown to predict the likely outcome and may assist in the decision process. This is the largest series of consecutive patients seen at a driving assessment centre reported to date, and the first to devise a scoring system for on-road driving assessment.

  4. Strongly correlating liquids and their isomorphs

    OpenAIRE

    Pedersen, Ulf R.; Gnan, Nicoletta; Bailey, Nicholas P.; Schröder, Thomas B.; Dyre, Jeppe C.

    2010-01-01

    This paper summarizes the properties of strongly correlating liquids, i.e., liquids with strong correlations between virial and potential energy equilibrium fluctuations at constant volume. We proceed to focus on the experimental predictions for strongly correlating glass-forming liquids. These predictions include i) density scaling, ii) isochronal superposition, iii) that there is a single function from which all frequency-dependent viscoelastic response functions may be calculated, iv) that...

  5. Atom collisions in a strong electromagnetic field

    International Nuclear Information System (INIS)

    Smirnov, V.S.; Chaplik, A.V.

    1976-01-01

    It is shown that the long-range part of interatomic interaction is considerably altered in a strong electromagnetic field. Instead of the van der Waals law the potential asymptote can best be described by a dipole-dipole R -3 law. Impact broadening and the line shift in a strong nonresonant field are calculated. The possibility of bound states of two atoms being formed in a strong light field is discussed

  6. Hydrodynamic and Membrane Binding Properties of Purified Rous Sarcoma Virus Gag Protein

    Energy Technology Data Exchange (ETDEWEB)

    Dick, Robert A.; Datta, Siddhartha A.K.; Nanda, Hirsh; Fang, Xianyang; Wen, Yi; Barros, Marilia; Wang, Yun-Xing; Rein, Alan; Vogt, Volker M. (NCI); (Cornell); (CM); (NIST)

    2016-05-06

    Previously, no retroviral Gag protein has been highly purified in milligram quantities and in a biologically relevant and active form. We have purified Rous sarcoma virus (RSV) Gag protein and in parallel several truncation mutants of Gag and have studied their biophysical properties and membrane interactionsin vitro. RSV Gag is unusual in that it is not naturally myristoylated. From its ability to assemble into virus-like particlesin vitro, we infer that RSV Gag is biologically active. By size exclusion chromatography and small-angle X-ray scattering, Gag in solution appears extended and flexible, in contrast to previous reports on unmyristoylated HIV-1 Gag, which is compact. However, by neutron reflectometry measurements of RSV Gag bound to a supported bilayer, the protein appears to adopt a more compact, folded-over conformation. At physiological ionic strength, purified Gag binds strongly to liposomes containing acidic lipids. This interaction is stimulated by physiological levels of phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2] and by cholesterol. However, unlike HIV-1 Gag, RSV Gag shows no sensitivity to acyl chain saturation. In contrast with full-length RSV Gag, the purified MA domain of Gag binds to liposomes only weakly. Similarly, both an N-terminally truncated version of Gag that is missing the MA domain and a C-terminally truncated version that is missing the NC domain bind only weakly. These results imply that NC contributes to membrane interactionin vitro, either by directly contacting acidic lipids or by promoting Gag multimerization.

    Retroviruses like HIV assemble at and bud from the plasma membrane of cells. Assembly requires the interaction between thousands of Gag molecules to form a lattice. Previous work indicated that lattice formation at the plasma membrane is influenced by the conformation of monomeric HIV. We have extended this work to the more tractable RSV Gag. Our

  7. A Group Action Method for Construction of Strong Substitution Box

    Science.gov (United States)

    Jamal, Sajjad Shaukat; Shah, Tariq; Attaullah, Atta

    2017-06-01

    In this paper, the method to develop cryptographically strong substitution box is presented which can be used in multimedia security and data hiding techniques. The algorithm of construction depends on the action of a projective general linear group over the set of units of the finite commutative ring. The strength of substitution box and ability to create confusion is assessed with different available analyses. Moreover, the ability of resistance against malicious attacks is also evaluated. The substitution box is examined by bit independent criterion, strict avalanche criterion, nonlinearity test, linear approximation probability test and differential approximation probability test. This substitution box is equated with well-recognized substitution boxes such as AES, Gray, APA, S8, prime of residue, Xyi and Skipjack. The comparison shows encouraging results about the strength of the proposed box. The majority logic criterion is also calculated to analyze the strength and its practical implementation.

  8. IGF binding proteins.

    Science.gov (United States)

    Bach, Leon A

    2017-12-18

    Insulin-like growth factor binding proteins (IGFBPs) 1-6 bind IGFs but not insulin with high affinity. They were initially identified as serum carriers and passive inhibitors of IGF actions. However, subsequent studies showed that, although IGFBPs inhibit IGF actions in many circumstances, they may also potentiate these actions. IGFBPs are widely expressed in most tissues, and they are flexible endocrine and autocrine/paracrine regulators of IGF activity, which is essential for this important physiological system. More recently, individual IGFBPs have been shown to have IGF-independent actions. Mechanisms underlying these actions include (i) interaction with non-IGF proteins in compartments including the extracellular space and matrix, the cell surface and intracellularly; (ii) interaction with and modulation of other growth factor pathways including EGF, TGF- and VEGF; and (iii) direct or indirect transcriptional effects following nuclear entry of IGFBPs. Through these IGF-dependent and IGF-independent actions, IGFBPs modulate essential cellular processes including proliferation, survival, migration, senescence, autophagy and angiogenesis. They have been implicated in a range of disorders including malignant, metabolic, neurological and immune diseases. A more complete understanding of their cellular roles may lead to the development of novel IGFBP-based therapeutic opportunities.

  9. HIV-1 clade promoters strongly influence spatial and temporal dynamics of viral replication in vivo

    NARCIS (Netherlands)

    Centlivre, Mireille; Sommer, Peter; Michel, Marie; Ho Tsong Fang, Raphaël; Gofflo, Sandrine; Valladeau, Jenny; Schmitt, Nathalie; Thierry, Françoise; Hurtrel, Bruno; Wain-Hobson, Simon; Sala, Monica

    2005-01-01

    Although the primary determinant of cell tropism is the interaction of viral envelope or capsid proteins with cellular receptors, other viral elements can strongly modulate viral replication. While the HIV-1 promoter is polymorphic for a variety of transcription factor binding sites, the impact of

  10. The role of early language abilities on math skills among Chinese children.

    Science.gov (United States)

    Zhang, Juan; Fan, Xitao; Cheung, Sum Kwing; Meng, Yaxuan; Cai, Zhihui; Hu, Bi Ying

    2017-01-01

    The present study investigated the role of early language abilities in the development of math skills among Chinese K-3 students. About 2000 children in China, who were on average aged 6 years, were assessed for both informal math (e.g., basic number concepts such as counting objects) and formal math (calculations including addition and subtraction) skills, language abilities and nonverbal intelligence. Correlation analysis showed that language abilities were more strongly associated with informal than formal math skills, and regression analyses revealed that children's language abilities could uniquely predict both informal and formal math skills with age, gender, and nonverbal intelligence controlled. Mediation analyses demonstrated that the relationship between children's language abilities and formal math skills was partially mediated by informal math skills. The current findings indicate 1) Children's language abilities are of strong predictive values for both informal and formal math skills; 2) Language abilities impacts formal math skills partially through the mediation of informal math skills.

  11. Interaction of Zn(II)bleomycin-A2 and Zn(II)peplomycin with a DNA hairpin containing the 5'-GT-3' binding site in comparison with the 5'-GC-3' binding site studied by NMR spectroscopy.

    Science.gov (United States)

    Follett, Shelby E; Ingersoll, Azure D; Murray, Sally A; Reilly, Teresa M; Lehmann, Teresa E

    2017-10-01

    Bleomycins are a group of glycopeptide antibiotics synthesized by Streptomyces verticillus that are widely used for the treatment of various neoplastic diseases. These antibiotics have the ability to chelate a metal center, mainly Fe(II), and cause site-specific DNA cleavage. Bleomycins are differentiated by their C-terminal regions. Although this antibiotic family is a successful course of treatment for some types of cancers, it is known to cause pulmonary fibrosis. Previous studies have identified that bleomycin-related pulmonary toxicity is linked to the C-terminal region of these drugs. This region has been shown to closely interact with DNA. We examined the binding of Zn(II)peplomycin and Zn(II)bleomycin-A 2 to a DNA hairpin of sequence 5'-CCAGTATTTTTACTGG-3', containing the binding site 5'-GT-3', and compared the results with those obtained from our studies of the same MBLMs bound to a DNA hairpin containing the binding site 5'-GC-3'. We provide evidence that the DNA base sequence has a strong impact in the final structure of the drug-target complex.

  12. LDA+DMFT Approach to Magnetocrystalline Anisotropy of Strong Magnets

    Directory of Open Access Journals (Sweden)

    Jian-Xin Zhu

    2014-05-01

    Full Text Available The new challenges posed by the need of finding strong rare-earth-free magnets demand methods that can predict magnetization and magnetocrystalline anisotropy energy (MAE. We argue that correlated electron effects, which are normally underestimated in band-structure calculations, play a crucial role in the development of the orbital component of the magnetic moments. Because magnetic anisotropy arises from this orbital component, the ability to include correlation effects has profound consequences on our predictive power of the MAE of strong magnets. Here, we show that incorporating the local effects of electronic correlations with dynamical mean-field theory provides reliable estimates of the orbital moment, the mass enhancement, and the MAE of YCo_{5}.

  13. Functional diversity of CTCFs is encoded in their binding motifs.

    Science.gov (United States)

    Fang, Rongxin; Wang, Chengqi; Skogerbo, Geir; Zhang, Zhihua

    2015-08-28

    The CCCTC-binding factor (CTCF) has diverse regulatory functions. However, the definitive characteristics of the CTCF binding motif required for its functional diversity still remains elusive. Here, we describe a new motif discovery workflow by which we have identified three CTCF binding motif variations with highly divergent functionalities. Supported by transcriptomic, epigenomic and chromatin-interactomic data, we show that the functional diversity of the CTCF binding motifs is strongly associated with their GC content, CpG dinucleotide coverage and relative DNA methylation level at the 12th position of the motifs. Further analysis suggested that the co-localization of cohesin, the key factor in cohesion of sister chromatids, is negatively correlated with the CpG coverage and the relative DNA methylation level at the 12th position. Finally, we present evidences for a hypothetical model in which chromatin interactions between promoters and distal regulatory regions are likely mediated by CTCFs binding to sequences with high CpG. These results demonstrate the existence of definitive CTCF binding motifs corresponding to CTCF's diverse functions, and that the functional diversity of the motifs is strongly associated with genetic and epigenetic features at the 12th position of the motifs.

  14. Measurement of plasma protein and lipoprotein binding of pyrethroids.

    Science.gov (United States)

    Sethi, Pankaj K; Muralidhara, S; Bruckner, James V; White, Catherine A

    2014-01-01

    A simple, reliable procedure was developed to measure binding of pyrethroid insecticides to total proteins and lipoproteins of rat and human plasma. The extent of binding of (14)C-labeled deltamethrin (DLM), cis-permethrin (CIS) and trans-permethrin (TRANS) was quantified by a 3-step organic solvent extraction technique. Rat and human plasma samples, containing NaF to inhibit esterases, were spiked with a range of concentrations of each radiolabeled pyrethroid. Protein binding reached equilibrium within ~1h of incubation at 37°C. The samples were extracted in turn with: isooctane to collect the unbound fraction; 2-octanol to extract the lipoprotein-bound fraction; and acetonitrile to obtain the protein-bound fraction. Absolute recoveries of DLM, CIS and TRANS ranged from 86 to 95%. Adherence of these very lipophilic chemicals to glass and plastic was minimized by using silanized glass vials and LoBind® plastic pipettes. The method's ability to distinguish lipoprotein from protein binding was confirmed by experiments with diazepam and cyclosporine, drugs that bind selectively to albumin and lipoproteins, respectively. This procedure was effectively utilized for studies of the species-dependence of plasma protein and lipoprotein binding of three pyrethroids for inclusion in physiologically-based pharmacokinetic models of pyrethroids for use in health risk assessments of the insecticides in children and adults. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Binding properties of halogenated biphenyls to cells and macromolecules

    International Nuclear Information System (INIS)

    Pepe, M.G.

    1982-01-01

    The interaction of polychlorinated biphenyls (PCB) with serum proteins may help explain the cellular incorporation of PCB as the effect of PCB on thyroid hormone function. PCB reduces serum thyroxine and triiodothyronine levels in rats; the mechanism for this effect is unknown. The initial distribution of PCB from blood to tissue is rapid and depends on blood perfusion and tissue affinity; however, the translocation of unmetabolized PCB from its initial storage sites to adipose tissue may depend on serum and cellular protein interactions. Therefore, the ability of PCB to displace triiodothyronine binding to albumin and antibodies, as well as the effect of binding to serum proteins as a mechanism for cellular incorporation was measured. PCB binding to albumin showed both high and low affinity binding sites. This binding was able to prevent triiodothyronine binding to albumin. The distribution of PCB inserum showed that lipoproteins contained 94% of the total 14 C PCB added, while 5% of the 14 C PCB was bound to albumin. The in vitro binding of 14 C PCB to serum obtained from rats pretreated with PCB in their diets for 6 months showed a significant decrease (p 14 C PCB was higher (p < 0.05) in liver, adrenal and adipose cells than pituitary and thyroid cells

  16. Ice-Binding Proteins in Plants

    Directory of Open Access Journals (Sweden)

    Melissa Bredow

    2017-12-01

    Full Text Available Sub-zero temperatures put plants at risk of damage associated with the formation of ice crystals in the apoplast. Some freeze-tolerant plants mitigate this risk by expressing ice-binding proteins (IBPs, that adsorb to ice crystals and modify their growth. IBPs are found across several biological kingdoms, with their ice-binding activity and function uniquely suited to the lifestyle they have evolved to protect, be it in fishes, insects or plants. While IBPs from freeze-avoidant species significantly depress the freezing point, plant IBPs typically have a reduced ability to lower the freezing temperature. Nevertheless, they have a superior ability to inhibit the recrystallization of formed ice. This latter activity prevents ice crystals from growing larger at temperatures close to melting. Attempts to engineer frost-hardy plants by the controlled transfer of IBPs from freeze-avoiding fish and insects have been largely unsuccessful. In contrast, the expression of recombinant IBP sequences from freeze-tolerant plants significantly reduced electrolyte leakage and enhanced freezing survival in freeze-sensitive plants. These promising results have spurred additional investigations into plant IBP localization and post-translational modifications, as well as a re-evaluation of IBPs as part of the anti-stress and anti-pathogen axis of freeze-tolerant plants. Here we present an overview of plant freezing stress and adaptation mechanisms and discuss the potential utility of IBPs for the generation of freeze-tolerant crops.

  17. Strong ideal convergence in probabilistic metric spaces

    Indian Academy of Sciences (India)

    sequence and strong ideal Cauchy sequence in a probabilistic metric (PM) space endowed with the strong topology, and ... also important applications in nonlinear analysis [2]. The theory was brought to ..... for each t > 0 since each set on the right-hand side of the relation (3.1) belongs to I. Thus, by Definition 2.11 and the ...

  18. Large N baryons, strong coupling theory, quarks

    International Nuclear Information System (INIS)

    Sakita, B.

    1984-01-01

    It is shown that in QCD the large N limit is the same as the static strong coupling limit. By using the static strong coupling techniques some of the results of large N baryons are derived. The results are consistent with the large N SU(6) static quark model. (author)

  19. Optimization of strong and weak coordinates

    NARCIS (Netherlands)

    Swart, M.; Bickelhaupt, F.M.

    2006-01-01

    We present a new scheme for the geometry optimization of equilibrium and transition state structures that can be used for both strong and weak coordinates. We use a screening function that depends on atom-pair distances to differentiate strong coordinates from weak coordinates. This differentiation

  20. Strong decays of nucleon and delta resonances

    International Nuclear Information System (INIS)

    Bijker, R.; Leviatan, A.

    1996-01-01

    We study the strong couplings of the nucleon and delta resonances in a collective model. In the ensuing algebraic treatment we derive closed expressions for decay widths which are used to analyze the experimental data for strong decays into the pion and eta channels. (Author)

  1. Theoretical studies of strongly correlated fermions

    Energy Technology Data Exchange (ETDEWEB)

    Logan, D. [Institut Max von Laue - Paul Langevin (ILL), 38 - Grenoble (France)

    1997-04-01

    Strongly correlated fermions are investigated. An understanding of strongly correlated fermions underpins a diverse range of phenomena such as metal-insulator transitions, high-temperature superconductivity, magnetic impurity problems and the properties of heavy-fermion systems, in all of which local moments play an important role. (author).

  2. Familial aggregation patterns in mathematical ability.

    Science.gov (United States)

    Wijsman, Ellen M; Robinson, Nancy M; Ainsworth, Kathryn H; Rosenthal, Elisabeth A; Holzman, Ted; Raskind, Wendy H

    2004-01-01

    Mathematical talent is an asset in modern society both at an individual and a societal level. Environmental factors such as quality of mathematics education undoubtedly affect an individual's performance, and there is some evidence that genetic factors also may play a role. The current study was performed to investigate the feasibility of undertaking genetics studies on mathematical ability. Because the etiology of low ability in mathematics is likely to be multifactorial and heterogeneous, we evaluated families ascertained through a proband with high mathematical performance in grade 7 on the SAT to eliminate, to some degree, adverse environmental factors. Families of sex-matched probands, selected for high verbal performance on the SAT, served as the comparison group. We evaluated a number of proxy measures for their usefulness in the study of clustering of mathematical talent. Given the difficulty of testing mathematics performance across developmental ages, especially with the added complexity of decreasing exposure to formal mathematics concepts post schooling, we also devised a semiquantitative scale that incorporated educational, occupational, and avocational information as a surrogate for an academic mathematics measure. Whereas several proxy measures showed no evidence of a genetic basis, we found that the semiquantitative scale of mathematical talent showed strong evidence of a genetic basis, with a differential response as a function of the performance measure used to select the proband. This observation suggests that there may be a genetic basis to specific mathematical talent, and that specific, as opposed to proxy, investigative measures that are designed to measure such talent in family members could be of benefit for this purpose.

  3. Characterization of 6-mercaptopurine binding to bovine serum albumin and its displacement from the binding sites by quercetin and rutin

    Energy Technology Data Exchange (ETDEWEB)

    Ehteshami, Mehdi [Nutrition Research Center, School of Health and Nutrition, Tabriz University of Medical Sciences, Tabriz 51644-14766 (Iran, Islamic Republic of); Rasoulzadeh, Farzaneh [Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz 51644-14766 (Iran, Islamic Republic of); Mahboob, Soltanali [Nutrition Research Center, School of Health and Nutrition, Tabriz University of Medical Sciences, Tabriz 51644-14766 (Iran, Islamic Republic of); Rashidi, Mohammad-Reza, E-mail: rashidi@tbzmed.ac.ir [Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz 51644-14766 (Iran, Islamic Republic of)

    2013-03-15

    Binding of a drug to the serum albumins as major serum transport proteins can be influenced by other ligands leading to alteration of its pharmacological properties. In the present study, binding characteristics of 6-mercaptopurine (6-MP) with bovine serum albumin (BSA) together with its displacement from its binding site by quercetin and rutin have been investigated by the spectroscopic method. According to the binding parameters, a static quenching component in overall dynamic quenching process is operative in the interaction between 6-MP and BSA. The binding of 6-MP to BSA occurred spontaneously due to entropy-driven hydrophobic interactions. The synchronous fluorescence spectroscopy study revealed that the secondary structure of BSA is changed in the presence of 6-MP and both Tyr and Trp residues participate in the interaction between 6-MP and BSA with the later one being more dominant. The binding constant value of 6-MP-BSA in the presence of quercetin and rutin increased. 6-MP was displaced by ibuprofen indicating that the binding site of 6-MP on albumin is site II. Therefore, the change of the pharmacokinetic and pharmacodynamic properties of 6-MP by quercetin and rutin through alteration of binding capacity of 6-MP to the serum albumin cannot be ruled out. In addition, the displacement study showed that 6-MP is located in site II of BSA. - Highlights: Black-Right-Pointing-Pointer Participation of both Tyr and particularly Trp residues in the interaction between 6-MP and BSA. Black-Right-Pointing-Pointer Involvement of a static quenching component in an overall dynamic quenching process. Black-Right-Pointing-Pointer Ability of quercetin and rutin to change the binding constants of 6-MP-BSA complex. Black-Right-Pointing-Pointer Binding of 6-MP to BSA through entropy-driven hydrophobic interactions.

  4. DNA binding and gel electrophoresis studies of a copper (II) complex containing mixed aliphatic and aromatic dinitrogen ligands.

    Science.gov (United States)

    Shahabadi, Nahid; Darabi, Farivash; Maghsudi, Maryam; Kashanian, Soheila

    2010-06-01

    The interaction of a novel mixed ligand copper (II) complex, [Cu(N-N)(L)(EtOH)](NO(3))(2) . 2H(2)O, in which N-N indicates 2,9-dimethyl-1,10-phenanthroline and L indicates N,N-dimethyltrimethylenediamine with calf thymus DNA was investigated by absorption, circular dichroism, voltammetric, and viscosimetric techniques. The absorption spectra of the complex with calf thymus DNA showed a marked hypochromism in the pi --> pi* and metal to ligand charge transfer (MLCT) transitions, with no obvious red shift attributed to a partial intercalation. The intrinsic binding constant (K(b)) was determined as 2 x 10(5) M(-1). There was slight to appreciable changes in the relative viscosity of DNA, which is consistent with enhanced hydrophobic interaction of the methyl-substituted phen ring and partial intercalation mode of binding. Electrochemical studies showed a decrease in the peak current, which is ascribed to the strong binding between Cu (II) complex and DNA. The fluorescence spectral characteristics showed that the Cu (II) complex is able to displace the methylene blue bound to DNA, but not as complete as intercalative molecules. It is remarkable that this mixed ligand complex, in contrast to [Cu(2,9-dmp)(2)](+) (2,9-dmp = 2,9-dimethyl-1,10-phenanthroline), which fails to cleave DNA, has ability to cleave the supercoiled plasmid DNA.

  5. Development of a novel affinity chromatography resin for platform purification of bispecific antibodies with modified protein a binding avidity.

    Science.gov (United States)

    Tustian, Andrew D; Laurin, Linus; Ihre, Henrik; Tran, Travis; Stairs, Robert; Bak, Hanne

    2018-02-21

    There is strong interest in the production of bispecific monoclonal antibodies that can simultaneously bind two distinct targets or epitopes to achieve novel mechanisms of action and efficacy. Regeneron's bispecific technology, based upon a standard IgG, consists of a heterodimer of two different heavy chains, and a common light chain. Co-expression of two heavy chains leads to the formation of two parental IgG impurities, the removal of which is facilitated by a dipeptide substitution in the Fc portion of one of the heavy chains that ablates Fc Protein A binding. Therefore the affinity capture (Protein A) step of the purification process must perform both bulk capture and high resolution of these mAb impurities, a task current commercially available resins are not designed for. Resolution can be further impaired by the ability of Protein A to bind some antibodies in the variable region of the heavy chain (V H ). This paper details development of a novel Protein A resin. This resin combines an alkali stable ligand with a base matrix exhibiting excellent mass transfer properties to allow high capacity single step capture and resolution of bispecific antibodies with high yields. The developed resin, named MabSelect SuRe™ pcc, is implemented in GMP production processes for several bispecific antibodies. This article is protected by copyright. All rights reserved. © 2018 American Institute of Chemical Engineers.

  6. Seismic switch for strong motion measurement

    Science.gov (United States)

    Harben, P.E.; Rodgers, P.W.; Ewert, D.W.

    1995-05-30

    A seismic switching device is described that has an input signal from an existing microseismic station seismometer and a signal from a strong motion measuring instrument. The seismic switch monitors the signal level of the strong motion instrument and passes the seismometer signal to the station data telemetry and recording systems. When the strong motion instrument signal level exceeds a user set threshold level, the seismometer signal is switched out and the strong motion signal is passed to the telemetry system. The amount of time the strong motion signal is passed before switching back to the seismometer signal is user controlled between 1 and 15 seconds. If the threshold level is exceeded during a switch time period, the length of time is extended from that instant by one user set time period. 11 figs.

  7. Assessing Algebraic Solving Ability: A Theoretical Framework

    Science.gov (United States)

    Lian, Lim Hooi; Yew, Wun Thiam

    2012-01-01

    Algebraic solving ability had been discussed by many educators and researchers. There exists no definite definition for algebraic solving ability as it can be viewed from different perspectives. In this paper, the nature of algebraic solving ability in terms of algebraic processes that demonstrate the ability in solving algebraic problem is…

  8. A class-A GPCR solubilized under high hydrostatic pressure retains its ligand binding ability

    Science.gov (United States)

    The effect of high hydrostatic pressure (HHP) on the solubilization of a class-A G protein-coupled receptor, the silkmoth pheromone biosynthesis-activating neuropeptide receptor (PBANR), was investigated. PBANR was expressed in expresSF+ insect cells as a C-terminal fusion protein with EGFP. The mem...

  9. Kinetics of fatty acid binding ability of glycated human serum albumin

    Indian Academy of Sciences (India)

    Unknown

    (Shapiro et al 1980), membrane collagen (Bailey et al. 1976), human serum albumin (HAS) (Iberg and Flückiger. 1986), and lens crystallin (Lyons et al 1991) ..... were reduced by NaBH4 and hydrolyzed by 6 N HCl containing. 1% wt/v phenol. Relative amount of residual lysine residues. (%) in glycated HSA were expressed ...

  10. Phenanthrene binding by humic acid–protein complexes as studied by passive dosing technique

    International Nuclear Information System (INIS)

    Zhao, Jian; Wang, Zhenyu; Ghosh, Saikat; Xing, Baoshan

    2014-01-01

    This work investigated the binding behavior of phenanthrene by humic acids (HA-2 and HA-5), proteins (bovine serum albumin (BSA)), lysozyme and pepsin), and their complexes using a passive dosing technique. All sorption isotherms were fitted well with Freundlich model and the binding capability followed an order of HA-5 > HA-2 > BSA > pepsin > lysozyme. In NaCl solution, phenanthrene binding to HA-BSA complexes was much higher than the sum of binding to individual HA and BSA, while there was no enhancement for HA-pepsin. Positively charged lysozyme slightly lowered phenanthrene binding on both HAs due to strong aggregation of HA-lysozyme complexes, leading to reduction in the number of binding sites. The binding enhancement by HA-BSA was observed under all tested ion species and ionic strengths. This enhancement can be explained by unfolding of protein, reduction of aggregate size and formation of HA-BSA complexes with favorable conformations for binding phenanthrene. Highlights: • Phenanthrene binding capability followed an order: HA-5>HA-2>BSA>pepsin>lysozyme. • Phenanthrene binding to HA-BSA was enhanced relative to individual HA and BSA. • Binding enhancement to HA-BSA was observed under all tested solution conditions. • The enhancement is related to BSA unfolding, size reduction and HA-BSA complexation. -- Phenanthrene binding to HA-BSA complexes is much higher than the sum to individual HA and BSA while there was no binding enhancement to HA-pepsin or HA-lysozyme

  11. γ Sulphate PNA (PNA S: highly selective DNA binding molecule showing promising antigene activity.

    Directory of Open Access Journals (Sweden)

    Concetta Avitabile

    Full Text Available Peptide Nucleic Acids (PNAs, nucleic acid analogues showing high stability to enzyme degradation and strong affinity and specificity of binding toward DNA and RNA are widely investigated as tools to interfere in gene expression. Several studies have been focused on PNA analogues with modifications on the backbone and bases in the attempt to overcome solubility, uptake and aggregation issues. γ PNAs, PNA derivatives having a substituent in the γ position of the backbone show interesting properties in terms of secondary structure and affinity of binding toward complementary nucleic acids. In this paper we illustrate our results obtained on new analogues, bearing a sulphate in the γ position of the backbone, developed to be more DNA-like in terms of polarity and charge. The synthesis of monomers and oligomers is described. NMR studies on the conformational properties of monomers and studies on the secondary structure of single strands and triplexes are reported. Furthermore the hybrid stability and the effect of mismatches on the stability have also been investigated. Finally, the ability of the new analogue to work as antigene, interfering with the transcription of the ErbB2 gene on a human cell line overexpressing ErbB2 (SKBR3, assessed by FACS and qPCR, is described.

  12. Reversible and Irreversible Binding of Nanoparticles to Polymeric Surfaces

    Directory of Open Access Journals (Sweden)

    Wolfgang H. Binder

    2009-01-01

    Full Text Available Reversible and irreversible binding of CdSe-nanoparticles and nanorods to polymeric surfaces via a strong, multiple hydrogen bond (= Hamilton-receptor/barbituric acid is described. Based on ROMP-copolymers, the supramolecular interaction on a thin polymer film is controlled by living polymerization methods, attaching the Hamilton-receptor in various architectures, and concentrations. Strong binding is observed with CdSe-nanoparticles and CdSe-nanorods, whose surfaces are equipped with matching barbituric acid-moieties. Addition of polar solvents, able to break the hydrogen bonds leads to the detachment of the nanoparticles from the polymeric film. Irreversible binding is observed if an azide/alkine-“click”-reaction is conducted after supramolecular recognition of the nanoparticles on the polymeric surface. Thus reversible or irreversible attachment of the nanosized objects can be achieved.

  13. Helium atoms and molecules in strong magnetic fields

    Science.gov (United States)

    Mori, K.

    Recent theoretical studies have shown that the neutron star surface may be composed of helium or heavier elements as hydrogen may be quickly depleted by diffuse nuclear burning Chang Bildsten However while Hydrogen atmospheres have been studied in great details atomic data for helium is available only for He ion Pavlov Bezchastnov 2005 We performed Hartree-Fock type calculation for Helium atom and molecules and computed their binding ionization and dissociation energies in strong magnetic fields B sim10 12 -- 10 15 G We will present ionization balance of Helium atmospheres at typical magnetic field strengths and temperatures to radio-quiet neutron stars and AXPs We will also discuss several implications of helium atmosphere to X-ray data of isolated neutron stars focusing on the detected spectral features

  14. Characterization of vanadium-binding sites of the vanadium-binding protein Vanabin2 by site-directed mutagenesis.

    Science.gov (United States)

    Ueki, Tatsuya; Kawakami, Norifumi; Toshishige, Masaaki; Matsuo, Koichi; Gekko, Kunihiko; Michibata, Hitoshi

    2009-10-01

    Vanabins are a unique protein family of vanadium-binding proteins with nine disulfide bonds. Possible binding sites for VO2+ in Vanabin2 from a vanadium-rich ascidian Ascidia sydneiensis samea have been detected by nuclear magnetic resonance study, but the metal selectivity and metal-binding ability of each site was not examined. In order to reveal functional contribution of each binding site, we prepared several mutants of Vanabin2 by in vitro site-directed mutagenesis and analyzed their metal selectivity and affinity by immobilized metal-ion affinity chromatography and Hummel Dreyer method. Mutation at K10/R60 (site 1) markedly reduced the affinity for VO2+. Mutation at K24/K38/R41/R42 (site 2) decreased the maximum binding number, but only slightly increased the overall affinity for VO2+. Secondary structure of both mutants was the same as that of the wild type as assessed by circular dichroism spectroscopy. Mutation in disulfide bonds near the site 1 did not affect its high affinity binding capacity, while those near the site 2 decreased the overall affinity for VO2+. These results suggested that the site 1 is a high affinity binding site for VO2+, while the site 2 composes a moderate affinity site for multiple VO2+.

  15. B700, a murine melanoma-specific antigen, binds Vitamin D3; conservation of binding among albuminoid molecules

    International Nuclear Information System (INIS)

    Farzaneh, N.K.; Walden, T.L. Jr.; Hearing, V.J.; Gersten, D.M.

    1990-01-01

    B700, a murine melanoma-specific antigen, is a member of the serum albumin protein family. Other members of this family include serum albumin (SMA), a-fetoprotein (AFP), vitamin D binding protein (DBP), and C700. The primary structure and biochemical functions of B700, as well as its in vivo metabolic fate are largely unknown. The authors examined the functional characteristics of MSA, AFP, and DBP, and for their ability to specifically bind [ 3 H]-1,25-dihydroxy-vitamin D 3 . Scatchard analysis revealed a single binding site for B700 with a Kd of 51,000 M and a Bmax of 4.51 x 10 -7 . There is no significant difference between the Kd and Bmax values among the albuminoid proteins. However, differences in the binding sites could be distinguished by competition of the 1,25-dihydroxy vitamin D 3 with other steroids. 2nM of vitamin D 3 , vitamin D 2 , or estrogen competed for the specific binding of 1,25-dihydroxy vitamin D 3 by B700 but not by DBP. The MSA binding site for 1,25 dihydroxy vitamin D 3 more closely resembles that of DBP than B700. These data indicate that the binding function of the albuminoid proteins has been conserved in the B700 melanoma antigen

  16. Describing the Peptide Binding Specificity of HLA-C

    DEFF Research Database (Denmark)

    Rasmussen, Michael; Harndahl, Mikkel Nors; Nielsen, Morten

    . We find preference for hydrophobic residues at the peptide C-terminus for all HLA-C molecules. Most molecules were found to have an additional strong anchor at P2 or P3, with auxiliary anchor observed at P1, P2, P3, and P7. The binding affinity is measured for peptides fitting the specificity matrix...

  17. Ligand-binding sites in human serum amyloid P component

    DEFF Research Database (Denmark)

    Heegaard, N.H.H.; Heegaard, Peter M. H.; Roepstorff, P.

    1996-01-01

    Amyloid P component (AP) is a naturally occurring glycoprotein that is found in serum and basement membranes, AP is also a component of all types of amyloid, including that found in individuals who suffer from Alzheimer's disease and Down's syndrome. Because AP has been found to bind strongly...

  18. Visually Relating Gene Expression and in vivo DNA Binding Data

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Min-Yu; Mackey, Lester; Ker?,; nen, Soile V. E.; Weber, Gunther H.; Jordan, Michael I.; Knowles, David W.; Biggin, Mark D.; Hamann, Bernd

    2011-09-20

    Gene expression and in vivo DNA binding data provide important information for understanding gene regulatory networks: in vivo DNA binding data indicate genomic regions where transcription factors are bound, and expression data show the output resulting from this binding. Thus, there must be functional relationships between these two types of data. While visualization and data analysis tools exist for each data type alone, there is a lack of tools that can easily explore the relationship between them. We propose an approach that uses the average expression driven by multiple of ciscontrol regions to visually relate gene expression and in vivo DNA binding data. We demonstrate the utility of this tool with examples from the network controlling early Drosophila development. The results obtained support the idea that the level of occupancy of a transcription factor on DNA strongly determines the degree to which the factor regulates a target gene, and in some cases also controls whether the regulation is positive or negative.

  19. DNA-binding specificity and molecular functions of NAC transcription factors

    DEFF Research Database (Denmark)

    Olsen, Addie Nina; Ernst, Heidi Asschenfeldt; Lo Leggio, Leila

    2005-01-01

    . The ability of NAC proteins to dimerize and to bind DNAwas analysed by structure-based mutagenesis. This identified two salt bridge-forming residues essential for NAC protein dimerization. Alteration of basic residues in a loop region containing several highly conserved residues abolished DNA binding. Thus....... Furthermore, NAC protein binding to the CaMV 35S promoter was shown to depend on sequences similar to the consensus of the selected oligonucleotides. Electrophoretic mobility shift assays demonstrated that NAC proteins bind DNA as homo- or heterodimers and that dimerization is necessary for stable DNA binding......The family of NAC (NAM/ATAF1,2/CUC2) transcription factors has been implicated in a wide range of plant processes, but knowledge on the DNA-binding properties of the family is limited. Using a reiterative selection procedure on random oligonucleotides, we have identified consensus binding sites...

  20. Big bang nucleosynthesis: The strong nuclear force meets the weak anthropic principle

    International Nuclear Information System (INIS)

    MacDonald, J.; Mullan, D. J.

    2009-01-01

    Contrary to a common argument that a small increase in the strength of the strong force would lead to destruction of all hydrogen in the big bang due to binding of the diproton and the dineutron with a catastrophic impact on life as we know it, we show that provided the increase in strong force coupling constant is less than about 50% substantial amounts of hydrogen remain. The reason is that an increase in strong force strength leads to tighter binding of the deuteron, permitting nucleosynthesis to occur earlier in the big bang at higher temperature than in the standard big bang. Photodestruction of the less tightly bound diproton and dineutron delays their production to after the bulk of nucleosynthesis is complete. The decay of the diproton can, however, lead to relatively large abundances of deuterium.

  1. Iodide Binding in Sodium-Coupled Cotransporters.

    Science.gov (United States)

    Vergara-Jaque, Ariela; Fong, Peying; Comer, Jeffrey

    2017-12-26

    Several apical iodide translocation pathways have been proposed for iodide efflux out of thyroid follicular cells, including a pathway mediated by the sodium-coupled monocarboxylate transporter 1 (SMCT1), which remains controversial. Herein, we evaluate structural and functional similarities between SMCT1 and the well-studied sodium-iodide symporter (NIS) that mediates the first step of iodide entry into the thyroid. Free-energy calculations using a force field with electronic polarizability verify the presence of a conserved iodide-binding pocket between the TM2, TM3, and TM7 segments in hNIS, where iodide is coordinated by Phe67, Gln72, Cys91, and Gln94. We demonstrate the mutation of residue Gly93 of hNIS to a larger amino acid expels the side chain of a critical tryptophan residue (Trp255) into the interior of the binding pocket, partially occluding the iodide binding site and reducing iodide affinity, which is consistent with previous reports associating mutation of this residue with iodide uptake deficiency and hypothyroidism. Furthermore, we find that the position of Trp255 in this hNIS mutant mirrors that of Trp253 in wild-type hSMCT1, where a threonine (Thr91) occupies the position homologous to that occupied by glycine in wild-type hNIS (Gly93). Correspondingly, mutation of Thr91 to glycine in hSMCT1 makes the pocket structure more like that of wild-type hNIS, increasing its iodide affinity. These results suggest that wild-type hSMCT1 in the inward-facing conformation may bind iodide only very weakly, which may have implications for its ability to transport iodide.

  2. A new method for measuring scouring efficiency of natural fibers based on the cellulose-binding domain-beta-glucuronidase fused protein.

    Science.gov (United States)

    Degani, Ofir; Gepstein, Shimon; Dosoretz, Carlos G

    2004-02-05

    Cellulose-binding domains (CBDs) are characterized by their ability to strongly bind to different forms of cellulose. This study examined the use of a recombinant CBD fused to the reporter enzyme beta-glucuronidase (CBD-GUS) to determine the extent of removal of the water-repellent waxy component of cotton fiber cuticles following hydrolytic treatment, i.e., scouring. The CBD-GUS test displayed higher sensitivity and repeatability than conventional water absorb techniques applied in the textile industry. Increases in the levels of CBD-GUS bound to the exposed cellulose correlated to increases in the fabric's hydrophilicity as a function of the severity of the scouring treatment applied, clearly indicating that the amount of bound enzyme increases proportionally with the amount of available binding sites. The binding of CBD-GUS also gave measurable and repeatable results when used on untreated or raw fabrics in comparison with conventional water drop techniques. The quantitative response of the reaction as bound enzyme activity was optimized for fully wettable fabrics. A minimal free enzyme concentration-to-swatch weight ratio of 75:1 was found to be necessary to ensure enzyme saturation (i.e., a linear response), corresponding to a free enzyme-to-bound enzyme ratio of at least 3:5.

  3. Quantum-chemical study of dispersion medium influence on the emulsifying ability of milk proteins

    Directory of Open Access Journals (Sweden)

    Borisenko A. A.

    2016-09-01

    Full Text Available Nowadays the products containing milk proteins are widely used in meat industry. Due to these substances application protein-fatty emulsions are stabilized, products consistency, succulence and appearance are made better. To investigate the influence of electrochemically activated water on the emulsifying ability of milk proteins computer molecular modeling and quantum chemical calculations of fragment molecules of αs1-casein in drinking water and catholyte in the presence of linoleic acid triacylglyceride has been conducted. It has been revealed that the negatively charged part of the test protein in the presence of fat molecules in the water is directed toward the polar component, and the nonpolar part is directed toward the hydrophobic component. It has been established that the dipole moment value of αs1-casein molecule fragment being studied in catholyte has been reduced by 10.55 D, the number of hydrogen bonds with molecules of the catholyte has increased by a factor of 1.3 and the number of intramolecular hydrogen bonds of the protein has increased by a factor of 1.7 comparing to the results of the system modeling on the basis of drinking water. On the fragment molecules of αs1-casein in the catholyte the strong electrostatic potential concentration with high electron density center displacement to the phosphoserine amino-acid residue area has been fixed; the protein emulsifying ability increase due to hydrophilic and hydrophobic properties strengthening at the corresponding sections of the peptide chain comparing to drinking water has been established. On the basis of the conducted researches it has been established that protein milk products hydrated with electrochemically activated water (catholyte are more effective as emulsifiers and water-binding components then when drinking water is used. This allows recommending them for the production of different meat products.

  4. Intrinsic thermodynamics of inhibitor binding to human carbonic anhydrase IX.

    Science.gov (United States)

    Linkuvienė, Vaida; Matulienė, Jurgita; Juozapaitienė, Vaida; Michailovienė, Vilma; Jachno, Jelena; Matulis, Daumantas

    2016-04-01

    Human carbonic anhydrase 9th isoform (CA IX) is an important marker of numerous cancers and is increasingly interesting as a potential anticancer drug target. Various synthetic aromatic sulfonamide-bearing compounds are being designed as potent inhibitors of CA IX. However, sulfonamide compound binding to CA IX is linked to several reactions, the deprotonation of the sulfonamide amino group and the protonation of the CA active site Zn(II)-bound hydroxide. These linked reactions significantly affect the affinities and other thermodynamic parameters such as enthalpies and entropies of binding. The observed and intrinsic affinities of compound binding to CA IX were determined by the fluorescent thermal shift assay. The enthalpies and entropies of binding were determined by the isothermal titration calorimetry. The pKa of CA IX was determined to be 6.8 and the enthalpy of CA IX-Zn(II)-bound hydroxide protonation was -24 kJ/mol. These values enabled the analysis of intrinsic thermodynamics of a library of compounds binding to CA IX. The most strongly binding compounds exhibited the intrinsic affinity of 0.01 nM and the observed affinity of 2 nM. The intrinsic thermodynamic parameters of compound binding to CA IX helped to draw the compound structure to thermodynamics relationship. It is important to distinguish the intrinsic from observed parameters of any disease target protein interaction with its inhibitors as drug candidates when drawing detailed compound structure to thermodynamics correlations. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Strong and superstrong pulsed magnetic fields generation

    CERN Document Server

    Shneerson, German A; Krivosheev, Sergey I

    2014-01-01

    Strong pulsed magnetic fields are important for several fields in physics and engineering, such as power generation and accelerator facilities. Basic aspects of the generation of strong and superstrong pulsed magnetic fields technique are given, including the physics and hydrodynamics of the conductors interacting with the field as well as an account of the significant progress in generation of strong magnetic fields using the magnetic accumulation technique. Results of computer simulations as well as a survey of available field technology are completing the volume.

  6. Impurity screening in strongly coupled plasma systems

    CERN Document Server

    Kyrkos, S

    2003-01-01

    We present an overview of the problem of screening of an impurity in a strongly coupled one-component plasma within the framework of the linear response (LR) theory. We consider 3D, 2D and quasi-2D layered systems. For a strongly coupled plasma the LR can be determined by way of the known S(k) structure functions. In general, an oscillating screening potential with local overscreening and antiscreening regions emerges. In the case of the bilayer, this phenomenon becomes global, as overscreening develops in the layer of the impurity and antiscreening in the adjacent layer. We comment on the limitations of the LR theory in the strong coupling situation.

  7. The lambda sigma calculus and strong normalization

    DEFF Research Database (Denmark)

    Schack-Nielsen, Anders; Schürmann, Carsten

    Explicit substitution calculi can be classified into several dis- tinct categories depending on whether they are confluent, meta-confluent, strong normalization preserving, strongly normalizing, simulating, fully compositional, and/or local. In this paper we present a variant of the λσ-calculus......, which satisfies all seven conditions. In particular, we show how to circumvent Mellies counter-example to strong normalization by a slight restriction of the congruence rules. The calculus is implemented as the core data structure of the Celf logical framework. All meta-theoretic aspects of this work...

  8. Escherichia coli lipoprotein binds human plasminogen via an intramolecular domain

    Directory of Open Access Journals (Sweden)

    Tammy eGonzalez

    2015-10-01

    Full Text Available Escherichia coli lipoprotein (Lpp is a major cellular component that exists in two distinct states, bound-form and free-form. Bound-form Lpp is known to interact with the periplasmic bacterial cell wall, while free-form Lpp is localized to the bacterial cell surface. A function for surface-exposed Lpp has yet to be determined. We hypothesized that the presence of C-terminal lysines in the surface-exposed region of Lpp would facilitate binding to the host zymogen plasminogen, a protease commandeered by a number of clinically important bacteria. Recombinant Lpp was synthesized and the binding of Lpp to plasminogen, the effect of various inhibitors on this binding, and the effects of various mutations of Lpp on Lpp-plasminogen interactions were examined. Additionally, the ability of Lpp-bound plasminogen to be converted to active plasmin was analyzed. We determined that Lpp binds plasminogen via an atypical domain located near the center of mature Lpp that may not be exposed on the surface of intact E. coli according to the current localization model. Finally, we found that plasminogen bound by Lpp can be converted to active plasmin. While the consequences of Lpp binding plasminogen are unclear, these results prompt further investigation of the ability of surface exposed Lpp to interact with host molecules such as extracellular matrix components and complement regulators, and the role of these interactions in infections caused by E. coli and other bacteria.

  9. Nucleic acid binding and other biomedical properties of artificial oligolysines

    Directory of Open Access Journals (Sweden)

    Roviello GN

    2016-11-01

    Full Text Available Giovanni N Roviello,1 Caterina Vicidomini,1 Vincenzo Costanzo,1 Valentina Roviello2 1CNR Istituto di Biostrutture e Bioimmagini, Via Mezzocannone site and Headquarters, 2Centro Regionale di Competenza (CRdC Tecnologie, Via Nuova Agnano, Napoli, Italy Abstract: In the present study, we report the interaction of an artificial oligolysine (referred to as AOL realized in our laboratory with targets of biomedical importance. These included polyinosinic acid (poly rI and its complex with polycytidylic acid (poly I:C, RNAs with well-known interferon-inducing ability, and double-stranded (ds DNA. The ability of the peptide to bind both single-stranded poly rI and ds poly I:C RNAs emerged from our circular dichroism (CD and ultraviolet (UV studies. In addition, we found that AOL forms complexes with dsDNA, as shown by spectroscopic binding assays and UV thermal denaturation experiments. These findings are encouraging for the possible use of AOL in biomedicine for nucleic acid targeting and oligonucleotide condensation, with the latter being a key step preceding their clinical application. Moreover, we tested the ability of AOL to bind to proteins, using serum albumin as a model protein. We demonstrated the oligolysine–protein binding by CD experiments which suggested that AOL, positively charged under physiological conditions, binds to the protein regions rich in anionic residues. Finally, the morphology characterization of the solid oligolysine, performed by scanning electron microscopy, showed different crystal forms including cubic-shaped crystals confirming the high purity of AOL. Keywords: nucleic acid binding, polyinosinic acid, double-stranded nucleic acids, oligolysine, circular dichroism

  10. Abilities of preschoolers: comparing different tools

    Directory of Open Access Journals (Sweden)

    Chiappedi Matteo

    2012-01-01

    Full Text Available Abstract Background There is a strong need for studies evaluating tests in terms both of psychometric properties (i.e. their efficacy or ability to be helpful in reaching a diagnosis and of their cost-effectiveness (i.e. their efficiency. These data are essential for planning a correct evaluation to identify children's needs (both educational and abilitative. Methods We evaluated 58 children attending for the first time the last year of the Scuola dell'Infanzia. Parental view was obtained with Child Behaviour Check-List and Conners' Rating Scales - Revised, and family socio-economic status was evaluated using Hollingshead's Four Factor Index; teacher compiled the IPDA questionnaire; children were administered Raven's Progressive Matrices, Modified Bell Cancellation Test, BVN 5-11 (a neuropsychological battery. Results A correlational analysis was conducted using Spearman's Rho (since variables were not normally distributed. These asymptomatic children show a good global cognitive functioning, but also a deficit of attention and of Executive Functions. Some of the tests used seem more cost-effective than others and there are some redundancies in information obtained. Conclusions Our data show that there are significant correlations between different neuropsychological and behavioural measures. It is therefore possible to rationalize diagnostic protocols without a significant information reduction. A deeper analysis will require a preliminary definition of the psychometric properties of used tools.

  11. Drug Promiscuity in PDB: Protein Binding Site Similarity Is Key.

    Science.gov (United States)

    Haupt, V Joachim; Daminelli, Simone; Schroeder, Michael

    2013-01-01

    Drug repositioning applies established drugs to new disease indications with increasing success. A pre-requisite for drug repurposing is drug promiscuity (polypharmacology) - a drug's ability to bind to several targets. There is a long standing debate on the reasons for drug promiscuity. Based on large compound screens, hydrophobicity and molecular weight have been suggested as key reasons. However, the results are sometimes contradictory and leave space for further analysis. Protein structures offer a structural dimension to explain promiscuity: Can a drug bind multiple targets because the drug is flexible or because the targets are structurally similar or even share similar binding sites? We present a systematic study of drug promiscuity based on structural data of PDB target proteins with a set of 164 promiscuous drugs. We show that there is no correlation between the degree of promiscuity and ligand properties such as hydrophobicity or molecular weight but a weak correlation to conformational flexibility. However, we do find a correlation between promiscuity and structural similarity as well as binding site similarity of protein targets. In particular, 71% of the drugs have at least two targets with similar binding sites. In order to overcome issues in detection of remotely similar binding sites, we employed a score for binding site similarity: LigandRMSD measures the similarity of the aligned ligands and uncovers remote local similarities in proteins. It can be applied to arbitrary structural binding site alignments. Three representative examples, namely the anti-cancer drug methotrexate, the natural product quercetin and the anti-diabetic drug acarbose are discussed in detail. Our findings suggest that global structural and binding site similarity play a more important role to explain the observed drug promiscuity in the PDB than physicochemical drug properties like hydrophobicity or molecular weight. Additionally, we find ligand flexibility to have a minor

  12. Strong Coupling Corrections in Quantum Thermodynamics

    Science.gov (United States)

    Perarnau-Llobet, M.; Wilming, H.; Riera, A.; Gallego, R.; Eisert, J.

    2018-03-01

    Quantum systems strongly coupled to many-body systems equilibrate to the reduced state of a global thermal state, deviating from the local thermal state of the system as it occurs in the weak-coupling limit. Taking this insight as a starting point, we study the thermodynamics of systems strongly coupled to thermal baths. First, we provide strong-coupling corrections to the second law applicable to general systems in three of its different readings: As a statement of maximal extractable work, on heat dissipation, and bound to the Carnot efficiency. These corrections become relevant for small quantum systems and vanish in first order in the interaction strength. We then move to the question of power of heat engines, obtaining a bound on the power enhancement due to strong coupling. Our results are exemplified on the paradigmatic non-Markovian quantum Brownian motion.

  13. Finding quantum effects in strong classical potentials

    Science.gov (United States)

    Hegelich, B. Manuel; Labun, Lance; Labun, Ou Z.

    2017-06-01

    The long-standing challenge to describing charged particle dynamics in strong classical electromagnetic fields is how to incorporate classical radiation, classical radiation reaction and quantized photon emission into a consistent unified framework. The current, semiclassical methods to describe the dynamics of quantum particles in strong classical fields also provide the theoretical framework for fundamental questions in gravity and hadron-hadron collisions, including Hawking radiation, cosmological particle production and thermalization of particles created in heavy-ion collisions. However, as we show, these methods break down for highly relativistic particles propagating in strong fields. They must therefore be improved and adapted for the description of laser-plasma experiments that typically involve the acceleration of electrons. Theory developed from quantum electrodynamics, together with dedicated experimental efforts, offer the best controllable context to establish a robust, experimentally validated foundation for the fundamental theory of quantum effects in strong classical potentials.

  14. The Charm and Beauty of Strong Interactions

    Science.gov (United States)

    El-Bennich, Bruno

    2018-01-01

    We briefly review common features and overlapping issues in hadron and flavor physics focussing on continuum QCD approaches to heavy bound states, their mass spectrum and weak decay constants in different strong interaction models.

  15. Atomica ionization by strong coherent radiation

    International Nuclear Information System (INIS)

    Brandi, H.S.; Davidovich, L.

    1979-07-01

    The relation among the three most frequently used non-perturbative methods proposed to study the ionization of atoms by strong electromagnetic fields is established. Their range of validity is also determined. (Author) [pt

  16. Perturbation of an exact strong gravity solution

    International Nuclear Information System (INIS)

    Baran, S.A.

    1982-10-01

    Perturbations of an exact strong gravity solution are investigated. It is shown, by using the new multipole expansions previously presented, that this exact and static spherically symmetric solution is stable under odd parity perturbations. (author)

  17. Strong-force theorists scoop Noble Prize

    CERN Multimedia

    Durrani, Matin

    2004-01-01

    Three US theorists have shared the 2004 Nobel Prize in Physics "for the discovery of asymptotic freedom in the theory of the strong interaction". Their theoretical work explains why quarks behave almost as free particles at high energies (½ page)

  18. Calculating hadronic properties in strong QCD

    International Nuclear Information System (INIS)

    Pennington, M.R.

    1996-01-01

    This talk gives a brief review of the progress that has been made in calculating the properties of hadrons in strong QCD. In keeping with this meeting I will concentrate on those properties that can be studied with electromagnetic probes. Though perturbative QCD is highly successful, it only applies in a limited kinematic regime, where hard scattering occur, and the quarks move in the interaction region as if they are free, pointlike objects. However, the bulk of strong interactions are governed by the long distance regime, where the strong interaction is strong. It is this regime of length scales of the order of a Fermi, that determines the spectrum of light hadrons and their properties. The calculation of these properties requires an understanding of non-perturbative QCD, of confinement and chiral symmetry breaking. (author)

  19. Dissecting electrostatic screening, specific ion binding, and ligand binding in an energetic model for glycine riboswitch folding

    Energy Technology Data Exchange (ETDEWEB)

    Lipfert, Jan; Sim, Adelene Y.L.; Herschlag, Daniel; Doniach, Sebastian (Stanford)

    2010-09-17

    Riboswitches are gene-regulating RNAs that are usually found in the 5{prime}-untranslated regions of messenger RNA. As the sugar-phosphate backbone of RNA is highly negatively charged, the folding and ligand-binding interactions of riboswitches are strongly dependent on the presence of cations. Using small angle X-ray scattering (SAXS) and hydroxyl radical footprinting, we examined the cation dependence of the different folding stages of the glycine-binding riboswitch from Vibrio cholerae. We found that the partial folding of the tandem aptamer of this riboswitch in the absence of glycine is supported by all tested mono- and divalent ions, suggesting that this transition is mediated by nonspecific electrostatic screening. Poisson-Boltzmann calculations using SAXS-derived low-resolution structural models allowed us to perform an energetic dissection of this process. The results showed that a model with a constant favorable contribution to folding that is opposed by an unfavorable electrostatic term that varies with ion concentration and valency provides a reasonable quantitative description of the observed folding behavior. Glycine binding, on the other hand, requires specific divalent ions binding based on the observation that Mg{sup 2+}, Ca{sup 2+}, and Mn{sup 2+} facilitated glycine binding, whereas other divalent cations did not. The results provide a case study of how ion-dependent electrostatic relaxation, specific ion binding, and ligand binding can be coupled to shape the energetic landscape of a riboswitch and can begin to be quantitatively dissected.

  20. Synthesis, CMC determination, and intercalative binding interaction with nucleic acid of a surfactant-copper(II) complex with modified phenanthroline ligand (dpq).

    Science.gov (United States)

    Nagaraj, Karuppiah; Ambika, Subramanian; Arunachalam, Sankaralingam

    2015-01-01

    A surfactant-copper(II) complex, [Cu(dpq)2DA](ClO4)2 (dpq = dipyrido[3,2-d:2'-3'-f]quinoxaline; DA-dodecylamine), was synthesized and characterized on the basis of elemental analyses, UV-vis, IR, and EPR spectra. The critical micelle concentration (CMC) value of this surfactant-copper(II) complex in aqueous solution was found out from conductance measurements. Specific conductivity data at different temperature served for the evaluation of the temperature-dependent CMC and the thermodynamics of micellization (ΔG°(m), ΔH°(m) and ΔS°(m)). In addition, the complex has been examined by its ability to bind to nucleic acids (DNA and RNA) in tris-HCl buffer by UV-vis absorption, emission spectroscopy techniques, and viscosity measurements. The complex has been found to bind strongly to nucleic acids with apparent binding constants at DNA and RNA is 4.3 × 10(5), 9.0 × 10(5) M(-1), respectively. UV-vis studies of the interaction of the complex with DNA/RNA have revealed that the complex can bind to both DNA and RNA by the intercalative binding mode via ligand dpq into the base pairs of DNA and RNA which has been verified by viscosity measurements. The presence of long aliphatic chain in the surfactant complex increases this hydrophobic interaction. The binding constants have been calculated. The cytotoxic activity of this complex on human liver carcinoma cancer cells was determined by adopting 3-(4, 5-dimethylthiazol-2-yl)-2, 5- diphenyl tetrazolium bromide assay and specific staining techniques. The antimicrobial and antifungal screening tests of this complex have shown good results.

  1. Building strong brands – does it matter?

    OpenAIRE

    Aure, Kristin Gaaseide; Nervik, Kristine Dybvik

    2014-01-01

    Brand equity has proven, through several decades of research, to be a primary source of competitive advantage and future earnings (Yoo & Donthu, 2001). Building strong brands has therefore become a priority for many organizations, with the presumption that building strong brands yields these advantages (Yasin et al., 2007). A quantitative survey was conducted at Sunnmøre in Norway in order to answer the two developed research questions. - Does the brand equity dimensions; brand...

  2. Algebra of strong and electroweak interactions

    International Nuclear Information System (INIS)

    Bolokhov, S.V.; Vladimirov, Yu.S.

    2004-01-01

    The algebraic approach to describing the electroweak and strong interactions is considered within the frames of the binary geometrophysics, based on the principles of the Fokker-Feynman direct interparticle interaction theories of the Kaluza-Klein multidimensional geometrical models and the physical structures theory. It is shown that in this approach the electroweak and strong elementary particles interaction through the intermediate vector bosons, are characterized by the subtypes of the algebraic classification of the complex 3 x 3-matrices [ru

  3. Photocontrol of Anion Binding Affinity to a Bis-urea Receptor Derived from Stiff-Stilbene

    NARCIS (Netherlands)

    Wezenberg, Sander J.; Feringa, Ben L.

    2017-01-01

    Toward the development of photoresponsive anion receptors, a stiff-stilbene photoswitch has been equipped' with two urea anion -binding motifs. Photoinduced E/Z isomerization has been studied in detail by UV-vis and NMR spectroscopy. Titration experiments (H-1 NMR) reveal strong binding of acetate

  4. Who Multi-Tasks and Why? Multi-Tasking Ability, Perceived Multi-Tasking Ability, Impulsivity, and Sensation Seeking

    Science.gov (United States)

    Sanbonmatsu, David M.; Strayer, David L.; Medeiros-Ward, Nathan; Watson, Jason M.

    2013-01-01

    The present study examined the relationship between personality and individual differences in multi-tasking ability. Participants enrolled at the University of Utah completed measures of multi-tasking activity, perceived multi-tasking ability, impulsivity, and sensation seeking. In addition, they performed the Operation Span in order to assess their executive control and actual multi-tasking ability. The findings indicate that the persons who are most capable of multi-tasking effectively are not the persons who are most likely to engage in multiple tasks simultaneously. To the contrary, multi-tasking activity as measured by the Media Multitasking Inventory and self-reported cell phone usage while driving were negatively correlated with actual multi-tasking ability. Multi-tasking was positively correlated with participants’ perceived ability to multi-task ability which was found to be significantly inflated. Participants with a strong approach orientation and a weak avoidance orientation – high levels of impulsivity and sensation seeking – reported greater multi-tasking behavior. Finally, the findings suggest that people often engage in multi-tasking because they are less able to block out distractions and focus on a singular task. Participants with less executive control - low scorers on the Operation Span task and persons high in impulsivity - tended to report higher levels of multi-tasking activity. PMID:23372720

  5. Antifogging abilities of model nanotextures

    Science.gov (United States)

    Mouterde, Timothée; Lehoucq, Gaëlle; Xavier, Stéphane; Checco, Antonio; Black, Charles T.; Rahman, Atikur; Midavaine, Thierry; Clanet, Christophe; Quéré, David

    2017-06-01

    Nanometre-scale features with special shapes impart a broad spectrum of unique properties to the surface of insects. These properties are essential for the animal’s survival, and include the low light reflectance of moth eyes, the oil repellency of springtail carapaces and the ultra-adhesive nature of palmtree bugs. Antireflective mosquito eyes and cicada wings are also known to exhibit some antifogging and self-cleaning properties. In all cases, the combination of small feature size and optimal shape provides exceptional surface properties. In this work, we investigate the underlying antifogging mechanism in model materials designed to mimic natural systems, and explain the importance of the texture’s feature size and shape. While exposure to fog strongly compromises the water-repellency of hydrophobic structures, this failure can be minimized by scaling the texture down to nanosize. This undesired effect even becomes non-measurable if the hydrophobic surface consists of nanocones, which generate antifogging efficiency close to unity and water departure of droplets smaller than 2 μm.

  6. Manipulating light with strongly modulated photonic crystals

    International Nuclear Information System (INIS)

    Notomi, Masaya

    2010-01-01

    Recently, strongly modulated photonic crystals, fabricated by the state-of-the-art semiconductor nanofabrication process, have realized various novel optical properties. This paper describes the way in which they differ from other optical media, and clarifies what they can do. In particular, three important issues are considered: light confinement, frequency dispersion and spatial dispersion. First, I describe the latest status and impact of ultra-strong light confinement in a wavelength-cubic volume achieved in photonic crystals. Second, the extreme reduction in the speed of light is reported, which was achieved as a result of frequency dispersion management. Third, strange negative refraction in photonic crystals is introduced, which results from their unique spatial dispersion, and it is clarified how this leads to perfect imaging. The last two sections are devoted to applications of these novel properties. First, I report the fact that strong light confinement and huge light-matter interaction enhancement make strongly modulated photonic crystals promising for on-chip all-optical processing, and present several examples including all-optical switches/memories and optical logics. As a second application, it is shown that the strong light confinement and slow light in strongly modulated photonic crystals enable the adiabatic tuning of light, which leads to various novel ways of controlling light, such as adiabatic frequency conversion, efficient optomechanics systems, photon memories and photons pinning.

  7. Gute Nerven und eine gewisse Chaosfähigkeit Strong Nerves and the Ability to Handle Chaos

    Directory of Open Access Journals (Sweden)

    Sabine Bangert

    2006-03-01

    Full Text Available Die Hessische Landesregierung hat mit „JAMBA“ (Junge allein erziehende Mütter in der Berufsausbildung ein Modell entwickelt und erprobt, um allein erziehenden jungen Müttern ohne Berufsausbildung eine Lehre im dualen System zu ermöglichen. An dem Modellversuch haben hundert junge Frauen an zehn Standorten in Hessen teilgenommen. Ziel des Projekts war es, den Personenkreis der jungen allein erziehenden Mütter zu ermutigen und zu unterstützen, eine betriebliche Ausbildung zu absolvieren. Gleichzeitig sollten Betriebe darin bestärkt werden, allein erziehende Frauen auszubilden. Prof. Dr. Angela Paul-Kohlhoff und Dr. Uta Zybell u. a. haben dieses Modellprojekt über vier Jahre wissenschaftlich begleitet. Das zweibändige Werk präsentiert die Ergebnisse des Modellprojektes und die Konsequenzen für die praktische Politik. Es zeigt Wege auf, Benachteiligungen junger Mütter nicht nur zu beseitigen, sondern aus den Erfahrungen mit der Ausbildung junger Mütter generelle Reformoptionen für die berufliche Ausbildung in Deutschland zu begründen. Flexibilisierung und Individualisierung ohne Abstriche an der Qualität der beruflichen Ausbildung stehen damit – nicht nur für die in den vorliegenden Veröffentlichungen untersuchten Zielgruppe „junge allein erziehende Mütter“ – auf der Tagesordnung der Reformagenda.The Hessian state government has developed and tested a model (JAMSA—young single mothers in career training to give young single mothers without career training an apprenticeship in Germany’s dual system of vocational education. Hundreds of young women took part in the test model at ten different locations in the state of Hessen. The project’s goal was to encourage and support young single mothers in their completion of a company-based traineeship. Concurrently, the intention was to support those companies that trained young single mothers. Prof. Dr. Angela Paul-Kohlhoff and Dr. Uta Zybell, among others, followed the project model for four years. The two-volume work presents the results of the model and the consequences for practical politics. It not only sketches ways in which disadvantages for young single mothers can be eradicated, but also establishes general options for reforming career education in Germany based on experiences in training young mothers. Thus, at the top of the agenda for reform in career education is flexibility and individuality without the reduction of quality—and this applies not only to the book’s target group “young single mothers.”

  8. Sea level rise, surface warming, and the weakened buffering ability of South China Sea to strong typhoons in recent decades.

    Science.gov (United States)

    Sun, Jingru; Oey, Leo; Xu, F-H; Lin, Y-C

    2017-08-07

    Each year, a number of typhoons in the western North Pacific pass through the Luzon Strait into South China Sea (SCS). Although the storms remain above a warm open sea, the majority of them weaken due to atmospheric and oceanic environments unfavorable for typhoon intensification in SCS, which therefore serves as a natural buffer that shields the surrounding coasts from potentially more powerful storms. This study examines how this buffer has changed over inter-decadal and longer time scales. We show that the buffer weakens (i.e. greater potential for more powerful typhoons) in negative Pacific Decadal Oscillation (PDO) years, as well as with sea-level-rise and surface warming, caused primarily by the deepening of the ocean's 26 °C isotherm Z 26 . A new Intensity Change Index is proposed to describe the typhoon intensity change as a function of Z 26 and other environmental variables. In SCS, the new index accounts for as high as 75% of the total variance of typhoon intensity change.

  9. Efficient and dynamic nuclear localization of green fluorescent protein via RNA binding.

    Science.gov (United States)

    Kitamura, Akira; Nakayama, Yusaku; Kinjo, Masataka

    2015-07-31

    Classical nuclear localization signal (NLS) sequences have been used for artificial localization of green fluorescent protein (GFP) in the nucleus as a positioning marker or for measurement of the nuclear-cytoplasmic shuttling rate in living cells. However, the detailed mechanism of nuclear retention of GFP-NLS remains unclear. Here, we show that a candidate mechanism for the strong nuclear retention of GFP-NLS is via the RNA-binding ability of the NLS sequence. GFP tagged with a classical NLS derived from Simian virus 40 (GFP-NLS(SV40)) localized not only in the nucleoplasm, but also to the nucleolus, the nuclear subdomain in which ribosome biogenesis takes place. GFP-NLS(SV40) in the nucleolus was mobile, and intriguingly, the diffusion coefficient, which indicates the speed of diffusing molecules, was 1.5-fold slower than in the nucleoplasm. Fluorescence correlation spectroscopy (FCS) analysis showed that GFP-NLS(SV40) formed oligomers via RNA binding, the estimated molecular weight of which was larger than the limit for passive nuclear export into the cytoplasm. These findings suggest that the nuclear localization of GFP-NLS(SV40) likely results from oligomerization mediated via RNA binding. The analytical technique used here can be applied for elucidating the details of other nuclear localization mechanisms, including those of several types of nuclear proteins. In addition, GFP-NLS(SV40) can be used as an excellent marker for studying both the nucleoplasm and nucleolus in living cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Lysine-functionalized nanodiamonds: synthesis, physiochemical characterization, and nucleic acid binding studies

    Science.gov (United States)

    Kaur, Randeep; Chitanda, Jackson M; Michel, Deborah; Maley, Jason; Borondics, Ferenc; Yang, Peng; Verrall, Ronald E; Badea, Ildiko

    2012-01-01

    Purpose: Detonation nanodiamonds (NDs) are carbon-based nanomaterials that, because of their size (4–5 nm), stable inert core, alterable surface chemistry, fluorescence, and biocompatibility, are emerging as bioimaging agents and promising tools for the delivery of biochemical molecules into cellular systems. However, diamond particles possess a strong propensity to aggregate in liquid formulation media, restricting their applicability in biomedical sciences. Here, the authors describe the covalent functionalization of NDs with lysine in an attempt to develop nanoparticles able to act as suitable nonviral vectors for transferring genetic materials across cellular membranes. Methods: NDs were oxidized and functionalized by binding lysine moieties attached to a three-carbon-length linker (1,3-diaminopropane) to their surfaces through amide bonds. Raman and Fourier transform infrared spectroscopy, zeta potential measurement, dynamic light scattering, atomic force microscopic imaging, and thermogravimetric analysis were used to characterize the lysine-functionalized NDs. Finally, the ability of the functionalized diamonds to bind plasmid DNA and small interfering RNA was investigated by gel electrophoresis assay and through size and zeta potential measurements. Results: NDs were successfully functionalized with the lysine linker, producing surface loading of 1.7 mmol g−1 of ND. These modified NDs formed highly stable aqueous dispersions with a zeta potential of 49 mV and particle size of approximately 20 nm. The functionalized NDs were found to be able to bind plasmid DNA and small interfering RNA by forming nanosized “diamoplexes”. Conclusion: The lysine-substituted ND particles generated in this study exhibit stable aqueous formulations and show potential for use as carriers for genetic materials. PMID:22904623

  11. Lysine-functionalized nanodiamonds: synthesis, physiochemical characterization, and nucleic acid binding studies.

    Science.gov (United States)

    Kaur, Randeep; Chitanda, Jackson M; Michel, Deborah; Maley, Jason; Borondics, Ferenc; Yang, Peng; Verrall, Ronald E; Badea, Ildiko

    2012-01-01

    Detonation nanodiamonds (NDs) are carbon-based nanomaterials that, because of their size (4-5 nm), stable inert core, alterable surface chemistry, fluorescence, and biocompatibility, are emerging as bioimaging agents and promising tools for the delivery of biochemical molecules into cellular systems. However, diamond particles possess a strong propensity to aggregate in liquid formulation media, restricting their applicability in biomedical sciences. Here, the authors describe the covalent functionalization of NDs with lysine in an attempt to develop nanoparticles able to act as suitable nonviral vectors for transferring genetic materials across cellular membranes. NDs were oxidized and functionalized by binding lysine moieties attached to a three-carbon-length linker (1,3-diaminopropane) to their surfaces through amide bonds. Raman and Fourier transform infrared spectroscopy, zeta potential measurement, dynamic light scattering, atomic force microscopic imaging, and thermogravimetric analysis were used to characterize the lysine-functionalized NDs. Finally, the ability of the functionalized diamonds to bind plasmid DNA and small interfering RNA was investigated by gel electrophoresis assay and through size and zeta potential measurements. NDs were successfully functionalized with the lysine linker, producing surface loading of 1.7 mmol g(-1) of ND. These modified NDs formed highly stable aqueous dispersions with a zeta potential of 49 mV and particle size of approximately 20 nm. The functionalized NDs were found to be able to bind plasmid DNA and small interfering RNA by forming nanosized "diamoplexes". The lysine-substituted ND particles generated in this study exhibit stable aqueous formulations and show potential for use as carriers for genetic materials.

  12. Pictorial binding: endeavor to classify

    Directory of Open Access Journals (Sweden)

    Zinchenko S.

    2015-01-01

    Full Text Available The article is devoted to the classification of bindings of the 1-19th centuries with a unique and untypical book binding decoration technique (encaustic, tempera and oil paintings. Analysis of design features, materials and techniques of art decoration made it possible to identify them as a separate type - pictorial bindings and divide them into four groups. The first group consists of Coptic bindings, decorated with icon-painting images in encaustic technique. The second group is made up of leather Western bindings of the 13-14th centuries, which have the decoration and technique of ornamentation close to iconography. The third group involves parchment bindings, ornamentation technique of which is closer to the miniature. The last group comprises bindings of East Slavic origin of the 15-19th centuries, decorated with icon-painting pictures made in the technique of tempera or oil painting. The proposed classification requires further basic research as several specific kinds of bindings have not yet been investigated

  13. New type of tachykinin binding site in the rat brain characterized by specific binding of a labeled eledoisin derivative

    Energy Technology Data Exchange (ETDEWEB)

    Beaujouan, J.C.; Torrens, Y.; Viger, A.; Glowinski, J.

    1984-09-01

    A new ligand for investigating tachykinin-binding site subtypes was synthesized by coupling the /sup 125/I-Bolton and Hunter reagent to eledoisin (/sup 125/I-BHE). Using a synaptosomal preparation (P2 fraction) of rat cerebral cortex, /sup 125/I-BHE was shown to bind with apparent high affinity (apparent Kd . 15.3 nM). When concentrations of up to 30 nM /sup 125/I-BHE were used, /sup 125/I-BHE binding was specific, saturable, reversible, and temperature-dependent. In contrast to (/sup 3/H)dopamine, /sup 125/I-BHE was not taken up within synaptosomes by an ouabain-sensitive process. Eledoisin, kassinin, and substance P were examined for their ability to inhibit specific /sup 125/I-BHE binding to cortical synaptosomes. Eledoisin and kassinin were considerably more potent than substance P, in contrast to the order of potency observed for specific /sup 125/I-Bolton-Hunter substance P (/sup 125/I-BHSP) binding. Specific /sup 125/I-BHE binding was highest in the cerebral cortex and hypothalamus; intermediate in the hippocampus, striatum, and thalamus; low in the mesencephalon, septum, and substantia nigra; and absent in the cerebellum. Comparison of these data with those previously obtained for /sup 125/I-BHSP binding to synaptosomes indicated that /sup 125/I-BHE-labeled binding sites differ markedly from those of /sup 125/I-BHSP-labeled binding sites. Therefore, tachykinin receptors other than substance P receptors seem to be present in the central nervous system.

  14. Binding of acyl CoA by fatty acid binding protein and the effect on fatty acid activation

    International Nuclear Information System (INIS)

    Burrier, R.E.; Manson, C.R.; Brecher, P.

    1987-01-01

    The ability of purified rat liver and heart fatty acid binding proteins (FABPs) to bind oleoyl CoA and modulate acyl CoA synthesis by microsomal membranes was investigated. Using binding assays employing either Lipidex 1000 or multilamellar liposomes to sequester unbound ligand, rat liver but not rat heart FABP was shown to bind radiolabeled acyl CoA. Binding studies suggest that liver FABP has a single binding site for acyl CoA which is separate from the two binding sites for fatty acids. Experiments were then performed to determine how binding may influence acyl CoA metabolism by liver microsomes or heart sarcoplasmic reticulum. Using liposomes as fatty acid donors, liver FABP stimulated acyl CoA production whereas heart FABP did not stimulate production over control values. 14 C-Fatty acid-FABP complexes were prepared, incubated with membranes and acyl CoA synthetase activity was determined. Up to 70% of the fatty acid could be converted to acyl CoA in the presence of liver FABP but in the presence of heart FABP, only 45% of the fatty acid was converted. The amount of product formed was not changed by additional membrane, enzyme cofactor, or incubation time. Liver but not heart FABP bound the acyl CoA formed and removed it from the membranes. These studies suggest that liver FABP can increase the amount of acyl CoA by binding this ligand thereby removing it from the membrane and possibly aiding transport within the cell

  15. Binding of acyl CoA by fatty acid binding protein and the effect on fatty acid activation

    Energy Technology Data Exchange (ETDEWEB)

    Burrier, R.E.; Manson, C.R.; Brecher, P.

    1987-05-01

    The ability of purified rat liver and heart fatty acid binding proteins (FABPs) to bind oleoyl CoA and modulate acyl CoA synthesis by microsomal membranes was investigated. Using binding assays employing either Lipidex 1000 or multilamellar liposomes to sequester unbound ligand, rat liver but not rat heart FABP was shown to bind radiolabeled acyl CoA. Binding studies suggest that liver FABP has a single binding site for acyl CoA which is separate from the two binding sites for fatty acids. Experiments were then performed to determine how binding may influence acyl CoA metabolism by liver microsomes or heart sarcoplasmic reticulum. Using liposomes as fatty acid donors, liver FABP stimulated acyl CoA production whereas heart FABP did not stimulate production over control values. /sup 14/C-Fatty acid-FABP complexes were prepared, incubated with membranes and acyl CoA synthetase activity was determined. Up to 70% of the fatty acid could be converted to acyl CoA in the presence of liver FABP but in the presence of heart FABP, only 45% of the fatty acid was converted. The amount of product formed was not changed by additional membrane, enzyme cofactor, or incubation time. Liver but not heart FABP bound the acyl CoA formed and removed it from the membranes. These studies suggest that liver FABP can increase the amount of acyl CoA by binding this ligand thereby removing it from the membrane and possibly aiding transport within the cell.

  16. Serum iron and total iron binding capacity levels among the abo ...

    African Journals Online (AJOL)

    Iron deficiency anaemia is a common tropical disease. Iron plays a very important role in the human body. The understanding of the different blood groups ability to retain iron in their system can give an insight into their ability to handle the disease Iron deficiency anaemia. Serum Iron, Total Iron Binding Capacity (TIBC) and ...

  17. Strong Motion Earthquake Data Values of Digitized Strong-Motion Accelerograms, 1933-1994

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Strong Motion Earthquake Data Values of Digitized Strong-Motion Accelerograms is a database of over 15,000 digitized and processed accelerograph records from...

  18. The mechanism of Lactobacillus strains for their ability to remove fumonisins B1 and B2.

    Science.gov (United States)

    Zhao, Hongfei; Wang, Xiao; Zhang, Junwen; Zhang, Jun; Zhang, Bolin

    2016-11-01

    Two Lactobacillus strains, L. plantarum B7 and L. pentosus X8, exhibited high efficiency in removing fumonisins (FB1 and FB2) from aqueous medium. 52.9% FB1 and 85.2% FB2 were bound by L. plantarum B7, and 58.0% FB1 and 86.5% FB2 by L. pentosus X8, respectively. Temperature, incubation time, and pH affected the binding ability of two strains. Cell viability was not necessary for the binding ability. The various components of cell wall were determined for their ability to absorb FBS. The results revealed that the intact peptidoglycans exhibited the greatest capacity in binding FBs. Especially the better structural integrity of the peptidoglycans the more FBs was bound. Thus, the absorption of two bacterial cells to FBs is proposed to be a physical process, and peptidoglycans should be the main binding site. Additionally, Caco-2 cell lines were used to evaluate the ability of the two strains to reduce the damage of FBs in vitro. Caco-2 cell's death was reduced after the cell lines were subjected to both viable and non-viable L. pentosus X8, respectively. The two Lactobacillus strains might be used as a biological detoxification for the removal of FBs from diet and feed in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Metal binding by food components

    DEFF Research Database (Denmark)

    Tang, Ning

    For calcium binding: Electrochemical method (calcium ion selective electrode) combined with quantum mechanical calculations (density functional theory) were used to investigate the calcium binding affinity of the amino acids and small glycine peptides. The effects of the ionic strength and p......, synergistic effect in calcium binding was found for the small glycine peptide rather than amino acids mixtures with the enhanced driving force up to -6 kJ/mol. Such study provides useful information for the future development of calcium supplements. For zinc binding: Isothermal titration calorimetry...... titration calorimetry and quantum mechanical calculations. This is due to the zinc binding affinity of the relatively softer ligands (investigated food components) will become much stronger than citrate or phytate when they present together in aqueous solution. This mechanism indicates these food components...

  20. A sequence-based dynamic ensemble learning system for protein ligand-binding site prediction

    KAUST Repository

    Chen, Peng

    2015-12-03

    Background: Proteins have the fundamental ability to selectively bind to other molecules and perform specific functions through such interactions, such as protein-ligand binding. Accurate prediction of protein residues that physically bind to ligands is important for drug design and protein docking studies. Most of the successful protein-ligand binding predictions were based on known structures. However, structural information is not largely available in practice due to the huge gap between the number of known protein sequences and that of experimentally solved structures

  1. Identifying differential transcription factor binding in ChIP-seq.

    Science.gov (United States)

    Wu, Dai-Ying; Bittencourt, Danielle; Stallcup, Michael R; Siegmund, Kimberly D

    2015-01-01

    ChIP seq is a widely used assay to measure genome-wide protein binding. The decrease in costs associated with sequencing has led to a rise in the number of studies that investigate protein binding across treatment conditions or cell lines. In addition to the identification of binding sites, new studies evaluate the variation in protein binding between conditions. A number of approaches to study differential transcription factor binding have recently been developed. Several of these methods build upon established methods from RNA-seq to quantify differences in read counts. We compare how these new approaches perform on different data sets from the ENCODE project to illustrate the impact of data processing pipelines under different study designs. The performance of normalization methods for differential ChIP-seq depends strongly on the variation in total amount of protein bound between conditions, with total read count outperforming effective library size, or variants thereof, when a large variation in binding was studied. Use of input subtraction to correct for non-specific binding showed a relatively modest impact on the number of differential peaks found and the fold change accuracy to biological validation, however a larger impact might be expected for samples with more extreme copy number variations between them. Still, it did identify a small subset of novel differential regions while excluding some differential peaks in regions with high background signal. These results highlight proper scaling for between-sample data normalization as critical for differential transcription factor binding analysis and suggest bioinformaticians need to know about the variation in level of total protein binding between conditions to select the best analysis method. At the same time, validation using fold-change estimates from qRT-PCR suggests there is still room for further method improvement.

  2. The extended reciprocity: Strong belief outperforms persistence.

    Science.gov (United States)

    Kurokawa, Shun

    2017-05-21

    The existence of cooperation is a mysterious phenomenon and demands explanation, and direct reciprocity is one key potential explanation for the evolution of cooperation. Direct reciprocity allows cooperation to evolve for cooperators who switch their behavior on the basis of information about the opponent's behavior. Here, relevant to direct reciprocity is information deficiency. When the opponent's last move is unknown, how should players behave? One possibility is to choose cooperation with some default probability without using any further information. In fact, our previous paper (Kurokawa, 2016a) examined this strategy. However, there might be beneficial information other than the opponent's last move. A subsequent study of ours (Kurokawa, 2017) examined the strategy which uses the own last move when the opponent's last move is unknown, and revealed that referring to the own move and trying to imitate it when information is absent is beneficial. Is there any other beneficial information else? How about strong belief (i.e., have infinite memory and believe that the opponent's behavior is unchanged)? Here, we examine the evolution of strategies with strong belief. Analyzing the repeated prisoner's dilemma game and using evolutionarily stable strategy (ESS) analysis against an invasion by unconditional defectors, we find the strategy with strong belief is more likely to evolve than the strategy which does not use information other than the opponent player's last move and more likely to evolve than the strategy which uses not only the opponent player's last move but also the own last move. Strong belief produces the extended reciprocity and facilitates the evolution of cooperation. Additionally, we consider the two strategies game between strategies with strong belief and any strategy, and we consider the four strategies game in which unconditional cooperators, unconditional defectors, pessimistic reciprocators with strong belief, and optimistic reciprocators with

  3. Improvement of Speaking Ability through Interrelated Skills

    Science.gov (United States)

    Liao, Guoqiang

    2009-01-01

    How to improve students' ability of speaking English? That is the key point we are concerned about. This paper discusses the possibility and necessity of improving students' ability by combining the four skills of speaking, listening, reading and writing.

  4. Digestibility and IgE-Binding of Glycosylated Codfish Parvalbumin

    Science.gov (United States)

    de Jongh, Harmen H. J.; Robles, Carlos López; Nordlee, Julie A.; Lee, Poi-Wah; Baumert, Joseph L.; Hamilton, Robert G.; Taylor, Steve L.; Koppelman, Stef J.

    2013-01-01

    Food-processing conditions may alter the allergenicity of food proteins by different means. In this study, the effect of the glycosylation as a result of thermal treatment on the digestibility and IgE-binding of codfish parvalbumin is investigated. Native and glycosylated parvalbumins were digested with pepsin at various conditions relevant for the gastrointestinal tract. Intact proteins and peptides were analysed for apparent molecular weight and IgE-binding. Glycosylation did not substantially affect the digestion. Although the peptides resulting from digestion were relatively large (3 and 4 kDa), the IgE-binding was strongly diminished. However, the glycosylated parvalbumin had a strong propensity to form dimers and tetramers, and these multimers bound IgE intensely, suggesting stronger IgE-binding than monomeric parvalbumin. We conclude that glycosylation of codfish parvalbumin does not affect the digestibility of parvalbumin and that the peptides resulting from this digestion show low IgE-binding, regardless of glycosylation. Glycosylation of parvalbumin leads to the formation of higher order structures that are more potent IgE binders than native, monomeric parvalbumin. Therefore, food-processing conditions applied to fish allergen can potentially lead to increased allergenicity, even while the protein's digestibility is not affected by such processing. PMID:23878817

  5. Digestibility and IgE-Binding of Glycosylated Codfish Parvalbumin

    Directory of Open Access Journals (Sweden)

    Harmen H. J. de Jongh

    2013-01-01

    Full Text Available Food-processing conditions may alter the allergenicity of food proteins by different means. In this study, the effect of the glycosylation as a result of thermal treatment on the digestibility and IgE-binding of codfish parvalbumin is investigated. Native and glycosylated parvalbumins were digested with pepsin at various conditions relevant for the gastrointestinal tract. Intact proteins and peptides were analysed for apparent molecular weight and IgE-binding. Glycosylation did not substantially affect the digestion. Although the peptides resulting from digestion were relatively large (3 and 4 kDa, the IgE-binding was strongly diminished. However, the glycosylated parvalbumin had a strong propensity to form dimers and tetramers, and these multimers bound IgE intensely, suggesting stronger IgE-binding than monomeric parvalbumin. We conclude that glycosylation of codfish parvalbumin does not affect the digestibility of parvalbumin and that the peptides resulting from this digestion show low IgE-binding, regardless of glycosylation. Glycosylation of parvalbumin leads to the formation of higher order structures that are more potent IgE binders than native, monomeric parvalbumin. Therefore, food-processing conditions applied to fish allergen can potentially lead to increased allergenicity, even while the protein’s digestibility is not affected by such processing.

  6. Strong coupling effects in hybrid plexitonic systems

    Science.gov (United States)

    Melnikau, Dzmitry; Esteban, Ruben; Govyadinov, Alexander A.; Savateeva, Diana; Simon, Thomas; Sánchez-Iglesias, Ana; Grzelczak, Marek; Schmidt, Mikolaj K.; Urban, Alexander S.; Liz-Marzán, Luis M.; Feldmann, Jochen; Aizpurua, Javier; Rakovich, Yury P.

    2017-08-01

    We investigated the interactions between localized plasmons in gold nanorods and excitons in J-aggregates and were able to track an anticrossing behavior of the hybridized modes both in the extinction and in the photoluminescence spectra of this hybrid system. We identified the nonlinear optical behavior of this system by transient absorption spectroscopy. Finally using magnetic circular dichroism spectroscopy we showed that nonmagnetic organic molecules exhibit magnetooptical response due to binding to a plasmonic nanoparticles. In our experiments we also studied the effect of detuning as well as the effect of off- and on resonance excitation on the hybrid states

  7. Discrimination ability of the Energy score

    DEFF Research Database (Denmark)

    Pinson, Pierre; Tastu, Julija

    as appealing since being proper, we show that its discrimination ability may be limited when focusing on the dependence structure of multivariate probabilistic forecasts. For the case of multivariate Gaussian process, a theoretical upper for such discrimination ability is derived and discussed. This limited...... discrimination ability may eventually get compromised by computational and sampling issues, as dimension increases....

  8. Innovative Allies: Spatial and Creative Abilities

    Science.gov (United States)

    Coxon, Steve V.

    2012-01-01

    Spatial and creative abilities are important for innovations in science, technology, engineering, and math (STEM) fields, but talents are rarely developed from these abilities by schools, including among gifted children and adolescents who have a high potential to become STEM innovators. This article provides an overview of each ability and makes…

  9. Judging the Ability of Friends and Foes.

    Science.gov (United States)

    Cook, Jennifer L; Murphy, Jennifer; Bird, Geoffrey

    2016-10-01

    Collaboration leads us to judge our own ability to be more similar to our collaborators and their ability to be more similar to our own, while competition leads us to exaggerate the gap between our abilities. How does this happen and what does it mean? Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. A strongly coupled quark-gluon plasma

    Energy Technology Data Exchange (ETDEWEB)

    Shuryak, Edward [Department of Physics and Astronomy, University at Stony Brook, NY 11794 (United States)

    2004-08-01

    Successful description of robust collective flow phenomena at RHIC by ideal hydrodynamics, recent observations of bound c-barc,q-barq states on the lattice, and other theoretical developments indicate that QGP produced at RHIC, and probably in a wider temperature region T{sub c} < T < 4T{sub c}, is not a weakly coupled quasiparticle gas as believed previously. We discuss how strong the interaction is and why it seems to generate hundreds of binary channels with bound states, surviving well inside the QGP phase. We in particular discuss their effect on pressure and viscosity. We conclude by reviewing the similar phenomena for other 'strongly coupled systems', such as (i) strongly coupled supersymmetric theories studied via Maldacena duality; (ii) trapped ultra-cold atoms with very large scattering length, tuned to Feschbach resonances.

  11. Strong Coupling between Plasmons and Organic Semiconductors

    Directory of Open Access Journals (Sweden)

    Joel Bellessa

    2014-05-01

    Full Text Available In this paper we describe the properties of organic material in strong coupling with plasmon, mainly based on our work in this field of research. The strong coupling modifies the optical transitions of the structure, and occurs when the interaction between molecules and plasmon prevails on the damping of the system. We describe the dispersion relation of different plasmonic systems, delocalized and localized plasmon, coupled to aggregated dyes and the typical properties of these systems in strong coupling. The modification of the dye emission is also studied. In the second part, the effect of the microscopic structure of the organics, which can be seen as a disordered film, is described. As the different molecules couple to the same plasmon mode, an extended coherent state on several microns is observed.

  12. A theory of the strong interactions

    International Nuclear Information System (INIS)

    Gross, D.J.

    1979-01-01

    The most promising candidate for a fundamental microscopic theory of the strong interactions is a gauge theory of colored quarks-Quantum Chromodynamics (QCD). There are many excellent reasons for believing in this theory. It embodies the broken symmetries, SU(3) and chiral SU(3)xSU(3), of the strong interactions and reflects the success of (albeit crude) quark models in explaining the spectrum of the observed hadrons. The hidden quantum number of color, necessary to account for the quantum numbers of the low lying hadrons, plays a fundamental role in this theory as the SU(3) color gauge vector 'gluons' are the mediators of the strong interactions. The absence of physical quark states can be 'explained' by the hypothesis of color confinement i.e. that hadrons are permanently bound in color singlet bound states. Finally this theory is unique in being asymptotically free, thus accounting for the almost free field theory behvior of quarks observed at short distances. (Auth.)

  13. Electromagnetic processes in strong crystalline fields

    CERN Multimedia

    2007-01-01

    We propose a number of new investigations on aspects of radiation from high energy electron and positron beams (10-300 GeV) in single crystals and amorphous targets. The common heading is radiation emission by electrons and positrons in strong electromagnetic fields, but as the setup is quite versatile, other related phenomena in radiation emission can be studied as well. The intent is to clarify the role of a number of important aspects of radiation in strong fields as e.g. observed in crystals. We propose to measure trident 'Klein-like' production in strong crystalline fields, 'crystalline undulator' radiation, 'sandwich' target phenomena, LPM suppression of pair production as well as axial and planar effects in contributions of spin to the radiation.

  14. Patterns of Strong Coupling for LHC Searches

    CERN Document Server

    Liu, Da; Rattazzi, Riccardo; Riva, Francesco

    2016-11-23

    Even though the Standard Model (SM) is weakly coupled at the Fermi scale, a new strong dynamics involving its degrees of freedom may conceivably lurk at slightly higher energies, in the multi TeV range. Approximate symmetries provide a structurally robust context where, within the low energy description, the dimensionless SM couplings are weak, while the new strong dynamics manifests itself exclusively through higher-derivative interactions. We present an exhaustive classification of such scenarios in the form of effective field theories, paying special attention to new classes of models where the strong dynamics involves, along with the Higgs boson, the SM gauge bosons and/or the fermions. The IR softness of the new dynamics suppresses its effects at LEP energies, but deviations are in principle detectable at the LHC, even at energies below the threshold for production of new states. Our construction provides the so far unique structurally robust context where to motivate several searches in Higgs physics, d...

  15. Electronic Structure of Strongly Correlated Materials

    CERN Document Server

    Anisimov, Vladimir

    2010-01-01

    Electronic structure and physical properties of strongly correlated materials containing elements with partially filled 3d, 4d, 4f and 5f electronic shells is analyzed by Dynamical Mean-Field Theory (DMFT). DMFT is the most universal and effective tool used for the theoretical investigation of electronic states with strong correlation effects. In the present book the basics of the method are given and its application to various material classes is shown. The book is aimed at a broad readership: theoretical physicists and experimentalists studying strongly correlated systems. It also serves as a handbook for students and all those who want to be acquainted with fast developing filed of condensed matter physics.

  16. Aperture averaging in strong oceanic turbulence

    Science.gov (United States)

    Gökçe, Muhsin Caner; Baykal, Yahya

    2018-04-01

    Receiver aperture averaging technique is employed in underwater wireless optical communication (UWOC) systems to mitigate the effects of oceanic turbulence, thus to improve the system performance. The irradiance flux variance is a measure of the intensity fluctuations on a lens of the receiver aperture. Using the modified Rytov theory which uses the small-scale and large-scale spatial filters, and our previously presented expression that shows the atmospheric structure constant in terms of oceanic turbulence parameters, we evaluate the irradiance flux variance and the aperture averaging factor of a spherical wave in strong oceanic turbulence. Irradiance flux variance variations are examined versus the oceanic turbulence parameters and the receiver aperture diameter are examined in strong oceanic turbulence. Also, the effect of the receiver aperture diameter on the aperture averaging factor is presented in strong oceanic turbulence.

  17. Electromagnetic Processes in strong Crystalline Fields

    CERN Multimedia

    2007-01-01

    We propose a number of new investigations on aspects of radiation from high energy electron and positron beams (10-300 GeV) in single crystals and amorphous targets. The common heading is radiation emission by electrons and positrons in strong electromagnetic fields, but as the setup is quite versatile, other related phenomena in radiation emission can be studied as well. The intent is to clarify the role of a number of important aspects of radiation in strong fields as e.g. observed in crystals. We propose to measure trident 'Klein-like' production in strong crystalline fields, 'crystalline undulator' radiation, 'sandwich' target phenomena, LPM suppression of pair production as well as axial and planar effects in contributions of spin to the radiation.

  18. Combined effect of back pain and stress on work ability.

    Science.gov (United States)

    Oberlinner, C; Yong, M; Nasterlack, M; Pluto, R-P; Lang, S

    2015-03-01

    Back pain and occupational stress are known risk factors for absenteeism and presenteeism. In addition, the relationship between back pain (BP) and psychosocial stressors has been examined in numerous studies. To examine the prevalence of BP and perceived stress among employees of different occupational status and to investigate their combined impact on work ability. A comprehensive survey combining questionnaire data and medical examination offered in one division of a major chemical company in Germany. Self-rated health and work ability were assessed using the Work Ability Index (WAI). A synergy index was used to assess a potential interaction between both exposures under an additive model. Of 867 voluntary participants, 653 returned complete questionnaires on BP and job stress perception. Although occupational stressors were perceived differently, there was no difference in the prevalence of BP between the occupational groups. Back pain and stress perception are correlated with each other and both are negatively associated with work ability. After adjustment for occupational status, demographic and lifestyle factors, we found a synergy effect of BP and stress perception with a modest to strong impact on declining WAI. Corporate health promotion interventions to reduce the impact of BP and stress perception on work ability should target both physical and psychological dimensions. Such interventions may be initiated in the context of regular (occupational) medical examinations. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Experimental investigation of strong field trident production

    CERN Document Server

    Esberg, J; Knudsen, H; Thomsen, H D; Uggerhøj, E; Uggerhøj, U I; Sona, P; Mangiarotti, A; Ketel, T J; Dizdar, A; Dalton, M M; Ballestrero, S; Connell, S H

    2010-01-01

    We show by experiment that an electron impinging on an electric field that is of critical magnitude in its rest frame, may produce an electron-positron pair. Our measurements address higher-order QED, using the strong electric fields obtainable along particular crystallographic directions in single crystals. For the amorphous material our data are in good agreement with theory, whereas a discrepancy with theory on the magnitude of the trident enhancement is found in the precisely aligned case where the strong electric field acts.

  20. Gluon scattering amplitudes at strong coupling

    Energy Technology Data Exchange (ETDEWEB)

    Alday, Luis F. [Institute for Theoretical Physics and Spinoza Institute, Utrecht University, 3508 TD Utrecht (Netherlands); Maldacena, Juan [School of Natural Sciences, Institute for Advanced Study, Princeton, NJ 08540 (United States)

    2007-06-15

    We describe how to compute planar gluon scattering amplitudes at strong coupling in N = 4 super Yang Mills by using the gauge/string duality. The computation boils down to finding a certain classical string configuration whose boundary conditions are determined by the gluon momenta. The results are infrared divergent. We introduce the gravity version of dimensional regularization to define finite quantities. The leading and subleading IR divergencies are characterized by two functions of the coupling that we compute at strong coupling. We compute also the full finite form for the four point amplitude and we find agreement with a recent ansatz by Bern, Dixon and Smirnov.

  1. Strong boundedness of analytic functions in tubes

    Directory of Open Access Journals (Sweden)

    Richard D. Carmichael

    1979-01-01

    Full Text Available Certain classes of analytic functions in tube domains TC=ℝn+iC in n-dimensional complex space, where C is an open connected cone in ℝn, are studied. We show that the functions have a boundedness property in the strong topology of the space of tempered distributions g′. We further give a direct proof that each analytic function attains the Fourier transform of its spectral function as distributional boundary value in the strong (and weak topology of g′.

  2. Including virtual photons in strong interactions

    International Nuclear Information System (INIS)

    Rusetsky, A.

    2003-01-01

    In the perturbative field-theoretical models we investigate the inclusion of the electromagnetic interactions into the purely strong theory that describes hadronic processes. In particular, we study the convention for splitting electromagnetic and strong interactions and the ambiguity of such a splitting. The issue of the interpretation of the parameters of the low-energy effective field theory in the presence of electromagnetic interactions is addressed, as well as the scale and gauge dependence of the effective theory couplings. We hope, that the results of these studies are relevant for the electromagnetic sector of ChPT. (orig.)

  3. Thermodynamical instabilities under strong magnetic fields

    Science.gov (United States)

    Chen, Y. J.

    2017-03-01

    The thermodynamical instabilities of low densities in the n p matter and n p e matter are studied within several relativistic nuclear models under some values of magnetic fields. The results are compared between each other and the effects of the symmetry energy slope at saturation density on the instability are investigated. The instability regions can exhibit bands due to the presence of Landau levels for very strong magnetic fields of the order of 1017 G, while for weaker magnetic fields, the bands are replaced by many diffused or scattered pieces. It also shows that the proton fraction in the inner crust of neutron stars may be complex under strong magnetic fields.

  4. Universal behavior of strongly correlated Fermi systems

    Energy Technology Data Exchange (ETDEWEB)

    Shaginyan, Vasilii R [B.P. Konstantinov St. Petersburg Institute of Nuclear Physics, Russian Academy of Sciences, Gatchina, Leningrad region, Rusian Federation (Russian Federation); Amusia, M Ya [A.F. Ioffe Physico-Technical Institute, Russian Academy of Sciences, St. Petersburg (Russian Federation); Popov, Konstantin G [Komi Scientific Center, Ural Branch of the Russian Academy of Sciences, Syktyvkar (Russian Federation)

    2007-06-30

    This review discusses the construction of a theory and the analysis of phenomena occurring in strongly correlated Fermi systems such as high-T{sub c} superconductors, heavy-fermion metals, and quasi-two-dimensional Fermi systems. It is shown that the basic properties and the universal behavior of strongly correlated Fermi systems can be described in the framework of the Fermi-condensate quantum phase transition and the well-known Landau paradigm of quasiparticles and the order parameter. The concept of fermion condensation may be fruitful in studying neutron stars, finite Fermi systems, ultra-cold gases in traps, and quark plasma. (reviews of topical problems)

  5. Universal behavior of strongly correlated Fermi systems

    International Nuclear Information System (INIS)

    Shaginyan, Vasilii R; Amusia, M Ya; Popov, Konstantin G

    2007-01-01

    This review discusses the construction of a theory and the analysis of phenomena occurring in strongly correlated Fermi systems such as high-T c superconductors, heavy-fermion metals, and quasi-two-dimensional Fermi systems. It is shown that the basic properties and the universal behavior of strongly correlated Fermi systems can be described in the framework of the Fermi-condensate quantum phase transition and the well-known Landau paradigm of quasiparticles and the order parameter. The concept of fermion condensation may be fruitful in studying neutron stars, finite Fermi systems, ultra-cold gases in traps, and quark plasma. (reviews of topical problems)

  6. Analytical solution of strongly nonlinear Duffing oscillators

    OpenAIRE

    El-Naggar, A.M.; Ismail, G.M.

    2016-01-01

    In this paper, a new perturbation technique is employed to solve strongly nonlinear Duffing oscillators, in which a new parameter α=α(ε)α=α(ε) is defined such that the value of α is always small regardless of the magnitude of the original parameter εε. Therefore, the strongly nonlinear Duffing oscillators with large parameter ε are transformed into a small parameter system with respect to αα. Approximate solution obtained by the present method is compared with the solution of energy balance m...

  7. De Sitter vacua of strongly interacting QFT

    Energy Technology Data Exchange (ETDEWEB)

    Buchel, Alex [Department of Applied Mathematics, University of Western Ontario,London, Ontario N6A 5B7 (Canada); Department of Physics and Astronomy, University of Western Ontario,London, Ontario N6A 5B7 (Canada); Perimeter Institute for Theoretical Physics,Waterloo, Ontario N2J 2W9 (Canada); Karapetyan, Aleksandr [Department of Applied Mathematics, University of Western Ontario,London, Ontario N6A 5B7 (Canada)

    2017-03-22

    We use holographic correspondence to argue that Euclidean (Bunch-Davies) vacuum is a late-time attractor of the dynamical evolution of quantum gauge theories at strong coupling. The Bunch-Davies vacuum is not an adiabatic state, if the gauge theory is non-conformal — the comoving entropy production rate is nonzero. Using the N=2{sup ∗} gauge theory holography, we explore prospects of explaining current accelerated expansion of the Universe as due to the vacuum energy of a strongly coupled QFT.

  8. Hetero-multivalent binding of cholera toxin subunit B with glycolipid mixtures.

    Science.gov (United States)

    Krishnan, Pratik; Singla, Akshi; Lee, Chin-An; Weatherston, Joshua D; Worstell, Nolan C; Wu, Hung-Jen

    2017-12-01

    GM 1 has generally been considered as the major receptor that binds to cholera toxin subunit B (CTB) due to its low dissociation constant. However, using a unique nanocube sensor technology, we have shown that CTB can also bind to other glycolipid receptors, fucosyl-GM 1 and GD 1 b. Additionally, we have demonstrated that GM 2 can contribute to CTB binding if present in a glycolipid mixture with a strongly binding receptor (GM 1 /fucosyl-GM 1 /GD 1 b). This hetero-multivalent binding result was unintuitive because the interaction between CTB and pure GM 2 is negligible. We hypothesized that the reduced dimensionality of CTB-GM 2 binding events is a major cause of the observed CTB binding enhancement. Once CTB has attached to a strong receptor, subsequent binding events are confined to a 2D membrane surface. Therefore, even a weak GM 2 receptor could now participate in second or higher binding events because its surface reaction rate can be up to 10 4 times higher than the bulk reaction rate. To test this hypothesis, we altered the surface reaction rate by modulating the fluidity and heterogeneity of the model membrane. Decreasing membrane fluidity reduced the binding cooperativity between GM 2 and a strong receptor. Our findings indicated a new protein-receptor binding assay, that can mimic complex cell membrane environment more accurately, is required to explore the inherent hetero-multivalency of the cell membrane. We have thus developed a new membrane perturbation protocol to efficiently screen receptor candidates involved in hetero-multivalent protein binding. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Human proteins that specifically bind to 8-oxoguanine-containing RNA and their responses to oxidative stress

    International Nuclear Information System (INIS)

    Hayakawa, Hiroshi; Fujikane, Aya; Ito, Riyoko; Matsumoto, Masaki; Nakayama, Keiichi I.; Sekiguchi, Mutsuo

    2010-01-01

    Research highlights: → We performed comprehensive survey for proteins that bind to oxidized RNA. → HNRNPD and HNRNPC proteins were identified as oxidized RNA binding proteins. → Knockdown of HNRNPD/C expression caused increased sensitivity to H 2 O 2 . → Amounts of HNRNPD protein rapidly decreased when cells were exposed to H 2 O 2 . -- Abstract: Exposure of cells to oxygen radicals damage various biologically important molecules. Among the oxidized bases produced in nucleic acids, 8-oxo-7,8-dihydroguanine (8-oxoguanine) is particularly important since it causes base mispairing. To ensure accurate gene expression, organisms must have a mechanism to discriminate 8-oxoguanine-containing RNA from normal transcripts. We searched for proteins that specifically bind to 8-oxoguanine-containing RNA from human HeLa cell extracts, and the candidate proteins were identified using mass spectrometry. Among the identified candidates, splicing isoform 1 of heterogeneous nuclear ribonucleoprotein D0 (HNRNPD) and splicing isoform C1 of heterogeneous nuclear ribonucleoprotein C1/C2 (HNRNPC) exhibited strong abilities to bind to oxidized RNA. The amount of HNRNPD protein rapidly decreased when cells were exposed to hydrogen peroxide, an agent that enhances oxidative stress. Moreover, the suppression of HNRNPD expression by siRNA caused cells to exhibit an increased sensitivity to hydrogen peroxide. The application of siRNA against HNRNPC also caused an increase in sensitivity to hydrogen peroxide. Since no additive effect was observed with a combined addition of siRNAs for HNRNPD and HNRNPC, we concluded that the two proteins may function in the same mechanism for the accurate gene expression.

  10. Characterization of the p53 cistrome--DNA binding cooperativity dissects p53's tumor suppressor functions.

    Directory of Open Access Journals (Sweden)

    Katharina Schlereth

    Full Text Available p53 protects us from cancer by transcriptionally regulating tumor suppressive programs designed to either prevent the development or clonal expansion of malignant cells. How p53 selects target genes in the genome in a context- and tissue-specific manner remains largely obscure. There is growing evidence that the ability of p53 to bind DNA in a cooperative manner prominently influences target gene selection with activation of the apoptosis program being completely dependent on DNA binding cooperativity. Here, we used ChIP-seq to comprehensively profile the cistrome of p53 mutants with reduced or increased cooperativity. The analysis highlighted a particular relevance of cooperativity for extending the p53 cistrome to non-canonical binding sequences characterized by deletions, spacer insertions and base mismatches. Furthermore, it revealed a striking functional separation of the cistrome on the basis of cooperativity; with low cooperativity genes being significantly enriched for cell cycle and high cooperativity genes for apoptotic functions. Importantly, expression of high but not low cooperativity genes was correlated with superior survival in breast cancer patients. Interestingly, in contrast to most p53-activated genes, p53-repressed genes did not commonly contain p53 binding elements. Nevertheless, both the degree of gene activation and repression were cooperativity-dependent, suggesting that p53-mediated gene repression is largely indirect and mediated by cooperativity-dependently transactivated gene products such as CDKN1A, E2F7 and non-coding RNAs. Since both activation of apoptosis genes with non-canonical response elements and repression of pro-survival genes are crucial for p53's apoptotic activity, the cistrome analysis comprehensively explains why p53-induced apoptosis, but not cell cycle arrest, strongly depends on the intermolecular cooperation of p53 molecules as a possible safeguard mechanism protecting from accidental cell

  11. Human proteins that specifically bind to 8-oxoguanine-containing RNA and their responses to oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Hayakawa, Hiroshi, E-mail: hiroshi@college.fdcnet.ac.jp [Department of Functional Bioscience and Advanced Science Research Center, Fukuoka Dental College, Fukuoka 814-0193 (Japan); Fujikane, Aya; Ito, Riyoko [Department of Functional Bioscience and Advanced Science Research Center, Fukuoka Dental College, Fukuoka 814-0193 (Japan); Matsumoto, Masaki; Nakayama, Keiichi I. [Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582 (Japan); Sekiguchi, Mutsuo [Department of Functional Bioscience and Advanced Science Research Center, Fukuoka Dental College, Fukuoka 814-0193 (Japan)

    2010-12-10

    Research highlights: {yields} We performed comprehensive survey for proteins that bind to oxidized RNA. {yields} HNRNPD and HNRNPC proteins were identified as oxidized RNA binding proteins. {yields} Knockdown of HNRNPD/C expression caused increased sensitivity to H{sub 2}O{sub 2}. {yields} Amounts of HNRNPD protein rapidly decreased when cells were exposed to H{sub 2}O{sub 2}. -- Abstract: Exposure of cells to oxygen radicals damage various biologically important molecules. Among the oxidized bases produced in nucleic acids, 8-oxo-7,8-dihydroguanine (8-oxoguanine) is particularly important since it causes base mispairing. To ensure accurate gene expression, organisms must have a mechanism to discriminate 8-oxoguanine-containing RNA from normal transcripts. We searched for proteins that specifically bind to 8-oxoguanine-containing RNA from human HeLa cell extracts, and the candidate proteins were identified using mass spectrometry. Among the identified candidates, splicing isoform 1 of heterogeneous nuclear ribonucleoprotein D0 (HNRNPD) and splicing isoform C1 of heterogeneous nuclear ribonucleoprotein C1/C2 (HNRNPC) exhibited strong abilities to bind to oxidized RNA. The amount of HNRNPD protein rapidly decreased when cells were exposed to hydrogen peroxide, an agent that enhances oxidative stress. Moreover, the suppression of HNRNPD expression by siRNA caused cells to exhibit an increased sensitivity to hydrogen peroxide. The application of siRNA against HNRNPC also caused an increase in sensitivity to hydrogen peroxide. Since no additive effect was observed with a combined addition of siRNAs for HNRNPD and HNRNPC, we concluded that the two proteins may function in the same mechanism for the accurate gene expression.

  12. Direct and indirect effects of organizational justice on work ability.

    Science.gov (United States)

    Spanier, K; Radoschewski, F M; Gutenbrunner, C; Bethge, M

    2014-12-01

    Organizational justice (OJ), involving transparent workplace procedures and treating staff members with respect, has been of growing concern in recent epidemiological research as a determinant of health-related outcomes. To examine the factorial validity of the German version of Moorman's Organizational Justice Questionnaire (OJQ), to investigate the direct cross-sectional effect of OJ on self-rated work ability and to analyse if there is an additional indirect effect of OJ on work ability mediated by effort-reward imbalance. An analysis of cross-sectional data from the Second German Sociomedical Panel of Employees, involving white-collar workers employed at least half time. We performed confirmatory factor analyses to test the factorial validity of the OJQ and analysed the direct and indirect associations of OJ and self-rated work ability by path model analysis. Of the 1217 participants (47% female; mean age: 51) 36% had poor work ability. Factor analyses confirmed the two-factor structure of the German OJQ. Work ability was explained directly by OJ (β = 0.30) and effort-reward imbalance (β = -0.27). Additionally, we identified an indirect effect of OJ that was mediated by effort-reward imbalance (β = 0.14). The total effect of OJ on work ability was remarkably strong (β = 0.44). Associations remained unchanged after adjustment for socio-demographic parameters. This study showed the importance of considering additional indirect pathways when examining the impact of OJ on the work ability of employees. © The Author 2014. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Robust prediction of individual creative ability from brain functional connectivity.

    Science.gov (United States)

    Beaty, Roger E; Kenett, Yoed N; Christensen, Alexander P; Rosenberg, Monica D; Benedek, Mathias; Chen, Qunlin; Fink, Andreas; Qiu, Jiang; Kwapil, Thomas R; Kane, Michael J; Silvia, Paul J

    2018-01-30

    People's ability to think creatively is a primary means of technological and cultural progress, yet the neural architecture of the highly creative brain remains largely undefined. Here, we employed a recently developed method in functional brain imaging analysis-connectome-based predictive modeling-to identify a brain network associated with high-creative ability, using functional magnetic resonance imaging (fMRI) data acquired from 163 participants engaged in a classic divergent thinking task. At the behavioral level, we found a strong correlation between creative thinking ability and self-reported creative behavior and accomplishment in the arts and sciences ( r = 0.54). At the neural level, we found a pattern of functional brain connectivity related to high-creative thinking ability consisting of frontal and parietal regions within default, salience, and executive brain systems. In a leave-one-out cross-validation analysis, we show that this neural model can reliably predict the creative quality of ideas generated by novel participants within the sample. Furthermore, in a series of external validation analyses using data from two independent task fMRI samples and a large task-free resting-state fMRI sample, we demonstrate robust prediction of individual creative thinking ability from the same pattern of brain connectivity. The findings thus reveal a whole-brain network associated with high-creative ability comprised of cortical hubs within default, salience, and executive systems-intrinsic functional networks that tend to work in opposition-suggesting that highly creative people are characterized by the ability to simultaneously engage these large-scale brain networks.

  14. Pro DNS and BIND 10

    CERN Document Server

    Aitchison, Ron

    2011-01-01

    Pro DNS and BIND 10 guides you through the challenging array of features surrounding DNS with a special focus on the latest release of BIND, the world's most popular DNS implementation. This book unravels the mysteries of DNS, offering insight into origins, evolution, and key concepts like domain names and zone files. This book focuses on running DNS systems based on BIND 10, the first stable release that includes support for the latest DNSSEC standards. Whether you administer a DNS system, are thinking about running one, or you simply want to understand the DNS system, then this book for you.

  15. Protein binding of psychotropic agents

    International Nuclear Information System (INIS)

    Hassan, H.A.

    1990-01-01

    Based upon fluorescence measurements, protein binding of some psychotropic agents (chlorpromazine, promethazine, and trifluoperazine) to human IgG and HSA was studied in aqueous cacodylate buffer, PH7. The interaction parameters determined from emission quenching of the proteins. The interaction parameters determined include the equilibrium constant (K), calculated from equations derived by Borazan and coworkers, the number of binding sites (n) available to the monomer molecules on a single protein molecule. The results revealed a high level of affinity, as reflected by high values of K, and the existence of specific binding sites, since a limited number of n values are obtained. 39 tabs.; 37 figs.; 83 refs

  16. New fluorescent reagents specific for Ca2+-binding proteins

    International Nuclear Information System (INIS)

    Ben-Hail, Danya; Lemelson, Daniela; Israelson, Adrian; Shoshan-Barmatz, Varda

    2012-01-01

    Highlights: ► New reagents specifically inhibit the activity of Ca 2+ -dependent proteins. ► FITC-Ru and EITC-Ru allow for mechanism-independent probing of Ca 2+ -binding proteins. ► Changes in reagents fluorescence allow characterization of protein Ca 2+ -binding properties. -- Abstract: Ca 2+ carries information pivotal to cell life and death via its interactions with specific binding sites in a protein. We previously developed a novel photoreactive reagent, azido ruthenium (AzRu), which strongly inhibits Ca 2+ -dependent activities. Here, we synthesized new fluorescent ruthenium-based reagents containing FITC or EITC, FITC-Ru and EITC-Ru. These reagents were purified, characterized and found to specifically interact with and markedly inhibit Ca 2+ -dependent activities but not the activity of Ca 2+ -independent reactions. In contrast to many reagents that serve as probes for Ca 2+ , FITC-Ru and EITC-Ru are the first fluorescent divalent cation analogs to be synthesized and characterized that specifically bind to Ca 2+ -binding proteins and inhibit their activity. Such reagents will assist in characterizing Ca 2+ -binding proteins, thereby facilitating better understanding of the function of Ca 2+ as a key bio-regulator.

  17. Artificial intelligence model for sustain ability measurement

    International Nuclear Information System (INIS)

    Navickiene, R.; Navickas, K.

    2012-01-01

    The article analyses the main dimensions of organizational sustain ability, their possible integrations into artificial neural network. In this article authors performing analyses of organizational internal and external environments, their possible correlations with 4 components of sustain ability, and the principal determination models for sustain ability of organizations. Based on the general principles of sustainable development organizations, a artificial intelligence model for the determination of organizational sustain ability has been developed. The use of self-organizing neural networks allows the identification of the organizational sustain ability and the endeavour to explore vital, social, antropogenical and economical efficiency. The determination of the forest enterprise sustain ability is expected to help better manage the sustain ability. (Authors)

  18. Earthquake source model using strong motion displacement

    Indian Academy of Sciences (India)

    The strong motion displacement records available during an earthquake can be treated as the response of the earth as the a structural system to unknown forces acting at unknown locations. Thus, if the part of the earth participating in ground motion is modelled as a known finite elastic medium, one can attempt to model the ...

  19. Vector mesons in strongly interacting matter

    Indian Academy of Sciences (India)

    probes like photons, pions or protons or the heated and compressed hadronic matter generated in a heavy-ion collision. Leaving any nuclear medium without strong final-state interactions, dileptons are the optimum decay channel as they avoid any final-state distortion of the 4- momenta of the decay products entering eq.

  20. Vector mesons in strongly interacting matter

    Indian Academy of Sciences (India)

    Properties of hadrons in strongly interacting matter provide a link between quantum chromodynamics in the ... Top: Spectral function of the ρ-meson at normal nuclear matter density as a function of mass and ... directly but folded with the branching ratio ΓV →p1+p2 /Γtot into the specific final channel one is investigating.

  1. Strong industrial base vital for economic revival

    CERN Multimedia

    2001-01-01

    At the inauguration of a 2-day conference on nuclear technology in Islamabad, the chairman of PAEC said that Pakistan needs to develop a strong industrial base and capability to export equipment to improve the economic condition of the country. He descibed how Pakistan has already had a breakthrough with the export of equipment to CERN, Geneva (1 page).

  2. Chaos desynchronization in strongly coupled systems

    International Nuclear Information System (INIS)

    Wu Ye; Liu Weiqing; Xiao, Jinghua; Zhan Meng

    2007-01-01

    The dynamics of chaos desynchronization in strongly coupled oscillator systems is studied. We find a new bifurcation from synchronous chaotic state, chaotic short wave bifurcation, i.e. a chaotic desynchronization attractor is new born in the systems due to chaos desynchronization. In comparison with the usual periodic short wave bifurcation, very rich but distinct phenomena are observed

  3. Strong wind climatic zones in South Africa

    CSIR Research Space (South Africa)

    Kruger, AC

    2010-01-01

    Full Text Available In this paper South Africa is divided into strong wind climate zones, which indicate the main sources of annual maximum wind gusts. By the analysis of wind gust data of 94 weather stations, which had continuous climate time series of 10 years...

  4. Reducing Weak to Strong Bisimilarity in CCP

    Directory of Open Access Journals (Sweden)

    Andrés Aristizábal

    2012-12-01

    Full Text Available Concurrent constraint programming (ccp is a well-established model for concurrency that singles out the fundamental aspects of asynchronous systems whose agents (or processes evolve by posting and querying (partial information in a global medium. Bisimilarity is a standard behavioural equivalence in concurrency theory. However, only recently a well-behaved notion of bisimilarity for ccp, and a ccp partition refinement algorithm for deciding the strong version of this equivalence have been proposed. Weak bisimiliarity is a central behavioural equivalence in process calculi and it is obtained from the strong case by taking into account only the actions that are observable in the system. Typically, the standard partition refinement can also be used for deciding weak bisimilarity simply by using Milner's reduction from weak to strong bisimilarity; a technique referred to as saturation. In this paper we demonstrate that, because of its involved labeled transitions, the above-mentioned saturation technique does not work for ccp. We give an alternative reduction from weak ccp bisimilarity to the strong one that allows us to use the ccp partition refinement algorithm for deciding this equivalence.

  5. Strong motion duration and earthquake magnitude relationships

    International Nuclear Information System (INIS)

    Salmon, M.W.; Short, S.A.; Kennedy, R.P.

    1992-06-01

    Earthquake duration is the total time of ground shaking from the arrival of seismic waves until the return to ambient conditions. Much of this time is at relatively low shaking levels which have little effect on seismic structural response and on earthquake damage potential. As a result, a parameter termed ''strong motion duration'' has been defined by a number of investigators to be used for the purpose of evaluating seismic response and assessing the potential for structural damage due to earthquakes. This report presents methods for determining strong motion duration and a time history envelope function appropriate for various evaluation purposes, for earthquake magnitude and distance, and for site soil properties. There are numerous definitions of strong motion duration. For most of these definitions, empirical studies have been completed which relate duration to earthquake magnitude and distance and to site soil properties. Each of these definitions recognizes that only the portion of an earthquake record which has sufficiently high acceleration amplitude, energy content, or some other parameters significantly affects seismic response. Studies have been performed which indicate that the portion of an earthquake record in which the power (average rate of energy input) is maximum correlates most closely with potential damage to stiff nuclear power plant structures. Hence, this report will concentrate on energy based strong motion duration definitions

  6. Morphological modelling of strongly curved islands

    NARCIS (Netherlands)

    Roelvink, D.; Den Heijer, C.; Van Thiel De Vries, J.S.M.

    2013-01-01

    Land reclamations and island coasts often involve strongly curved shorelines, which are challenging to be properly modeled by numerical morphological models. Evaluation of the long term development of these types of coasts as well as their response to storm conditions requires proper representation

  7. Nonlinear Electron Waves in Strongly Magnetized Plasmas

    DEFF Research Database (Denmark)

    Pécseli, Hans; Juul Rasmussen, Jens

    1980-01-01

    Weakly nonlinear dispersive electron waves in strongly magnetized plasma are considered. A modified nonlinear Schrodinger equation is derived taking into account the effect of particles resonating with the group velocity of the waves (nonlinear Landau damping). The possibility of including the ion...

  8. Strong and Reversible Monovalent Supramolecular Protein Immobilization

    NARCIS (Netherlands)

    Young, Jacqui F.; Nguyen, Hoang D.; Yang, Lanti; Huskens, Jurriaan; Jonkheijm, Pascal; Brunsveld, Luc

    2010-01-01

    Proteins with an iron clasp: Site-selective incorporation of a ferrocene molecule into a protein allows for easy, strong, and reversible supramolecular protein immobilization through a selective monovalent interaction of the ferrocene with a cucurbit[7]uril immobilized on a gold surface. The

  9. Experimental investigation of strong field trident production

    NARCIS (Netherlands)

    Esberg, J.; Kirsebom, K.; Knudsen, H.; Thomsen, H.D.; Uggerhøj, E.; Uggerhøj, U.I.; Sona, P.; Mangiarotti, A.; Ketel, T.J.; Ditzdar, A.; Dalton, M.M.; Ballestrero, S.; Connell, S.H.

    2010-01-01

    We show by experiment that an electron impinging on an electric field that is of critical magnitude in its rest frame, may produce an electron-positron pair. Our measurements address higher-order QED, using the strong electric fields obtainable along particular crystallographic directions in single

  10. Strong-coupling diffusion in relativistic systems

    Indian Academy of Sciences (India)

    hanced values needed to interpret the data at higher energies point towards the importance of strong-coupling effects. ... when all secondary particles have been created. For short times in the initial phase ... It is decisive for a proper representation of the available data for relativistic heavy-ion collisions at and beyond SPS.

  11. Bottomonia: open bottom strong decays and spectrum

    Directory of Open Access Journals (Sweden)

    Santopinto E.

    2014-05-01

    Full Text Available We present our results for the bottomonium spectrum with self energy corrections. The bare masses used in the calculation are computed within Godfrey and Isgur’s relativized quark model. We also discuss our results for the open bottom strong decay widths of higher bottomonia in the 3P0 pair-creation model.

  12. Strong motion duration and earthquake magnitude relationships

    Energy Technology Data Exchange (ETDEWEB)

    Salmon, M.W.; Short, S.A. [EQE International, Inc., San Francisco, CA (United States); Kennedy, R.P. [RPK Structural Mechanics Consulting, Yorba Linda, CA (United States)

    1992-06-01

    Earthquake duration is the total time of ground shaking from the arrival of seismic waves until the return to ambient conditions. Much of this time is at relatively low shaking levels which have little effect on seismic structural response and on earthquake damage potential. As a result, a parameter termed ``strong motion duration`` has been defined by a number of investigators to be used for the purpose of evaluating seismic response and assessing the potential for structural damage due to earthquakes. This report presents methods for determining strong motion duration and a time history envelope function appropriate for various evaluation purposes, for earthquake magnitude and distance, and for site soil properties. There are numerous definitions of strong motion duration. For most of these definitions, empirical studies have been completed which relate duration to earthquake magnitude and distance and to site soil properties. Each of these definitions recognizes that only the portion of an earthquake record which has sufficiently high acceleration amplitude, energy content, or some other parameters significantly affects seismic response. Studies have been performed which indicate that the portion of an earthquake record in which the power (average rate of energy input) is maximum correlates most closely with potential damage to stiff nuclear power plant structures. Hence, this report will concentrate on energy based strong motion duration definitions.

  13. Controlling Josephson dynamics by strong microwave fields

    NARCIS (Netherlands)

    Chesca, B.; Savel'ev, E.; Rakhmanov, A.L.; Smilde, H.J.H.; Hilgenkamp, Johannes W.M.

    2008-01-01

    We observe several sharp changes in the slope of the current-voltage characteristics (CVCs) of thin-film ramp-edge Josephson junctions between YBa2Cu3O7−delta and Nb when applying strong microwave fields. Such behavior indicates an intriguing Josephson dynamics associated with the switching from a

  14. Strong-coupling diffusion in relativistic systems

    Indian Academy of Sciences (India)

    Different from the early universe, heavy-ion collisions at very high energies do not reach statistical equilibrium, although thermal models explain many of their features. To account for nonequilibrium strong-coupling effects, a Fokker–Planck equation with time-dependent diffusion coefficient is proposed. A schematic model ...

  15. Weak and strong nonlinearities in magnetic bearings

    Czech Academy of Sciences Publication Activity Database

    Půst, Ladislav

    2004-01-01

    Roč. 39, č. 7 (2004), s. 779-795 ISSN 0094-114X R&D Projects: GA ČR GA101/00/1471; GA AV ČR IBS2076301 Institutional research plan: CEZ:AV0Z2076919 Keywords : weak nonlinearitiy * strong nonlinearity * magnetics bearings Subject RIV: BI - Acoustics Impact factor: 0.605, year: 2004

  16. Rotating compressible fluids under strong stratification

    Czech Academy of Sciences Publication Activity Database

    Feireisl, Eduard; Lu, Y.; Novotný, A.

    2014-01-01

    Roč. 19, October (2014), s. 11-18 ISSN 1468-1218 Keywords : rotating fluid * compressible Navier-Stokes * strong stratification Subject RIV: BA - General Mathematics Impact factor: 2.519, year: 2014 http://www.sciencedirect.com/science/article/pii/S1468121814000212#

  17. Super-strong Magnetic Field in Sunspots

    Science.gov (United States)

    Okamoto, Takenori J.; Sakurai, Takashi

    2018-01-01

    Sunspots are the most notable structure on the solar surface with strong magnetic fields. The field is generally strongest in a dark area (umbra), but sometimes stronger fields are found in non-dark regions, such as a penumbra and a light bridge. The formation mechanism of such strong fields outside umbrae is still puzzling. Here we report clear evidence of the magnetic field of 6250 G, which is the strongest field among Stokes I profiles with clear Zeeman splitting ever observed on the Sun. The field was almost parallel to the solar surface and located in a bright region sandwiched by two opposite-polarity umbrae. Using a time series of spectral data sets, we discuss the formation process of the super-strong field and suggest that this strong field region was generated as a result of compression of one umbra pushed by the horizontal flow from the other umbra, such as the subduction of the Earth’s crust in plate tectonics.

  18. Strongly coupled semidirect mediation of supersymmetry breaking

    International Nuclear Information System (INIS)

    Ibe, M.; Izawa, K.-I.; Nakai, Y.

    2009-01-01

    Strongly coupled semidirect gauge mediation models of supersymmetry breaking through massive mediators with standard-model charges are investigated by means of composite degrees of freedom. Sizable mediation is realized to generate the standard-model gaugino masses for a small mediator mass without breaking the standard-model symmetries.

  19. A Note on Strongly Dense Matrices

    Czech Academy of Sciences Publication Activity Database

    Fiedler, Miroslav; Hall, F.J.

    2015-01-01

    Roč. 1, č. 4 (2015), s. 721-730 ISSN 2199-675X Institutional support: RVO:67985807 Keywords : strongly dense matrix * Boolean matrix * nonnegative matrix * idempotent matrix * intrinsic product * generalized complementary basic matrix Subject RIV: BA - General Mathematics

  20. Strongly 2-connected orientations of graphs

    DEFF Research Database (Denmark)

    Thomassen, Carsten

    2014-01-01

    We prove that a graph admits a strongly 2-connected orientation if and only if it is 4-edge-connected, and every vertex-deleted subgraph is 2-edge-connected. In particular, every 4-connected graph has such an orientation while no cubic 3-connected graph has such an orientation....