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Sample records for stable binding characteristics

  1. Biosensors engineered from conditionally stable ligand-binding domains

    Energy Technology Data Exchange (ETDEWEB)

    Church, George M.; Feng, Justin; Mandell, Daniel J.; Baker, David; Fields, Stanley; Jester, Benjamin Ward; Tinberg, Christine Elaine

    2017-09-19

    Disclosed is a biosensor engineered to conditionally respond to the presence of specific small molecules, the biosensors including conditionally stable ligand-binding domains (LBDs) which respond to the presence of specific small molecules, wherein readout of binding is provided by reporter genes or transcription factors (TFs) fused to the LBDs.

  2. Petrography, compositional characteristics and stable isotope ...

    African Journals Online (AJOL)

    Petrography, compositional characteristics and stable isotope geochemistry of the Ewekoro formation from Ibese Corehole, eastern Dahomey basin, southwestern Nigeria. ME Nton, MO ... Preserved pore types such as; intercrystaline, moldic and vuggy pores were observed as predominant conduits for fluids. The major ...

  3. Binding characteristics of swine erythrocyte insulin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Dieberg, G.; Bryan, G.S.; Sartin, J.L.; Williams, J.C.; Prince, T.J.; Kemppainen, R.J.

    1985-09-01

    Crossbred gilts had 8.8 +/- 1.1% maximum binding of ( SVI)insulin to insulin receptors on erythrocytes. The number of insulin-binding sites per cell was 137 +/- 19, with a binding affinity ranging from 7.4 X 10(7)M-1 to 11.2 X 10(7)M-1 and mean of 8.8 X 10(7)M-1. Pregnant sows had a significant increase in maximum binding due to an increase in number of receptor sites per cell. Lactating sows fed a high-fiber diet and a low-fiber diet did not develop a significant difference in maximum binding of insulin. Sows fed the low-fiber diet had a significantly higher number of binding sites and a significantly lower binding affinity than did sows fed a high-fiber diet. Receptor-binding affinity was lower in the low-fiber diet group than in cycling gilts, whereas data from sows fed the high-fiber diet did not differ from data for cycling gilts. Data from this study indicated that insulin receptors of swine erythrocytes have binding characteristics similar to those in other species. Pregnancy and diet will alter insulin receptor binding in swine.

  4. petrography, compositional characteristics and stable isotope ...

    African Journals Online (AJOL)

    PROF EKWUEME

    Subsurface samples of the predominantly carbonate Ewekoro Formation, obtained from Ibese core hole within the Dahomey basin were used in this study. Investigations entail petrographic, elemental composition as well as stable isotopes (carbon and oxygen) geochemistry in order to deduce the different microfacies and ...

  5. Stable MCC binding to the APC/C is required for a functional spindle assembly checkpoint

    DEFF Research Database (Denmark)

    Hein, Jamin B; Nilsson, Jakob

    2014-01-01

    normally, but IR motif integrity is particularly important for stable binding to the APC/C. Cells expressing Cdc20 with a mutated IR motif have a compromised SAC, as uninhibited Cdc20 can compete with the MCC for APC/C binding and activate it. We thus show that stable MCC association with the APC....../C is critical for a functional SAC....

  6. Antimicrobial Peptides with Differential Bacterial Binding Characteristics

    Science.gov (United States)

    2013-03-01

    wherein each residue in the sequence is systematically replaced with alanine to produce a set of well-defined mutations, and 3) sequence generation...peptide sequences with differential binding behavior toward select microorganisms .  viii    Acknowledgements The authors would like to thank Mr. Steven...A., Sandri, L., & Giangaspero, A. (2000). Amphipathic, α-Helical Antimicrobial Peptides. Biopolymers , 55, 4-30.  2 Epand, R. M., & Vogel, H. J. (1999

  7. Binding Characteristics Of Ivermectin To Blood Cells | Nweke ...

    African Journals Online (AJOL)

    The binding characteristics of Ivermectin were determined using scatchard plots. The percentage binding to platelet rich plasma, white blood cells and red blood cells were 90.00 + 1.00, 96-90 + 1.05 and 46.20 + 1.10 S.D respectively. It was found to bind the highest to white blood cells and the least to red blood cells.

  8. Stable nocturnal spectral characteristics over a vineyard (Conference Presentation)

    Science.gov (United States)

    Prueger, John H.; Alfieri, joesph G.; Hipps, Lawrence E.; Kustas, William P.; Neale, Christopher M.

    2016-10-01

    Vineyards are agricultural surfaces that present a unique structural perturbation to the mean wind flow. As part of the Grape Remote Sensing Atmospheric Profiling and Evapotranspiration Experiment (GRAPEX) a 10-m profile tower of three sonic anemometers at 2, 3.75 and 8 m above ground level in in a mature vineyard having was deployed to measure high frequency diurnal variations of 3-dimensional velocity components (u, v, w) and temperature (T) throughout the growing season. Previous work has been published involving eddy covariance measurements in vineyards but these mostly represented convective daytime unstable conditions. Significantly less has been published about turbulence in vineyards during stable nocturnal periods. Hence, in this study we focused on the nocturnal stable periods under clear skies and relatively light winds typical of the northern portion of California's Central Valley. Our objective was to characterize and evaluate turbulent exchange processes in the layer near the top of a vine canopy during nocturnal periods which are often characterized by weak and intermittent turbulence. Spectra, cospectra and coherence plots were evaluated for nocturnal periods. The spectra suggest there are periods of intermittent turbulence with features indicative of local and regional scale processes. Additionally the impact of the vine structure and spacing on slow meandering flows enhance the decomposition of organized turbulent eddies resulting in intricate mechanical turbulence generated by intermittent eddies that are rapidly decomposed as eddies interact with the vine structure and spacing. Preliminary results will be discussed that provide insight into turbulence characteristics at several heights above a canopy vineyard as affected by vine structure and spacing, wind speed, direction and stable conditions.

  9. Characteristics of stable carbon isotopic composition of shale gas

    Directory of Open Access Journals (Sweden)

    Zhenya Qu

    2016-04-01

    Full Text Available A type Ⅱ kerogen with low thermal maturity was adopted to perform hydrocarbon generation pyrolysis experiments in a vacuum (Micro-Scale Sealed Vessel system at the heating rates of 2 °C/h and 20 °C/h. The stable carbon isotopic compositions of gas hydrocarbons were measured to investigate their evolving characteristics and the possible reasons for isotope reversal. The δ13C values of methane became more negative with the increasing pyrolysis temperatures until it reached the lightest point, after which they became more positive. Meanwhile, the δ13C values of ethane and propane showed a positive trend with elevating pyrolysis temperatures. The carbon isotopic compositions of shale gasses were mainly determined by the type of parent organic matter, thermal evolutionary extent, and gas migration in shale systems. Our experiments and study proved that the isotope reversal shouldn't occur in a pure thermogenic gas reservoir, it must be involved with some other geochemical process/es; although mechanisms responsible for the reversal are still vague. Carbon isotopic composition of the Fayetteville and Barnett shale gas demonstrated that the isotope reversal was likely involved with water–gas reaction and Fischer-Tropsch synthesis during its generation.

  10. Computational characteristics of valproic acid binding to histone deacetylase

    International Nuclear Information System (INIS)

    Abou-Zeid, Laila A.; El-Mowafy, Abdalla M.; Eikel, D.; Nau, H.; El-Mazar, M.

    2007-01-01

    Recently, the anticpileptic drug valproic acid (VPA) has also demonstrated efficacy in the management of cancer and bipolar disorders. These actions are largely mediated by inhibition of the HDAC enzyme/induction of certain genes. Relative to other HDAC inhibitors such as trichostatin-A (TSA), VPA offers higher selectivity on cancer cells with virtually no detrimental effects on normal cells. The molecular underpinnings of these biological profiles for VPA remain undefined. We currently propose for an attempt to identify differences in the binding of VPA and TSA to HDAC. In this paper, conformational changes and energy calculations have derived. VPA had to accomplish conformational changes in its structure for best accommodation at the HDAC binding site. Energy computations showed that VPA has a lower binding affinitythan TSA (-53.80 vs. -66.30 Kcal/mol). These findings demonstrate that VPA binding to HDAC confers catalytic, conformational and computational characteristics that are distinct from those of TSA. These findings of VPA are consistent with a moderate inhibition of HDAC, a low toxicity on normal cells, and a higher selectivity on cancer cells than TSA. Accordingly, these newly identified binding properties of VPA can state a framework strategy for the rational design of VPA-related anticancer drugs with superior cytodifferentiating-and/or safety-profiles. (author)

  11. Stable Isotope Characteristics of Akiri Vein Copper Mineralization ...

    African Journals Online (AJOL)

    The Akiri vein copper mineralization was investigated for its carbon and oxygen isotopic composition to determine the characteristics of the mineralizing fluid. Carbon and oxygen isotope analyses of Akiri siderite range between δ13C values (-1.05 to -1.71‰) and δ13O values (-14.94 to -15.18) respectively. δ 13C isotopic ...

  12. Binding characteristics of copper and cadmium by cyanobacterium Spirulina platensis

    Energy Technology Data Exchange (ETDEWEB)

    Fang Linchuan [State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070 (China); Zhou Chen; Cai Peng [Key Laboratory of Subtropical Agricultural Resources and Environment, Ministry of Agriculture, College of Resources and Environment, Huazhong Agricultural University, Wuhan 430070 (China); Chen Wenli [State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070 (China); Rong Xingmin; Dai Ke; Liang Wei [Key Laboratory of Subtropical Agricultural Resources and Environment, Ministry of Agriculture, College of Resources and Environment, Huazhong Agricultural University, Wuhan 430070 (China); Gu Jidong [Department of Ecology and Biodiversity, University of Hong Kong, Pokfulam Road, Hong Kong (Hong Kong); Huang Qiaoyun, E-mail: qyhuang@mail.hzau.edu.cn [State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070 (China); Key Laboratory of Subtropical Agricultural Resources and Environment, Ministry of Agriculture, College of Resources and Environment, Huazhong Agricultural University, Wuhan 430070 (China)

    2011-06-15

    Highlights: {yields} The carboxyl groups play a vital role in the binding of Cu(II) and Cd(II) to S. platensis cells. {yields} Ion exchange and complexation are the dominating mechanism for Cu(II) and Cd(II) adsorption. {yields} XAFS analysis provided evidence for the inner-sphere complexation of Cu by carboxyl ligands and showed that Cu is complexed by two 5-membered chelate rings on S. platensis surface. - Abstract: Cyanobacteria are promising biosorbent for heavy metals in bioremediation. Although sequestration of metals by cyanobacteria is known, the actual mechanisms and ligands involved are not very well understood. The binding characteristics of Cu(II) and Cd(II) by the cyanobacterium Spirulina platensis were investigated using a combination of chemical modifications, batch adsorption experiments, Fourier transform infrared (FTIR) spectroscopy and X-ray absorption fine structure (XAFS) spectroscopy. A significant increase in Cu(II) and Cd(II) binding was observed in the range of pH 3.5-5.0. Dramatical decrease in adsorption of Cu(II) and Cd(II) was observed after methanol esterification of the nonliving cells demonstrating that carboxyl functional groups play an important role in the binding of metals by S. platensis. The desorption rate of Cu(II) and Cd(II) from S. platensis surface was 72.7-80.7% and 53.7-58.0% by EDTA and NH{sub 4}NO{sub 3}, respectively, indicating that ion exchange and complexation are the dominating mechanisms for Cu(II) and Cd(II) adsorption. XAFS analysis provided further evidence on the inner-sphere complexation of Cu by carboxyl ligands and showed that Cu is complexed by two 5-membered chelate rings on S. platensis surface.

  13. Immobilized purified folate-binding protein: binding characteristics and use for quantifying folate in erythrocytes

    International Nuclear Information System (INIS)

    Hansen, S.I.; Holm, J.; Nexo, E.

    1987-01-01

    Purified folate-binding protein from cow's milk was immobilized on monodisperse polymer particles (Dynospheres) activated by rho-toluenesulfonyl chloride. Leakage from the spheres was less than 0.1%, and the binding properties were similar to those of the soluble protein with regard to dissociation, pH optimum for binding pteroylglutamic acid, and specificity for binding various folate derivatives. We used the immobilized folate-binding protein as binding protein in an isotope-dilution assay for quantifying folate in erythrocytes. The detection limit was 50 nmol/L and the CV over a six-month period was 2.3% (means = 1.25 mumol/L, n = 15). The reference interval, for folate measured in erythrocytes of 43 blood donors, was 0.4-1.5 mumol/L

  14. Receptor binding characteristics of tritiated misoprostol free acid in enriched canine parietal cells

    International Nuclear Information System (INIS)

    Tsai, B.S.; Kessler, L.K.; Conway, R.G.; Schoenhard, G.; Stolzenbach, J.; Collins, P.; Kramer, S.; Butchko, G.M.; Bauer, R.F.

    1986-01-01

    Misoprostol (MISO) is a synthetic prostaglandin (PG) E 1 methyl ester with gastric antisecretory and mucosal protective properties. MISO is rapidly de-esterified to misoprostol free acid (MISO-FA) in enriched (65-80%) canine parietal cell preparations. Both forms appear to possess equivalent antisecretory potency and [ 3 H] MISO-FA is stable in these preparations. [ 3 H] MISO-FA binding was reversible and saturable with a maximal number of binding sites estimated at 8138 +/- 1893 per cell. The scatchard plot was linear, indicating a single, high affinity receptor population with a dissociation constant of 11 +/- 2.6 x 10 -9 M. Unlabeled MISO-FA and MISO were equally potent inhibitors [IC 50 , approx. 10 -8 M] of [ 3 H] MISO-FA binding. At 10 -5 M, the dinor and tetranor β-oxidation metabolites of MISO were weak binding inhibitors. Strict stereospecific binding was shown by MISO stereoisomers, and the 11R, 16S isomer was most active. Both PGE 1 and 16,16 dimethyl PGE 2 were potent binding inhibitors, but PGF 1 α (10 -6 M) and Hoe 892 (10 -5 M), a stable PGI 2 analog, were weak inhibitors. Neither histamine or cimetidine competed for binding sites. These data indicate the presence of stereospecific E-type prostaglandin receptors in enriched canine parietal cell preparations

  15. Receptor binding characteristics of tritiated misoprostol free acid in enriched canine parietal cells

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, B.S.; Kessler, L.K.; Conway, R.G.; Schoenhard, G.; Stolzenbach, J.; Collins, P.; Kramer, S.; Butchko, G.M.; Bauer, R.F.

    1986-03-01

    Misoprostol (MISO) is a synthetic prostaglandin (PG) E/sub 1/ methyl ester with gastric antisecretory and mucosal protective properties. MISO is rapidly de-esterified to misoprostol free acid (MISO-FA) in enriched (65-80%) canine parietal cell preparations. Both forms appear to possess equivalent antisecretory potency and (/sup 3/H) MISO-FA is stable in these preparations. (/sup 3/H) MISO-FA binding was reversible and saturable with a maximal number of binding sites estimated at 8138 +/- 1893 per cell. The scatchard plot was linear, indicating a single, high affinity receptor population with a dissociation constant of 11 +/- 2.6 x 10/sup -9/ M. Unlabeled MISO-FA and MISO were equally potent inhibitors (IC/sub 50/, approx. 10/sup -8/M) of (/sup 3/H) MISO-FA binding. At 10/sup -5/ M, the dinor and tetranor ..beta..-oxidation metabolites of MISO were weak binding inhibitors. Strict stereospecific binding was shown by MISO stereoisomers, and the 11R, 16S isomer was most active. Both PGE/sub 1/ and 16,16 dimethyl PGE/sub 2/ were potent binding inhibitors, but PGF/sub 1/..cap alpha.. (10/sup -6/ M) and Hoe 892 (10/sup -5/ M), a stable PGI/sub 2/ analog, were weak inhibitors. Neither histamine or cimetidine competed for binding sites. These data indicate the presence of stereospecific E-type prostaglandin receptors in enriched canine parietal cell preparations.

  16. An immunoglobulin binding protein (antigen 5) of the stable fly (Diptera: Muscidae) salivary gland stimulates bovine immune responses.

    Science.gov (United States)

    Ameri, M; Wang, X; Wilkerson, M J; Kanost, M R; Broce, A B

    2008-01-01

    The stable fly, Stomoxys calcitrans (L.) (Diptera: Muscidae), is an economically important pest of livestock. Previous studies demonstrated lymphocyte suppression by crude salivary gland extract (SGE) of the stable fly. A dominant 27-kDa protein identified in the SGE was reported to stimulate immunodominant antibody responses in exposed cattle. The purpose of this study was to determine whether this protein, now identified as ahomolog of insect proteins named antigen 5 (Ag5), was responsible for the lymphocyte suppression and whether naive calves can mount an immune response to it. Calves raised in the winter were immunized with recombinant Ag5 (rAg5) expressed in Drosophila S2 cells or with "natural" Ag5 protein isolated by preparative gel electrophoresis of SGE. Control calves were immunized with adjuvant alone. Rising antibody concentrations to rAg5 were detected in two of three calves immunized with rAg5 and one of three calves immunized with natural Ag5. Recall lymphocyte responses to rAg5 were detected at 21 and 28 d postimmunization in calves immunized with rAg5 but not in calves immunized with the natural Ag5 or those exposed to adjuvant alone. Mitogen-stimulated bovine lymphocyte responses were not suppressed by rAg5. Further investigation using immunoblotting revealed that rAg5 binds to the Fc and F (ab')2 portions of bovine IgG, but not to an Fab fragment. These findings suggest that Ag5 of the stable fly salivary gland is not immunosuppressive but that it has immunoglobulin binding properties and can invoke specific antibody and memory lymphocyte responses in immunized calves.

  17. Rationale, design, and baseline characteristics of the CLARIFY registry of outpatients with stable coronary artery disease.

    Science.gov (United States)

    Sorbets, Emmanuel; Greenlaw, Nicola; Ferrari, Roberto; Ford, Ian; Fox, Kim M; Tardif, Jean-Claude; Tendera, Michal; Steg, Philippe Gabriel

    2017-10-01

    Despite major advances in prevention and treatment, coronary artery disease (CAD) remains the leading cause of death worldwide. Whereas many sources of data are available on the epidemiology of acute coronary syndromes, fewer datasets reflect the contemporary management and outcomes of stable CAD patients. A worldwide contemporary registry would improve our knowledge about stable CAD. The main objectives are to describe the demographics, clinical profile, contemporary management and outcomes of outpatients with stable CAD; to identify gaps between evidence and treatment; and to investigate long-term prognostic determinants. CLARIFY (ProspeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease) is an ongoing international observational longitudinal registry. Stable CAD patients from 45 countries in Europe, Asia, America, Middle East, Australia and Africa were enrolled between November 2009 and June 2010. The inclusion criteria were previous myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischemia or prior revascularization procedure. The main exclusion criteria were serious non-cardiovascular disease, conditions interfering with life expectancy or severe other cardiovascular disease (including advanced heart failure). Follow-up visits were planned annually for up to 5 years, interspersed with 6-month telephone calls. Of the 32,703 patients enrolled, most (77.6%) were male, age (mean ± SD) was 64.2 ± 10.5 years, and 71.0% were receiving treatment for hypertension; mean ± SD resting heart rate was 68.2 ± 10.6 bpm. Patients were enrolled based on a history of myocardial infarction >3 months earlier (57.7%), having at least one stenosis >50% on coronary angiography (61.1%), proven symptomatic myocardial ischemia on non-invasive testing (23.1%), or history of percutaneous coronary intervention or coronary artery bypass graft (69.8%). Baseline characteristics were similar across the four

  18. A Novel, Highly Stable Fold of the Immunoglobulin Binding Domain of Streptococcal Protein G

    Science.gov (United States)

    Gronenborn, Angela M.; Filpula, David R.; Essig, Nina Z.; Achari, Aniruddha; Whitlow, Marc; Wingfield, Paul T.; Marius Clore, G.

    1991-08-01

    The high-resolution three-dimensional structure of a single immunoglobulin binding domain (B1, which comprises 56 residues including the NH_2-terminal Met) of protein G from group G Streptococcus has been determined in solution by nuclear magnetic resonance spectroscopy on the basis of 1058 experimental restraints. The average atomic root-mean-square distribution about the mean coordinate positions is 0.27 angstrom (overset{circ}{mathrm A}) for the backbone atoms, 0.65 overset{circ}{mathrm A} for all atoms, and 0.39 overset{circ}{mathrm A} for atoms excluding disordered surface side chains. The structure has no disulfide bridges and is composed of a four-stranded β sheet, on top of which lies a long helix. The central two strands (β 1 and β 4), comprising the NH_2- and COOH-termini, are parallel, and the outer two strands (β 2 and β 3) are connected by the helix in a +3x crossover. This novel topology (-1, +3x, -1), coupled with an extensive hydrogen-bonding network and a tightly packed and buried hydrophobic core, is probably responsible for the extreme thermal stability of this small domain (reversible melting at 87^circC).

  19. Insights on Structural Characteristics and Ligand Binding Mechanisms of CDK2

    Directory of Open Access Journals (Sweden)

    Yan Li

    2015-04-01

    Full Text Available Cyclin-dependent kinase 2 (CDK2 is a crucial regulator of the eukaryotic cell cycle. However it is well established that monomeric CDK2 lacks regulatory activity, which needs to be aroused by its positive regulators, cyclins E and A, or be phosphorylated on the catalytic segment. Interestingly, these activation steps bring some dynamic changes on the 3D-structure of the kinase, especially the activation segment. Until now, in the monomeric CDK2 structure, three binding sites have been reported, including the adenosine triphosphate (ATP binding site (Site I and two non-competitive binding sites (Site II and III. In addition, when the kinase is subjected to the cyclin binding process, the resulting structural changes give rise to a variation of the ATP binding site, thus generating an allosteric binding site (Site IV. All the four sites are demonstrated as being targeted by corresponding inhibitors, as is illustrated by the allosteric binding one which is targeted by inhibitor ANS (fluorophore 8-anilino-1-naphthalene sulfonate. In the present work, the binding mechanisms and their fluctuations during the activation process attract our attention. Therefore, we carry out corresponding studies on the structural characterization of CDK2, which are expected to facilitate the understanding of the molecular mechanisms of kinase proteins. Besides, the binding mechanisms of CDK2 with its relevant inhibitors, as well as the changes of binding mechanisms following conformational variations of CDK2, are summarized and compared. The summary of the conformational characteristics and ligand binding mechanisms of CDK2 in the present work will improve our understanding of the molecular mechanisms regulating the bioactivities of CDK2.

  20. Stable isotopic characteristic of Taiwan's precipitation: A case study of western Pacific monsoon region

    Science.gov (United States)

    Peng, Tsung-Ren; Wang, Chung-Ho; Huang, Chi-Chao; Fei, Li-Yuan; Chen, Chen-Tung Arthur; Hwong, Jeen-Lian

    2010-01-01

    The stable oxygen and hydrogen isotopic features of precipitation in Taiwan, an island located at the western Pacific monsoon area, are presented from nearly 3,500 samples collected during the past decade for 20 stations. Results demonstrate that moisture sources from diverse air masses with different isotopic signals are the main parameter in controlling the precipitation's isotope characteristics. The air mass from polar continental (Pc) region contributes the precipitation with high deuterium excess values (up to 23‰) and relatively enriched isotope compositions (e.g., - 3.2‰ for δ 18O) during the winter with prevailing northeasterly monsoon. By contrast, air masses from equatorial maritime (Em) and tropical maritime (Tm) supply the precipitation with low deuterium excess values (as low as about 7‰) and more depleted isotope values (e.g., - 8.9‰ and - 6.0‰ for δ 18O of Tm and Em, respectively) during the summer with prevailing southwesterly monsoon. Thus seasonal differences in terms of δ 18O, δD, and deuterium excess values are primarily influenced by the interactions among various precipitation sources. While these various air masses travel through Taiwan, secondary evaporation effects further modify the isotope characteristics of the inland precipitation, such as raindrop evaporation (reduces the deuterium excess of winter precipitation) and moisture recycling (increases the deuterium excess of summer precipitation). The semi-quantitative estimations in terms of evaluation for changes in the deuterium excess suggest that the raindrop evaporation fractions for winter precipitation range 7% to 15% and the proportions of recycling moisture in summer precipitation are less than 5%. Additionally, the isotopic altitude gradient in terms of δ 18O for summer precipitation is - 0.22‰/100 m, greater than - 0.17‰/100 m of winter precipitation. The greater isotopic gradient in summer can be attributed to a higher temperature vs. altitude gradient

  1. Deciphering the kinetic binding mechanism of dimeric ligands using a potent plasma-stable dimeric inhibitor of postsynaptic density protein-95 as an example

    DEFF Research Database (Denmark)

    Chi, Celestine N; Bach, Anders; Gottschalk, Marie

    2010-01-01

    Dimeric ligands can be potent inhibitors of protein-protein or enzyme-substrate interactions. They have increased affinity and specificity toward their targets due to their ability to bind two binding sites simultaneously and are therefore attractive in drug design. However, few studies have...... addressed the kinetic mechanism of interaction of such bivalent ligands. We have investigated the binding interaction of a recently identified potent plasma-stable dimeric pentapeptide and PDZ1-2 of postsynaptic density protein-95 (PSD-95) using protein engineering in combination with fluorescence...

  2. Analysis of the Global Changes in SH2 Binding Properties Using Mass Spectrometry Supported by Quantitative Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) Technique.

    Science.gov (United States)

    Sobota, Radoslaw M

    2017-01-01

    Quantitative mass spectrometry (MS)-based proteomics enables fast and reliable analysis of protein complexes. Its robustness and sensitivity effectively substitute traditional antibody-based approaches. Here, we describe the combination of mass spectrometry and Stable Isotope Labeling by Amino acids in Cell culture (SILAC) in characterization of the SH2 domain binding capacity.

  3. Stiffness characteristics of compliant three segment leg with the self-stable region in slow and fast running

    Energy Technology Data Exchange (ETDEWEB)

    Kwak, Oh Seok; Ha, Sung Mok; Lee, Dong Ha [Convergence Research Center for WellnessDaegu Gyeongbuk Institute of Science and TechnologyDaegu (Korea, Republic of)

    2016-12-15

    In this paper, we propose the stiffness characteristics of compliant three segment leg that can have a self-stable region in slow and fast running. This proposition can contribute to reducing the control effort and enhancing the locomotion energy efficiency for the compliant three segment legged robot in slow and fast running. Previous research indicated that the running self-stable region of the spring-mass system is located in a relatively fast running region and that of the two segment leg is located in a relatively slow running region. In this paper, we analyze the stiffness characteristics of the spring-mass system and the two segment leg to explain the previous research results. From this analysis, we propose the stiffness characteristics of the compliant three segment leg with a self-stable region in slow and fast running. We further design the compliant three segment leg based on this proposition and check its structural stability. We examine the running self-stable region of this compliant three segment leg to determine whether it has a self-stable region in slow and fast running. We also examine the walking self-stable region of this compliant three segment leg.

  4. Insulin binding characteristics in canine muscle tissue: effects of the estrous cycle phases

    Directory of Open Access Journals (Sweden)

    Álan G. Pöppl

    Full Text Available Abstract: Hormonal fluctuations during the different estrous cycle are a well-recognized cause of insulin resistance in bitches, and little is known about insulin receptor binding or post-binding defects associated with insulin resistance in dogs. To evaluate insulin binding characteristics in muscle tissue of bitches during the estrous cycle, 17 owned bitches were used in the study (six in anestrus, five in estrus, and six in diestrus. An intravenous glucose tolerance test (IVGTT was performed in all patients by means of injection of 1mL/kg of a glucose 50% solution (500mg/kg, with blood sample collection for glucose determination at 0, 3, 5, 7, 15, 30, 45 and 60 minutes after glucose infusion. Muscle samples, taken after spaying surgery, were immediately frozen in liquid nitrogen and then stored at -80 ºC until the membranes were prepared by sequential centrifugation after being homogenized. For binding studies, membranes were incubated in the presence of 20,000cpm of human 125I-insulin and in increasing concentrations of unlabeled human regular insulin for cold saturation. The IVGTT showed no differences among bitches during the estrous cycle regarding baseline glycemia or glycemic response after glucose infusion. Two insulin binding sites - high-affinity and low-affinity ones - were detected by Scatchard analysis, and significant statistical differences were observed in the dissociation constant (Kd1 and maximum binding capacity (Bmax1 of the high-affinity binding sites. The Kd1 for the anestrus group (6.54±2.77nM/mg of protein was smaller (P<0.001 than for the estrus (28.54±6.94nM/mg of protein and diestrus (15.56±3.88nM/mg of protein groups. Bmax1 in the estrus (0.83±0.42nM/mg of protein and diestrus (1.24±0.24nM/mg of protein groups were also higher (P<0.001 than the values observed in anestrus (0.35±0.06nM/mg of protein. These results indicate modulation of insulin binding characteristics during different phases of the estrous

  5. Duplex structural differences and not 2′-hydroxyls explain the more stable binding of HIV-reverse transcriptase to RNA-DNA versus DNA-DNA

    OpenAIRE

    Olimpo, Jeffrey T.; DeStefano, Jeffrey J.

    2010-01-01

    Human immunodeficiency virus reverse transcriptase (HIV-RT) binds more stably in binary complexes with RNA–DNA versus DNA–DNA. Current results indicate that only the -2 and -4 RNA nucleotides (-1 hybridized to the 3′ recessed DNA base) are required for stable binding to RNA–DNA, and even a single RNA nucleotide conferred significantly greater stability than DNA–DNA. Replacing 2′- hydroxyls on pivotal RNA bases with 2′-O-methyls did not affect stability, indicating that interactions between hy...

  6. Human corpus luteum: presence of epidermal growth factor receptors and binding characteristics

    International Nuclear Information System (INIS)

    Ayyagari, R.R.; Khan-Dawood, F.S.

    1987-01-01

    Epidermal growth factor receptors are present in many reproductive tissues but have not been demonstrated in the human corpus luteum. To determine the presence of epidermal growth factor receptors and its binding characteristics, we carried out studies on the plasma cell membrane fraction of seven human corpora lutea (days 16 to 25) of the menstrual cycle. Specific epidermal growth factor receptors were present in human corpus luteum. Insulin, nerve growth factor, and human chorionic gonadotropin did not competitively displace epidermal growth factor binding. The optimal conditions for corpus luteum-epidermal growth factor receptor binding were found to be incubation for 2 hours at 4 degrees C with 500 micrograms plasma membrane protein and 140 femtomol 125 I-epidermal growth factor per incubate. The number (mean +/- SEM) of epidermal growth factor binding sites was 12.34 +/- 2.99 X 10(-19) mol/micrograms protein; the dissociation constant was 2.26 +/- 0.56 X 10(-9) mol/L; the association constant was 0.59 +/- 0.12 X 10(9) L/mol. In two regressing corpora lutea obtained on days 2 and 3 of the menstrual cycle, there was no detectable specific epidermal growth factor receptor binding activity. Similarly no epidermal growth factor receptor binding activity could be detected in ovarian stromal tissue. Our findings demonstrate that specific receptors for epidermal growth factor are present in the human corpus luteum. The physiologic significance of epidermal growth factor receptors in human corpus luteum is unknown, but epidermal growth factor may be involved in intragonadal regulation of luteal function

  7. Protein binding characteristics and pharmacokinetics of ceftriaxone in intensive care unit patients.

    Science.gov (United States)

    Schleibinger, Michael; Steinbach, Cathérine L; Töpper, Christoph; Kratzer, Alexander; Liebchen, Uwe; Kees, Frieder; Salzberger, Bernd; Kees, Martin G

    2015-09-01

    The aim of the present study was to assess the pharmacokinetics of total and unbound ceftriaxone in intensive care unit (ICU) patients and its protein binding characteristics. Twenty patients (m/f 15/5, age 25-86 years, body weight 60-121 kg, APACHE II 7-40, estimated glomerular filtration rate 19-157 ml min(-1) , albumin 11.7-30.1 g l(-1) , total bilirubin ICU patients (33.0%; 20.2-44.5%) than reported in healthy volunteers, particularly when renal impairment or severe hyperbilirubinaemia was present. In all patients, unbound concentrations during treatment with ceftriaxone 2 g once daily remained above the EUCAST susceptibility breakpoint (≤1 mg l(-1) ) throughout the whole dosing interval. Protein binding of ceftriaxone is reduced and variable in ICU patients due to hypoalbuminaemia, but also to altered binding characteristics. Despite these changes, the pharmacokinetics of unbound ceftriaxone is governed by renal function. For patients with normal or reduced renal function, standard doses are sufficient. © 2015 The British Pharmacological Society.

  8. β-Amyloid binding in elderly subjects with declining or stable episodic memory function measured with PET and [{sup 11}C]AZD2184

    Energy Technology Data Exchange (ETDEWEB)

    Mattsson, Patrik [Karolinska Institutet, Centre for Psychiatry Research, Department of Clinical Neuroscience, Stockholm (Sweden); Karolinska University Hospital, Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm (Sweden); Forsberg, Anton; Halldin, Christer [Karolinska Institutet, Centre for Psychiatry Research, Department of Clinical Neuroscience, Stockholm (Sweden); Persson, Jonas; Nilsson, Lars-Goeran [Karolinska Institute and Stockholm University, Aging Research Center (ARC), Stockholm (Sweden); Nyberg, Lars [Umeaa University, Department of Radiation Sciences (Diagnostic Radiology), Umeaa (Sweden); Farde, Lars [Karolinska Institutet, Centre for Psychiatry Research, Department of Clinical Neuroscience, Stockholm (Sweden); AstraZeneca Translational Science Center at Karolinska Institutet, Stockholm (Sweden)

    2015-09-15

    Cognitive decline has been suggested as an early marker for later onset of Alzheimer's disease. We therefore explored the relationship between decline in episodic memory and β-amyloid using positron emission tomography (PET) and [{sup 11}C]AZD2184, a radioligand with potential to detect low levels of amyloid deposits. Healthy elderly subjects with declining (n = 10) or stable (n = 10) episodic memory over 15 years were recruited from the population-based Betula study and examined with PET. Brain radioactivity was measured after intravenous administration of [{sup 11}C]AZD2184. The binding potential BP{sub ND} was calculated using linear graphical analysis with the cerebellum as reference region. The binding of [{sup 11}C]AZD2184 in total grey matter was generally low in the declining group, whereas some binding could be observed in the stable group. Mean BP{sub ND} was significantly higher in the stable group compared to the declining group (p = 0.019). An observation was that the three subjects with the highest BP{sub ND} were ApoE ε4 allele carriers. We conclude that cognitive decline in the general population does not seem to stand by itself as an early predictor for amyloid deposits. (orig.)

  9. β-Amyloid binding in elderly subjects with declining or stable episodic memory function measured with PET and [11C]AZD2184

    International Nuclear Information System (INIS)

    Mattsson, Patrik; Forsberg, Anton; Halldin, Christer; Persson, Jonas; Nilsson, Lars-Goeran; Nyberg, Lars; Farde, Lars

    2015-01-01

    Cognitive decline has been suggested as an early marker for later onset of Alzheimer's disease. We therefore explored the relationship between decline in episodic memory and β-amyloid using positron emission tomography (PET) and [ 11 C]AZD2184, a radioligand with potential to detect low levels of amyloid deposits. Healthy elderly subjects with declining (n = 10) or stable (n = 10) episodic memory over 15 years were recruited from the population-based Betula study and examined with PET. Brain radioactivity was measured after intravenous administration of [ 11 C]AZD2184. The binding potential BP ND was calculated using linear graphical analysis with the cerebellum as reference region. The binding of [ 11 C]AZD2184 in total grey matter was generally low in the declining group, whereas some binding could be observed in the stable group. Mean BP ND was significantly higher in the stable group compared to the declining group (p = 0.019). An observation was that the three subjects with the highest BP ND were ApoE ε4 allele carriers. We conclude that cognitive decline in the general population does not seem to stand by itself as an early predictor for amyloid deposits. (orig.)

  10. Characteristics of stable chronic obstructive pulmonary disease patients in the pulmonology clinics of seven Asian cities

    Directory of Open Access Journals (Sweden)

    Oh YM

    2013-01-01

    Full Text Available Yeon-Mok Oh,1 Arvind B Bhome,2 Watchara Boonsawat,3 Kirthi Dias Gunasekera,4 Dushantha Madegedara,5 Luisito Idolor,6 Camilo Roa,6 Woo Jin Kim,7 Han-Pin Kuo,8 Chun-Hua Wang,8 Le Thi Tuyet Lan,9 Li-Cher Loh,10 Choo-Khoon Ong,10 Alan Ng,11 Masaharu Nishimura,12 Hironi Makita,12 Edwin K Silverman,13 Jae Seung Lee,1 Ting Yang,14 Yingxiang Lin,14 Chen Wang,14 Sang-Do Lee1  1Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 2Department of Pulmonary and Critical Care, "Friends of the Breathless" Foundation, Pune, India; 3Department of Medicine, Khon Kaen University, Khon Kaen, Thailand; 4Central Chest Clinic, Colombo and National Hospital of Sri Lanka; 5Respiratory Disease Treatment Unit and Teaching Hospital Kandy, Sri Lanka; 6Section of Respiratory Services and Physical Therapy and Rehabilitation Lung Center of the Philippines, Quezon City, Philippines; 7Department of Internal Medicine, Kangwon National University, Kang Won, Korea; 8Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; 9Respiratory Care Center, University Medical Center Ho Chi Minh City, Vietnam; 10Department of Medicine, Penang Medical College, Penang, Malaysia; 11Department of Respiratory and Critical Care Medicine, Tan Tock Seng Hospital, Singapore; 12Division of Respiratory Medicine, Department of Internal Medicine, Hokkaido University Hospital, Sapporo, Japan; 13Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; 14Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaAll authors made an equal contribution to this studyBackground and objectives: Chronic obstructive pulmonary disease (COPD is responsible for significant morbidity and mortality worldwide. We evaluated the characteristics of stable COPD patients in

  11. Binding characteristics of arylamine, o-toluidine, in rodent blood proteins, hemoglobin and albumin

    International Nuclear Information System (INIS)

    DeBord, D.G.; Swearengin, T.F.; Booth-Jones, A.B.; Wissinger, L.A.

    1991-01-01

    o-Toluidine (OT), an arylamine used as an anti-oxidant in the tire and rubber industry, is a suspect human carcinogen. In order to develop a method for biological monitoring of OT, the authors have examined the binding characteristics of OT to the blood proteins, albumin (Alb) and hemoglobin (Hb). Male Sprague-Dawley rats were treated with 10, 20, 40, 50, or 100 mg/kg [ 14 C0]-OT ip and terminated at 2, 4, 8, 18, or 24 hrs. Alb and Hb were isolated from the blood. OT binding was determined by radioactivity associated with Alb and Hb. Maximum OT binding occurred at 4 hrs for Alb and 24 hrs for Hb. The radioactivity associated with Alb was 2x greater than that associated with Hb at 4 hrs, and approximately 30% greater at 24 hrs. Similar OT binding to Alb was observed at the 50 and 100 mg/kg doses, while for Hb maximum binding was seen at 100 mg/kg. Extended time points were studied to determine which blood protein would be more useful for biological monitoring purposes. Rats were treated with 100 mg/kg bw [ 14 C]-OT and terminated at 1, 2 and 4 wks. The remaining radioactivity associated with Alb was 12% after 1 wk, and < 2% after 2 and 4 wks. Conversely, the radioactivity associated with Hb was 64% after 1 wk, 52% by 2 wks, and 24% by 4 wks. These results suggest that Hb may be more useful than Alb as a biological monitoring tool for OT

  12. Different characteristics and nucleotide binding properties of inosine monophosphate dehydrogenase (IMPDH isoforms.

    Directory of Open Access Journals (Sweden)

    Elaine C Thomas

    Full Text Available We recently reported that Inosine Monophosphate Dehydrogenase (IMPDH, a rate-limiting enzyme in de novo guanine nucleotide biosynthesis, clustered into macrostructures in response to decreased nucleotide levels and that there were differences between the IMPDH isoforms, IMPDH1 and IMPDH2. We hypothesised that the Bateman domains, which are present in both isoforms and serve as energy-sensing/allosteric modules in unrelated proteins, would contribute to isoform-specific differences and that mutations situated in and around this domain in IMPDH1 which give rise to retinitis pigmentosa (RP would compromise regulation. We employed immuno-electron microscopy to investigate the ultrastructure of IMPDH macrostructures and live-cell imaging to follow clustering of an IMPDH2-GFP chimera in real-time. Using a series of IMPDH1/IMPDH2 chimera we demonstrated that the propensity to cluster was conferred by the N-terminal 244 amino acids, which includes the Bateman domain. A protease protection assay suggested isoform-specific purine nucleotide binding characteristics, with ATP protecting IMPDH1 and AMP protecting IMPDH2, via a mechanism involving conformational changes upon nucleotide binding to the Bateman domain without affecting IMPDH catalytic activity. ATP binding to IMPDH1 was confirmed in a nucleotide binding assay. The RP-causing mutation, R224P, abolished ATP binding and nucleotide protection and this correlated with an altered propensity to cluster. Collectively these data demonstrate that (i the isoforms are differentially regulated by AMP and ATP by a mechanism involving the Bateman domain, (ii communication occurs between the Bateman and catalytic domains and (iii the RP-causing mutations compromise such regulation. These findings support the idea that the IMPDH isoforms are subject to distinct regulation and that regulatory defects contribute to human disease.

  13. Side Fenestrations Provide an "Anchor" for a Stable Binding of A1899 to the Pore of TASK-1 Potassium Channels.

    Science.gov (United States)

    Ramírez, David; Arévalo, Bárbara; Martínez, Gonzalo; Rinné, Susanne; Sepúlveda, Francisco V; Decher, Niels; González, Wendy

    2017-07-03

    A1899 is a potent and selective inhibitor of the two-pore domain potassium (K 2P ) channel TASK-1. It was previously reported that A1899 acts as an open-channel blocker and binds to residues of the P1 and P2 regions, the M2 and M4 segments, and the halothane response element. The recently described crystal structures of K 2P channels together with the newly identified side fenestrations indicate that residues relevant for TASK-1 inhibition are not purely facing the central cavity as initially proposed. Accordingly, the TASK-1 binding site and the mechanism of inhibition might need a re-evaluation. We have used TASK-1 homology models based on recently crystallized K 2P channels and molecular dynamics simulation to demonstrate that the highly potent TASK-1 blocker A1899 requires binding to residues located in the side fenestrations. Unexpectedly, most of the previously described residues that interfere with TASK-1 blockade by A1899 project their side chains toward the fenestration lumina, underlining the relevance of these structures for drug binding in K 2P channels. Despite its hydrophobicity, A1899 does not seem to use the fenestrations to gain access to the central cavity from the lipid bilayer. In contrast, binding of A1899 to residues of the side fenestrations might provide a physical "anchor", reflecting an energetically favorable binding mode that after pore occlusion stabilizes the closed state of the channels.

  14. [Characteristics of soil water movement using stable isotopes in red soil hilly region of northwest Hunan].

    Science.gov (United States)

    Tian, Ri-Chang; Chen, Hong-Song; Song, Xian-Fang; Wang, Ke-Lin; Yang, Qing-Qing; Meng, Wei

    2009-09-15

    Stable isotope techniques provide a new approach to study soil water movement. The process of water movement in soils under two kinds of plant types (oil tea and corn) were studied based on the observed values of hydrogen and oxygen isotopes of precipitation and soil water at different depths in red-soil sloping land. The results showed that stable isotopes of precipitation in this area had obvious seasonal effect and rainfall effect. The stable isotopes at 0-50 cm depth in oil tea forestland and at 0-40 cm depth in corn cropland increased with the increase in depth, respectively, but they had the opposite tendency after rainfall in arid time. The stable isotopes decreased with the increase in depth below 50 cm depth in oil tea forestland and below 40 cm depth in corn cropland where evaporation influence was weak. The infiltrate rate of soil in oil tea land was affected by precipitation obviously, and it was about 50-100 mm/d after 2-3 days in heavy rain, slowed sharply later, and soil water at 50 cm depth often became a barrier layer. The permeability of soil in corn land was poor and the infiltration rate was lower. The change of stable isotopes in soil water in red soil hilly region was mainly affected by the mixing water which was formed by the antecedent precipitation, and evaporation effect took the second place. The evaporation intensity in oil tea land was lower than that in corn land, but the evaporation depth was higher.

  15. An analysis of the binding characteristics of a panel of recently selected ICAM-1 binding Plasmodium falciparum patient isolates

    DEFF Research Database (Denmark)

    Madkhali, Aymen M; Alkurbi, Mohammed O; Szestak, Tadge

    2014-01-01

    patterns of lab-adapted patient isolates after selecting on ICAM-1. We investigated the binding phenotypes using variant ICAM-1 proteins including ICAM-1Ref, ICAM-1Kilifi, ICAM-1S22/A, ICAM-1L42/A and ICAM-1L44/A using static assays. The study also examined ICAM-1 blocking by four anti-ICAM-1 monoclonal...... antibodies (mAb) under static conditions. We also characterised the binding phenotypes using Human Dermal Microvascular Endothelial Cells (HDMEC) under flow conditions. The results show that different isolates have variant-specific binding phenotypes under both static and flow conditions, extending our...

  16. Study on insulin receptor binding characteristics of insulin-IUdR

    International Nuclear Information System (INIS)

    Ou Xiaohong; Kuang Anren; Liang Zhenglu; Peng Xian; Zhong Yuguo

    2002-01-01

    Objective: It has been reported that several kinds of tumors express increased insulin receptors and the molecule of insulin can be internalized in cells and enter the nuclei through the mediation of the insulin receptor. The authors investigated the receptor binding characteristics of insulin-IUdR for the possibility of using insulin as carriers for carcinoma targeted therapy by receptor mediation. Methods: IUdR (idoxuridine) was covalently linked to insulin using the bifunctional reagent succinic acid. The insulin-IUdR conjugate was purified by polyacrylamide agarose gel electrophoresis. The human hepatocellular carcinoma specimens confirmed histologically were obtained from patients at surgery and immediately frozen under -80 degree C. Cell membrane fractions were isolated by sucrose density gradient centrifugation. Competitive displacement of 125 I-insulin with insulin and insulin-IUdR binding to the insulin receptor were carried out. Values of IC 50 and KI were calculated to observe the characteristics of insulin-IUdR binding to the insulin receptor. Results: Insulin-IUdR competed as effectively as insulin with 125 I-insulin for binding to insulin receptors. The values of IC 50 1 and IC 50 2 for insulin-IUdR were (11.50 +- 2.83) nmol/L and (19.35 +- 5.11) nmol/L, respectively; the values of KI1 and KI2 for insulin-IUdR were (11.26 +- 2.65) nmol/L and (19.30 +- 5.02) nmol/L, respectively, while values of IC 50 1 and IC 50 2 for insulin were (5.01 +- 1.24) nmol/L and (17.75 +- 4.86) nmol/L, respectively. The values of KI1 and KI2 for insulin were (4.85 +- 1.12) nmol/L and (17.69 +- 4.81) nmol/L, respectively. Conclusions: Insulin-IUdR could bind with the insulin receptor with high affinity. The result shows that there is a possibility of using insulin as carriers for carcinoma targeted therapy through receptor mediation

  17. Geochemical and stable isotope characteristics of urban heavy rain in the downtown of Tokyo, Japan

    Science.gov (United States)

    Uchiyama, Ryunosuke; Okochi, Hiroshi; Ogata, Hiroko; Katsumi, Naoya; Asai, Daisuke; Nakano, Takanori

    2017-09-01

    In order to make clear the impact of air pollution on the formation of sudden and locally-distributed heavy rain in urban area (hereafter Urban Heavy Rain: UHR), we analyzed inorganic ion concentration and stable isotope ratio of water (δD and δ18O) in rainwater. Rainwater samples were collected in Shinjuku, which is a representative downtown of Tokyo, Japan, during four years from October 2012 to December 2015. The concentration and wet deposition fluxes of acidic components (H+, NH4+, NO3-, and nss-SO42 -) in UHR were especially higher than those in other types of rain events, i.e. normal rain, typhoon heavy rain, and frontal heavy rain. UHR had distinctly lower stable isotope ratios than those in other urban rains with same rainfall amount and summer precipitation systems. There was a high negative correlation between δ18O and the distances from the sampling point to the formation area of UHR within 10 km, while there were high positive correlations between δ18O and the concentration of acidic components in UHR. These findings indicate that UHR could effectively scavenge acidic substances within cloud and suggest the use of stable isotope ratios as tracers of an urban heavy rain's water and in-cloud scavenging process.

  18. Design and synthesis of a stable oxidized phospholipid mimic with specific binding recognition for macrophage scavenger receptors

    DEFF Research Database (Denmark)

    Turner, William W; Hartvigsen, Karsten; Boullier, Agnes

    2012-01-01

    Macrophage scavenger receptors appear to play a major role in the clearance of oxidized phospholipid (OxPL) products. Discrete peptide-phospholipid conjugates with the phosphatidylcholine headgroup have been shown to exhibit binding affinity for these receptors. We report the preparation of a water...

  19. Characteristics of the turbulence in the stable boundary layer over complex terrain of the Loess Plateau, China

    Science.gov (United States)

    Liang, J.; Zhang, L.; Yuan, G.

    2017-12-01

    Accurate determination of surface turbulent fluxes in a stable boundary layer is of great practical importance in weather prediction and climate simulations, as well as applications related to air pollution. To gain an insight into the characteristics of turbulence in a stable boundary layer over the complex terrain of the Loess Plateau, we analyzed the data from the Semi-Arid Climate and Environment Observatory of Lanzhou University (SACOL). We proposed a method to identify and efficiently isolate nonstationary motions from turbulence series, and examined the characteristics of nonstationary motions (nonstationary motions refer to gusty events on a greater scale than local shear-generated turbulence). The occurrence frequency of nonstationary motions was found to depend on the mean flow, being more frequent in weak wind conditions and vanishing when the wind speed, U, was greater than 3.0 m s-1. When U exceeded the threshold value of 1.0 m s-1 for the gradient Richardson number Ri ≤ 0.3 and 1.5 m s-1 for Ri > 0.3, local shear-generated turbulence depended systematically on U with an average rate of 0.05 U. However, for the weak wind condition, neither the mean wind speed nor the stability was an important factor for local turbulence. Under the weak wind stable condition, affected by topography-induced nonstationary motions, the local turbulence was anisotropic with a strong horizontal fluctuation and a weak vertical fluctuation, resulting in weakened heat mixing in the vertical direction and stronger un-closure of energy. These findings accessed the validity of similarity theory in the stable boundary layer over complex terrain, and revealed one reason for the stronger un-closure of energy in the night.

  20. Comparison of weak-wind characteristics across different Surface Types in stable stratification

    Science.gov (United States)

    Freundorfer, Anita; Rehberg, Ingo; Thomas, Christoph

    2017-04-01

    Atmospheric transport in weak winds and very stable conditions is often characterized by phenomena collectively referred to as submeso motions since their time and spatial scales exceed those of turbulence, but are smaller than synoptic motions. Evidence is mounting that submeso motions invalidate models for turbulent dispersion and diffusion since their physics are not captured by current similarity theories. Typical phenomena in the weak-wind stable boundary layer include meandering motions, quasi two-dimensional pancake-vortices or wavelike motions. These motions may be subject to non-local forcing and sensitive to small topographic undulations. The invalidity of Taylor's hypothesis of frozen turbulence for submeso motions requires the use of sensor networks to provide observations in both time and space domains simultaneously. We present the results from the series of Advanced Resolution Canopy Flow Observations (ARCFLO) experiments using a sensor network consisting of 12 sonic anemometers and 12 thermohygrometers. The objective of ARCFLO was to observe the flow and the turbulent and submeso transport at a high spatial and temporal resolution at 4 different sites in the Pacific Northwest, USA. These sites represented a variable degree of terrain complexity (flat to mountainous) and vegetation architecture (grass to forest, open to dense). In our study, a distinct weak-wind regime was identified for each site using the threshold velocity at which the friction velocity becomes dependent upon the mean horizontal wind speed. Here we used the scalar mean of the wind speed because the friction velocity showed a clearer dependence on the scalar mean compared to the vector mean of the wind velocity. It was found that the critical speed for the weak wind regime is higher in denser vegetation. For an open agricultural area (Botany and Plant Pathology Farm) we found a critical wind speed of v_crit= (0.24±0.05) ms-1 while for a very dense forest (Mary's River Douglas Fir

  1. Fusion of a xylan-binding module to gluco-oligosaccharide oxidase increases activity and promotes stable immobilization.

    Directory of Open Access Journals (Sweden)

    Thu V Vuong

    Full Text Available The xylan-binding module Clostridium thermocellum CBM22A was successfully fused to a gluco-oligosaccharide oxidase, GOOX-VN, from Sarocladium strictum via a short TP linker, allowing the fused protein to effectively bind different xylans. The presence of the CtCBM22A at the N-terminal of GOOX-VN increased catalytic activity on mono- and oligo-saccharides by 2-3 fold while not affecting binding affinity to these substrates. Notably, both GOOX-VN and its CBM fusion also showed oxidation of xylo-oligosaccharides with degrees of polymerization greater than six. Whereas fusion to CtCBM22A did not alter the thermostability of GOOX-VN or reduce substrate inhibition, CtCBM22A_GOOX-VN could be immobilized to insoluble oat spelt xylan while retaining wild-type activity. QCM-D analysis showed that the fused enzyme remained bound during oxidation. These features could be harnessed to generate hemicellulose-based biosensors that detect and quantify the presence of different oligosaccharides.

  2. Some Characteristics of Good Adjustment Observed in Emotionally Stable, Highly Productive Managers.

    Science.gov (United States)

    Cangemi, Joseph P.; Kowalski, Cash J.

    1986-01-01

    Describes 21 characteristics of a good manager, including: confidence with knowledge of personal limitations, responsible, decisive and principled, motivated in regard to life and work, handles stress effectively, intuitive, learns from mistakes, always learning, caring, empathetic, believes in people, has helpful attitude, strives towards goals,…

  3. Atmospherically stable nanoscale zero-valent iron particles formed under controlled air contact: characteristics and reactivity.

    Science.gov (United States)

    Kim, Hong-Seok; Ahn, Jun-Young; Hwang, Kyung-Yup; Kim, Il-Kyu; Hwang, Inseong

    2010-03-01

    Atmospherically stable NZVI (nanoscale zero-valent iron) particles were produced by modifying shell layers of Fe(H2) NZVI particles (RNIP-10DS) by using a controlled air contact method. Shell-modified NZVI particles were resistant to rapid aerial oxidation and were shown to have TCE degradation rate constants that were equivalent to 78% of those of pristine NZVI particles. Fe(H2) NZVI particles that were vigorously contacted with air (rapidly oxidized) showed a substantially compromised reactivity. Aging of shell-modified particles in water for one day resulted in a rate increase of 54%, implying that depassivation of the shell would play an important role in enhancing reactivity. Aging of shell-modified particles in air led to rate decreases by 14% and 46% in cases of one week and two months of aging, respectively. A series of instrumental analyses using transmission electron microscopy, X-ray diffractography, X-ray photoelectron spectroscopy, and X-ray absorption near-edge structure showed that the shells of modified NZVI particles primarily consisted of magnetite (Fe(3)O(4)). Analyses also implied that the new magnetite layer produced during shell modification was protective against shell passivation. Aging of shell-modified particles in water yielded another major mineral phase, goethite (alpha-FeOOH), whereas aging in air produced additional shell phases such as wustite (FeO), hematite (alpha-Fe(2)O(3)), and maghemite (gamma-Fe(2)O(3)).

  4. Characteristics of a stable arc based on FAST and MIRACLE observations

    Directory of Open Access Journals (Sweden)

    P. Janhunen

    2000-02-01

    Full Text Available A stable evening sector arc is studied using observations from the FAST satellite at 1250 km altitude and the MIRACLE ground-based network, which contains all-sky cameras, coherent radars (STARE, and magnetometers. Both FAST and STARE observe a northward electric field region of about 200 km width and a field magnitude of about 50 mV/m southward of the arc, which is a typical signature for an evening-sector arc. The field-aligned current determined from FAST electron and magnetometer data are in rather good agreement within the arcs. Outside the arcs, the electron data misses the current carriers of the downward FAC probably because it is mainly carried by electrons of smaller energy than the instrument threshold. Studying the westward propagation speed of small undulations associated with the arc using the all-sky cameras gives a velocity of about 2 km/s. This speed is higher than the background ionospheric plasma speed (about 1 km/s, but it agrees rather well with the idea originally proposed by Davis that the undulations reflect an E × B motion in the acceleration region. The ground magnetograms indicate that the main current flows slightly south of the arc. Computing the ionospheric conductivity from FAST electron data and using the ground magnetograms to estimate the current yields an ionospheric electric field pattern, in rather good agreement with FAST results.Key words: Ionosphere (auroral ionosphere; ionosphere-magnetosphere interactions - Magnetospheric physics (auroral phenomena

  5. Stable detonation characteristics of premixed C2H4/O2 gas in narrow gaps

    Science.gov (United States)

    Zhu, Yuejin; Pan, Zhenhua; Zhang, Penggang; Pan, Jianfeng

    2017-09-01

    The detonation initiation and propagation characteristics of premixed gas in a confined channel are greatly influenced by some external factors, such as the channel size and the initial pressure. The influences of different gap height and initial pressure of stoichiometric C2H4/O2 combustible premixed gas on the detonation characteristics were investigated using the self-made narrow gaps. The flame propagation processes were captured by the high-speed photography and the detonation trajectories were recorded by the soot-foil technology. The results show that the gap height is found to be proportional to P0^{ - 1.493} of the dividing lines, which are used to distinguish the three different detonation states. The detonation initiation process can be accelerated by either decreasing the gap height or increasing the initial pressure. Furthermore, the detonation velocity deficit is closely related to the gap height and the initial pressure, and the relation can be expressed as dV ∝ H^{ - 0.8} P0^{ - 0.5}.

  6. Altered combustion characteristics of metallized energetics due to stable secondary material inclusion

    Science.gov (United States)

    Terry, Brandon C.

    Though metals and metalloids have been widely considered as reactive fuels, the ability to tune their ignition and combustion characteristics remains challenging. One means to accomplish this may be through low-level inclusion of secondary materials into the metallized fuel. While there are several potential methods to stably introduce secondary inclusion materials, this work focuses on the use of mechanical activation (MA) and metal alloys. Recent work has shown that low-level inclusion of fluoropolymers into aluminum particles can have a substantial effect on their combustion characteristics. The reflected shock ignition of mechanically activated aluminum/polytetrafluoroethylene (MA Al/PTFE) is compared to a physical mixture (PM) of Al/PTFE, neat spherical aluminum, and flake aluminum. It was found that the powders with higher specific surface areas ignited faster than the spherical particles of the same size, and had ignition delay times comparable to agglomerates of aluminum particles that were two orders of magnitude smaller in size. Flake aluminum powder had the same ignition delay as MA Al/PTFE, indicating that any initial aluminum/fluoropolymer reactions did not yield an earlier onset of aluminum oxidation. However, MA Al/PTFE did have a shorter total burn time. The PM of Al/PTFE powder had a shorter ignition delay than neat spherical aluminum due to the rapid decomposition of PTFE into reactive fluorocarbon compounds, but the subsequent fluorocarbon reactions also created a secondary luminosity profile that significantly increased the total burn time of the system. The explosive shock ignition of aluminum and aluminum-silicon eutectic alloy compacts was evaluated with and without polymer inclusions. A statistical analysis was completed, investigating the effects of: detonation train orientation (into or not into a hard surface); the high explosive driver; whether the metal/polymer system is mechanically activated; particle size; particle morphology

  7. Determination of mixing characteristics of the river Kabul and the river Indus using physico-chemical and stable isotope parameters

    International Nuclear Information System (INIS)

    Qureshi, R.M.; Hussain, Q.M.; Sajjad, M.I.; Hussain, S.D.; Latif, Z.

    1990-11-01

    This report presents a comparative study on the usefulness of stable isotope parameters (hydrogen and oxygen) versus the physico-chemical parameters (electrical conductivity, temperature, pH value) of water to determine the extent of mixing of the river Kabul with the river Indus near Attock. In view of the sampling techniques employed in the present investigations, electrical conductivity and temperature are found to be the best field parameters for a quick estimate of mixing path length. However, the stable isotopes of the water molecule, due to their greater sensitivity and measuring accuracy, provide a better scenario of mixing characteristics as compared to the physico-chemical parameters. It appears that under normal flow condition, it takes about 5 km channel distance for complete mixing of the Kabul river water in the Indus river channel. A computer code MIXABC is developed to determine the percentage contribution of one river water along a mixing channel in the other river. Details of the source programs are presented. The code can be used on any IBM-compatible microsystem. (author)

  8. Stable Binding of Alternative Protein-enriched Food Matrices with Concentrated Cranberry Bioflavonoids for Functional Food Applications

    Science.gov (United States)

    Grace, Mary H.; Guzman, Ivette; Roopchand, Diana E.; Moskal, Kristin; Cheng, Diana M.; Pogrebnyak, Natasha; Raskin, Ilya; Howell, Amy; Lila, Mary Ann

    2013-01-01

    Defatted soy flour (DSF), soy protein isolate (SPI), hemp protein isolate (HPI), medium roast peanut flour (MPF) and pea protein isolate (PPI) stably bind and concentrate cranberry (CB) polyphenols, creating protein/polyphenol-enriched matrices. Proanthocyanidins (PAC) in the enriched matrices ranged from 20.75 mg/g (CB-HPI) to 10.68 mg/g (CB-SPI). Anthocyanins (ANC) ranged from 3.19 mg/g (CB-DSF) to 1.68 mg/g (CB-SPI), while total phenolics (TP) ranged from 37.61 mg/g (CB-HPI) to 21.29 mg/g (CB-SPI). LC-MS indicated that the enriched matrices contained all identifiable ANC, PAC and flavonols present in CB juice. Complexation with SPI stabilized and preserved the integrity of the CB polyphenolic components for at least 15 weeks at 37 °C. PAC isolated from enriched matrices demonstrated comparable anti-adhesion bioactivity to PAC isolated directly from CB juice (MIC 0.4 to 0.16 mg/mL), indicating their potential utility for maintenance of urinary tract health. Approximately 1.0 g of polyphenol-enriched matrix delivered the same amount of PAC available in one cup (300 mL) of commercial CB juice cocktail; which has been shown clinically to be the prophylactic dose for reducing recurring urinary tract infections. CB-SPI inhibited gram- positive and gram-negative bacterial growth. Nutritional and sensory analyses indicated that the targeted CB-matrix combinations have high potential for incorporation in functional food formulations. PMID:23786629

  9. Kv3.3 Channels Bind Hax-1 and Arp2/3 to Assemble a Stable Local Actin Network that Regulates Channel Gating.

    Science.gov (United States)

    Zhang, Yalan; Zhang, Xiao-Feng; Fleming, Matthew R; Amiri, Anahita; El-Hassar, Lynda; Surguchev, Alexei A; Hyland, Callen; Jenkins, David P; Desai, Rooma; Brown, Maile R; Gazula, Valeswara-Rao; Waters, Michael F; Large, Charles H; Horvath, Tamas L; Navaratnam, Dhasakumar; Vaccarino, Flora M; Forscher, Paul; Kaczmarek, Leonard K

    2016-04-07

    Mutations in the Kv3.3 potassium channel (KCNC3) cause cerebellar neurodegeneration and impair auditory processing. The cytoplasmic C terminus of Kv3.3 contains a proline-rich domain conserved in proteins that activate actin nucleation through Arp2/3. We found that Kv3.3 recruits Arp2/3 to the plasma membrane, resulting in formation of a relatively stable cortical actin filament network resistant to cytochalasin D that inhibits fast barbed end actin assembly. These Kv3.3-associated actin structures are required to prevent very rapid N-type channel inactivation during short depolarizations of the plasma membrane. The effects of Kv3.3 on the actin cytoskeleton are mediated by the binding of the cytoplasmic C terminus of Kv3.3 to Hax-1, an anti-apoptotic protein that regulates actin nucleation through Arp2/3. A human Kv3.3 mutation within a conserved proline-rich domain produces channels that bind Hax-1 but are impaired in recruiting Arp2/3 to the plasma membrane, resulting in growth cones with deficient actin veils in stem cell-derived neurons. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Ultra-stable phosphoglucose isomerase through immobilization of cellulose-binding module-tagged thermophilic enzyme on low-cost high-capacity cellulosic adsorbent.

    Science.gov (United States)

    Myung, Suwan; Zhang, Xiao-Zhou; Zhang, Y-H Percival

    2011-07-01

    One-step enzyme purification and immobilization were developed based on simple adsorption of a family 3 cellulose-binding module (CBM)-tagged protein on the external surface of high-capacity regenerated amorphous cellulose (RAC). An open reading frame (ORF) Cthe0217 encoding a putative phosphoglucose isomerase (PGI, EC 5.3.1.9) from a thermophilic bacterium Clostridium thermocellum was cloned and the recombinant proteins with or without CBM were over-expressed in Escherichia coli. The rate constant (kcat ) and Michaelis-Menten constant (Km ) of CBM-free PGI at 60°C were 2,765 s(-1) and 2.89 mM, respectively. PGI was stable at a high protein concentration of 0.1 g/L but deactivated rapidly at low concentrations. Immobilized CBM (iCBM)-PGI on RAC was extremely stable at ∼60°C, nearly independent of its mass concentration in bulk solution, because its local concentration on the solid support was constant. iCBM-PGI at a low concentration of 0.001 g/L had a half-life time of 190 h, approximately 80-fold of that of free PGI. Total turn-over number of iCBM-PGI was as high as 1.1×10(9) mole of product per mole of enzyme at 60°C. These results suggest that a combination of low-cost enzyme immobilization and thermoenzyme led to an ultra-stable enzyme building block suitable for cell-free synthetic pathway biotransformation that can implement complicated biochemical reactions in vitro. Copyright © 2011 American Institute of Chemical Engineers (AIChE).

  11. Characteristics of binding of a low affinity, noncooperative insulin [(LeuB25]insulin) to IM-9 lymphocytes

    International Nuclear Information System (INIS)

    Green, A.; Frank, B.H.; Rubenstein, A.; Tager, H.; Olefsky, J.M.

    1983-01-01

    [Leu-B25]insulin is a low affinity insulin analog which does not increase the rate of dissociation of 125 I-insulin from insulin receptors (i.e. does not display negative cooperativity). We have studied the characteristics of binding of this analog to IM-9 cultured lymphocytes, in order to determine the contribution of negative cooperativity to the curvilinear nature of Scatchard plots typical of insulin binding data. The affinity of [LeuB25]insulin for receptors was approximately 1% that of insulin, as determined by its ability to inhibit 125 I-insulin binding. Monoiodinated preparations of insulin and of [LeuB25]insulin were produced, labeled in the tyrosine at position 14 of the A chain. These 125 I-TyrA14-labeled species were used in all studies. Both native insulin and a serum containing antiinsulin receptor antibodies were equally potent at inhibiting binding of 125 I-[LeuB25]insulin and 125 I-native insulin, suggesting that they bind to the same population of receptors. Native insulin (100 ng/ml) increased the rate of dissociation of both 125 I-insulin and 125 I-[LeuB25]insulin. However, [LeuB25]insulin (2.5 micrograms/ml) did not increase the rates of dissociation of either 125 I-insulin or 125 I-[LeuB25]insulin (i.e. it did not display negative cooperativity). Competition curves and Scatchard plots were constructed using 125 I-[LeuB25]insulin and unlabeled analog. Half-maximal inhibition of 125 I-[LeuB25]insulin binding was seen at a [LeuB25]insulin concentration of approximately 500 ng/ml. More importantly, the Scatchard plot of these binding data was markedly curvilinear, as is typical of insulin binding data

  12. Antigen binding characteristics of immunoglobulin free light chains: crosslinking by antigen is essential to induce allergic inflammation.

    Directory of Open Access Journals (Sweden)

    Marco Thio

    Full Text Available Beside the production of complete immunoglobulins IgG, IgE, IgA, IgM and IgD, consisting of tetrameric heterodimers of immunoglobulin heavy and light chains, B cells also secrete immunoglobulin free light chains (Ig-fLC. Previous studies showed that Ig-fLCs are able to induce immediate hypersensitivity reactions. It is apparent that recognition and binding of antigen are crucial steps in the onset of these inflammatory responses. In this study, the binding characteristics of Ig-fLC to antigen were further investigated using various biochemical approaches. In addition, we investigated whether antigen-mediated crosslinking of Ig-fLC is required to initiate allergic skin inflammation in vivo. Our study shows that binding of Ig-fLCs to antigen can be measured with different experimental setups. Surface plasmon resonance analysis showed real-time antigen binding characteristics. Specific antigen binding by Ig-fLCs was further detected using immunoblotting and ELISA. Using the ELISA-based assay, a binding affinity of 76.9±3.8 nM was determined for TNP-specific Ig-fLC. Antigen-induced ear swelling in mice passively sensitized with trinitrophenol-specific Ig-fLC was inhibited when multivalent antigen was combined with excess of monovalent antigen during challenge. We conclude that Ig-fLCs are able to interact with antigen, a prerequisite for antigen-specific cellular activation. In analogy to antigen-specific Fc receptor-induced mast cell activation, crosslinking of Ig-fLCs is necessary to initiate a local allergic response.

  13. Seasonal variation in glucocorticoid receptor binding characteristics in human mononuclear leucocytes.

    Science.gov (United States)

    Blackhurst, G; McElroy, P K; Fraser, R; Swan, R L; Connell, J M

    2001-11-01

    Glucocorticoid sensitivity varies between individuals and between tissues in the same individual. Although some of this variation is explained by the activity of the 11 beta-hydroxysteroid dehydrogenase enzymes, the possibility that glucocorticoid receptor sensitivity is modulated remains unexplored. This study examined glucocorticoid receptor binding in leucocytes and assessed the effects of seasonal hormonal variation on receptor binding. Two populations were studied. In the first, 318 healthy subjects were studied over 2 years with a single measurement of receptor binding made on each. In the second study nine healthy male subjects each had receptor binding measurements made at 3-week intervals over 1 year. In both populations there was significant seasonal variation in receptor binding. In the first population Kd for dexamethasone was highest in November and lowest in July (8.37 +/- 0.5 nmol/l vs. 1.58 +/- 0.7, mean +/- SEM P vs. 4969 +/- 302, P melatonin raised Kd without affecting receptor number. Co-incubation with forskolin lowered Kd suggesting that melatonin might act through the ML1 receptor class by inhibiting adenylyl cyclase. No correlations were found with 0900 h plasma cortisol. The results suggest that the glucocorticoid receptor might be modulated by season. Melatonin might mediate part of these effects. The lack of correlation with cortisol suggests that it is not an important determinant of receptor binding and that leucocyte receptors are regulated differently from central receptors.

  14. Comparison of characteristics of dopamine uptake and mazindol binding in mouse striatum.

    Science.gov (United States)

    Zimányi, I; Lajtha, A; Reith, M E

    1989-12-01

    Biochemical and pharmacological studies suggest that the binding of [3H]mazindol is functionally related to the dopamine uptake carrier complex in rodent striatum. In order to study further the relationship between the substrate recognition site for dopamine uptake and the high-affinity binding site for mazindol the uptake of [3H]dopamine and the binding of [3H]mazindol was studied in BALB/cBy mouse striatum in various buffers (Tris, HEPES, bicarbonate-phosphate). Kinetic analysis showed that the Kd of the binding of [3H]mazindol and the Km of the uptake of [3H]dopamine was changed by different sodium concentrations and/or by the presence of Tris, while the Bmax and the Vmax remained essentially the same. However, the shape of the Na+ dependency curves was not the same for mazindol binding and dopamine uptake in the various buffers. The inhibitory effect of other cations such as K+ and Tris was also different on binding and uptake under similar experimental circumstances. Dopamine did not slow down the dissociation of mazindol from its site and this effect was not sodium-sensitive. These complexities can be accommodated by a model that involves overlapping sites for mazindol and dopamine on the dopamine uptake carrier complex, and translocation-reorientation steps.

  15. Binding characteristics of 9-fluoropropyl-(+)-dihydrotetrabenzazine (AV-133) to the vesicular monoamine transporter type 2 in rats

    Energy Technology Data Exchange (ETDEWEB)

    Tsao, H.-H. [Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan (China); Lin, K.-J. [Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan (China); Department of Nuclear Medicine, Chang Gung University and Memorial Hospital, Taoyuan, Taiwan (China); Juang, J.-H. [Division of Endocrinology and Metabolism, Chung Gung University and Chung Gung Memorial Hospital, Taoyuan, Taiwan (China); Skovronsky, Daniel M. [Avid Radiopharmaceuticals, Philadelphia, PA (United States); Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Yen, T.-C. [Department of Nuclear Medicine, Chang Gung University and Memorial Hospital, Taoyuan, Taiwan (China); Wey, S.-P. [Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan (China); Kung, M.-P. [Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan (China); Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States)], E-mail: kungmp@sunmac.spect.upenn.edu

    2010-05-15

    The vesicular monoamine transporter type 2 (VMAT2) is highly expressed in pancreatic {beta}-cells and thus has been proposed to be a potential target for measuring {beta}-cell mass (BCM) by molecular imaging. C-11- and F-18-labeled tetrabenazine derivatives targeting VMAT2 have shown some promising results as potential biomarkers for BCM. In the present study, we examined the binding characteristics of 9-fluoropropyl-(+)-dihydrotetrabenzazine ([{sup 18}F]AV-133), a potential PET tracer for BCM imaging, in rat pancreas and rat brain. Methods: Pancreatic exocrine cells and pancreatic islet cells were isolated and purified from Sprague-Dawley rats. Membrane homogenates, prepared from both pancreatic exocrine and islet cells as well as from brain striatum and hypothalamus regions, were used for in vitro binding studies. In vitro and ex vivo autoradiography studies with [{sup 18}F]AV-133 were performed on rat brain and rat pancreas sections. Immunohistochemistry studies were performed to confirm the distribution of VMAT2 on islet {beta}-cells. Results: Excellent binding affinities of [{sup 18}F]AV-133 were observed in rat striatum and hypothalamus homogenates with K{sub d} values of 0.19 and 0.25 nM, respectively. In contrast to single-site binding observed in rat striatum homogenates, rat islet cell homogenates showed two saturable binding sites (site A: K{sub d}=6.76 nM, B{sub max}=60 fmol/mg protein; site B: K{sub d}=241 nM, B{sub max}=1500 fmol/mg protein). Rat exocrine pancreas homogenates showed only a single low-affinity binding site (K{sub d}=209 nM), which was similar to site B in islet cells. In vitro autoradiography of [{sup 18}F]AV-133 using frozen sections of rat pancreas showed specific labeling of islets, as evidenced by co-localization with anti-insulin antibody. Ex vivo VMAT2 pancreatic autoradiography in the rat, however, was not successful, in contrast to the excellent ex vivo autoradiography of VMAT2 binding sites in the brain. In vivo/ex vivo islet

  16. Platelet [3H]imipramine binding in affective disorders: trait versus state characteristics

    International Nuclear Information System (INIS)

    Baron, M.; Barkai, A.; Gruen, R.; Peselow, E.; Fieve, R.R.; Quitkin, F.

    1986-01-01

    Platelet [3H]imipramine binding (Bmax) was determined in 67 patients with major affective illness (33 euthymic bipolar, 34 depressed unipolar) and 58 normal control subjects. Bipolar patients had significantly lower Bmax values than did control subjects. The mean Bmax in the unipolar patients was lower than in the control subjects, but the difference was not statistically significant. Dissociation constant (Kd) values did not distinguish patients in either category from control subjects. The significantly lower Bmax in euthymic bipolar patients and the apparent state independence of Bmax in some but not all unipolar patients suggest that platelet imipramine binding may be a trait marker in a subset of affective disorders

  17. Antibody Binding Alters the Characteristics and Contents of Extracellular Vesicles Released by Histoplasma capsulatum.

    Science.gov (United States)

    Matos Baltazar, Ludmila; Nakayasu, Ernesto S; Sobreira, Tiago J P; Choi, Hyungwon; Casadevall, Arturo; Nimrichter, Leonardo; Nosanchuk, Joshua D

    2016-01-01

    Histoplasma capsulatum produces extracellular vesicles containing virulence-associated molecules capable of modulating host machinery, benefiting the pathogen. Treatment of H. capsulatum cells with monoclonal antibodies (MAbs) can change the outcome of infection in mice. We evaluated the sizes, enzymatic contents, and proteomic profiles of the vesicles released by fungal cells treated with either protective MAb 6B7 (IgG1) or nonprotective MAb 7B6 (IgG2b), both of which bind H. capsulatum heat shock protein 60 (Hsp60). Our results showed that treatment with either MAb was associated with changes in size and vesicle loading. MAb treatments reduced vesicle phosphatase and catalase activities compared to those of vesicles from untreated controls. We identified 1,125 proteins in vesicles, and 250 of these manifested differences in abundance relative to that of proteins in vesicles isolated from yeast cells exposed to Hsp60-binding MAbs, indicating that surface binding of fungal cells by MAbs modified protein loading in the vesicles. The abundance of upregulated proteins in vesicles upon MAb 7B6 treatment was 44.8% of the protein quantities in vesicles from fungal cells treated with MAb 6B7. Analysis of orthologous proteins previously identified in vesicles from other fungi showed that different ascomycete fungi have similar proteins in their extracellular milieu, many of which are associated with virulence. Our results demonstrate that antibody binding can modulate fungal cell responses, resulting in differential loading of vesicles, which could alter fungal cell susceptibility to host defenses. This finding provides additional evidence that antibody binding modulates microbial physiology and suggests a new function for specific immunoglobulins through alterations of fungal secretion. IMPORTANCE Diverse fungal species release extracellular vesicles, indicating that this is a common pathway for the delivery of molecules to the extracellular space. However, there has

  18. Lectin-binding characteristics of a Lyme borreliosis spirochete Borrelia burgdorferi sensu stricto

    Czech Academy of Sciences Publication Activity Database

    Vancová, M.; Nebesářová, J.; Grubhoffer, Libor

    2005-01-01

    Roč. 50, č. 3 (2005), s. 229-238 ISSN 0015-5632 R&D Projects: GA ČR GA206/03/1323; GA AV ČR KSK6005114 Institutional research plan: CEZ:AV0Z60220518 Keywords : Borrelia burgdorferi * electron microscopy * lectin binding Subject RIV: EE - Microbiology, Virology Impact factor: 0.918, year: 2005

  19. Binding and functional pharmacological characteristics of gepant-type antagonists in rat brain and mesenteric arteries

    DEFF Research Database (Denmark)

    Sheykhzade, Majid; Amandi, Nilofar; Pla, Monica Vidal

    2017-01-01

    AIM: The neuropeptide calcitonin gene-related peptide (CGRP) is found in afferent sensory nerve fibers innervating the resistance arteries and plays a pivotal role in a number of neurovascular diseases such as migraine and subarachnoid bleedings. The present study investigates the binding and ant...

  20. Stable alterations of CD44 isoform expression in prostate cancer cells decrease invasion and growth and alter ligand binding and chemosensitivity

    International Nuclear Information System (INIS)

    Yang, Kui; Tang, Yaqiong; Habermehl, Gabriel K; Iczkowski, Kenneth A

    2010-01-01

    Dysregulated CD44 expression characterizes most human cancers, including prostate cancer (PCa). PCa loses expression of CD44 standard (CD44s) that is present in benign epithelium, and overexpresses the novel splice variant isoform, CD44v7-10. Using retroviral gene delivery to PC-3M PCa cells, we expressed luciferase-only, enforced CD44s re-expression as a fusion protein with luciferase at its C-terminus or as a protein separate from luciferase, or knocked down CD44v7-10 by RNAi. Invasion, migration, proliferation, soft agar colony formation, adhesion, Docetaxel sensitivity, and xenograft growth assays were carried out. Expression responses of merlin, a CD44 binding partner, and growth-permissive phospho-merlin, were assessed by western blot. Compared to luciferase-only PC-3M cells, all three treatments reduced invasion and migration. Growth and soft agar colony formation were reduced only by re-expression of CD44s as a separate or fusion protein but not CD44v7-10 RNAi. Hyaluronan and osteopontin binding were greatly strengthened by CD44s expression as a separate protein, but not a fusion protein. CD44v7-10 RNAi in PC-3M cells caused marked sensitization to Docetaxel; the two CD44s re-expression approaches caused minimal sensitization. In limited numbers of mouse subcutaneous xenografts, all three alterations produced only nonsignificant trends toward slower growth compared with luciferase-only controls. The expression of CD44s as a separate protein, but not a fusion protein, caused emergence of a strongly-expressed, hypophosphorylated species of phospho-merlin. Stable re-expression of CD44s reduces PCa growth and invasion in vitro, and possibly in vivo, suggesting CD44 alterations have potential as gene therapy. When the C-terminus of CD44s is fused to another protein, most phenotypic effects are lessened, particularly hyaluronan adhesion. Finally, CD44v7-10, although it was not functionally significant for growth, may be a target for chemosensitization

  1. Characteristics of the brown hagfish Paramyxine atami transthyretin: Metal ion-dependent thyroid hormone binding.

    Science.gov (United States)

    Suzuki, Shunsuke; Kasai, Kentaro; Nishiyama, Norihito; Ishihara, Akinori; Yamauchi, Kiyoshi

    2017-08-01

    Transthyretin (TTR) is a vertebrate-specific protein involved in thyroid hormone distribution in plasma, and its gene is thought to have emerged by gene duplication from the gene for the ancient TTR-related protein, 5-hydroxyisourate hydrolase, at some early stage of chordate evolution. We investigated the molecular and hormone-binding properties of the brown hagfish Paramyxine atami TTR. The amino acid sequence deduced from the cloned hagfish TTR cDNA shared 33-50% identities with those of other vertebrate TTRs but less than 24% identities with those of vertebrate and deuterostome invertebrate 5-hydroxyisourate hydrolases. Hagfish TTR, as well as lamprey and little skate TTRs, had an N-terminal histidine-rich segment, allowing purification by metal-affinity chromatography. The affinity of hagfish TTR for 3,3',5-triiodo-L-thyronine (T3) was 190 times higher than that for L-thyroxine, with a dissociation constant of 1.5-3.9nM at 4°C. The high-affinity binding sites were strongly sensitive to metal ions. Zn 2+ and Cu 2+ decreased the dissociation constant to one-order of magnitude, whereas a chelator, o-phenanthroline, increased it four times. The number of metal ions (mainly Zn 2+ and Cu 2+ ) was approximately 12/TTR (mol/mol). TTR was also a major T3-binding protein in adult hagfish sera and its serum concentration was approximately 8μM. These results suggest that metal ions and the acquisition of N-terminal histidine-rich segment may cooperatively contribute to the evolution toward an ancient TTR with high T3 binding activity from either 5-hydroxyisourate hydrolase after gene duplication. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Mineral-binding milk proteins and peptides; occurrence, biochemical and technological characteristics.

    Science.gov (United States)

    Vegarud, G E; Langsrud, T; Svenning, C

    2000-11-01

    Minerals and trace elements in cow's milk occur as inorganic ions and salts or form complexes with proteins and peptides, carbohydrates, fats and small molecules. The main mineral binder or chelators of calcium are the caseins, alphas1-casein, alphas2-casein, beta-casein and kappa-casein, but also whey proteins and lactoferrin bind specific minerals like calcium, magnesium, zinc, iron, sodium and potassium. Less documented is the binding of trace elements. Peptides obtained by in vitro or in vivo hydrolysis act as mineral trappers through specific and non-specific binding sites. They may then function as carriers, chelators, of various minerals and thus enhance or inhibit bioavailability. Peptides from milk proteins have found interesting new applications in the food industry as products with improved functionality or as ingredients of dietary products, or used in pharmaceutical industry. Fortification of foods with minerals in a low concentration has for a long time been used in some countries to overcome mineral deficiency, which is an increasing problem in humans. These types of foods are being used to create a new generation of super foods in the industry today.

  3. A Study on Solubilization of Poorly Soluble Drugs by Cyclodextrins and Micelles: Complexation and Binding Characteristics of Sulfamethoxazole and Trimethoprim

    Directory of Open Access Journals (Sweden)

    Sinem Göktürk

    2012-01-01

    > α-CD. With taking into consideration of solubilization capacity of SDS micelles, it has been found that the solubility enhancement of TMP is much higher than that of SMX in the presence of SDS micelles. The binding constants of SMX and TMP obtained from the Benesi-Hildebrand equation are also confirmed by the estimated surface properties of SDS, employing the surface tension measurements. In order to elucidate the solubilization characteristics the surface tension measurements were also performed for nonionic surfactant Triton X-100. Polarity of the microenvironment and probable location of SMX and TMP were also discussed in the presence of various organic solvents.

  4. Anti-Japanese-encephalitis-viral effects of kaempferol and daidzin and their RNA-binding characteristics.

    Directory of Open Access Journals (Sweden)

    Ting Zhang

    Full Text Available BACKGROUND: New therapeutic tools and molecular targets are needed for treatment of Japanese encephalitis virus (JEV infections. JEV requires an α-1 translational frameshift to synthesize the NS1' protein required for viral neuroinvasiveness. Several flavonoids have been shown to possess antiviral activity in vitro against a wide spectrum of viruses. To date, the antiviral activities of flavonol kaempferol (Kae and isoflavonoid daidzin (Dai against JEV have not been described. METHODOLOGY/PRINCIPAL FINDINGS: The 50% cytotoxic concentration (CC(50 and 50% effective concentration (EC(50 against JEV were investigated in BHK21 cells by MTS reduction. Activity against viral genomic RNA and proteins was measured by real-time RT-PCR and western blotting. The frameshift site RNA-binding characterization was also determined by electrospray ionization mass spectrometry, isothermal titration calorimetry and autodocking analysis. EC(50 values of Kae and Dai were 12.6 and 25.9 µM against JEV in cells pretreated before infection, whereas in cells infected before treatment, EC(50 was 21.5 and 40.4 µM, respectively. Kae exhibited more potent activity against JEV and RNA binding in cells following internalization through direct inhibition of viral replication and protein expression, indicating that its antiviral activity was principally due to direct virucidal effects. The JEV frameshift site RNA (fsRNA was selected as a target for assaying Kae and Dai. ITC of fsRNA revealed an apparent K(b value for Kae that was nine fold stronger than that for Dai. This binding was confirmed and localized to the RNA using ESI-MS and autodock analysis. Kae could form non-covalent complexes with fsRNA more easily than Dai could. CONCLUSIONS/SIGNIFICANCE: Kae demonstrates more potent antiviral activity against JEV than does Dai. The mode of action of Kae as an anti-JEV agent seems to be related to its ability to inactivate virus by binding with JEV fsRNA.

  5. Sexually dimorphic development and binding characteristics of NMDA receptors in the brain of the platyfish

    Science.gov (United States)

    Flynn, K. M.; Schreibman, M. P.; Yablonsky-Alter, E.; Banerjee, S. P.

    1999-01-01

    This study investigated age- and gender-specific variations in properties of the glutamate N-methyl-d-aspartate receptor (NMDAR) in a freshwater teleost, the platyfish (Xiphophorus maculatus). Prior localization of the immunoreactive (ir)-R1 subunit of the NMDAR protein (R1) in cells of the nucleus olfactoretinalis (NOR), a primary gonadotropin-releasing hormone (GnRH)-containing brain nucleus in the platyfish, suggests that NMDAR, as in mammals, is involved in modulation of the platyfish brain-pituitary-gonad (BPG) axis. The current study shows that the number of cells in the NOR displaying ir-R1 is significantly increased in pubescent and mature female platyfish when compared to immature and senescent animals. In males, there is no significant change in ir-R1 expression in the NOR at any time in their lifespan. The affinity of the noncompetitive antagonist ((3)H)MK-801 for the NMDAR is significantly increased in pubescent females while maximum binding of ((3)H)MK-801 to the receptor reaches a significant maximum in mature females. In males, both MK-801 affinity and maximum binding remain unchanged throughout development. This is the first report of gender differences in the association of NMDA receptors with neuroendocrine brain areas during development. It is also the first report to suggest NMDA receptor involvement in the development of the BPG axis in a nonmammalian vertebrate. Copyright 1999 Academic Press.

  6. Characteristics of central binding sites for ( sup 3 H) DAMGO in spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Gulati, A.; Bhargava, H.N. (Univ. of Illinois, Chicago (USA))

    1990-01-01

    The binding of ({sup 3}H) DAMGO, a highly selective ligand for {mu}-opiate receptors, to membranes of discrete brain regions and spinal cord of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were determined. The brain regions examined were hypothalamus, amygdala, hippocampus, corpus striatum, pons and medulla, midbrain and cortex. ({sup 3}H) DAMGO bound to membranes of brain regions and spinal cord at a single high affinity site. The receptor density (B{sub max} value) and apparent dissociation constant (K{sub d} value) of ({sup 3}H) DAMGO to bind to membranes of hippocampus, corpus striatum, pons and medulla, cortex and spinal cord of WKY and SHR rats did not differ. The B{sub max} value of ({sup 3}H) DAMGO in membranes of hypothalamus and midbrain of SHR rats was significantly higher than in WKY rats but the K{sub d} values in the two strains did not differ. On the other hand, the B{sub max} value of ({sup 3}H) DAMGO in membranes of amygdala of SHR rats was lower than that of WKY rats but the K{sub d} values in the two strains were similar.

  7. Evaluation of human and bovine serum albumin on oxidation characteristics by a photosensitization reaction under complete binding of talaporfin sodium.

    Science.gov (United States)

    Kurotsu, Mariko; Yajima, Masahiro; Takahashi, Mei; Ogawa, Emiyu; Arai, Tsunenori

    2015-09-01

    In order to investigate the therapeutic interaction of an extra-cellular photosensitization reaction, we evaluated the oxidation characteristics of human and bovine serum albumin by this reaction with talaporfin sodium under complete binding with albumin by spectroscopic analysis in a cell-free solution. The solution was composed of 20μg/ml talaporfin sodium and 2.1mg/ml human or bovine serum albumin. A 662nm laser light was used to irradiate the solution. Visible absorbance spectra of solutions were measured to obtain the oxidized and non-oxidized relative densities of albumin and talaporfin sodium before and after the photosensitization reaction. The defined oxidation path ratio of talaporfin sodium to albumin reflected the oxidation of the solution. Absorbance wavelengths at approximately 240 and 660nm were used to calculate normalized molecular densities of oxidized albumin and talaporfin sodium, respectively. The oxidation path ratio of talaporfin sodium to albumin when binding human serum albumin was approximately 1.8 times larger than that of bovine serum albumin during the photosensitization reaction from 1 to 50J/cm(2). We hypothesized that the oxidation path ratio results might have been caused by talaporfin sodium binding affinity or binding location difference between the two albumins, because the fluorescence lifetimes of talaporfin sodium bound to human and bovine serum albumin were 7.0 and 4.9ns, respectively. Therefore, the photodynamic therapeutic interaction might be stronger with human serum albumin than with bovine serum albumin in the case of extracellular photosensitization reaction. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. A chemometric analysis of ligand-induced changes in intrinsic fluorescence of folate binding protein indicates a link between altered conformational structure and physico-chemical characteristics

    DEFF Research Database (Denmark)

    Bruun, Susanne W; Holm, Jan; Hansen, Steen Ingemann

    2009-01-01

    Ligand binding alters the conformational structure and physico-chemical characteristics of bovine folate binding protein (FBP). For the purpose of achieving further information we analyzed ligand (folate and methotrexate)-induced changes in the fluorescence landscape of FBP. Fluorescence excitation...... of folate accords fairly well with the disappearance of strongly hydrophobic tryptophan residues from the solvent-exposed surface of FBP. The PARAFAC has thus proven useful to establish a hitherto unexplained link between parallel changes in conformational structure and physico-chemical characteristics...... of FBP induced by folate binding. Parameters for ligand binding derived from PARAFAC analysis of the fluorescence data were qualitatively and quantitatively similar to those obtained from binding of radiofolate to FBP. Herein, methotrexate exhibited a higher affinity for FBP than in competition...

  9. Neuronal Calcium Sensor 1 Has Two Variants with Distinct Calcium Binding Characteristics.

    Science.gov (United States)

    Wang, Baisheng; Boeckel, Göran R; Huynh, Larry; Nguyen, Lien; Cao, Wenxiang; De La Cruz, Enrique M; Kaftan, Edward J; Ehrlich, Barbara E

    2016-01-01

    Neuronal calcium sensor-1 (NCS-1 Var1) is a calcium-binding protein expressed in most tissues. We examined a poorly characterized variant of NCS-1 (Var2), identified only in humans where the N-terminal 22 amino acid residues of native NCS-1(MGKSNSKLKPEVVEELTRKTY) were replaced with 4 different residues (MATI). Because alterations in the level of expression of NCS-1 Var1 and the expression of NCS-1 variants have been correlated with several neurological diseases, the relative expression and functional role of NCS-1 Var2 was examined. We found that NCS-1 Var2 mRNA levels are not found in mouse tissues and are expressed at levels ~1000-fold lower than NCS-1 Var1 in three different human cell lines (SHSY5Y, HEK293, MB231). Protein expression of both variants was only identified in cell lines overexpressing exogenous NCS-1 Var2. The calcium binding affinity is ~100 times weaker in purified NCS-1 Var2 than NCS-1 Var1. Because truncation of NCS-1 Var1 has been linked to functional changes in neurons, we determined whether the differing properties of the NCS-1 variants could potentially contribute to the altered cell function. In contrast to previous reports showing that overexpression of NCS-1 Var1 increases calcium-dependent processes, functional differences in cells overexpressing NCS-1 Var2 were undetectable in assays for cell growth, cell death and drug (paclitaxel) potency. Our results suggest that NCS-1 Var1 is the primary functional version of NCS-1.

  10. Modeling of arylamide helix mimetics in the p53 peptide binding site of hDM2 suggests parallel and anti-parallel conformations are both stable.

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    Jonathan C Fuller

    Full Text Available The design of novel α-helix mimetic inhibitors of protein-protein interactions is of interest to pharmaceuticals and chemical genetics researchers as these inhibitors provide a chemical scaffold presenting side chains in the same geometry as an α-helix. This conformational arrangement allows the design of high affinity inhibitors mimicking known peptide sequences binding specific protein substrates. We show that GAFF and AutoDock potentials do not properly capture the conformational preferences of α-helix mimetics based on arylamide oligomers and identify alternate parameters matching solution NMR data and suitable for molecular dynamics simulation of arylamide compounds. Results from both docking and molecular dynamics simulations are consistent with the arylamides binding in the p53 peptide binding pocket. Simulations of arylamides in the p53 binding pocket of hDM2 are consistent with binding, exhibiting similar structural dynamics in the pocket as simulations of known hDM2 binders Nutlin-2 and a benzodiazepinedione compound. Arylamide conformations converge towards the same region of the binding pocket on the 20 ns time scale, and most, though not all dihedrals in the binding pocket are well sampled on this timescale. We show that there are two putative classes of binding modes for arylamide compounds supported equally by the modeling evidence. In the first, the arylamide compound lies parallel to the observed p53 helix. In the second class, not previously identified or proposed, the arylamide compound lies anti-parallel to the p53 helix.

  11. Binding characteristics and interactive region of 2-phenylpyrazolo[1,5-c]quinazoline with DNA.

    Science.gov (United States)

    Song, Yonghai; Zhong, Dandan; Luo, Jinhui; Tan, Hongliang; Chen, Shouhui; Li, Ping; Wang, Li; Wang, Tao

    2014-12-01

    The interaction between 2-phenylpyrazolo[1,5-c]quinazoline (PQ) and DNA under physiological conditions was investigated using multi-spectroscopic techniques, atomic force microscopy and gel electrophoresis. The thermodynamic parameters were estimated and were discussed in detail. The results of fluorescence-quenching experiments indicated that the main interactive force between PQ and DNA was a hydrophobic interaction and that it was a static quenching process. Potassium iodide and single-strand (ss)DNA quenching studies, together with circular dichroism spectra implied groove binding of PQ with DNA. Atomic force microscopy and gel electrophoresis experiments suggested that there were no major conformational changes in DNA upon interaction with PQ. In addition, UV/vis absorption titration of DNA bases confirmed that PQ bound with DNA mainly through a minor groove interaction and preferentially interacted with adenine and thymine. We anticipate that this work will provide useful information for the application of quinazoline derivatives in the fields of medicinal and pharmaceutical chemistry. Copyright © 2014 John Wiley & Sons, Ltd.

  12. [ISCHEMIA - the Largest Ever R andomized Study in Stable Coronary Artery Disease. Baseline Characteristics of Enrolled Patients in One Russian Site].

    Science.gov (United States)

    Sayganov, S A; Bershteyn, L L; Andreeva, A E; Katamadze, N O; Zbyshevskaya, E V; Kuzmina-Krutetskaya, A M; Volkov, A V; Gumerova, V E; Bitakova, F I

    2017-10-01

    Indications for coronary revascularization in patients with stable coronary heart disease (CHD), presented in the current international guidelines are largely based on the clinical trials conducted sometimes more than 30 years ago. ISCHEMIA is the major multicenter international randomized trial intended to answer the question about the optimal treatment strategy in stable coronary artery disease at the present time. To analyze the most important baseline characteristics of patients enrolled in the ISCHEMIA study in one Russian site. The principal inclusion criteria are a positive stress test (in our center, exercise stress echocardiography) of at least moderate risk and obstructive coronary heart disease confirmed by coronary computed tomography angiography (CCTA). Main exclusion criteria are a significant stenosis of the left main coronary artery by CCTA, clinical progression/destabilization of the ischemic heart disease, angina of IV CCS class, left ventricular ejection fraction (EF) 80% - beta blockers, >80% - ACE inhibitors/ARBs. They are at well controlled resting heart rate (.

  13. Dissociation and metal-binding characteristics of yellow lichen substances suggest a relationship with site preferences of lichens.

    Science.gov (United States)

    Hauck, Markus; Jürgens, Sascha-René; Willenbruch, Karen; Huneck, Siegfried; Leuschner, Christoph

    2009-01-01

    Many species of lichen-forming fungi contain yellow or orange extracellular pigments belonging to the dibenzofurans (usnic acid), anthraquinones (e.g. parietin) or pulvinic acid group. These pigments are all equally efficient light screens, leading us to question the potential ecological and evolutionary significance of diversity in yellow and orange lichen substances. Here the hypothesis is tested that the different pigments differ in metal-binding characteristics, which suggest that they may contribute to adaptation to sites differing in pH and metal availability. UV spectroscopy was used to study the dissociation and the pH dependence of the metal-binding behaviour of seven isolated lichen substances in methanol. Metals applied were selected macro- and micro-nutrients (Cu(2+), Fe(2+), Fe(3+), Mg(2+), Mn(2+) and Zn(2+)). All the pigments studied are strong to moderate acids with pK(a1) values between 2.8 and 4.5. Metal complexation is common in the lichen substances studied. Complexation takes place under acidic conditions with usnic acid, but under alkaline conditions with parietin and most compounds of the pulvinic acid group. The pulvinic acid derivative rhizocarpic acid forms metal complexes both in the acidic and the alkaline range. Metal complexation by lichen substances could be a prerequisite for lichen substance-mediated control of metal uptake. Assuming such an effect at pH values where the affinity of the metal for the lichen substance is intermediate would explain the strong preference of lichens with usnic or rhizocarpic acids to acidic substrata. Moreover, it would explain the preference of lichens with parietin and some lichens with compounds of the pulvinic acid group either for nutrient-rich substrata at low pH or for calcareous substrata.

  14. Stable Operation and Electricity Generating Characteristics of a Single-Cylinder Free Piston Engine Linear Generator: Simulation and Experiments

    Directory of Open Access Journals (Sweden)

    Huihua Feng

    2015-01-01

    Full Text Available We present a novel design of a single-cylinder free piston engine linear generator (FPELG incorporating a linear motor as a rebound device. A systematic simulation model of this FPELG system was built containing a kinematic and dynamic model of the piston and mover, a magneto-electric model of the linear generator, a thermodynamic model of the single-cylinder engine, and a friction model between the piston ring and cylinder liner. Simulations were performed to understand the relationships between pre-set motor parameters and the running performance of the FPELG. From the simulation results, it was found that a motor rebound force with a parabolic profile had clear advantages over a force with a triangular profile, such as a higher running frequency and peak cylinder pressure, faster piston motion, etc. The rebound position and the amplitude of rebound force were also determined by simulations. The energy conversion characteristics of the generator were obtained from our FPELG test rig. The parameters of intake pressure, motor frequency, and load resistance were varied over certain ranges, and relationships among these three parameters were obtained. The electricity-generating characteristic parameters include output power and system efficiency, which can measure the quality of matching the controllable parameters. The output power can reach 25.9 W and the system efficiency can reach 13.7%. The results in terms of matching parameters and electricity-generating characteristics should be useful to future research in adapting these engines to various operating modes.

  15. H-NOX from Clostridium botulinum, like H-NOX from Thermoanaerobacter tengcongensis, Binds Oxygen but with a Less Stable Oxyferrous Heme Intermediate.

    Science.gov (United States)

    Wu, Gang; Liu, Wen; Berka, Vladimir; Tsai, Ah-Lim

    2015-12-08

    Heme nitric oxide/oxygen binding protein isolated from the obligate anaerobe Clostridium botulinum (Cb H-NOX) was previously reported to bind NO with a femtomolar K(D) (Nioche, P. et al. Science 2004, 306, 1550-1553). On the other hand, no oxyferrous Cb H-NOX was observed despite full conservation of the key residues that stabilize the oxyferrous complex in the H-NOX from Thermoanaerobacter tengcongensis (Tt H-NOX) (the same study). In this study, we re-measured the kinetics/affinities of Cb H-NOX for CO, NO, and O2. K(D)(CO) for the simple one-step equilibrium binding was 1.6 × 10(-7) M. The K(D)(NO) of Cb H-NOX was 8.0 × 10(-11) M for the first six-coordinate NO complex, and the previous femtomolar K(D)(NO) was actually an apparent K(D) for its multiple-step NO binding. An oxyferrous Cb H-NOX was clearly observed with a K(D)(O2) of 5.3 × 10(-5) M, which is significantly higher than Tt H-NOX's K(D)(O2) = 4.4 × 10(-8) M. The gaseous ligand binding of Cb H-NOX provides another supportive example for the "sliding scale rule" hypothesis (Tsai, A.-L. et al. Antioxid. Redox Signal. 2012, 17, 1246-1263), and the presence of hydrogen bond donor Tyr139 in Cb H-NOX selectively enhanced its affinity for oxygen.

  16. SOUL in mouse eyes is a new hexameric heme-binding protein with characteristic optical absorption, resonance Raman spectral, and heme-binding properties.

    Science.gov (United States)

    Sato, Emiko; Sagami, Ikuko; Uchida, Takeshi; Sato, Akira; Kitagawa, Teizo; Igarashi, Jotaro; Shimizu, Toru

    2004-11-09

    SOUL is specifically expressed in the retina and pineal gland and displays more than 40% sequence homology with p22HBP, a heme protein ubiquitously expressed in numerous tissues. SOUL was purified as a dimer in the absence of heme from the Escherichia coli expression system but displayed a hexameric structure upon heme binding. Heme-bound SOUL displayed optical absorption and resonance Raman spectra typical of 6-coordinate low-spin heme protein, with one heme per monomeric unit for both the Fe(III) and Fe(II) complexes. Spectral data additionally suggest that one of the axial ligands of the Fe(III) heme complex is His. Mutation of His42 (the only His of SOUL) to Ala resulted in loss of heme binding, confirming that this residue is an axial ligand of SOUL. The K(d) value of heme for SOUL was estimated as 4.8 x 10(-9) M from the association and dissociation rate constants, suggesting high binding affinity. On the other hand, p22HBP was obtained as a monomer containing one heme per subunit, with a K(d) value of 2.1 x 10(-11) M. Spectra of heme-bound p22HBP were different from those of SOUL but similar to those of heme-bound bovine serum albumin in which heme bound to a hydrophobic cavity with no specific axial ligand coordination. Therefore, the heme-binding properties and coordination structure of SOUL are distinct from those of p22HBP, despite high sequence homology. The physiological role of the new heme-binding protein, SOUL, is further discussed in this report.

  17. A characteristic back support structure in the bisphenol A-binding pocket in the human nuclear receptor ERRγ.

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    Xiaohui Liu

    Full Text Available The endocrine disruptor bisphenol A (BPA affects various genes and hormones even at merely physiological levels. We recently demonstrated that BPA binds strongly to human nuclear receptor estrogen-related receptor (ERR γ and that the phenol-A group of BPA is in a receptacle pocket with essential amino acid residues to provide structural support at the backside. This led BPA to bind to ERRγ in an induced-fit-type binding mode, for example, with a rotated motion of Val313 to support the Tyr326-binding site. A similar binding mechanism appears to occur at the binding site of the BPA phenol-B ring. X-ray crystal analysis of the ERRγ-ligand-binding domain/BPA complex suggested that the ERRγ receptor residues Leu342, Leu345, Asn346, and Ile349 function as intrinsic binding sites of the BPA phenol-B, whereas Leu265, Leu268, Ile310, Val313, Leu324, Tyr330, Lys430, Ala431, and His434 work as structural elements to assist these binding sites. In the present study, by evaluating the mutant receptors replaced by a series of amino acids, we demonstrated that a finely assembled structural network indeed exists around the two adjacent Leu342-Asn346 and Leu345-Ile349 ridges on the same α-helix 7 (H7, constructing a part of the binding pocket structure with back support residues for the BPA phenol-B ring. The results reveal that the double-layer binding sites, namely, the ordinary ligand binding sites and their back support residues, substantiate the strong binding of BPA to ERRγ. When ERRγ-Asn346 was replaced by the corresponding Gly and Tyr in ERRα and ERRβ, respectively, the binding affinity of BPA and even 4-hydroxytamxifen (4-OHT is much reduced. Asn346 was found to be one of the residues that make ERRγ to be exclusive to BPA.

  18. Development and quality characteristics of shelf-stable soy-agushie: a residual by-product of soymilk production.

    Science.gov (United States)

    Nti, Christina A; Plahar, Wisdom A; Annan, Nana T

    2016-03-01

    A process was developed for the production of a high-protein food ingredient, soy-agushie, from the residual by-product of soymilk production. The product, with a moisture content of about 6%, was evaluated for its quality characteristics and performance in traditional dishes. The protein content was about 26% with similar amino acids content as that of the whole soybean. Lysine remained high in the dehydrated product (6.57 g/16 g N). While over 60% of the original B vitamins content in the beans was extracted with the milk, high proportions of the minerals were found to be retained in the residual by-product. The process adequately reduced the trypsin inhibitor levels in the beans from 25 to 1.5 mg/g. High sensory scores were obtained for recipes developed with soy-agushie in traditional dishes. The scope of utilization of the soy-agushie could be widened to include several traditional foods and bakery products for maximum nutritional benefits.

  19. Acousto-optical and SAW propagation characteristics of temperature stable multilayered structures based on LiNbO3 and diamond

    International Nuclear Information System (INIS)

    Shandilya, Swati; Sreenivas, K; Gupta, Vinay

    2008-01-01

    Theoretical studies on the surface acoustic wave (SAW) properties of c-axis oriented LiNbO 3 /IDT/diamond and diamond/IDT/128 0 rotated Y-X cut LiNbO 3 multilayered structures have been considered. Both layered structures exhibit a positive temperature coefficient of delay (TCD) characteristic, and a zero TCD device is obtained after integrating with an over-layer of either tellurium dioxide (TeO 2 ) or silicon dioxide (SiO 2 ). The presence of a TeO 2 over-layer enhanced the electromechanical coupling coefficients of both multilayered structures, which acts as a better temperature compensation layer than SiO 2 . The temperature stable TeO 2 /LiNbO 3 /IDT/diamond layered structure exhibits good electromechanical coefficient and higher phase velocity for SAW device applications. On the other hand, a high acousto-optical (AO) figure of merit (30-37) x 10 -15 s 3 kg -1 has been obtained for the temperature stable SiO 2 /diamond/IDT/LiNbO 3 layered structure indicating a promising device structure for AO applications

  20. Relationships between stable fly infestation with some physical facility characteristics and sanitation practices in several dairy farms in the State of Aguascalientes, Mexico.

    Science.gov (United States)

    Cruz-Vázquez, C; Ramos-Parra, M; Vitela-Mendoza, I; García-Vázquez, Z; Quintero-Martínez, M T

    2007-11-10

    The possible relationships between stable fly infestation with dairy farm facilities and sanitation practices were studied using path analysis. Twelve dairies located in four counties of Aguascalientes dairy region were selected. The dairies were monitored from May to November 2003. In each occasion, fly infestation, individual physical facility characteristics, and sanitation practices were recorded. In all, 11 independent variables were involved in the study and related variables were grouped together and analyzed in two blocks by path analysis for each one of five population events (begin of fly season, first peak, fluctuation, second peak and decrease). There were significant regression coefficients only in the second peak for two variables, the distance to the silos and the distance to the dung heap (r(2)=0.96 for the full model). Among the 11 variables examined in the study, none had a statistical significant indirect contribution to fly infestation; direct contribution was observed for distance to the silos and for distance to the dung heap variables. However, only the distance to the silos variable was significantly related to stable fly Infestation.

  1. The mycobacterial DNA-binding protein 1 (MDP1 from Mycobacterium bovis BCG influences various growth characteristics

    Directory of Open Access Journals (Sweden)

    Maurischat Sven

    2008-06-01

    Full Text Available Abstract Background Pathogenic mycobacteria such as M. tuberculosis, M. bovis or M. leprae are characterised by their extremely slow growth rate which plays an important role in mycobacterial virulence and eradication of the bacteria. Various limiting factors influence the generation time of mycobacteria, and the mycobacterial DNA-binding protein 1 (MDP1 has also been implicated in growth regulation. Our strategy to investigate the role of MDP1 in mycobacterial growth consisted in the generation and characterisation of a M. bovis BCG derivative expressing a MDP1-antisense gene. Results The expression rate of the MDP1 protein in the recombinant M. bovis BCG containing the MDP1-antisense plasmid was reduced by about 50% compared to the reference strain M. bovis BCG containing the empty vector. In comparison to this reference strain, the recombinant M. bovis BCG grew faster in broth culture and reached higher cell masses in stationary phase. Likewise its intracellular growth in mouse and human macrophages was ameliorated. Bacterial clumping in broth culture was reduced by the antisense plasmid. The antisense plasmid increased the susceptibility of the bacteria towards Ampicillin. 2-D protein gels of bacteria maintained under oxygen-poor conditions demonstrated a reduction in the number and the intensity of many protein spots in the antisense strain compared to the reference strain. Conclusion The MDP1 protein has a major impact on various growth characteristics of M. bovis BCG. It plays an important role in virulence-related traits such as aggregate formation and intracellular multiplication. Its impact on the protein expression in a low-oxygen atmosphere indicates a role in the adaptation to the hypoxic conditions present in the granuloma.

  2. Pertussis toxin modifies the characteristics of both the inhibitory GTP binding proteins and the somatostatin receptor in anterior pituitary tumor cells

    International Nuclear Information System (INIS)

    Mahy, N.; Woolkalis, M.; Thermos, K.; Carlson, K.; Manning, D.; Reisine, T.

    1988-01-01

    The effects of pertussis toxin treatment on the characteristics of somatostatin receptors in the anterior pituitary tumor cell line AtT-20 were examined. Pertussis toxin selectively catalyzed the ADP ribosylation of the alpha subunits of the inhibitory GTP binding proteins in AtT-20 cells. Toxin treatment abolished somatostatin inhibition of forskolin-stimulated adenylyl cyclase activity and somatostatin stimulation of GTPase activity. To examine the effects of pertussis toxin treatment on the characteristics of the somatostatin receptor, the receptor was labeled by the somatostatin analog [125I]CGP 23996. [125I]CGP 23996 binding to AtT-20 cell membranes was saturable and within a limited concentration range was to a single high affinity site. Pertussis toxin treatment reduced the apparent density of the high affinity [125I]CGP 23996 binding sites in AtT-20 cell membranes. Inhibition of [125I]CGP 23996 binding by a wide concentration range of CGP 23996 revealed the presence of two binding sites. GTP predominantly reduced the level of high affinity sites in control membranes. Pertussis toxin treatment also diminished the amount of high affinity sites. GTP did not affect [125I]CGP 23996 binding in the pertussis toxin-treated membranes. The high affinity somatostatin receptors were covalently labeled with [125I] CGP 23996 and the photoactivated crosslinking agent n-hydroxysuccinimidyl-4-azidobenzoate. No high affinity somatostatin receptors, covalently bound to [125I]CGP 23996, were detected in the pertussis toxin-treated membranes. These results are most consistent with pertussis toxin uncoupling the inhibitory G proteins from the somatostatin receptor thereby converting the receptor from a mixed population of high and low affinity sites to only low affinity receptors

  3. Clinical characteristics and usage of statins in patients with stable ischemic heart disease referred for angiography or coronary artery bypass grafting

    Directory of Open Access Journals (Sweden)

    I.V. Shklianka

    2017-12-01

    Full Text Available The aim – to compare the clinical characteristics and frequency of statins usage in real clinical practice in patients referred to a specialized clinic for angiography or coronary artery bypass grafting. Materials and methods. In a retrospective slice single-center study data from a primary examination of 155 patients with stable ischemic heart disease, consecutively selected for coronary artery bypass grafting surgery, were analyzed. Depending on the inclusion of statins in the list of medicinal prescriptions, patients were retrospectively divided into two groups: those who had been prescribed statins while they were initially referred to a specialized cardiac surgery center for angiography or revascularization (n = 84 and those who were not prescribed statins (n ​​= 71. Results. The studied patients’ cohort was characterized by earlier coronary events, signs of the peripheral artery atherosclerosis and other absolute indications for treatment with statins in vast majority of cases. At the same time, groups of patients who had been and had not been prescribed statins, did not differ by vast majority of demographic, clinical and instrumental characteristics, concomitant diseases and risk factors. No statin therapy was associated with higher levels of total cholesterol and interleukin-6 compared with the group of patients taking statins (total cholesterol, respectively, 4.8 versus 4.2 mmol/l (p = 0.016 and interleukin-6, respectively, 4.4 versus. 3.1 p/ml (p = 0.022. In general, statins were prescribed in 54,2 % of patients, among them high doses – in 17 patients (20.2 %, moderate – 46 patients (54.8 %, low – 21 patients (25 %. Conclusions. The obtained data show the insufficient level of ambulatory statins usage in patients with ischemic heart disease referred for myocardial revascularization and significant discrepancy between clinical characteristics and real statins usage. Therefore, there is a great need to determine the

  4. Importance of the alphaC-helix in the cyclic nucleotide binding domain for the stable channel regulation and function of cyclic nucleotide gated ion channels in Arabidopsis.

    Science.gov (United States)

    Chin, Kimberley; Moeder, Wolfgang; Abdel-Hamid, Huda; Shahinas, Dea; Gupta, Deepali; Yoshioka, Keiko

    2010-05-01

    The involvement of cyclic nucleotide gated ion channels (CNGCs) in the signal transduction of animal light and odorant perception is well documented. Although plant CNGCs have recently been revealed to mediate multiple stress responses and developmental pathways, studies that aim to elucidate their structural and regulatory properties are still very much in their infancy. The structure-function relationship of plant CNGCs was investigated here by using the chimeric Arabidopsis AtCNGC11/12 gene that induces multiple defence responses in the Arabidopsis mutant constitutive expresser of PR genes 22 (cpr22) for the identification of functionally essential residues. A genetic screen for mutants that suppress cpr22-conferred phenotypes identified over 20 novel mutant alleles in AtCNGC11/12. One of these mutants, suppressor S58 possesses a single amino acid substitution, arginine 557 to cysteine, in the alphaC-helix of the cyclic nucleotide-binding domain (CNBD). The suppressor S58 lost all cpr22 related phenotypes, such as spontaneous cell death formation under ambient temperature conditions. However, these phenotypes were recovered at 16 degrees C suggesting that the stability of channel function is affected by temperature. In silico modelling and site-directed mutagenesis analyses suggest that arginine 557 in the alphaC-helix of the CNBD is important for channel regulation, but not for basic function. Furthermore, another suppressor mutant, S136 that lacks the entire alphaC-helix due to a premature stop codon, lost channel function completely. Our data presented here indicate that the alphaC-helix is functionally important in plant CNGCs.

  5. How Hinge Positioning in Cross-Country Ski Bindings Affect Exercise Efficiency, Cycle Characteristics and Muscle Coordination during Submaximal Roller Skiing.

    Directory of Open Access Journals (Sweden)

    Conor M Bolger

    Full Text Available The purposes of the current study were to 1 test if the hinge position in the binding of skating skis has an effect on gross efficiency or cycle characteristics and 2 investigate whether hinge positioning affects synergistic components of the muscle activation in six lower leg muscles. Eleven male skiers performed three 4-min sessions at moderate intensity while cross-country ski-skating and using a klapskate binding. Three different positions were tested for the binding's hinge, ranging from the front of the first distal phalange to the metatarsal-phalangeal joint. Gross efficiency and cycle characteristics were determined, and the electromyographic (EMG signals of six lower limb muscles were collected. EMG signals were wavelet transformed, normalized, joined into a multi-dimensional vector, and submitted to a principle component analysis (PCA. Our results did not reveal any changes to gross efficiency or cycle characteristics when altering the hinge position. However, our EMG analysis found small but significant effects of hinge positioning on muscle coordinative patterns (P < 0.05. The changed patterns in muscle activation are in alignment with previously described mechanisms that explain the effects of hinge positioning in speed-skating klapskates. Finally, the within-subject results of the EMG analysis suggested that in addition to the between-subject effects, further forms of muscle coordination patterns appear to be employed by some, but not all participants.

  6. Identification and Comparison of Receptor Binding Characteristics of the Spike Protein of Two Porcine Epidemic Diarrhea Virus Strains

    Directory of Open Access Journals (Sweden)

    Feng Deng

    2016-02-01

    Full Text Available Porcine epidemic diarrhea virus (PEDV, a member of Alphacoronavirus, has caused huge economic losses for the global pork industry recently. The spike (S protein mediates PEDV entry into host cells. Herein, we investigated the interactions between the S protein and its receptor porcine aminopeptidase N (pAPN or co-receptor sugars. The C-terminal domain (CTD of the S1 domain is bound to pAPN. The prototype strain demonstrated similar receptor-binding activity compared with the variant field isolate. Three loops at the tips of the β-barrel domains did not play crucial roles in the PEDV S-pAPN association, indicating that PEDV conforms to a different receptor recognition model compared with transmissible gastroenteritis virus (TGEV, porcine respiratory CoV (PRCV, and human coronavirus NL63 (HCoV-NL63. The N-terminal domain (NTD of the PEDV S1 domain could bind sugar, a possible co-receptor for PEDV. The prototype strain exhibited weaker sugar-binding activity compared with the variant field isolate. Strategies targeting the receptor binding domain (RBD may be helpful for developing vaccines or antiviral drugs for PEDV. Understanding the differences in receptor binding between the prototype and the variant strains may provide insight into PEDV pathogenesis.

  7. Spectroscopic and molecular docking approaches for investigating conformation and binding characteristics of clonazepam with bovine serum albumin (BSA).

    Science.gov (United States)

    Lou, Yan-Yue; Zhou, Kai-Li; Pan, Dong-Qi; Shen, Jia-Le; Shi, Jie-Hua

    2017-02-01

    Clonazepam, a type of benzodiazepine, is a classical drug used to prevent and treat seizures, panic disorder, movement disorder, among others. For further clarifying the distribution of clonazepam in vivo and the pharmacodynamic and pharmacokinetic mechanisms, the binding interaction between clonazepam and bovine serum albumin (BSA) was investigated using ultraviolet spectroscopy (UV), steady-state fluorescence spectroscopy, synchronous fluorescence spectroscopy, three-dimensional (3D) fluorescence spectroscopy, Fourier transform infrared spectroscopy (FT-IR) and molecular docking methods. The results well confirmed that clonazepam bound on the subdomain III A (Site II) of BSA through van der Waals force and hydrogen bonding interaction, and quenched the intrinsic fluorescence of BSA through a static quenching process. The number of binding sites (n) and binding constant (K b ) of clonazepam-BSA complex were about 1 and 7.94×10 4 M -1 at 308K, respectively. The binding process of clonazepam with BSA was spontaneous and enthalpy-driven process due to ΔG 0 T|ΔS 0 | over the studied temperature range. Meanwhile, the binding interaction of clonazepam with BSA resulted in the slight change in the conformation of BSA and the obvious change in the conformation of clonazepam, implying that the flexibility of clonazepam also played an important role in increasing the stability of the clonazepam-BSA complex. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Stable isotopes

    International Nuclear Information System (INIS)

    Evans, D.K.

    1986-01-01

    Seventy-five percent of the world's stable isotope supply comes from one producer, Oak Ridge Nuclear Laboratory (ORNL) in the US. Canadian concern is that foreign needs will be met only after domestic needs, thus creating a shortage of stable isotopes in Canada. This article describes the present situation in Canada (availability and cost) of stable isotopes, the isotope enrichment techniques, and related research programs at Chalk River Nuclear Laboratories (CRNL)

  9. Antibody Binding Alters the Characteristics and Contents of Extracellular Vesicles Released by Histoplasma capsulatum

    Energy Technology Data Exchange (ETDEWEB)

    Baltazar, Ludmila M.; Nakayasu, Ernesto S.; Sobreira, Tiago; Choi, Hyungwon; Casadevall, Arturo; Nimrichter, Leonardo; Nosanchuk, Joshua D.

    2016-03-30

    ABSTRACT

    Histoplasma capsulatumproduces extracellular vesicles containing virulence-associated molecules capable of modulating host machinery, benefiting the pathogen. Treatment ofH. capsulatumcells with monoclonal antibodies (MAbs) can change the outcome of infection in mice. We evaluated the sizes, enzymatic contents, and proteomic profiles of the vesicles released by fungal cells treated with either protective MAb 6B7 (IgG1) or nonprotective MAb 7B6 (IgG2b), both of which bindH. capsulatumheat shock protein 60 (Hsp60). Our results showed that treatment with either MAb was associated with changes in size and vesicle loading. MAb treatments reduced vesicle phosphatase and catalase activities compared to those of vesicles from untreated controls. We identified 1,125 proteins in vesicles, and 250 of these manifested differences in abundance relative to that of proteins in vesicles isolated from yeast cells exposed to Hsp60-binding MAbs, indicating that surface binding of fungal cells by MAbs modified protein loading in the vesicles. The abundance of upregulated proteins in vesicles upon MAb 7B6 treatment was 44.8% of the protein quantities in vesicles from fungal cells treated with MAb 6B7. Analysis of orthologous proteins previously identified in vesicles from other fungi showed that different ascomycete fungi have similar proteins in their extracellular milieu, many of which are associated with virulence. Our results demonstrate that antibody binding can modulate fungal cell responses, resulting in differential loading of vesicles, which could alter fungal cell susceptibility to host defenses. This finding provides additional evidence that antibody binding modulates microbial physiology and suggests a new function for specific immunoglobulins through alterations of fungal secretion.

    IMPORTANCEDiverse fungal species release extracellular vesicles, indicating that this is a

  10. Evaluation of the binding characteristics of [5-{sup 11}C-methoxy]donepezil in the rat brain for in vivo visualization of acetylcholinesterase

    Energy Technology Data Exchange (ETDEWEB)

    Funaki, Yoshihito; Iwata, Ren; Ido, Tatsuo [Tohoku Univ., Sendai (Japan). Cyclotron and Radioisotope Center; Kato, Motohisa; Sakurai, Eiko; Tashiro, Manabu; Yanai, Kazuhiko [Tohoku Univ., Sendai (Japan). Graduate School of Medicine; Sakurai, Eiichi [Tohoku Coll. of Pharmacy, Sendai (Japan)

    2003-02-01

    Donepezil, an acetylcholinesterase (AChE) inhibitor, has not been evaluated for its binding characteristics using a radioactive tracer, although its inhibitory action on AChE has been studied. The aim of this research is to examine whether AChE can be visualized in vivo and in vitro with [{sup 11}C]donepezil. [5-{sup 11}C-methoxy]donepezil was synthesized by O-methylation using [{sup 11}C]methyl triflate. The binding of [{sup 11}C]donepezil to brain homogenates was higher in the brain stem and striatum, and it was lowest in the cerebellum. The in vitro autoradiographic study successfully demonstrated the specific binding of [{sup 11}C]donepezil to AChE in the rat brain. The IC{sub 50} value of binding was approximately 10 nM, which is comparable to the reported value for inhibiting enzyme activity (6 nM). Saturation experiments revealed that the B{sub max} and K{sub d} of [{sup 11}C]donepezil binding in vitro are 65 fmol/mg tissue and 39.8 nM, respectively. In accordance with the in vitro bindings, the in vivo distribution of [{sup 11}C]donepezil was heterogeneous in the rat brain. In the blocking experiments, the heterogeneous distribution disappeared in the presence of a large amount of unlabeled donepezil. These data suggest that [5-{sup 11}C-methoxy]donepezil can be potentially useful to image AChE non-invasively in the human brain by positron emission tomography. (author)

  11. Earthworm eco-physiological characteristics and quantification of earthworm feeding in vermifiltration system for sewage sludge stabilization using stable isotopic natural abundance

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiaowei; Xing, Meiyan, E-mail: lixiaowei419@163.com; Yang, Jian; Dai, Xiaohu

    2014-07-15

    Highlights: • Earthworm growth biomass and activity decreased with the VF depth. • Earthworm gut microbial communities were dominated by Gammaproteobacteria. • δ{sup 15}N and δ{sup 13}C in earthworms decreased with time, and increased with the VF depth. • Effect of earthworm feeding in enhanced VSS reduction was analyzed quantitatively. • Earthworm feeding had low contribution to the enhanced VSS reduction. - Abstract: Previous studies showed that the presence of earthworm improves treatment performance of vermifilter (VF) for sewage sludge stabilization, but earthworm eco-physiological characteristics and effects in VF were not fully investigated. In this study, earthworm population, enzymatic activity, gut microbial community and stable isotopic abundance were investigated in the VF. Results showed that biomass, average weight, number and alkaline phosphatase activity of the earthworms tended to decrease, while protein content and activities of peroxidase and catalase had an increasing tendency as the VF depth. Earthworm gut microbial communities were dominated by Gammaproteobacteria, and the percentages arrived to 76–92% of the microbial species detected. {sup 15}N and {sup 13}C natural abundance of the earthworms decreased with operation time, and increased as the VF depth. Quantitative analysis using δ{sup 15}N showed that earthworm feeding and earthworm–microorganism interaction were responsible for approximately 21% and 79%, respectively, of the enhanced volatile suspended solid reduction due to the presence of earthworm. The finding provides a quantitative insight into how earthworms influence on sewage sludge stabilization in vermifiltration system.

  12. Binding characteristics of thrombin-activatable fibrinolysis inhibitor to streptococcal surface collagen-like proteins A and B

    NARCIS (Netherlands)

    Seron, Mercedes Valls; Plug, Tom; Marquart, J. Arnoud; Marx, Pauline F.; Herwald, Heiko; de Groot, Philip G.; Meijers, Joost C. M.

    2011-01-01

    Streptococcus pyogenes is the causative agent in a wide range of diseases in humans. Thrombin-activatable fibrinolysis inhibitor (TAFI) binds to collagen-like proteins ScIA and ScIB at the surface of S. pyogenes. Activation of TAFI at this surface redirects inflammation from a transient to chronic

  13. Characteristics Studies of 125I- and total PSA antibody's Binding with prostate specific antigen (PSA) in Human Uterus Tumors

    International Nuclear Information System (INIS)

    Al-Mudaffar, S.; Al-Salihi, J.

    2005-01-01

    Two groups of uterus tumors (benign and malignant) postmenopausal patients were used to investigate the presence of prostate specific antigen (PSA). Preliminary experiments were performed to follow the binding of '1 25 I-anti total PSA antibody with PSA in uterus tissues homogenates of the two groups with their corresponding antigen and found to be (8.8,7.1%) for benign and malignant tumors, respectively. An Immuno Radio Metric Assay (IRMA) procedure was developed for measuring PSA in benign and malignant uterus tumors homogenates. The optimum conditions of the binding of 125 I-anti total PSA antibody with PSA were as follows: PSA concentration (150,200 μg protein),tracer antibody concentration (125,250 μg protein), p H (7.6,7.2), temp (15,25?C) and time (1.5 hrs) for postmenopausal benign and malignant uterus tumors tissue homogenates, respectively. The use of different concentrations of Na + and Mg 2+ ions were shown to cause an increase in the binding at concentration of (125,75 mΜ) of Na 1+ ions (75,225 mΜ) of Mg 2+ ions for benign and malignant uterus tumors homogenates, respectively, while the use of different concentrations of urea and polyethylene glycol (PEG) Caused a decrease in the binding with the increase in the concentration of each of urea and PEG in the both cases

  14. Size-exclusion chromatographic reconstitution of the bovine brain benzodiazepine receptor : Effects of lipid environment on the binding characteristics

    NARCIS (Netherlands)

    Viel, G.T; Yang, Q; Lundahl, P; Ensing, K; de Zeeuw, R.A

    1997-01-01

    The benzodiazepine receptor from calf brain was solubilized with sodium deoxycholate (2 mg/ml) in the presence of 0.5 M KCl and protease inhibitors, and bound flunitrazepam with an equilibrium dissociation constant (K-d) of 2.7+/-1.2 nM and with 0.40+/-0.04 pmol binding sites per mg protein (B-max).

  15. Influence of transposition and insertion of additional binding domain on expression and characteristics of xylanase C of Clostridium thermocellum.

    Science.gov (United States)

    Khan, M Imran Mahmood; Sajjad, Muhammad; Ali, Imran; Ahmad, Sajjad; Akhtar, M Waheed

    2010-10-01

    Clostridium thermocellum encodes a xylanase gene (xynC) which is the major component of its cellulosome. XynC is a multidomain enzyme comprising of a substrate binding domain at the N-terminal followed by the catalytic domain and a dockerin domain. To study the influence of binding domain on activity, stability and expression of the enzyme the protein with the binding domain at C-terminal (XynC-CB), and the one with the binding domain at both N- and C-terminal (XynC-BCB) were expressed in E. coli. Recombinant plasmids, pXynC-CB and pXynC-BCB were constructed by inserting the corresponding gene in pET22b(+). XynC-CB and XynC-BCB were expressed at levels around 30% and 33% of the total E. coli cell proteins, respectively, while losing 40% and 20% of their activities at 70°C for 120 min, respectively. The specific activities of XynC-CB, XynC-BCB were 76 and 98 U mg(-1), while the activities on equimolar basis were 4410 and 7450 U μM(-1) against birchwood xylan, respectively. Their overall activities produced in the culture were 3660 and 5430 U L(-1) OD(600)(-1). Substrate binding studies showed that in case of XynC-C 51% of the activity remained unbound to birchwood xylan, whereas in the cases of XynC-BC, XynC-CB and XynC-BCB the activities left unbound were 33%, 32% and 12%, respectively, under the assay conditions used. Similar binding values were obtained in the case of oat spelt xylan. K(m) values for XynC-CB and XynC-BCB against birchwood xylan were found to be 3.1 and 1.47 mg ml(-1), respectively. Thus addition of a second carbohydrate binding domain at the C-terminal of the catalytic domain enhances activity, substrate affinity as well as thermostability. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Binding characteristics of brain-derived neurotrophic factor to its receptors on neurons from the chick embryo

    International Nuclear Information System (INIS)

    Rodriguez-Tebar, A.; Barde, Y.A.

    1988-01-01

    Brain-derived neurotrophic factor (BDNF), a protein known to support the survival of embryonic sensory neurons and retinal ganglion cells, was derivatized with 125I-Bolton-Hunter reagent and obtained in a biologically active, radioactive form (125I-BDNF). Using dorsal root ganglion neurons from chick embryos at 9 d of development, the basic physicochemical parameters of the binding of 125I-BDNF with its receptors were established. Two different classes of receptors were found, with dissociation constants of 1.7 x 10(-11) M (high-affinity receptors) and 1.3 x 10(-9) M (low-affinity receptors). Unlabeled BDNF competed with 125I-BDNF for binding to the high-affinity receptors with an inhibition constant essentially identical to the dissociation constant of the labeled protein: 1.2 x 10(-11) M. The association and dissociation rates from both types of receptors were also determined, and the dissociation constants calculated from these kinetic experiments were found to correspond to the results obtained from steady-state binding. The number of high-affinity receptors (a few hundred per cell soma) was 15 times lower than that of low-affinity receptors. No high-affinity receptors were found on sympathetic neurons, known not to respond to BDNF, although specific binding of 125I-BDNF to these cells was detected at a high concentration of the radioligand. These results are discussed and compared with those obtained with nerve growth factor on the same neuronal populations

  17. [Impact of instantaneous uniformity of SonoVue microbubbles on binding characteristics of a new contrast agent targeted to choriocarcinoma cells in vitro].

    Science.gov (United States)

    Zhou, Li-Xue; Ding, Hong; Jia, Cai-Xia; Li, Yan; Wei, Qing

    2008-07-01

    At present, the investigation of microbubble contrast agents is a hot spot. Although these contrast agents can increase the ultrasound detection rate of tumor vessels, they lack tissue specificity. This study was to evaluate the impact of instantaneous uniformity of SonoVue microbubbles on binding characteristics, including the adhesion rate and stability, of a new contrast agent targeted to choriocarcinoma cells (JARs) in vitro, in order to establish a foundation to explore targeted ultrasound imaging for localization of tumor cell antigens and increase the early diagnostic rate for tumors. The objects were divided into three groups: the uneven microbubble group (n=10), the uniform microbubble group (n=10) and the tiny microbubble group (n=10). The rosette formation rate was counted. JARs were calculated by flow cytometry (FCM). The shape of the rosette was recorded. The targeted contrast agent was prepared by mixing SonoVue microbubbles of different uniformity with rabbit anti-human chorionic gonadotrophin (HCG) antibody. The binding rates of the contrast agent to JARs before and after PBS rinse were analyzed. The binding rate was significantlylower in the uneven microbubble group (60.4+/-1.5)% than in the uniform microbubble group (84.3+/-5.5)% and the tiny microbubble group (90.6+/-6.8)% (P0.05). The binding rates of the targeted microbubbles labeled with fluorescence to JARs were 72.9%, 81.03% and 88.5% in the uneven microbubble group, the uniform microbubble group and the tiny microbubble group, respectively (PSonoVue microbubbles to JARs is related to instantaneous uniformity of the microbubble, which is determined by the shaking method before preparation. Improving instantaneous uniformity of SonoVue microbubbles may increase the binding rate and stability of targeted microbubbles to JARs, thus to improve the image of JARs.

  18. Binding of the Bi (III Complex of Naringin with β-Cyclodextrin/Calf Thymus DNA: Absorption and Fluorescence Characteristics

    Directory of Open Access Journals (Sweden)

    Sameena Yousuf

    2014-01-01

    Full Text Available Naringin-Bi (III complex (Narb was prepared and analysed by UV-Visible absorption and fluorescence measurements. The inclusion complex of Narb with β-Cyclodextrin (β-CD was characterized by the UV-Visible absorption, Infrared, scanning dlectron microscopic, and X-ray diffractometric techniques. The stoichiometry of the inclusion complex of Narb with β-CD was 1 : 1 with a binding constant of 5.18 × 102 mol−1 dm3. The interaction of Narb with Calf Thymus DNA (ctDNA was investigated in the presence and the absence of β-CD. The binding constants for the interaction of Narb with ctDNA in the absence and the presence of β-CD were 1.29 × 105 mol−1 dm3 and 6.89 × 104 mol−1 dm3, respectively. The Stern-Volmer constants for the interaction of Narb with ctDNA in the absence and the presence of β-CD were 1.25 × 104 mol−1 dm3 and 5.10 × 103 mol−1 dm3, respectively. The lowering of the binding affinity and the Ksv were observed for the interaction of Narb with ctDNA in the presence of β-CD.

  19. binding characteristics of 125I-labelled tetanus toxin to primary tissue cultures from mouse embryonic CNS

    International Nuclear Information System (INIS)

    Dimpfel, W.; Habermann, E.

    1977-01-01

    The interaction of 125 I-labelled tetanus toxin with cells in tissue cultures derived from embryonic CNS has been studied. The optimum toxin binding occurs about 2 to 3 weeks after transfer of the cells to culture conditions. The amount of label bound per culture was doubled at this time in comparison to the fourth day after inoculation. The amount of toxin bound depended on the concentration applied. It reached its maximum 8 h after application then decreased slowly. Low amounts of radioactivity were still detectable 97 h after washing off the unbound toxin. Up to 80% of the label could be replaced by simultaneous application of 'cold' toxin. Fixation of the toxin was higher at 4 0 C than at 37 0 C. Preincubation of the cultures with neuraminidase prevented about 75% of the binding. The presence of cytochalasin B led to a small but reproducible decrease of binding, whereas colchicine had no measurable effect. The radioactive ( 125 I) material was identified by a double-isotope technique in disc gel electrophoresis before and after reductive cleavage of its disulphide bonds. In every test it was indistinguishable from 131 I-labelled toxin added as standard. These results largely parallel those obtained with synaptosomes and other systems. They suggest that gangliosides might be the acceptor molecules, and that the culture system will be suitable for studying the actions of this toxin in vitro. (author)

  20. [Distribution characteristics of soil humus fractions stable carbon isotope natural abundance (delta 13C) in paddy field under long-term ridge culture].

    Science.gov (United States)

    Tang, Xiao-hong; Luo, You-jin; Ren, Zhen-jiang; Lü, Jia-ke; Wei, Chao-fu

    2011-04-01

    A 16-year field experiment was conducted in a ridge culture paddy field in the hilly region of Sichuan Basin, aimed to investigate the distribution characteristics of stable carbon isotope natural abundance (delta 13C) in soil humus fractions. The soil organic carbon (SOC) content in the paddy field under different cultivation modes ranked in the order of wide ridge culture > ridge culture > paddy and upland rotation. In soil humus substances (HS), humin (HU) was the main composition, occupying 21% - 30% of the total SOC. In the extracted soil carbon, humic acid (HA) dominated, occupying 17% - 21% of SOC and 38% - 65% of HS. The delta 13C value of SOC ranged from -27.9 per thousand to -25.6 per thousand, and the difference of the delta 13C value between 0-5 cm and 20-40 cm soil layers was about 1.9 per thousand. The delta 13C value of HA under different cultivation modes was 1 per thousand - 2 per thousand lower than that of SOC, and more approached to the delta 13C value of rapeseed and rice residues. As for fulvic acid (FA), its delta 13C value was about 2 per thousand and 4 per thousand higher than that of SOC and HA, respectively. The delta 13C value of HU in plough layer (0-20 cm) and plow layer (20-40 cm) ranged from -23.7 per thousand - -24.9 per thousand and -22.6 per thousand - -24.2 per thousand, respectively, reflecting the admixture of young and old HS. The delta 13C value in various organic carbon fractions was HU>FA>SOC>rapeseed and rice residues>HA. Long-term rice planting benefited the increase of SOC content, and cultivation mode played an important role in affecting the distribution patterns of soil humus delta 13C in plough layer and plow layer.

  1. Comparing the heterogeneity of copper-binding characteristics for two different-sized soil humic acid fractions using fluorescence quenching combined with 2D-COS.

    Science.gov (United States)

    Hur, Jin; Lee, Bo-Mi

    2011-01-01

    Heterogeneous distributions of copper-binding characteristics were compared for two ultrafiltered size fractions of a soil HA using fluorescence quenching combined with two-dimensional correlation spectroscopy (2D-COS). The apparent shapes of the original synchronous fluorescence spectra and the extent of the fluorescence quenching upon the addition of copper were similar for the two fractions. The stability constants calculated at their highest peaks were not significantly different. However, the 2D-COS results revealed that the fluorescence quenching behaviors were strongly affected by the associated wavelengths and the fraction's size. The spectral change preferentially occurred in the wavelength order of 467 nm → 451 nm → 357 nm for the 1-10 K fraction and of 376 nm → 464 nm for the >100 K fraction. The extent of the binding affinities exactly followed the sequential orders interpreted from the 2D-COS, and they exhibited the distinctive ranges of the logarithmic values from 5.86 to 4.91 and from 6.48 to 5.95 for the 1-10 K and the >100 K fractions, respectively. Our studies demonstrated that fluorescence quenching combined with 2D-COS could be successfully utilized to give insight into the chemical heterogeneity associated with metal-binding sites within the relatively homogeneous HA size fractions.

  2. Receptors for corticotropin-releasing hormone in human pituitary: Binding characteristics and autoradiographic localization to immunocytochemically defined proopiomelanocortin cells

    Energy Technology Data Exchange (ETDEWEB)

    Smets, G.; Vauquelin, G.; Moons, L.; Smitz, J.; Kloeppel, G. (Department of Experimental Pathology, Vrije Universiteit Brussel (Belgium))

    1991-08-01

    Using autoradiography combined with immunocytochemistry, the authors demonstrated that the target cells of CRH in the human pituitary were proopiomelanocortin cells. Scatchard analysis of (125I)Tyr0-oCRH saturation binding revealed the presence of one class of saturable, high affinity sites on pituitary tissue homogenate. The equilibrium dissociation constant (Kd) for (125I)Tyr0-oCRH ranged from 1.1-1.6 nM, and the receptor density was between 200-350 fmol/mg protein. Fixation of cryostat sections with 4% paraformaldehyde before tracer incubation improved both tissue preservation and localization of the CRH receptor at the cellular level. Additional postfixation with 1% glutaraldehyde inhibited tracer diffusion during subsequent immunocytochemistry and autoradiography. (125I)Tyr0-oCRH was found in cytoplasmic inclusions or at the cell periphery of ACTH/beta-endorphin cells in the anterior pituitary. Single cells of the posterior pituitary were also CRH receptor positive. Cells staining for PRL or GH were CRH receptor negative. They conclude that CRH binds only to high affinity receptors on ACTH/{beta}-endorphin cells in the human pituitary.

  3. Non-enolisable Knoevenagel condensate appended Schiff bases-metal (II) complexes: Spectral characteristics, DNA-binding and nuclease activities

    Science.gov (United States)

    Gubendran, Ammavasi; Kesavan, Mookkandi Palsamy; Ayyanaar, Srinivasan; Mitu, Liviu; Athappan, Periyakaruppan; Rajesh, Jegathalaprathaban

    2017-06-01

    New Schiff base complexes [Cu(L1)Cl] (1), [Ni(L1)Cl] (2), [Zn(L1)Cl] (3), and [Fe(L2)H2OCl] (4) {L1 = (4E)-3-(2-hydroxybenzylidene)-4-(2-hydroxyphenylimino)pentan-2-one, L2 = 2,2‧-(1E,1‧E)-(3-(2-hydroxybenzylidene)-pentane-2,4-diylidene)bis(azan-1-yl-1 idene)diphenol} have been synthesized and characterized by elemental analysis, UV-Vis, IR, FAB-mass, EPR, spectral studies and electrochemical studies, the ligands L1 &L2 were characterized by 1H and 13C NMR spectra. Complex 1 show a visible spectral d-d band near 600 nm and display cyclic voltammetric quasireversible response for the Cu(II)/Cu(I) couple vs Ag/AgCl in DMSO. The EPR spectrum of 1 show g‖ > g⊥ suggesting a square planar geometry around copper with dx2 - y2 as the ground state. The mass spectral results have confirmed the proposed structure for complexes 1-4. DNA binding properties of these complexes 1-4 have been investigated by absorption titrations, cyclic voltammetric studies and circular dichroism studies. On titration with DNA, the complexes 1-4 show hypochromism at the MLCT band (13-31%) with a red shift of 1-8 nm in the electronic spectrum and positive shift of voltammetric E1/2 in the CV studies are in favour of intercalative binding. CD spectra of 1 showed an increase in molar ellipticity (θ278) of the positive band with a minor red shift indicating the transition of B-form of DNA to A like form. DNA cleavage studies of complexes 1 and 4 with pUC18 DNA were studied by gel electrophoresis and complex 4 cleaves supercoiled pUC18 DNA in an oxidative manner in the presence of H2O2 and on photo irradiation at 312 nm.

  4. Genotoxic effect and antigen binding characteristics of SLE auto-antibodies to peroxynitrite-modified human DNA.

    Science.gov (United States)

    Khan, Md Asad; Alam, Khursheed; Mehdi, Syed Hassan; Rizvi, M Moshahid A

    2017-12-01

    Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease characterized by auto-antibodies against native deoxyribonucleic acid after modification and is one of the reasons for the development of SLE. Here, we have evaluated the structural perturbations in human placental DNA by peroxynitrite using spectroscopy, thermal denaturation and high-performance liquid chromatography (HPLC). Peroxynitrite is a powerful potent bi-functional oxidative/nitrative agent that is produced both endogenously and exogenously. In experimental animals, the peroxynitrite-modified DNA was found to be highly immunogenic. The induced antibodies showed cross-reactions with different types of DNA and nitrogen bases that were modified with peroxynitrite by inhibition ELISA. The antibody activity was inhibited by approximately 89% with its immunogen as the inhibitor. The antigen-antibodies interaction between induced antibodies with peroxynitrite-modified DNA showed retarded mobility as compared to the native form. Furthermore, significantly increased binding was also observed in SLE autoantibodies with peroxynitrite-modified DNA than native form. Moreover, DNA isolated from lymphocyte of SLE patients revealed significant recognition of anti-peroxynitrite-modified DNA immunoglobulin G (IgG). Our data indicates that DNA modified with peroxynitrite presents unique antigenic determinants that may induce autoantibody response in SLE. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Stable particles

    International Nuclear Information System (INIS)

    Samios, N.P.

    1994-01-01

    I have been asked to review the subject of stable particles, essentially the particles that eventually comprised the meson and baryon octets, with a few more additions - with an emphasis on the contributions made by experiments utilizing the bubble chamber technique. In this activity, much work had been done by the photographic emulsion technique and cloud chambers - exposed to cosmic rays as well as accelerator based beams. In fact, many if not most of the stable particles were found by these latter two techniques, however, the foree of the bubble chamber (coupled with the newer and more powerful accelerators) was to verify, and reinforce with large statistics, the existence of these states, to find some of the more difficult ones, mainly neutrals and further to elucidate their properties, i.e., spin, parity, lifetimes, decay parameters, etc. (orig.)

  6. Stable particles

    International Nuclear Information System (INIS)

    Samios, N.P.

    1993-01-01

    I have been asked to review the subject of stable particles, essentially the particles that eventually comprised the meson and baryon octets. with a few more additions -- with an emphasis on the contributions made by experiments utilizing the bubble chamber technique. In this activity, much work had been done by the photographic emulsion technique and cloud chambers-exposed to cosmic rays as well as accelerator based beams. In fact, many if not most of the stable particles were found by these latter two techniques, however, the forte of the bubble chamber (coupled with the newer and more powerful accelerators) was to verify, and reinforce with large statistics, the existence of these states, to find some of the more difficult ones, mainly neutrals and further to elucidate their properties, i.e., spin, parity, lifetimes, decay parameters, etc

  7. Glacial-interglacial changes in the surface water characteristics of the Andaman Sea: Evidence from stable isotopic ratios of planktonic foraminifera

    Digital Repository Service at National Institute of Oceanography (India)

    Ahmad, S.M.; Patil, D.J.; Rao, P.S.; Nath, B.N.; Rao, B.R.; Rajagopalan, G.

    Stable carbon and oxygen isotopic analyses of the planktonic foraminifera (Globigerinoides ruber) from a deep sea sediment core (GC-1) in the Andaman Sea show high glacial-to-Holocene d18O amplitude of 2.1% which is consistent...

  8. Stable beams

    CERN Multimedia

    2015-01-01

    Stable beams: two simple words that carry so much meaning at CERN. When LHC page one switched from "squeeze" to "stable beams" at 10.40 a.m. on Wednesday, 3 June, it triggered scenes of jubilation in control rooms around the CERN sites, as the LHC experiments started to record physics data for the first time in 27 months. This is what CERN is here for, and it’s great to be back in business after such a long period of preparation for the next stage in the LHC adventure.   I’ve said it before, but I’ll say it again. This was a great achievement, and testimony to the hard and dedicated work of so many people in the global CERN community. I could start to list the teams that have contributed, but that would be a mistake. Instead, I’d simply like to say that an achievement as impressive as running the LHC – a machine of superlatives in every respect – takes the combined effort and enthusiasm of everyone ...

  9. Stable isotope mass spectrometry in petroleum exploration

    International Nuclear Information System (INIS)

    Mathur, Manju

    1997-01-01

    The stable isotope mass spectrometry plays an important role to evaluate the stable isotopic composition of hydrocarbons. The isotopic ratios of certain elements in petroleum samples reflect certain characteristics which are useful for petroleum exploration

  10. The chaperone and potential mannan-binding lectin (MBL) co-receptor calreticulin interacts with MBL through the binding site for MBL-associated serine proteases

    DEFF Research Database (Denmark)

    Pagh, Rasmus; Duus, Karen; Laursen, Inga

    2008-01-01

    was immobilized on a solid surface or bound to mannan on a surface. The binding was non-covalent and biphasic with an initial salt-sensitive phase followed by a more stable salt-insensitive interaction. For plasma-derived MBL, known to be complexed with MBL-associated serine proteases (MASPs), no binding...... with calreticulin. Comparative analysis of MBL with complement component C1q, its counterpart of the classical pathway, revealed that they display similar binding characteristics for calreticulin, providing further indication that calreticulin is a common co-receptor/chaperone for both proteins. In conclusion......The chaperone calreticulin has been suggested to function as a C1q and collectin receptor. The interaction of calreticulin with mannan-binding lectin (MBL) was investigated by solid-phase binding assays. Calreticulin showed saturable and time-dependent binding to recombinant MBL, provided that MBL...

  11. Consensus of sample-balanced classifiers for identifying ligand-binding residue by co-evolutionary physicochemical characteristics of amino acids

    KAUST Repository

    Chen, Peng

    2013-01-01

    Protein-ligand binding is an important mechanism for some proteins to perform their functions, and those binding sites are the residues of proteins that physically bind to ligands. So far, the state-of-the-art methods search for similar, known structures of the query and predict the binding sites based on the solved structures. However, such structural information is not commonly available. In this paper, we propose a sequence-based approach to identify protein-ligand binding residues. Due to the highly imbalanced samples between the ligand-binding sites and non ligand-binding sites, we constructed several balanced data sets, for each of which a random forest (RF)-based classifier was trained. The ensemble of these RF classifiers formed a sequence-based protein-ligand binding site predictor. Experimental results on CASP9 targets demonstrated that our method compared favorably with the state-of-the-art. © Springer-Verlag Berlin Heidelberg 2013.

  12. Evaluation of loading characteristics and IgG binding performance of Staphylococcal protein A on polypropylene capillary-channeled polymer fibers.

    Science.gov (United States)

    Trang, Hung K; Schadock-Hewitt, Abby J; Jiang, Liuwei; Marcus, R Kenneth

    2016-03-15

    The loading characteristics of recombinant Staphyloccocus aureus protein A (rSPA) on polypropylene (PP) capillary-channeled polymer (C-CP) fibers were investigated through breakthrough curves and frontal analysis. The dynamic adsorption data was fit to various isotherm models to assess the possible mode of rSPA-PP fiber adsorption. Among them, the Langmuir-linear model fit the experimental data best, suggesting a two-stage mechanism of adsorption. The first stage involves the formation of a monolayer coverage, which follows the Langmuir isotherm. When the adsorbate concentration increases, solute starts to adsorb onto the already adsorbed layer, following a linear adsorption response. The relationship between the rSPA loading and flow rate and column length was also investigated. These two parameters are related through the residence time of rSPA in the column. It was determined that loading at the flow rate of 0.5 mL min(-1) (∼28 mm s(-1)) with a 1×10(-5) M (0.5 mg mL(-1)) rSPA feed concentration on a 30-cm (0.762 mm i.d.) column could conveniently produce a reasonable binding capacity of rSPA on PP surface within only 6 min. Under those conditions, the rSPA binding at 50% breakthrough was found to be ∼2.1 mg g(-1) fiber. Operation of the rSPA-modified columns across ten complete processing cycles using clean-in-place conditions (including urea, guanidine HCl, and NaOH) commonly used in the bioprocessing industry allows assessment of the robustness of the rSPA capture layers. In all cases, the robustness was quite good, with the relative responses providing insights to the rSPA/PP surface structure. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Springtime carbon emission episodes at the Gosan background site revealed by total carbon, stable carbon isotopic composition, and thermal characteristics of carbonaceous particles

    Directory of Open Access Journals (Sweden)

    J. Jung

    2011-11-01

    Full Text Available In order to investigate the emission of carbonaceous aerosols at the Gosan background super-site (33.17° N, 126.10° E in East Asia, total suspended particles (TSP were collected during spring of 2007 and 2008 and analyzed for particulate organic carbon, elemental carbon, total carbon (TC, total nitrogen (TN, and stable carbon isotopic composition (δ13C of TC. The stable carbon isotopic composition of TC (δ13CTC was found to be lowest during pollen emission episodes (range: −26.2‰ to −23.5‰, avg. −25.2 ± 0.9‰, approaching those of the airborne pollen (−28.0‰ collected at the Gosan site. Based on a carbon isotope mass balance equation, we found that ~42% of TC in the TSP samples during the pollen episodes was attributed to airborne pollen from Japanese cedar trees planted around tangerine farms in Jeju Island. A negative correlation between the citric acid-carbon/TC ratios and δ13CTC was obtained during the pollen episodes. These results suggest that citric acid emitted from tangerine fruit may be adsorbed on the airborne pollen and then transported to the Gosan site. Thermal evolution patterns of organic carbon during the pollen episodes were characterized by high OC evolution in the OC2 temperature step (450 °C. Since thermal evolution patterns of organic aerosols are highly influenced by their molecular weight, they can be used as additional information on the formation of secondary organic aerosols and the effect of aging of organic aerosols during the long-range atmospheric transport and sources of organic aerosols.

  14. Aggregation induced emission enhancement (AIEE) characteristics of quinoline based compound - A versatile fluorescent probe for pH, Fe(III) ion, BSA binding and optical cell imaging

    Science.gov (United States)

    Manikandan, Irulappan; Chang, Chien-Huei; Chen, Chia-Ling; Sathish, Veerasamy; Li, Wen-Shan; Malathi, Mahalingam

    2017-07-01

    Novel benzimidazoquinoline derivative (AVT) was synthesized through a substitution reaction and characterized by various spectral techniques. Analyzing the optical properties of AVT under absorption and emission spectral studies in different environments exclusively with respect to solvents and pH, intriguing characteristics viz. aggregation induced emission enhancement (AIEE) in the THF solvent and 'On-Off' pH sensing were found at neutral pH. Sensing nature of AVT with diverse metal ions and bovine serum albumin (BSA) was also studied. Among the metal ions, Fe3 + ion alone tunes the fluorescence intensity of AVT probe in aqueous medium from ;turn-on; to ;turn-off; through ligand (probe) to metal charge transfer (LMCT) mechanism. The probe AVT in aqueous medium interacts strongly with BSA due to Fluorescence Resonance Energy Transfer (FRET) and the conformational change in BSA was further analyzed using synchronous fluorescence techniques. Docking study of AVT with BSA reveals that the active site of binding is tryptophan residue which is also supported by the experimental results. Interestingly, fluorescent AVT probe in cells was examined through cellular imaging studies using BT-549 and MDA-MB-231 cells. Thus, the single molecule probe based detection of multiple species and stimuli were described.

  15. A microfluidic design to provide a stable and uniform in vitro microenvironment for cell culture inspired by the redundancy characteristic of leaf areoles.

    Science.gov (United States)

    Li, Jingmin; Wei, Juan; Liu, Yuanchang; Liu, Bo; Liu, Tao; Jiang, Yang; Ding, Laiqian; Liu, Chong

    2017-11-07

    The leaf venation is considered to be an optimal transportation system with the mesophyll cells being divided by minor veins into small regions named areoles. The transpiration of water in different regions of a leaf fluctuates over time making the transportation of water in veins fluctuate as well. However, because of the existence of multiple paths provided by the leaf venation network and the pits on the walls of the vessels, the pressure field and nutrient concentration in the areoles that the mesophyll cells live in are almost uniform. Therefore, inspired by such structures, a microfluidic design of a novel cell culture chamber has been proposed to obtain a stable and uniform microenvironment. The device consists of a novel microchannel system imitating the vessels in the leaf venation to transport the culture medium, a cell culture chamber imitating the areole and microgaps imitating the pits. The effects of the areole and pit on flow fields in the cell culture chamber have been discussed. The results indicate that the bio-inspired microfluidic device is a robust platform to provide an in vivo like fluidic microenvironment.

  16. Spectroscopic study of drug-binding characteristics of unmodified and pNPA-based acetylated human serum albumin: Does esterase activity affect microenvironment of drug binding sites on the protein?

    International Nuclear Information System (INIS)

    Moradi, Nastaran; Ashrafi-Kooshk, Mohammad Reza; Ghobadi, Sirous; Shahlaei, Mohsen; Khodarahmi, Reza

    2015-01-01

    Human serum albumin (HSA) is the most prominent extracellular protein in blood plasma. There are several binding sites on the protein which provide accommodation for structurally-unrelated endogenous and exogenous ligands and a wide variety of drugs. “Esterase-like” activity (hydrolysis of p-nitrophenyl esters) by the protein has been also reported. In the current study, we set out to investigate the interaction of indomethacin and ibuprofen with the unmodified and modified HSA (pNPA-modified HSA) using various spectroscopic techniques. Fluorescence data showed that 1:1 binding of drug to HSA is associated with quenching of the protein intrinsic fluorescence. Decrease of protein surface hydrophobicity (PSH), alteration in drug binding affinity and change of the protein stability, after esterase-like activity and permanent acetylation of HSA, were also documented. Analysis of the quenching and thermodynamic parameters indicated that forces involved in drug–HSA interactions change upon the protein modification. - Highlights: • Binding propensity of indomethacin extremely decreased upon the protein acetylation. • There is no ibuprofen binding after protein acetylation. • Protein stability changes upon drug binding as well as protein acetylation. • Drug pharmacokinetics may be influenced under co-administration of HSA-modifier drugs

  17. Spectroscopic study of drug-binding characteristics of unmodified and pNPA-based acetylated human serum albumin: Does esterase activity affect microenvironment of drug binding sites on the protein?

    Energy Technology Data Exchange (ETDEWEB)

    Moradi, Nastaran [Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Faculty of Pharmaceutical Sciences, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Ashrafi-Kooshk, Mohammad Reza [Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Ghobadi, Sirous [Department of Biology, Faculty of Sciences, Razi University, Kermanshah (Iran, Islamic Republic of); Shahlaei, Mohsen [Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Faculty of Pharmaceutical Sciences, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Khodarahmi, Reza, E-mail: rkhodarahmi@mbrc.ac.ir [Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Faculty of Pharmaceutical Sciences, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of)

    2015-04-15

    Human serum albumin (HSA) is the most prominent extracellular protein in blood plasma. There are several binding sites on the protein which provide accommodation for structurally-unrelated endogenous and exogenous ligands and a wide variety of drugs. “Esterase-like” activity (hydrolysis of p-nitrophenyl esters) by the protein has been also reported. In the current study, we set out to investigate the interaction of indomethacin and ibuprofen with the unmodified and modified HSA (pNPA-modified HSA) using various spectroscopic techniques. Fluorescence data showed that 1:1 binding of drug to HSA is associated with quenching of the protein intrinsic fluorescence. Decrease of protein surface hydrophobicity (PSH), alteration in drug binding affinity and change of the protein stability, after esterase-like activity and permanent acetylation of HSA, were also documented. Analysis of the quenching and thermodynamic parameters indicated that forces involved in drug–HSA interactions change upon the protein modification. - Highlights: • Binding propensity of indomethacin extremely decreased upon the protein acetylation. • There is no ibuprofen binding after protein acetylation. • Protein stability changes upon drug binding as well as protein acetylation. • Drug pharmacokinetics may be influenced under co-administration of HSA-modifier drugs.

  18. [Expression of fatty acid synthase and adipocyte fatty acid-binding protein and the relationship with the clinicopathological characteristics in human infiltrating ductal breast cancer].

    Science.gov (United States)

    Zhou, Lan; Zhao, Yu-hua; Wang, Xiao-dong; Jiang, Su-fang; Li, Hua

    2015-03-01

    To study the expression of fatty acid synthase (FASN) and adipocyte fatty acid-binding protein (A-FABP) in human infiltrating ductal breast cancer (IDC) tissues and hunman breast cancer cells and the relationship with the clinicopathogical characteristics. To further explore the relationship between FASN and A-FABP, and the relevance of the invasion in cancer cell. The expression of FASN and A-FABP was detected in 58 cases of human infiltrating ductal breast cancer and 12 cases of human normal breast tissues by immunohistochemistry technique, calculated positive expression percentage according to the number of positive cells percentage and the staining degree of positive sediment. The cell wound-healing assay was applied to detect the invasion of SKBR3 and MCF-7 cells. Western blot was used to detect the expression of FASN and A-FABP in MCF-7 and SKBR3 cells. The positive rates of FASN and A-FABP were 8.3% (1/12) and 16.7% (1/6) respectively in 12 cases of normal breast tissues by immunohistochemistry. In 58 cases of IDC tissues, the positive rates of FASN and A-FABP were 72.4% (42/58) and 79.3% (46/58) respectively. The differences of the positive rates of FASN and A-FABP in normal breast and IDC tissues were statistically significant (P2 cm) when compared with lymph node metastasis negative group or the diameter SKBR3 was significantly higher than MCF-7 cell at 12, 24 h (PSKBR3 was higher than that in MCF-7. FASN and A-FABP might associated with the lymph node metastasis and tumor size, and there was correlation between FASN and A-FABP in human IDC tissues. FASN may associated with the invasion and metastasis in breast cancer cells.

  19. Positively-charged semi-tunnel is a structural and surface characteristic of polyphosphate-binding proteins: an in-silico study.

    Directory of Open Access Journals (Sweden)

    Zheng Zachory Wei

    Full Text Available Phosphate is essential for all major life processes, especially energy metabolism and signal transduction. A linear phosphate polymer, polyphosphate (polyP, linked by high-energy phosphoanhydride bonds, can interact with various proteins, playing important roles as an energy source and regulatory factor. However, polyP-binding structures are largely unknown. Here we proposed a putative polyP binding site, a positively-charged semi-tunnel (PCST, identified by surface electrostatics analyses in polyP kinases (PPKs and many other polyP-related proteins. We found that the PCSTs in varied proteins were folded in different secondary structure compositions. Molecular docking calculations revealed a significant value for binding affinity to polyP in PCST-containing proteins. Utilizing the PCST identified in the β subunit of PPK3, we predicted the potential polyP-binding domain of PPK3. The discovery of this feature facilitates future searches for polyP-binding proteins and discovery of the mechanisms for polyP-binding activities. This should greatly enhance the understanding of the many physiological functions of protein-bound polyP and the involvement of polyP and polyP-binding proteins in various human diseases.

  20. Characteristic and Mixing Mechanisms of Thermal Fluid at the Tampomas Volcano, West Java, Using Hydrogeochemistry, Stable Isotope and 222Rn Analyses

    Directory of Open Access Journals (Sweden)

    Irwan Iskandar

    2018-03-01

    Full Text Available The Tampomas Volcano is a Quaternary volcano located on Java Island and controlled by a west-northwest–east-southeast (WNW-ESE regional fault trend. This regional structure acts as conduits for the hydrothermal fluids to ascend from a deeper system toward the surface and, in the end, mix with groundwater. In this research, water geochemistry, gas chemistry and isotopes 2H, 18O and 13C were used to explore the subsurface fluid characteristics and mixing mechanisms of the hydrothermal fluids with groundwater. In addition to those geochemical methods, soil-gas and dissolved 222Rn observations were performed to understand the geological control of fluid chemistry. Based on the analytical results, the hydrothermal system of Tampomas is only developed at the northeastern flank of the volcano, which is mainly controlled by NE-SW structures as deep fluid conduits, while the Cimalaka Caldera Rim around Sekarwangi act as the boundary flow of the system. This system is also categorized as an “intermediate temperature system” wherein fluid is derived from the interaction between the volcanic host-rock at 170 ± 10 °C mixed with trace organic gas input from sedimentary formation; afterwards, the fluid flows laterally and is diluted with groundwater near the surface. Soil-gas and dissolved 222Rn confirm that these permeable zones are effective conduits for the ascending thermal fluids. It is found that NE faults carry higher trace elements from the deeper system, while the circular feature of the Caldera Rim acts as the boundary of the hydrothermal system.

  1. Stable Isotope Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Tissue samples (skin, bone, blood, muscle) are analyzed for stable carbon, stable nitrogen, and stable sulfur analysis. Many samples are used in their entirety for...

  2. Substrate-induced stable enzyme-inhibitor complex formation allows tight binding of novel 2-aminopyrimidin-4(3H)-ones to drug-resistant HIV-1 reverse transcriptase mutants.

    Science.gov (United States)

    Samuele, Alberta; Facchini, Marcella; Rotili, Dante; Mai, Antonello; Artico, Marino; Armand-Ugón, Mercedes; Esté, José A; Maga, Giovanni

    2008-09-01

    We recently reported the synthesis and biological evaluation of a novel series of 5-alkyl-2-(N,N-disubstituted)amino-6-(2,6-difluorophenylalkyl)-3,4-dihydropyrimidin-4(3H)-ones (F(2)-N,N-DABOs). These compounds are highly active against both wild-type HIV-1 and the K103N, Y181C, and Y188L mutant strains. Herein we present novel 6-(2-chloro-6-fluorophenylalkyl)-N,N-DABO (2-Cl-6-F-N,N-DABO) derivatives and investigate the molecular basis for their high-affinity binding to HIV-1 reverse transcriptase (RT). Our results show that the new compounds display higher association rates than the difluoro derivatives toward wild-type HIV-1 RT or drug-resistant RT mutant forms. We also show that they preferentially associate to either the free enzyme or the enzyme-nucleic acid binary complex, and that this binding is stabilized upon formation of the ternary complex between HIV-1 RT and both the nucleic acid and nucleotide substrates. Interestingly, one compound showed dissociation rates from the ternary complex with RT mutants K103N and Y181I 10-20-fold slower than from the corresponding complex with wild-type RT.

  3. Structural characteristics of anabolic androgenic steroids contributing to binding to the androgen receptor and to their anabolic and androgenic activities. Applied modifications in the steroidal structure.

    Science.gov (United States)

    Fragkaki, A G; Angelis, Y S; Koupparis, M; Tsantili-Kakoulidou, A; Kokotos, G; Georgakopoulos, C

    2009-02-01

    Anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone introduced for therapeutic purposes providing enhanced anabolic potency with reduced androgenic effects. Androgens mediate their action through their binding to the androgen receptor (AR) which is mainly expressed in androgen target tissues, such as the prostate, skeletal muscle, liver and central nervous system. This paper reviews some of the wide spectrum of testosterone and synthetic AAS structure modifications related to the intended enhancement in anabolic activity. The structural features of steroids necessary for effective binding to the AR and those which contribute to the stipulation of the androgenic and anabolic activities are also presented.

  4. petrography, compositional characteristics and stable isotope ...

    African Journals Online (AJOL)

    PROF EKWUEME

    The relatively high concentration of SiO2 and its interrelationship with other major oxides, ... The Mg/Ca ratio ranges from 0.02 and 0.1(av. 0.04), with an outlier value of 0.1, indicating a strong diagenetic influence and the precipitation of dolomite in the mixing zone. ..... may define the extent to which the heavier brines near.

  5. Peptide binding characteristics of the non-classical class Ib MHC molecule HLA-E assessed by a recombinant random peptide approach

    Directory of Open Access Journals (Sweden)

    Joly Etienne

    2001-06-01

    Full Text Available Abstract Background Increasing evidence suggests that the effect of HLA-E on Natural Killer (NK cell activity can be affected by the nature of the peptides bound to this non-classical, MHC class Ib molecule. However, its reduced cell surface expression, and until recently, the lack of specific monoclonal antibodies hinder studying the peptide-binding specificity HLA-E. Results An in vitro refolding system was used to assess binding of recombinant HLA-E to either specific peptides or a nonamer random peptide library. Peptides eluted from HLA-E molecules refolded around the nonamer library were then used to determine a binding motif for HLA-E. Hydrophobic and non-charged amino acids were found to predominate along the peptide motif, with a leucine anchor at P9, but surprisingly there was no methionine preference at P2, as suggested by previous studies. Conclusions Compared to the results obtained with rat classical class Ia MHC molecules, RT1-A1c and RT1-Au, HLA-E appears to refold around a random peptide library to reduced but detectable levels, suggesting that this molecule's specificity is tight but probably not as exquisite as has been previously suggested. This, and a previous report that it can associate with synthetic peptides carrying a viral sequence, suggests that HLA-E, similar to its mouse counterpart (Qa-1b, could possibly bind peptides different from MHC class I leader peptides and present them to T lymphocytes.

  6. Peptide binding characteristics of the non-classical class Ib MHC molecule HLA-E assessed by a recombinant random peptide approach

    Science.gov (United States)

    Stevens, James; Joly, Etienne; Trowsdale, John; Butcher, Geoffrey W

    2001-01-01

    Background Increasing evidence suggests that the effect of HLA-E on Natural Killer (NK) cell activity can be affected by the nature of the peptides bound to this non-classical, MHC class Ib molecule. However, its reduced cell surface expression, and until recently, the lack of specific monoclonal antibodies hinder studying the peptide-binding specificity HLA-E. Results An in vitro refolding system was used to assess binding of recombinant HLA-E to either specific peptides or a nonamer random peptide library. Peptides eluted from HLA-E molecules refolded around the nonamer library were then used to determine a binding motif for HLA-E. Hydrophobic and non-charged amino acids were found to predominate along the peptide motif, with a leucine anchor at P9, but surprisingly there was no methionine preference at P2, as suggested by previous studies. Conclusions Compared to the results obtained with rat classical class Ia MHC molecules, RT1-A1c and RT1-Au, HLA-E appears to refold around a random peptide library to reduced but detectable levels, suggesting that this molecule's specificity is tight but probably not as exquisite as has been previously suggested. This, and a previous report that it can associate with synthetic peptides carrying a viral sequence, suggests that HLA-E, similar to its mouse counterpart (Qa-1b), could possibly bind peptides different from MHC class I leader peptides and present them to T lymphocytes. PMID:11432755

  7. A critical look at the calculation of the binding characteristics and concentration of iron complexing ligands in seawater with suggested improvements

    NARCIS (Netherlands)

    Gerringa, L.J.A.; Rijkenberg, M.J.A.; Thuróczy, C.-E.; Maas, L.R.M.

    2014-01-01

    Environmental context
    The low concentration of iron in the oceans limits growth of phytoplankton. Dissolved organic molecules, called ligands, naturally present in seawater, bind iron thereby increasing its solubility and, consequently, its availability for biological uptake by phytoplankton. The

  8. CART (cocaine- and amphetamine-regulated transcript) peptide specific binding sites in PC12 cells have characteristics of CART peptide receptors

    Czech Academy of Sciences Publication Activity Database

    Nagelová, Veronika; Pirnik, Z.; Železná, Blanka; Maletínská, Lenka

    2014-01-01

    Roč. 1547, Feb 14 (2014), s. 16-24 ISSN 0006-8993 R&D Projects: GA ČR GAP303/10/1368 Institutional support: RVO:61388963 Keywords : CART peptide * PC12 cell * differentiation * binding * signaling * c-Jun Subject RIV: CE - Biochemistry Impact factor: 2.843, year: 2014

  9. Comparison of the binding characteristics of [{sup 18}F]THK-523 and other amyloid imaging tracers to Alzheimer's disease pathology

    Energy Technology Data Exchange (ETDEWEB)

    Harada, Ryuichi; Okamura, Nobuyuki; Yoshikawa, Takeo; Yanai, Kazuhiko [Tohoku University School of Medicine, Department of Pharmacology, Sendai (Japan); Furumoto, Shozo [Tohoku University School of Medicine, Department of Pharmacology, Sendai (Japan); Tohoku University, Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Sendai (Japan); Tago, Tetsuro; Iwata, Ren [Tohoku University, Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Sendai (Japan); Maruyama, Masahiro; Higuchi, Makoto [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba (Japan); Arai, Hiroyuki [Tohoku University, Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Sendai (Japan); Kudo, Yukitsuka [Tohoku University, Innovation of New Biomedical Engineering Center, Sendai (Japan)

    2013-01-15

    Extensive deposition of senile plaques and neurofibrillary tangles in the brain is a pathological hallmark of Alzheimer's disease (AD). Although several PET imaging agents have been developed for in vivo detection of senile plaques, no PET probe is currently available for selective detection of neurofibrillary tangles in the living human brain. Recently, [{sup 18}F]THK-523 was developed as a potential in vivo imaging probe for tau pathology. The purpose of this study was to compare the binding properties of [{sup 18}F]THK-523 and other amyloid imaging agents, including PiB, BF-227 and FDDNP, to synthetic protein fibrils and human brain tissue. In vitro radioligand binding assays were conducted using synthetic amyloid {beta}{sub 42} and K18{Delta}K280-tau fibrils. Nonspecific binding was determined by the addition of unlabelled compounds at a concentration of 2 {mu}M. To examine radioligand binding to neuropathological lesions, in vitro autoradiography was conducted using sections of AD brain. [{sup 18}F]THK-523 showed higher affinity for tau fibrils than for A{beta} fibrils, whereas the other probes showed a higher affinity for A{beta} fibrils. The autoradiographic analysis indicated that [{sup 18}F]THK-523 accumulated in the regions containing a high density of tau protein deposits. Conversely, PiB and BF-227 accumulated in the regions containing a high density of A{beta} plaques. These findings suggest that the unique binding profile of [{sup 18}F]THK-523 can be used to identify tau deposits in AD brain. (orig.)

  10. Stable convergence and stable limit theorems

    CERN Document Server

    Häusler, Erich

    2015-01-01

    The authors present a concise but complete exposition of the mathematical theory of stable convergence and give various applications in different areas of probability theory and mathematical statistics to illustrate the usefulness of this concept. Stable convergence holds in many limit theorems of probability theory and statistics – such as the classical central limit theorem – which are usually formulated in terms of convergence in distribution. Originated by Alfred Rényi, the notion of stable convergence is stronger than the classical weak convergence of probability measures. A variety of methods is described which can be used to establish this stronger stable convergence in many limit theorems which were originally formulated only in terms of weak convergence. Naturally, these stronger limit theorems have new and stronger consequences which should not be missed by neglecting the notion of stable convergence. The presentation will be accessible to researchers and advanced students at the master's level...

  11. Characteristic vibration patterns of odor compounds from bread-baking volatiles upon protein binding: density functional and ONIOM study and principal component analysis.

    Science.gov (United States)

    Treesuwan, Witcha; Hirao, Hajime; Morokuma, Keiji; Hannongbua, Supa

    2012-05-01

    As the mechanism underlying the sense of smell is unclear, different models have been used to rationalize structure-odor relationships. To gain insight into odorant molecules from bread baking, binding energies and vibration spectra in the gas phase and in the protein environment [7-transmembrane helices (7TMHs) of rhodopsin] were calculated using density functional theory [B3LYP/6-311++G(d,p)] and ONIOM [B3LYP/6-311++G(d,p):PM3] methods. It was found that acetaldehyde ("acid" category) binds strongly in the large cavity inside the receptor, whereas 2-ethyl-3-methylpyrazine ("roasted") binds weakly. Lys296, Tyr268, Thr118 and Ala117 were identified as key residues in the binding site. More emphasis was placed on how vibrational frequencies are shifted and intensities modified in the receptor protein environment. Principal component analysis (PCA) suggested that the frequency shifts of C-C stretching, CH(3) umbrella, C = O stretching and CH(3) stretching modes have a significant effect on odor quality. In fact, the frequency shifts of the C-C stretching and C = O stretching modes, as well as CH(3) umbrella and CH(3) symmetric stretching modes, exhibit different behaviors in the PCA loadings plot. A large frequency shift in the CH(3) symmetric stretching mode is associated with the sweet-roasted odor category and separates this from the acid odor category. A large frequency shift of the C-C stretching mode describes the roasted and oily-popcorn odor categories, and separates these from the buttery and acid odor categories.

  12. Evaluation of the binding characteristics of [{sup 18}F]fluoroproxyfan in the rat brain for in vivo visualization of histamine H{sub 3} receptor

    Energy Technology Data Exchange (ETDEWEB)

    Funaki, Yoshihito [Cyclotron and Radioisotope Center, Tohoku University, Sendai 980-8578 (Japan)], E-mail: zen@cyric.tohoku.ac.jp; Sato, Kimihiko [Cyclotron and Radioisotope Center, Tohoku University, Sendai 980-8578 (Japan); Kato, Motohisa [Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai 980-8575 (Japan); Ishikawa, Yoichi; Iwata, Ren [Cyclotron and Radioisotope Center, Tohoku University, Sendai 980-8578 (Japan); Yanai, Kazuhiko [Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai 980-8575 (Japan)

    2007-11-15

    Histamine H{sub 3} receptors play an important role in biological functions. The aim of this research was to examine whether histamine H{sub 3} receptors can be visualized in vivo and in vitro with [{sup 18}F]3-(1H-imidazol-4-yl)propyl 4-fluorobenzyl ether (fluoroproxyfan). [{sup 18}F]Fluoroproxyfan was synthesized with high specific activity using [{sup 18}F]benzyl bromide. The binding of [{sup 18}F]fluoroproxyfan to rat brain homogenates was higher in the striatum and thalamus and was lowest in the cerebellum. The in vitro autoradiographic study successfully demonstrated the specific binding of [{sup 18}F]fluoroproxyfan to the H{sub 3} receptor in the rat brain. In accordance with the in vitro bindings, the in vivo distribution of [{sup 18}F]fluoroproxyfan was heterogeneous in the rat brain. In the blocking experiments, the heterogeneous distribution disappeared in the presence of large amounts of fluoroproxyfan. These data suggest that [{sup 18}F]fluoroproxyfan can be potentially useful to image histamine H{sub 3} receptor noninvasively in the human brain by positron emission tomography.

  13. Binding characteristics of homogeneous molecularly imprinted polymers for acyclovir using an (acceptor-donor-donor)-(donor-acceptor-acceptor) hydrogen-bond strategy, and analytical applications for serum samples.

    Science.gov (United States)

    Wu, Suqin; Tan, Lei; Wang, Ganquan; Peng, Guiming; Kang, Chengcheng; Tang, Youwen

    2013-04-12

    This paper demonstrates a novel approach to assembling homogeneous molecularly imprinted polymers (MIPs) based on mimicking multiple hydrogen bonds between nucleotide bases by preparing acyclovir (ACV) as a template and using coatings grafted on silica supports. (1)H NMR studies confirmed the AAD-DDA (A for acceptor, D for donor) hydrogen-bond array between template and functional monomer, while the resultant monodisperse molecularly imprinted microspheres (MIMs) were evaluated using a binding experiment, high performance liquid chromatography (HPLC), and solid phase extraction. The Langmuir isothermal model and the Langmuir-Freundlich isothermal model suggest that ACV-MIMs have more homogeneous binding sites than MIPs prepared through normal imprinting. In contrast to previous MIP-HPLC columns, there were no apparent tailings for the ACV peaks, and ACV-MIMs had excellent specific binding properties with a Ka peak of 3.44 × 10(5)M(-1). A complete baseline separation is obtained for ACV and structurally similar compounds. This work also successfully used MIMs as a specific sorbent for capturing ACV from serum samples. The detection limit and mean recovery of ACV was 1.8 ng/mL(-1) and 95.6%, respectively, for molecularly imprinted solid phase extraction coupled with HPLC. To our knowledge, this was the first example of MIPs using AAD-DDA hydrogen bonds. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. N-(2-chloroethyl)-N-nitrosoureas covalently bound to nonionic and monocationic lexitropsin dipeptides. Synthesis, DNA affinity binding characteristics, and reactions with 32P-end-labeled DNA

    International Nuclear Information System (INIS)

    Church, K.M.; Wurdeman, R.L.; Zhang, Yi; Chen, Faxian; Gold, B.

    1990-01-01

    The synthesis and characterization of a series of compounds that contain an N-alkyl-N-nitrosourea functionality linked to DNA minor groove binding bi- and tripeptides (lexitropsins or information-reading peptides) based on methylpyrrole-2-carboxamide subunits are described. The lexitropsins (lex) synthesized have either a 3-(dimethylamino)propyl or propyl substituent on the carboxyl terminus. The preferred DNA affinity binding sequences of these compounds were footprinted in 32 P-end-labeled restriction fragments with methidiumpropyl-EDTA·Fe(II), and in common with other structural analogues, e.g., distamycin and netropsin, these nitrosoureas recognize A-T-rich runs. The affinity binding of the compound with the dimethylamino terminus, which is ionized at near-neutral pH, appeared stronger than that observed for the neutral dipeptide. The sequence specificity for DNA alkylation by (2-chloroethyl)nitrosourea-lex dipeptides (Cl-ENU-lex), with neutral and charged carboxyl termini, using 32 P-end-labeled restriction fragments, was determined by the conversion of the adducted sites into single-strand breaks by sequential heating at neutral pH and exposure to base. The DNA cleavage sites were visualized by polyacrylamide gel electrophoresis and autoradiography. Linking the Cl-ENU moiety to minor groove binders is a viable strategy to qualitatively and quantitatively control the delivery and release of the ultimate DNA alkylating agent in a sequence-dependent fashion

  15. Investigation of reference gene expression during human herpesvirus 6B infection indicates peptidylprolyl isomerase A as a stable reference gene and TATA box binding protein as a gene up-regulated by this virus.

    Science.gov (United States)

    Engdahl, Elin; Dunn, Nicky; Fogdell-Hahn, Anna

    2016-01-01

    When using relative gene expression for quantification of RNA it is crucial that the reference genes used for normalization do not change with the experimental condition. We aimed at investigating the expressional stability of commonly used reference genes during Human herpesvirus 6B (HHV-6B) infection. Expression of eight commonly used reference genes were investigated with quantitative PCR in a T-cell line infected with HHV-6B. The stability of genes was investigated using the 2(-ΔΔCT) method and the algorithms BestKeeper, GeNorm and NormFinder. Our results indicate that peptidylprolyl isomerase A (PPIA) is the most stably expressed gene while TATA box binding protein (TBP) is the least stably expressed gene during HHV-6B infection. In a confirmatory experiment, TBP was demonstrated to be dose and time dependently upregulated by HHV-6B. The stability of PPIA is in line with other studies investigating different herpesvirus infections whereas the finding that HHV-6B significantly upregulates TBP is novel and most likely specific to HHV-6B. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. The dnaE173 mutator mutation confers on the alpha subunit of Escherichia coli DNA polymerase III a capacity for highly processive DNA synthesis and stable binding to primer/template DNA.

    Science.gov (United States)

    Yanagihara, Fusamitsu; Yoshida, Shohei; Sugaya, Yutaka; Maki, Hisaji

    2007-08-01

    The strong mutator mutation dnaE173 which causes an amino-acid substitution in the alpha subunit of DNA polymerase III is unique in its ability to induce sequence-substitution mutations. We showed previously that multiple biochemical properties of DNA polymerase III holoenzyme of Escherichia coli are simultaneously affected by the dnaE173 mutation. These effects include a severely reduced proofreading capacity, an increased resistance to replication-pausing on the template DNA, a capability to readily promote strand-displacement DNA synthesis, a reduced rate of DNA chain elongation, and an ability to catalyze highly processive DNA synthesis in the absence of the beta-clamp subunit. Here we show that, in contrast to distributive DNA synthesis exhibited by wild-type alpha subunit, the dnaE173 mutant form of alpha subunit catalyzes highly processive DNA chain elongation without the aid of the beta-clamp. More surprisingly, the dnaE173 alpha subunit appeared to form a stable complex with primer/template DNA, while no such affinity was detected with wild-type alpha subunit. We consider that the highly increased affinity of alpha subunit for primer/template DNA is the basis for the pleiotropic effects of the dnaE173 mutation on DNA polymerase III, and provides a clue to the molecular mechanisms underlying sequence substitution mutagenesis.

  17. Tannaka duality and stable infinity-categories

    OpenAIRE

    Iwanari, Isamu

    2014-01-01

    We introduce the notion of fine tannakian infinity-categories and prove Tannaka duality results for symmetric monoidal stable infinity-categories over a field of characteristic zero. We also discuss several examples.

  18. 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.

  19. stableGP

    Data.gov (United States)

    National Aeronautics and Space Administration — The code in the stableGP package implements Gaussian process calculations using efficient and numerically stable algorithms. Description of the algorithms is in the...

  20. Plasmodium falciparum Liver Stage Infection and Transition to Stable Blood Stage Infection in Liver-Humanized and Blood-Humanized FRGN KO Mice Enables Testing of Blood Stage Inhibitory Antibodies (Reticulocyte-Binding Protein Homolog 5 In Vivo

    Directory of Open Access Journals (Sweden)

    Lander Foquet

    2018-03-01

    Full Text Available The invention of liver-humanized mouse models has made it possible to directly study the preerythrocytic stages of Plasmodium falciparum. In contrast, the current models to directly study blood stage infection in vivo are extremely limited. Humanization of the mouse blood stream is achievable by frequent injections of human red blood cells (hRBCs and is currently the only system with which to study human malaria blood stage infections in a small animal model. Infections have been primarily achieved by direct injection of P. falciparum-infected RBCs but as such, this modality of infection does not model the natural route of infection by mosquito bite and lacks the transition of parasites from liver stage infection to blood stage infection. Including these life cycle transition points in a small animal model is of relevance for testing therapeutic interventions. To this end, we used FRGN KO mice that were engrafted with human hepatocytes and performed a blood exchange under immune modulation to engraft the animals with more than 50% hRBCs. These mice were infected by mosquito bite with sporozoite stages of a luciferase-expressing P. falciparum parasite, resulting in noninvasively measurable liver stage burden by in vivo bioluminescent imaging (IVIS at days 5–7 postinfection. Transition to blood stage infection was observed by IVIS from day 8 onward and then blood stage parasitemia increased with a kinetic similar to that observed in controlled human malaria infection. To assess the utility of this model, we tested whether a monoclonal antibody targeting the erythrocyte invasion ligand reticulocyte-binding protein homolog 5 (with known growth inhibitory activity in vitro was capable of blocking blood stage infection in vivo when parasites emerge from the liver and found it highly effective. Together, these results show that a combined liver-humanized and blood-humanized FRGN mouse model infected with luciferase-expressing P. falciparum will be a

  1. Sequence characteristics required for cooperative binding and efficient in vivo titration of the replication initiator protein DnaA in E. coli

    DEFF Research Database (Denmark)

    Hansen, Flemming G.; Christensen, Bjarke Bak; Atlung, Tove

    2007-01-01

    Plasmids carrying the mioC promoter region, which contains two DnaA boxes, R5 and R6 with one misfit to the consensus TT(A)/(T)TNCACA, are as efficient in in vivo titration of the DnaA protein as plasmids carrying a replication-inactivated oriC region with its eight DnaA boxes. Three additional Dna......A boxes around the promoter proximal R5 DnaA box were identified and shown by mutational analysis to be necessary for the cooperative binding of DnaA required for titration. These four DnaA boxes are located in the same orientation and with a spacing of two or three base-pairs. The cooperative binding...... was eliminated by insertion of half a helical turn between any of the DnaA boxes. Titration strongly depends on the presence and orientation of the promoter distal R6 DnaA box located 104 bp upstream of the R5 box as well as neighbouring sequences downstream of R6. Titration depends on the integrity of a 43 bp...

  2. An Experimental Approach to Assess the Impact of Post Processing Variables on the Mechanical Characteristics of 3D Printed (Powder Binding Process) Parts

    Science.gov (United States)

    Impens, David

    The study is designed to provide a robust understanding of the mechanical characteristic of a 3D printed part for selected post processing conditions. The `green' printed parts are generally very brittle and porous, therefore, infiltrates are introduced to alter the mechanical characteristics, which will introduce new opportunities for this technology. Exploratory testing is performed to shape the choices for post processing with the infiltrates. Specimen geometry, specific for tensile, compression and flexural testing were rendered in CAD software and printed on the Z-printer 450 (Zp150 powder / Zb59 binder) with three different build orientations (horizontal/ angled /vertical). Results show that infiltrates can significantly improve the mechanical characteristics and material-infiltrate performance varies per build orientation. It is now understood that this material does not react similar to other materials and cannot be easily predicted. Additional physical testing should be performed and this complete test set should be conducted for new infiltrates.

  3. [The morphometric characteristics of the erythrocytes and their catecholamine-binding properties in the treatment of stage-II hypertension patients with Renitec].

    Science.gov (United States)

    Vizir, A D; Ostrovskaia, S V

    2000-01-01

    Morphometric and catecholamine-binding properties of erythrocytes were studied as were their changes in monotherapy with Renitec, an inhibitor of the angiotensin-converting enzyme, of patients with stage II hypertensive disease, using the image digital analysis computing system VIDAS-386 (Kontron Electronik, Germany). Patients with hypertensive disease were shown to develop degenerative changes in their erythrocytes, with catecholamine accumulation in them being a prominent feature, these events taking their course against the background of abnormalities in primary parameters characterizing cardiochemodynamics and regulation of the heart's rhythm. The above patients derived apparent benefit from treatment with Renitec, which fact was evidenced by improvement in parameters associated with the cardiochemodynamics and regulation of the cardiac rhythm, by alleviating the degree of severity of degenerative changes in erythrocytes, and by increase in their content of catecholamines.

  4. Molecular characteristics of penicillin-binding protein 2b, 2x and 1a sequences in Streptococcus pneumoniae isolates causing invasive diseases among children in Northeast China.

    Science.gov (United States)

    Zhou, X; Liu, J; Zhang, Z; Liu, Y; Wang, Y; Liu, Y

    2016-04-01

    Streptococcus pneumoniae is one of the common pathogens causing severe invasive infections in children. This study aimed to investigate the serotype distribution and variations of penicillin-binding proteins (PBPs) 2b, 2x and 1a in S. pneumoniae isolates causing invasive diseases in Northeast China. A total of 256 strains were isolated from children with invasive pneumococcal disease (IPD) from January 2000 to October 2014. All strains were serotyped and determined for antibiotic resistance. The amplicons of penicillin-binding domains in pbp1a, pbp2b and pbp2x genes were sequenced for variation identification. The most prevalent serotypes of isolates in IPD children were 19A, 14, 19F, 23F and 6B. 19A and 19F were the most frequent serotypes of penicillin-resistant S. pneumoniae (PRSP), which present with high resistance to amoxicillin, cefotaxime, ceftriaxone and meropenem. The numbers of amino acid substitutions of penicillin-non-susceptible S. pneumoniae (PNSP) isolates were higher than those of penicillin-sensitive S. pneumoniae isolates in all the PBP genes (p isolates carried 25 amino acid mutations, including Ala618 → Gly between positions 560 and 675 in PBP2b and Thr338 → Ala substitutions in PBP2x. The amino acid alterations in PBP2b, PBP2x and PBP1a from S. pneumoniae were closely associated with resistance to β-lactam antibiotics. This study provides new data for further monitoring of genetic changes related to the emergence and spread of resistance to β-lactam antibiotics in China.

  5. Binding of alkylpyridinium chloride surfactants to sodium polystyrene sulfonate

    NARCIS (Netherlands)

    Ishiguro, M.; Koopal, L.K.

    2009-01-01

    Binding of cationic surfactants to anionic polymers is well studied. However, the surfactant binding characteristics at very low concentration near the start of binding and at high concentration, where charge compensation may Occur. are less well known. Therefore, the binding characteristics of

  6. Bacterial Heat-Stable Enterotoxins: Translation of Pathogenic Peptides into Novel Targeted Diagnostics and Therapeutics

    Directory of Open Access Journals (Sweden)

    Chang Chang

    2010-08-01

    Full Text Available Heat-stable toxins (STs produced by enterotoxigenic bacteria cause endemic and traveler’s diarrhea by binding to and activating the intestinal receptor guanylyl cyclase C (GC-C. Advances in understanding the biology of GC-C have extended ST from a diarrheagenic peptide to a novel therapeutic agent. Here, we summarize the physiological and pathophysiological role of GC-C in fluid-electrolyte regulation and intestinal crypt-villus homeostasis, as well as describe translational opportunities offered by STs, reflecting the unique characteristics of GC-C, in treating irritable bowel syndrome and chronic constipation, and in preventing and treating colorectal cancer.

  7. Stable isotopes labelled compounds

    International Nuclear Information System (INIS)

    1982-09-01

    The catalogue on stable isotopes labelled compounds offers deuterium, nitrogen-15, and multiply labelled compounds. It includes: (1) conditions of sale and delivery, (2) the application of stable isotopes, (3) technical information, (4) product specifications, and (5) the complete delivery programme

  8. Stable Boundary Layer Issues

    NARCIS (Netherlands)

    Steeneveld, G.J.

    2012-01-01

    Understanding and prediction of the stable atmospheric boundary layer is a challenging task. Many physical processes are relevant in the stable boundary layer, i.e. turbulence, radiation, land surface coupling, orographic turbulent and gravity wave drag, and land surface heterogeneity. The

  9. Evolutionary Stable Strategy

    Indian Academy of Sciences (India)

    IAS Admin

    After Maynard-Smith and Price [1] mathematically derived why a given behaviour or strategy was adopted by a certain proportion of the population at a given time, it was shown that a strategy which is currently stable in a population need not be stable in evolutionary time (across generations). Additionally it was sug-.

  10. Normal modified stable processes

    DEFF Research Database (Denmark)

    Barndorff-Nielsen, Ole Eiler; Shephard, N.

    2002-01-01

    This paper discusses two classes of distributions, and stochastic processes derived from them: modified stable (MS) laws and normal modified stable (NMS) laws. This extends corresponding results for the generalised inverse Gaussian (GIG) and generalised hyperbolic (GH) or normal generalised inverse...... Gaussian (NGIG) laws. The wider framework thus established provides, in particular, for added flexibility in the modelling of the dynamics of financial time series, of importance especially as regards OU based stochastic volatility models for equities. In the special case of the tempered stable OU process...

  11. Applications of stable isotopes

    International Nuclear Information System (INIS)

    Letolle, R.; Mariotti, A.; Bariac, T.

    1991-06-01

    This report reviews the historical background and the properties of stable isotopes, the methods used for their measurement (mass spectrometry and others), the present technics for isotope enrichment and separation, and at last the various present and foreseeable application (in nuclear energy, physical and chemical research, materials industry and research; tracing in industrial, medical and agronomical tests; the use of natural isotope variations for environmental studies, agronomy, natural resources appraising: water, minerals, energy). Some new possibilities in the use of stable isotope are offered. A last chapter gives the present state and forecast development of stable isotope uses in France and Europe

  12. Comparison of plaque characteristics in narrowings with ST-elevation myocardial infarction (STEMI), non-STEMI/unstable angina pectoris and stable coronary artery disease (from the ADAPT-DES IVUS Substudy).

    Science.gov (United States)

    Dong, Liang; Mintz, Gary S; Witzenbichler, Bernhard; Metzger, D Christopher; Rinaldi, Michael J; Duffy, Peter L; Weisz, Giora; Stuckey, Thomas D; Brodie, Bruce R; Yun, Kyeong Ho; Xu, Ke; Kirtane, Ajay J; Stone, Gregg W; Maehara, Akiko

    2015-04-01

    Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents (ADAPT-DES) was a prospective, multicenter registry of 8,582 consecutive stable and unstable patients who underwent percutaneous coronary intervention using a drug-eluting stent. We sought to identify key morphologic features leading to ST-segment elevation myocardial infarction (STEMI) versus non-STEMI (NSTEMI) or unstable angina pectoris (UA) versus stable coronary artery disease (CAD) presentation. In the prespecified grayscale and virtual histology (VH) substudy of ADAPT-DES, preintervention imaging identified 676 patients with a single culprit lesion. The relation between lesion morphology and clinical presentation was compared among patients with (1) STEMI, (2) NSTEMI or UA, and (3) stable CAD. Intravascular ultrasound identified more plaque rupture and VH thin-cap fibroatheroma (TCFA) in STEMI lesions compared with NSTEMI/UA or stable CAD lesions; conversely, fibroatheromas appeared more often calcified with a thick fibrous cap in stable CAD. Minimum lumen cross-sectional area (MLA) was smaller with larger plaque burden and positive remodeling in STEMI lesions. Lesions with plaque rupture versus those without plaque rupture showed higher prevalence of VH-TCFA and larger plaque burden with positive remodeling, especially in patients with STEMI. Multivariate analysis showed that in the lesions with plaque rupture, plaque burden at the MLA site was the only independent predictor for STEMI (cutoff of plaque burden = 85%) and in lesions without plaque rupture, MLA was the only independent predictor for STEMI (cutoff of MLA = 2.3 mm(2)). In conclusion, culprit lesions causing STEMI have smaller lumen areas, greater plaque burden, and more plaque rupture or VH-TCFA compared with NSTEMI/UA or stable CAD; in lesions with plaque rupture, only plaque burden predicted STEMI, and in lesions without plaque rupture, only MLA area predicted STEMI. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Analysing Stable Time Series

    National Research Council Canada - National Science Library

    Adler, Robert

    1997-01-01

    We describe how to take a stable, ARMA, time series through the various stages of model identification, parameter estimation, and diagnostic checking, and accompany the discussion with a goodly number...

  14. Calcium stable isotope geochemistry

    Energy Technology Data Exchange (ETDEWEB)

    Gausonne, Nikolaus [Muenster Univ. (Germany). Inst. fuer Mineralogie; Schmitt, Anne-Desiree [Strasbourg Univ. (France). LHyGeS/EOST; Heuser, Alexander [Bonn Univ. (Germany). Steinmann-Inst. fuer Geologie, Mineralogie und Palaeontologie; Wombacher, Frank [Koeln Univ. (Germany). Inst. fuer Geologie und Mineralogie; Dietzel, Martin [Technische Univ. Graz (Austria). Inst. fuer Angewandte Geowissenschaften; Tipper, Edward [Cambridge Univ. (United Kingdom). Dept. of Earth Sciences; Schiller, Martin [Copenhagen Univ. (Denmark). Natural History Museum of Denmark

    2016-08-01

    This book provides an overview of the fundamentals and reference values for Ca stable isotope research, as well as current analytical methodologies including detailed instructions for sample preparation and isotope analysis. As such, it introduces readers to the different fields of application, including low-temperature mineral precipitation and biomineralisation, Earth surface processes and global cycling, high-temperature processes and cosmochemistry, and lastly human studies and biomedical applications. The current state of the art in these major areas is discussed, and open questions and possible future directions are identified. In terms of its depth and coverage, the current work extends and complements the previous reviews of Ca stable isotope geochemistry, addressing the needs of graduate students and advanced researchers who want to familiarize themselves with Ca stable isotope research.

  15. Evolutionary Stable Strategy

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... Home; Journals; Resonance – Journal of Science Education; Volume 21; Issue 9. Evolutionary Stable Strategy: Application of Nash Equilibrium in Biology. General ... Using some examples of classical games, we show how evolutionary game theory can help understand behavioural decisions of animals.

  16. The Stable Concordance Genus

    OpenAIRE

    Kearney, M. Kate

    2013-01-01

    The concordance genus of a knot is the least genus of any knot in its concordance class. Although difficult to compute, it is a useful invariant that highlights the distinction between the three-genus and four-genus. In this paper we define and discuss the stable concordance genus of a knot, which describes the behavior of the concordance genus under connected sum.

  17. Manifolds admitting stable forms

    Czech Academy of Sciences Publication Activity Database

    Le, Hong-Van; Panák, Martin; Vanžura, Jiří

    2008-01-01

    Roč. 49, č. 1 (2008), s. 101-11 ISSN 0010-2628 R&D Projects: GA ČR(CZ) GP201/05/P088 Institutional research plan: CEZ:AV0Z10190503 Keywords : stable forms * automorphism groups Subject RIV: BA - General Mathematics

  18. Stable isotope studies

    International Nuclear Information System (INIS)

    Ishida, T.

    1992-01-01

    The research has been in four general areas: (1) correlation of isotope effects with molecular forces and molecular structures, (2) correlation of zero-point energy and its isotope effects with molecular structure and molecular forces, (3) vapor pressure isotope effects, and (4) fractionation of stable isotopes. 73 refs, 38 figs, 29 tabs

  19. Interactive Stable Ray Tracing

    DEFF Research Database (Denmark)

    Dal Corso, Alessandro; Salvi, Marco; Kolb, Craig

    2017-01-01

    Interactive ray tracing applications running on commodity hardware can suffer from objectionable temporal artifacts due to a low sample count. We introduce stable ray tracing, a technique that improves temporal stability without the over-blurring and ghosting artifacts typical of temporal post-pr...

  20. The stable subgroup graph

    Directory of Open Access Journals (Sweden)

    Behnaz Tolue

    2018-07-01

    Full Text Available In this paper we introduce stable subgroup graph associated to the group $G$. It is a graph with vertex set all subgroups of $G$ and two distinct subgroups $H_1$ and $H_2$ are adjacent if $St_{G}(H_1\\cap H_2\

  1. Water binding in legume seeds

    Science.gov (United States)

    Vertucci, C. W.; Leopold, A. C.

    1987-01-01

    The physical status of water in seeds has a pivotal role in determining the physiological reactions that can take place in the dry state. Using water sorption isotherms from cotyledon and axis tissue of five leguminous seeds, the strength of water binding and the numbers of binding sites have been estimated using van't Hoff analyses and the D'Arcy/Watt equation. These parameters of water sorption are calculated for each of the three regions of water binding and for a range of temperatures. Water sorption characteristics are reflective of the chemical composition of the biological materials as well as the temperature at which hydration takes place. Changes in the sorption characteristics with temperature and hydration level may suggest hydration-induced structural changes in cellular components.

  2. Periodicity of the stable isotopes

    CERN Document Server

    Boeyens, J C A

    2003-01-01

    It is demonstrated that all stable (non-radioactive) isotopes are formally interrelated as the products of systematically adding alpha particles to four elementary units. The region of stability against radioactive decay is shown to obey a general trend based on number theory and contains the periodic law of the elements as a special case. This general law restricts the number of what may be considered as natural elements to 100 and is based on a proton:neutron ratio that matches the golden ratio, characteristic of biological and crystal growth structures. Different forms of the periodic table inferred at other proton:neutron ratios indicate that the electronic configuration of atoms is variable and may be a function of environmental pressure. Cosmic consequences of this postulate are examined. (author)

  3. Stable isotope analysis

    International Nuclear Information System (INIS)

    Tibari, Elghali; Taous, Fouad; Marah, Hamid

    2014-01-01

    This report presents results related to stable isotopes analysis carried out at the CNESTEN DASTE in Rabat (Morocco), on behalf of Senegal. These analyzes cover 127 samples. These results demonstrate that Oxygen-18 and Deuterium in water analysis were performed by infrared Laser spectroscopy using a LGR / DLT-100 with Autosampler. Also, the results are expressed in δ values (‰) relative to V-SMOW to ± 0.3 ‰ for oxygen-18 and ± 1 ‰ for deuterium.

  4. Forensic Stable Isotope Biogeochemistry

    Science.gov (United States)

    Cerling, Thure E.; Barnette, Janet E.; Bowen, Gabriel J.; Chesson, Lesley A.; Ehleringer, James R.; Remien, Christopher H.; Shea, Patrick; Tipple, Brett J.; West, Jason B.

    2016-06-01

    Stable isotopes are being used for forensic science studies, with applications to both natural and manufactured products. In this review we discuss how scientific evidence can be used in the legal context and where the scientific progress of hypothesis revisions can be in tension with the legal expectations of widely used methods for measurements. Although this review is written in the context of US law, many of the considerations of scientific reproducibility and acceptance of relevant scientific data span other legal systems that might apply different legal principles and therefore reach different conclusions. Stable isotopes are used in legal situations for comparing samples for authenticity or evidentiary considerations, in understanding trade patterns of illegal materials, and in understanding the origins of unknown decedents. Isotope evidence is particularly useful when considered in the broad framework of physiochemical processes and in recognizing regional to global patterns found in many materials, including foods and food products, drugs, and humans. Stable isotopes considered in the larger spatial context add an important dimension to forensic science.

  5. The risk of stable partnerships: associations between partnership characteristics and unprotected anal intercourse among men who have sex with men and transgender women recently diagnosed with HIV and/or STI in Lima, Peru.

    Directory of Open Access Journals (Sweden)

    Mary C Cambou

    Full Text Available Partnership type is an important factor associated with unprotected anal intercourse (UAI and subsequent risk for HIV and sexually transmitted infections (STI. We examined the association of partnership type with UAI among men who have sex with men (MSM and male-to-female transgender women (TGW in Lima, Peru, recently diagnosed with HIV and/or STI.We report data from a cross-sectional analysis of MSM and TGW recently diagnosed with HIV and/or STI in Lima, Peru between 2011 and 2012. We surveyed participants regarding UAI with up to their three most recent sexual partners according to partner type. Multivariable Generalized Estimate Equating (GEE models with Poisson distribution were used to estimate prevalence ratios (PR for UAI according to partner type.Among 339 MSM and TGW recently diagnosed with HIV and/or STI (mean age: 30.6 years, SD 9.0, 65.5% self-identified as homosexual/gay, 16.0% as bisexual, 15.2% as male-to-female transgender, and 3.3% as heterosexual. Participants provided information on 893 recent male or TGW partners with whom they had engaged in insertive or receptive anal intercourse: 28.9% stable partners, 56.4% non-stable/non-transactional partners (i.e. casual or anonymous, and 14.7% transactional partners (i.e. transactional sex client or sex worker. Unprotected anal intercourse was reported with 41.3% of all partners. In multivariable analysis, factors associated with UAI included partnership type (non-stable/non-transactional partner APR 0.73, [95% CI 0.59-0.91], transactional partner APR 0.53 [0.36-0.78], p10 encounters APR 1.43 [1.06-1.92], p10 sexual encounters, suggesting UAI is more prevalent in partnerships with a greater degree of interpersonal commitment. Further research assessing partner-level factors and behavior is critical for improving HIV and/or STI prevention efforts among Peruvian MSM and TGW.

  6. The risk of stable partnerships: associations between partnership characteristics and unprotected anal intercourse among men who have sex with men and transgender women recently diagnosed with HIV and/or STI in Lima, Peru.

    Science.gov (United States)

    Cambou, Mary C; Perez-Brumer, Amaya G; Segura, Eddy R; Salvatierra, H Javier; Lama, Javier R; Sanchez, Jorge; Clark, Jesse L

    2014-01-01

    Partnership type is an important factor associated with unprotected anal intercourse (UAI) and subsequent risk for HIV and sexually transmitted infections (STI). We examined the association of partnership type with UAI among men who have sex with men (MSM) and male-to-female transgender women (TGW) in Lima, Peru, recently diagnosed with HIV and/or STI. We report data from a cross-sectional analysis of MSM and TGW recently diagnosed with HIV and/or STI in Lima, Peru between 2011 and 2012. We surveyed participants regarding UAI with up to their three most recent sexual partners according to partner type. Multivariable Generalized Estimate Equating (GEE) models with Poisson distribution were used to estimate prevalence ratios (PR) for UAI according to partner type. Among 339 MSM and TGW recently diagnosed with HIV and/or STI (mean age: 30.6 years, SD 9.0), 65.5% self-identified as homosexual/gay, 16.0% as bisexual, 15.2% as male-to-female transgender, and 3.3% as heterosexual. Participants provided information on 893 recent male or TGW partners with whom they had engaged in insertive or receptive anal intercourse: 28.9% stable partners, 56.4% non-stable/non-transactional partners (i.e. casual or anonymous), and 14.7% transactional partners (i.e. transactional sex client or sex worker). Unprotected anal intercourse was reported with 41.3% of all partners. In multivariable analysis, factors associated with UAI included partnership type (non-stable/non-transactional partner APR 0.73, [95% CI 0.59-0.91], transactional partner APR 0.53 [0.36-0.78], p10 encounters APR 1.43 [1.06-1.92], p10 sexual encounters, suggesting UAI is more prevalent in partnerships with a greater degree of interpersonal commitment. Further research assessing partner-level factors and behavior is critical for improving HIV and/or STI prevention efforts among Peruvian MSM and TGW.

  7. Presence of specific growth hormone binding sites in rainbow trout (Oncorhynchus mykiss) tissues: characterization of the hepatic receptor

    International Nuclear Information System (INIS)

    Yao, K.; Niu, P.D.; Le Gac, F.; Le Bail, P.Y.

    1991-01-01

    The present work outlines the presence of specific binding for chinook salmon growth hormone (sGH) in different tissue preparations of rainbow trout. Optimal incubation conditions (pH, Tris, MgCl 2 ) were determined. Specific binding was very sensitive to salt concentration during incubation. The specific binding reached a plateau after 15 and 25 hr of incubation at 12 and 4 degree. At 20 degree, specific and nonspecific binding were not stable. Specific binding dissociation was slower than association and was only partial. The binding was saturable (Bmax = 187 +/- 167 pmol), of high affinity (Ka = 2.4 +/- 0.8 10(9) M-1), and very specific for GH, properties which are in agreement with the characteristics of hormonal receptors. Sea bream and mammalian GH appeared 2- and 30-fold, respectively, less potent than cold sGH2 for displacing 125 I-sGH2. Tissue preparations from ovary, testis, fat, skin, cartilage, gill, blood pellet, brain, spleen, kidney, and muscle showed significant saturable binding

  8. Bordism, stable homotopy and adams spectral sequences

    CERN Document Server

    Kochman, Stanley O

    1996-01-01

    This book is a compilation of lecture notes that were prepared for the graduate course "Adams Spectral Sequences and Stable Homotopy Theory" given at The Fields Institute during the fall of 1995. The aim of this volume is to prepare students with a knowledge of elementary algebraic topology to study recent developments in stable homotopy theory, such as the nilpotence and periodicity theorems. Suitable as a text for an intermediate course in algebraic topology, this book provides a direct exposition of the basic concepts of bordism, characteristic classes, Adams spectral sequences, Brown-Peter

  9. Clinical characteristics and methods of treatment of patients with stable coronary heart disease in the primary care settings--the results of the Polish, Multicentre Angina Treatment Pattern (ATP) study.

    Science.gov (United States)

    Ruzyllo, W; Ponikowski, P; Wilkins, A

    2004-12-01

    For further improvement of coronary heart disease (CHD) management large epidemiological studies are required to characterise the real population of patients with CHD, treated in the primary care settings, and to evaluate how the guidelines are implemented in the everyday clinical practice. The aim of the Angina Treatment Pattern (ATP) survey was to characterise (i) the population of patients, treated by the primary care physicians for stable CHD, (ii) the methods applied by the primary care physicians to establish diagnosis of CHD and (iii) the pharmacological therapies for CHD. Across Poland, 397 primary care physicians were randomly selected. They recruited 7420 patients (49% men; mean age, 62 +/- 10 years; range: 25-93 years), treated for stable CHD. The duration of CHD was 7.4 +/- 6.6 years (range: 6 months-50 years), 2750 (37%) patients had myocardial infarction. The following risk factors of CHD were present: arterial hypertension in 58%, dyslipidaemia in 52%, smoking in 40%, family history of CHD in 56% and obesity or overweight in 73% of patients. Primary care physicians based a diagnosis of CHD predominantly on a history of anginal pain (in 33% patients), accompanied either by abnormal resting ECG or positive exercise test (in additional 31% patients). Only in 5% of patients, coronary angiography was applied to diagnose CAD. The following groups of drugs have been used: long-acting nitrates in 90%, anti-platelet drugs or anti-coagulants in 71% (aspirin in 65%), angiotensin-converting enzyme inhibitors in 51%, beta-blockers in 48%, calcium antagonists 31%, hypolipaemic drugs in 23% (statins in 10%) and metabolic agents in 16% of patients. Despite an extensive use of classical anti-anginal drugs (including at least one of the following: long-acting nitrates, beta-blockers, calcium antagonists in 95% of patients), 85% of patients still complained of anginal symptoms. Neither prevalence of angina among patients nor nitroglycerin intake depended on the number

  10. Marginally Stable Nuclear Burning

    Science.gov (United States)

    Strohmayer, Tod E.; Altamirano, D.

    2012-01-01

    Thermonuclear X-ray bursts result from unstable nuclear burning of the material accreted on neutron stars in some low mass X-ray binaries (LMXBs). Theory predicts that close to the boundary of stability oscillatory burning can occur. This marginally stable regime has so far been identified in only a small number of sources. We present Rossi X-ray Timing Explorer (RXTE) observations of the bursting, high- inclination LMXB 4U 1323-619 that reveal for the first time in this source the signature of marginally stable burning. The source was observed during two successive RXTE orbits for approximately 5 ksec beginning at 10:14:01 UTC on March 28, 2011. Significant mHz quasi- periodic oscillations (QPO) at a frequency of 8.1 mHz are detected for approximately 1600 s from the beginning of the observation until the occurrence of a thermonuclear X-ray burst at 10:42:22 UTC. The mHz oscillations are not detected following the X-ray burst. The average fractional rms amplitude of the mHz QPOs is 6.4% (3 - 20 keV), and the amplitude increases to about 8% below 10 keV.This phenomenology is strikingly similar to that seen in the LMXB 4U 1636-53. Indeed, the frequency of the mHz QPOs in 4U 1323-619 prior to the X-ray burst is very similar to the transition frequency between mHz QPO and bursts found in 4U 1636-53 by Altamirano et al. (2008). These results strongly suggest that the observed QPOs in 4U 1323-619 are, like those in 4U 1636-53, due to marginally stable nuclear burning. We also explore the dependence of the energy spectrum on the oscillation phase, and we place the present observations within the context of the spectral evolution of the accretion-powered flux from the source.

  11. STABLE DIAMOND GRINDING

    Directory of Open Access Journals (Sweden)

    Yury Gutsalenko

    2010-06-01

    Full Text Available The paper generalizes on the one hand theory of kinematic-geometrical simulation of grinding processes by means of tools with working part as binding matrix with abrasive grains located in it in random manner, for example diamond grains, and on the other hand practical performance of combined grinding process, based on introduction of additional energy as electric discharges and called by the organization-developer (Kharkov Polytechnic Institute «diamond-spark grinding» as applied to processing by means of diamond wheel. Implementation of diamond-spark grinding technologies on the basis of developed generalized theoretical approach allows to use the tool with prescribed tool-life, moreover to make the most efficient use of it up to full exhausting of tool-life, determined by diamond-bearing thickness. Development is directed forward computer-aided manufacturing.

  12. The status of applying stable isotope in the studies of environmental science

    International Nuclear Information System (INIS)

    Bai Zhipeng; Zhang Liwen; Zhu Tan; Feng Yinchang

    2007-01-01

    The stable isotope composition is characteristic in the pollution source, and it is relatively fixed in the process of transferring and reaction. At present the precise analysis result of stable isotope ratio can be obtained easily. So the stable isotopes can be applied to the pollution affair arbitration and source study. The concept and analytical method of stable isotopes are introduced. The research status of the stable isotopes in the field of environmental science and the isotope fractionation is reviewed. (authors)

  13. Rational automatic search method for stable docking models of protein and ligand.

    Science.gov (United States)

    Mizutani, M Y; Tomioka, N; Itai, A

    1994-10-21

    An efficient automatic method has been developed for docking a ligand molecule to a protein molecule. The method can construct energetically favorable docking models, considering specific interactions between the two molecules and conformational flexibility in the ligand. In the first stage of docking, likely binding modes are searched and estimated effectively in terms of hydrogen bonds, together with conformations in part of the ligand structure that includes hydrogen bonding groups. After that part is placed in the protein cavity and is optimized, conformations in the remaining part are also examined systematically. Finally, several stable docking models are obtained after optimization of the position, orientation and conformation of the whole ligand molecule. In all the screening processes, the total potential energy including intra- and intermolecular interaction energy, consisting of van der Waals, electrostatic and hydrogen bonding energies, is used as the index. The characteristics of our docking method are high accuracy of the results, fully automatic generation of models and short computational time. The efficiency of the method was confirmed by four docking trials using two enzyme systems. In two attempts to dock methotrexate to dihydrofolate reductase and 2'-GMP to ribonuclease T1, the exact structures of complexes in crystals were reproduced as the most stable docking models, without any assumptions concerning the binding modes and ligand conformations. The most stable docking models of dihydrofolate and trimethoprim, respectively, to dihydrofolate reductase were also in good agreement with those suggested by experiment. In all test cases, it was shown that our method can accurately predict the correct docking structures, discriminating the correct model from incorrect ones. The efficiency of our method was further tested from the viewpoint of ability to predict the relative stability of the docking structures of two triazine derivatives to

  14. Characteristics of the binding of (/sup 3/H)nitrendipine to rabbit ventricular membranes: modification by other Ca++ channel antagonists and by the Ca++ channel agonist Bay K 8644

    Energy Technology Data Exchange (ETDEWEB)

    Janis, R.A.; Sarmiento, J.G.; Maurer, S.C.; Bolger, G.T.; Triggle, D.J.

    1984-10-01

    This study was carried out to characterize (/sup 3/H)nitrendipine binding to cardiac membranes and to test the hypothesis that high affinity binding of Ca++ channel antagonists and agonists is to Ca++ channels. Binding was specific, rapid, reversible and stereoselective. The relative order of potency of nifedipine analogs for inhibition of binding was the same as that for inhibition of smooth and cardiac muscle contraction. Results with diltiazem, verapamil and lidoflazine were consistent with the hypothesis that nondihydropyridine Ca++ channel antagonists act at one or more sites allosterically linked to the 1,4-dihydropyridine site in cardiac cells. The Ca++ channel agonist Bay K 8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine- 5-carboxylate) displaced specifically bound (/sup 3/H)nitrendipine in an apparently competitive manner with an IC50 value of 5 nM. The results suggest that organic antagonists do not act by physically blocking the Ca++ channel. The data also support the hypothesis that the high affinity binding sites for (/sup 3/H)nitrendipine in isolated cardiac membranes are associated with Ca++ channels that are inactivated or are otherwise unavailable for opening.

  15. Dynamical attraction to stable processes

    OpenAIRE

    Fisher, Albert M.; Talet, Marina

    2012-01-01

    We apply dynamical ideas within probability theory, proving an almost-sure invariance principle in log density for stable processes. The familiar scaling property (self-similarity) of the stable process has a stronger expression, that the scaling flow on Skorokhod path space is a Bernoulli flow. We prove that typical paths of a random walk with i.i.d. increments in the domain of attraction of a stable law can be paired with paths of a stable process so that, after applying a non-random regula...

  16. 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 ...

  17. The structure, stability and pheromone binding of the male mouse protein sex pheromone darcin.

    Directory of Open Access Journals (Sweden)

    Marie M Phelan

    Full Text Available Mouse urine contains highly polymorphic major urinary proteins that have multiple functions in scent communication through their abilities to bind, transport and release hydrophobic volatile pheromones. The mouse genome encodes for about 20 of these proteins and are classified, based on amino acid sequence similarity and tissue expression patterns, as either central or peripheral major urinary proteins. Darcin is a male specific peripheral major urinary protein and is distinctive in its role in inherent female attraction. A comparison of the structure and biophysical properties of darcin with MUP11, which belongs to the central class, highlights similarity in the overall structure between the two proteins. The thermodynamic stability, however, differs between the two proteins, with darcin being much more stable. Furthermore, the affinity of a small pheromone mimetic is higher for darcin, although darcin is more discriminatory, being unable to bind bulkier ligands. These attributes are due to the hydrophobic ligand binding cavity of darcin being smaller, caused by the presence of larger amino acid side chains. Thus, the physical and chemical characteristics of the binding cavity, together with its extreme stability, are consistent with darcin being able to exert its function after release into the environment.

  18. Visual evaluation of kinetic characteristics of PET probe for neuroreceptors using a two-phase graphic plot analysis.

    Science.gov (United States)

    Ito, Hiroshi; Ikoma, Yoko; Seki, Chie; Kimura, Yasuyuki; Kawaguchi, Hiroshi; Takuwa, Hiroyuki; Ichise, Masanori; Suhara, Tetsuya; Kanno, Iwao

    2017-05-01

    Objectives In PET studies for neuroreceptors, tracer kinetics are described by the two-tissue compartment model (2-TCM), and binding parameters, including the total distribution volume (V T ), non-displaceable distribution volume (V ND ), and binding potential (BP ND ), can be determined from model parameters estimated by kinetic analysis. The stability of binding parameter estimates depends on the kinetic characteristics of radioligands. To describe these kinetic characteristics, we previously developed a two-phase graphic plot analysis in which V ND and V T can be estimated from the x-intercept of regression lines for early and delayed phases, respectively. In this study, we applied this graphic plot analysis to visual evaluation of the kinetic characteristics of radioligands for neuroreceptors, and investigated a relationship between the shape of these graphic plots and the stability of binding parameters estimated by the kinetic analysis with 2-TCM in simulated brain tissue time-activity curves (TACs) with various binding parameters. Methods 90-min TACs were generated with the arterial input function and assumed kinetic parameters according to 2-TCM. Graphic plot analysis was applied to these simulated TACs, and the curvature of the plot for each TAC was evaluated visually. TACs with several noise levels were also generated with various kinetic parameters, and the bias and variation of binding parameters estimated by kinetic analysis were calculated in each TAC. These bias and variation were compared with the shape of graphic plots. Results The graphic plots showed larger curvature for TACs with higher specific binding and slower dissociation of specific binding. The quartile deviations of V ND and BP ND determined by kinetic analysis were smaller for radioligands with slow dissociation. Conclusions The larger curvature of graphic plots for radioligands with slow dissociation might indicate a stable determination of V ND and BP ND by kinetic analysis. For

  19. Mannose-Binding Lectin Binds to Amyloid Protein and Modulates Inflammation

    Directory of Open Access Journals (Sweden)

    Mykol Larvie

    2012-01-01

    Full Text Available Mannose-binding lectin (MBL, a soluble factor of the innate immune system, is a pattern recognition molecule with a number of known ligands, including viruses, bacteria, and molecules from abnormal self tissues. In addition to its role in immunity, MBL also functions in the maintenance of tissue homeostasis. We present evidence here that MBL binds to amyloid β peptides. MBL binding to other known carbohydrate ligands is calcium-dependent and has been attributed to the carbohydrate-recognition domain, a common feature of other C-type lectins. In contrast, we find that the features of MBL binding to Aβ are more similar to the reported binding characteristics of the cysteine-rich domain of the unrelated mannose receptor and therefore may involve the MBL cysteine-rich domain. Differences in MBL ligand binding may contribute to modulation of inflammatory response and may correlate with the function of MBL in processes such as coagulation and tissue homeostasis.

  20. Stable isotope characteristics of precipitation of Pamba River basin ...

    Indian Academy of Sciences (India)

    The land use of the basin is dominated by forest. (52.4%) and the rest 25.4% by plantations (rubber, coconut, teak, tea, etc.), 16.3% by agriculture, and. 5.9% by fallow lands. 2.1 Climate. The Pamba River basin experiences ∼3000 mm of rainfall per year. The south-west and north- east monsoons have great influence over ...

  1. Stable isotope characteristics of precipitation of Pamba River basin ...

    Indian Academy of Sciences (India)

    Journal of Earth System Science. Current Issue : Vol. 126, Issue 8 · Current Issue Volume 126 | Issue 8. December 2017. Home · Volumes & Issues · Special Issues · Forthcoming Articles · Search · Editorial Board · Information for Authors · Subscription ...

  2. Stable isotope characteristics of precipitation of Pamba River basin ...

    Indian Academy of Sciences (India)

    defined as δ2H = 8 δ18O+10 SMOW by Craig. (1961) is known as the global meteoric water line ..... Std. Dev. 2.56. 19.3. 4.55 that standard deviation was highest for samples collected from the highland region, followed by the midlands and lowest for the lowland region. Since the standard deviation was high among the ...

  3. Shelf-Stable Food Safety

    Science.gov (United States)

    ... is an MRE? Is an MRE shelf stable? What foods are packaged in retort packages? What is aseptic ... type of package is used for aseptic processing? What foods are packaged in aseptic packages? Can I microwave ...

  4. Pharmaceuticals labelled with stable isotopes

    International Nuclear Information System (INIS)

    Krumbiegel, P.

    1986-11-01

    The relatively new field of pharmaceuticals labelled with stable isotopes is reviewed. Scientific, juridical, and ethical questions are discussed concerning the application of these pharmaceuticals in human medicine. 13 C, 15 N, and 2 H are the stable isotopes mainly utilized in metabolic function tests. Methodical contributions are given to the application of 2 H, 13 C, and 15 N pharmaceuticals showing new aspects and different states of development in the field under discussion. (author)

  5. Stable isotope research pool inventory

    International Nuclear Information System (INIS)

    1984-03-01

    This report contains a listing of electromagnetically separated stable isotopes which are available at the Oak Ridge National Laboratory for distribution for nondestructive research use on a loan basis. This inventory includes all samples of stable isotopes in the Research Materials Collection and does not designate whether a sample is out on loan or is in reprocessing. For some of the high abundance naturally occurring isotopes, larger amounts can be made available; for example, Ca-40 and Fe-56

  6. 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.

  7. 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

  8. The nature of stable insomnia phenotypes.

    Science.gov (United States)

    Pillai, Vivek; Roth, Thomas; Drake, Christopher L

    2015-01-01

    We examined the 1-y stability of four insomnia symptom profiles: sleep onset insomnia; sleep maintenance insomnia; combined onset and maintenance insomnia; and neither criterion (i.e., insomnia cases that do not meet quantitative thresholds for onset or maintenance problems). Insomnia cases that exhibited the same symptom profile over a 1-y period were considered to be phenotypes, and were compared in terms of clinical and demographic characteristics. Longitudinal. Urban, community-based. Nine hundred fifty-four adults with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition based current insomnia (46.6 ± 12.6 y; 69.4% female). None. At baseline, participants were divided into four symptom profile groups based on quantitative criteria. Follow-up assessment 1 y later revealed that approximately 60% of participants retained the same symptom profile, and were hence judged to be phenotypes. Stability varied significantly by phenotype, such that sleep onset insomnia (SOI) was the least stable (42%), whereas combined insomnia (CI) was the most stable (69%). Baseline symptom groups (cross-sectionally defined) differed significantly across various clinical indices, including daytime impairment, depression, and anxiety. Importantly, however, a comparison of stable phenotypes (longitudinally defined) did not reveal any differences in impairment or comorbid psychopathology. Another interesting finding was that whereas all other insomnia phenotypes showed evidence of an elevated wake drive both at night and during the day, the 'neither criterion' phenotype did not; this latter phenotype exhibited significantly higher daytime sleepiness despite subthreshold onset and maintenance difficulties. By adopting a stringent, stability-based definition, this study offers timely and important data on the longitudinal trajectory of specific insomnia phenotypes. With the exception of daytime sleepiness, few clinical differences are apparent across stable phenotypes.

  9. Characteristics of novel polymer based on pseudo-polyamino acids GluLa-DPG-PEG600: binding of albumin, biocompatibility, biodistribution and potential crossing the blood-brain barrier in rats

    Directory of Open Access Journals (Sweden)

    B. O. Chekh

    2017-08-01

    Full Text Available The aim of our work was to study biological properties of the polymer based on pseudo-polyamino acids GluLa-DPG-PEG600, its ability to bind albumin, as well as its localization in rat body and influence on physio­logical and functional state of rat kidneys and liver. We have found the ability of GluLa-DPG-PEG600 to bind bovine serum albumin (BSA using electrophoresis in 5% polyacrylamide gel. Structural and functional state of the liver and kidneys of rats after injections of polymer were investigated by histological analysis of organs and determination the activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase and content of cholesterol and creatinine in blood. Our results showed little toxic effect of GluLa-DPG-PEG600 on rat body. Using fluorescent microscopy we have studied polymer in complex with BSA distribution in rat body: after intravenous injection polymer are localized in kidneys and spleen, and after intramuscular – in liver and brain. It has been shown that polymer passed through the blood-brain barrier and are localized in the immune organ – spleen, indicating GluLa-DPG-PEG600 as a potential drug transporter.

  10. Stable Boundary Layer Education (STABLE) Final Campaign Summary

    Energy Technology Data Exchange (ETDEWEB)

    Turner, David D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-03-01

    The properties of, and the processes that occur in, the nocturnal stable boundary layer are not well understood, making it difficult to represent adequately in numerical models. The nocturnal boundary layer often is characterized by a temperature inversion and, in the Southern Great Plains region, a low-level jet. To advance our understanding of the nocturnal stable boundary layer, high temporal and vertical resolution data on the temperature and wind properties are needed, along with both large-eddy simulation and cloud-resolving modeling.

  11. 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.

  12. 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.

  13. 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.

  14. 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)

  15. 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

  16. Principles for computational design of binding antibodies.

    Science.gov (United States)

    Baran, Dror; Pszolla, M Gabriele; Lapidoth, Gideon D; Norn, Christoffer; Dym, Orly; Unger, Tamar; Albeck, Shira; Tyka, Michael D; Fleishman, Sarel J

    2017-10-10

    Natural proteins must both fold into a stable conformation and exert their molecular function. To date, computational design has successfully produced stable and atomically accurate proteins by using so-called "ideal" folds rich in regular secondary structures and almost devoid of loops and destabilizing elements, such as cavities. Molecular function, such as binding and catalysis, however, often demands nonideal features, including large and irregular loops and buried polar interaction networks, which have remained challenging for fold design. Through five design/experiment cycles, we learned principles for designing stable and functional antibody variable fragments (Fvs). Specifically, we ( i ) used sequence-design constraints derived from antibody multiple-sequence alignments, and ( ii ) during backbone design, maintained stabilizing interactions observed in natural antibodies between the framework and loops of complementarity-determining regions (CDRs) 1 and 2. Designed Fvs bound their ligands with midnanomolar affinities and were as stable as natural antibodies, despite having >30 mutations from mammalian antibody germlines. Furthermore, crystallographic analysis demonstrated atomic accuracy throughout the framework and in four of six CDRs in one design and atomic accuracy in the entire Fv in another. The principles we learned are general, and can be implemented to design other nonideal folds, generating stable, specific, and precise antibodies and enzymes.

  17. Crystal structure of glucose isomerase in complex with xylitol inhibitor in one metal binding mode.

    Science.gov (United States)

    Bae, Ji-Eun; Kim, In Jung; Nam, Ki Hyun

    2017-11-04

    Glucose isomerase (GI) is an intramolecular oxidoreductase that interconverts aldoses and ketoses. These characteristics are widely used in the food, detergent, and pharmaceutical industries. In order to obtain an efficient GI, identification of novel GI genes and substrate binding/inhibition have been studied. Xylitol is a well-known inhibitor of GI. In Streptomyces rubiginosus, two crystal structures have been reported for GI in complex with xylitol inhibitor. However, a structural comparison showed that xylitol can have variable conformation at the substrate binding site, e.g., a nonspecific binding mode. In this study, we report the crystal structure of S. rubiginosus GI in a complex with xylitol and glycerol. Our crystal structure showed one metal binding mode in GI, which we presumed to represent the inactive form of the GI. The metal ion was found only at the M1 site, which was involved in substrate binding, and was not present at the M2 site, which was involved in catalytic function. The O 2 and O 4 atoms of xylitol molecules contributed to the stable octahedral coordination of the metal in M1. Although there was no metal at the M2 site, no large conformational change was observed for the conserved residues coordinating M2. Our structural analysis showed that the metal at the M2 site was not important when a xylitol inhibitor was bound to the M1 site in GI. Thus, these findings provided important information for elucidation or engineering of GI functions. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Stable limits for sums of dependent infinite variance random variables

    DEFF Research Database (Denmark)

    Bartkiewicz, Katarzyna; Jakubowski, Adam; Mikosch, Thomas

    2011-01-01

    of these results are qualitative in the sense that the parameters of the limit distribution are expressed in terms of some limiting point process. In this paper we will be able to determine the parameters of the limiting stable distribution in terms of some tail characteristics of the underlying stationary...

  19. Radiation-stable polyolefin compositions

    International Nuclear Information System (INIS)

    Rekers, J.W.

    1986-01-01

    This invention relates to compositions of olefinic polymers suitable for high energy radiation treatment. In particular, the invention relates to olefinic polymer compositions that are stable to sterilizing dosages of high energy radiation such as a gamma radiation. Stabilizers are described that include benzhydrol and benzhydrol derivatives; these stabilizers may be used alone or in combination with secondary antioxidants or synergists

  20. Monitoring of stable glaucoma patients

    NARCIS (Netherlands)

    K.M. Holtzer-Goor (Kim); N.S. Klazinga (Niek); M.A. Koopmanschap (Marc); H.G. Lemij (Hans); T. Plochg; E. van Sprundel (Esther)

    2010-01-01

    textabstractA high workload for ophthalmologists and long waiting lists for patients challenge the organization of ophthalmic care. Tasks that require less specialized skills, like the monitoring of stable (well controlled) glaucoma patients could be substituted from ophthalmologists to other

  1. Conformational flexibility of avidin: the influence of biotin binding

    International Nuclear Information System (INIS)

    Soledad Celej, M.; Montich, Guillermo G.; Fidelio, Gerardo D.

    2004-01-01

    Ligand binding to proteins is a key process in cell biochemistry. The interaction usually induces modifications in the unfolding thermodynamic parameters of the macromolecule due to the coupling of unfolding and binding equilibria. In addition, these modifications can be attended by changes in protein structure and/or conformational flexibility induced by ligand binding. In this work, we have explored the effect of biotin binding on conformation and dynamic properties of avidin by using infrared spectroscopy including kinetics of hydrogen/deuterium exchange. Our results, along with previously thermodynamic published data, indicate a clear correlation between thermostability and protein compactness. In addition, our results also help to interpret the thermodynamic binding parameters of the exceptionally stable biotin:AVD complex

  2. CaMELS: In silico prediction of calmodulin binding proteins and their binding sites.

    Science.gov (United States)

    Abbasi, Wajid Arshad; Asif, Amina; Andleeb, Saiqa; Minhas, Fayyaz Ul Amir Afsar

    2017-09-01

    Due to Ca 2+ -dependent binding and the sequence diversity of Calmodulin (CaM) binding proteins, identifying CaM interactions and binding sites in the wet-lab is tedious and costly. Therefore, computational methods for this purpose are crucial to the design of such wet-lab experiments. We present an algorithm suite called CaMELS (CalModulin intEraction Learning System) for predicting proteins that interact with CaM as well as their binding sites using sequence information alone. CaMELS offers state of the art accuracy for both CaM interaction and binding site prediction and can aid biologists in studying CaM binding proteins. For CaM interaction prediction, CaMELS uses protein sequence features coupled with a large-margin classifier. CaMELS models the binding site prediction problem using multiple instance machine learning with a custom optimization algorithm which allows more effective learning over imprecisely annotated CaM-binding sites during training. CaMELS has been extensively benchmarked using a variety of data sets, mutagenic studies, proteome-wide Gene Ontology enrichment analyses and protein structures. Our experiments indicate that CaMELS outperforms simple motif-based search and other existing methods for interaction and binding site prediction. We have also found that the whole sequence of a protein, rather than just its binding site, is important for predicting its interaction with CaM. Using the machine learning model in CaMELS, we have identified important features of protein sequences for CaM interaction prediction as well as characteristic amino acid sub-sequences and their relative position for identifying CaM binding sites. Python code for training and evaluating CaMELS together with a webserver implementation is available at the URL: http://faculty.pieas.edu.pk/fayyaz/software.html#camels. © 2017 Wiley Periodicals, Inc.

  3. New trends in bio/nanotechnology: stable proteins as advanced molecular tools for health and environment.

    Science.gov (United States)

    Staiano, M; Baldassarre, M; Esposito, M; Apicella, E; Vitale, R; Aurilia, V; D'Auria, S

    2010-01-01

    In this work the thermophilic trehalose/maltose-binding protein from Thermococcus litoralis is presented as a probe for the design of a high stable fluorescence biosensor for glucose. In particular, we show the possibility of modulating the protein specificity by changing temperature. In addition to glucose sensing, we also report on the possibility of utilizing odorant-binding proteins as a probe for the development of optical sensors for analytes of environmental interests.

  4. Application of stable isotope to breath test

    International Nuclear Information System (INIS)

    Sasaki, Yasuto

    1988-01-01

    Needles to say, radioisotopes have good characteristics as a tracer for examining biological functions. In fact, scyntigraphy is widely used over Japan. It is true, however, that there are some difficulties in applying radioisotopes to humans. Thus, greater attention began to be attracted to stable isotopes in the late 1960s, because these substances can be used for infants and pregnant women. They can be stored for a long period of time since they do not suffer damping as in the case of radioisotopes. In addition to serving as a tracer, stable isotopes can provide structural-chemical information including the position of isotope labels, and the mass and atomic composition of fragment ions. Such techniques as NMR spectroscopy is employed for this purpose. The method is currently used to perform examinations of congenital metabolic disorders. The carbon isotopes of 13 C and 14 C are used for breath test. Compounds labeled with these isotopes are administered and their ratio to the total CO 2 in breath is measured to diagnose diseases. In the early 1970s, 13 C has come into use for breath test. Similar breath test is applied to diagnosis of the bacterial overgrowth syndrome and ileal dysfunction syndrome. (Nogami, K.)

  5. 26 S proteasomes function as stable entities

    DEFF Research Database (Denmark)

    Hendil, Klavs B; Hartmann-Petersen, Rasmus; Tanaka, Keiji

    2002-01-01

    , shuttles between a free state and the 26-S proteasome, bringing substrate to the complex. However, S5a was not found in the free state in HeLa cells. Besides, all subunits in PA700, including S5a, exchanged at similar low rates. It therefore seems that 26-S proteasomes function as stable entities during...... dissociate and reassemble during initiation of protein degradation in a ternary complex with the substrate, as in the dissociation-reassembly cycles found for ribosomes and the chaperonin GroEL/GroES. Here we followed disassembly and assembly of 26-S proteasomes in cell extracts as the exchange of PA700...... subunits between mouse and human 26-S proteasomes. Compared to the rate of proteolysis in the same extract, the disassembly-reassembly cycle was much too slow to present an obligatory step in a degradation cycle. It has been suggested that subunit S5a (Mcb1, Rpn10), which binds poly-ubiquitin substrates...

  6. Toward Practical Secure Stable Matching

    Directory of Open Access Journals (Sweden)

    Riazi M. Sadegh

    2017-01-01

    Full Text Available The Stable Matching (SM algorithm has been deployed in many real-world scenarios including the National Residency Matching Program (NRMP and financial applications such as matching of suppliers and consumers in capital markets. Since these applications typically involve highly sensitive information such as the underlying preference lists, their current implementations rely on trusted third parties. This paper introduces the first provably secure and scalable implementation of SM based on Yao’s garbled circuit protocol and Oblivious RAM (ORAM. Our scheme can securely compute a stable match for 8k pairs four orders of magnitude faster than the previously best known method. We achieve this by introducing a compact and efficient sub-linear size circuit. We even further decrease the computation cost by three orders of magnitude by proposing a novel technique to avoid unnecessary iterations in the SM algorithm. We evaluate our implementation for several problem sizes and plan to publish it as open-source.

  7. Towards stable acceleration in LINACS

    CERN Document Server

    Dubrovskiy, A D

    2014-01-01

    Ultra-stable and -reproducible high-energy particle beams with short bunches are needed in novel linear accelerators and, in particular, in the Compact Linear Collider CLIC. A passive beam phase stabilization system based on a bunch compression with a negative transfer matrix element R56 and acceleration at a positive off-crest phase is proposed. The motivation and expected advantages of the proposed scheme are outlined.

  8. 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...

  9. 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....

  10. A Single Rainbow Trout Cobalamin-binding Protein Stands in for Three Human Binders

    DEFF Research Database (Denmark)

    Greibe, Eva Holm; Fedosov, Sergey; Sorensen, Boe S

    2012-01-01

    Cobalamin uptake and transport in mammals are mediated by three cobalamin-binding proteins: haptocorrin, intrinsic factor, and transcobalamin. The nature of cobalamin-binding proteins in lower vertebrates remains to be elucidated. The aim of this study was to characterize the cobalamin......-binding proteins of the rainbow trout (Oncorhynchus mykiss) and to compare their properties with those of the three human cobalamin-binding proteins. High cobalamin-binding capacity was found in trout stomach (210 pmol/g), roe (400 pmol/g), roe fluid (390 nmol/liter), and plasma (2500 nmol/liter). In all cases......, it appeared to be the same protein based on analysis of partial sequences and immunological responses. The trout cobalamin-binding protein was purified from roe fluid, sequenced, and further characterized. Like haptocorrin, the trout cobalamin-binding protein was stable at low pH and had a high binding...

  11. Stable Hemiaminals: 2-Aminopyrimidine Derivatives

    Directory of Open Access Journals (Sweden)

    Anna Kwiecień

    2015-08-01

    Full Text Available Stable hemiaminals can be obtained in the one-pot reaction between 2-aminopyrimidine and nitrobenzaldehyde derivatives. Ten new hemiaminals have been obtained, six of them in crystal state. The molecular stability of these intermediates results from the presence of both electron-withdrawing nitro groups as substituents on the phenyl ring and pyrimidine ring, so no further stabilisation by intramolecular interaction is required. Hemiaminal molecules possess a tetrahedral carbon atom constituting a stereogenic centre. As the result of crystallisation in centrosymmetric space groups both enantiomers are present in the crystal structure.

  12. Organic synthesis with stable isotopes

    International Nuclear Information System (INIS)

    Daub, G.H.; Kerr, V.N.; Williams, D.L.; Whaley, T.W.

    1978-01-01

    Some general considerations concerning organic synthesis with stable isotopes are presented. Illustrative examples are described and discussed. The examples include DL-2-amino-3-methyl- 13 C-butanoic-3,4- 13 C 2 acid (DL-valine- 13 C 3 ); methyl oleate-1- 13 C; thymine-2,6- 13 C 2 ; 2-aminoethanesulfonic- 13 C acid (taurine- 13 C); D-glucose-6- 13 C; DL-2-amino-3-methylpentanoic-3,4- 13 C 2 acid (DL-isoleucine- 13 C 2 ); benzidine- 15 N 2 ; and 4-ethylsulfonyl-1-naphthalene-sulfonamide- 15 N

  13. Stable agents for imaging investigations

    International Nuclear Information System (INIS)

    Tofe, A.J.

    1976-01-01

    This invention concerns highly stable compounds useful in preparing technetium 99m based scintiscanning exploration agents. The compounds of this invention include a pertechnetate reducing agent or a solution of oxidized pertechnetate and an efficient proportion, sufficient to stabilize the compounds in the presence of oxygen and of radiolysis products, of ascorbic acid or a pharmaceutically acceptable salt or ester of this acid. The invention also concerns a perfected process for preparing a technetium based exploration agent, consisting in codissolving the ascorbic acid or a pharmaceutically acceptable salt or ester of such an acid and a pertechnetate reducing agent in a solution of oxidized pertechnetate [fr

  14. Postmortem Pittsburgh Compound B (PiB) binding increases with Alzheimer's disease progression.

    Science.gov (United States)

    Beckett, Tina L; Webb, Robin L; Niedowicz, Dana M; Holler, Christopher J; Matveev, Sergey; Baig, Irfan; LeVine, Harry; Keller, Jeffrey N; Murphy, M Paul

    2012-01-01

    The development of imaging reagents is of considerable interest in the Alzheimer's disease (AD) field. Some of these, such as Pittsburgh Compound B (PiB), were designed to bind to the amyloid-β peptide (Aβ), the major component of amyloid deposits in the AD brain. Although these agents were designed for imaging amyloid deposits in vivo, a major avenue of evaluation relies on postmortem cross validation with established indices of AD pathology. In this study, we evaluated changes in the postmortem binding of PiB and its relationship to other aspects of Aβ-related pathology in a series of AD cases and age-matched controls. We also examined cases of preclinical AD (PCAD) and amnestic mild cognitive impairment (MCI), both considered early points in the AD continuum. PiB binding was found to increase with the progression of the disease and paralleled increases in the less soluble forms of Aβ, including SDS-stable Aβ oligomers. Increased PiB binding and its relationship to Aβ was only significant in a brain region vulnerable to the development of AD pathology (the superior and middle temporal gyri) but not in an unaffected region (cerebellum). This implies that the amyloid deposited in disease-affected regions may possess fundamental, brain region specific characteristics that may not as yet be fully appreciated. These data support the idea that PiB is a useful diagnostic tool for AD, particularly in the early stage of the disease, and also show that PiB could be a useful agent for the discovery of novel disease-related properties of amyloid.

  15. Design of partially optically stable reflector systems and prisms

    Science.gov (United States)

    Tsai, Chuang-Yu

    2010-09-01

    The characteristics and design method of the total optically stable (TOS) reflector systems/prisms were introduced in an early paper (Tsai and Lin in Appl. Opt. 47:4158-4163, 2008), where only two types of TOS reflector system exist, namely preservation or retroreflection. In this paper, we introduce the partially optically stable (POS) reflector system, which is only optically stable about a specific directional vector; nevertheless, the exiting light ray is not restricted to preservation or retroreflection. The proposed paper also presents an analytic method for the design of POS reflector systems comprised of multiple reflectors. Furthermore, it is shown that a POS prism can be obtained by adding two refracting flat boundary surfaces with specific conditions at the entrance and exit positions of the light ray in an optical system with multiple reflectors.

  16. Ranking stability and super-stable nodes in complex networks.

    Science.gov (United States)

    Ghoshal, Gourab; Barabási, Albert-László

    2011-07-19

    Pagerank, a network-based diffusion algorithm, has emerged as the leading method to rank web content, ecological species and even scientists. Despite its wide use, it remains unknown how the structure of the network on which it operates affects its performance. Here we show that for random networks the ranking provided by pagerank is sensitive to perturbations in the network topology, making it unreliable for incomplete or noisy systems. In contrast, in scale-free networks we predict analytically the emergence of super-stable nodes whose ranking is exceptionally stable to perturbations. We calculate the dependence of the number of super-stable nodes on network characteristics and demonstrate their presence in real networks, in agreement with the analytical predictions. These results not only deepen our understanding of the interplay between network topology and dynamical processes but also have implications in all areas where ranking has a role, from science to marketing.

  17. High precision and stable structures for particle detectors

    CERN Document Server

    Da Mota Silva, S; Hauviller, Claude

    1999-01-01

    The central detectors used in High Energy Physics Experiments require the use of light and stable structures capable of supporting delicate and precise radiation detection elements. These structures need to be highly stable under environmental conditions where external vibrations, high radiation levels, temperature and humidity gradients should be taken into account. Their main design drivers are high dimension and dynamic stability, high stiffness to mass ratio and large radiation length. For most applications, these constraints lead us to choose Carbon Fiber Reinforced Plastics ( CFRP) as structural element. The construction of light and stable structures with CFRP for these applications can be achieved by careful design engineering and further confirmation at the prototyping phase. However, the experimental environment can influence their characteristics and behavior. In this case, theuse of adaptive structures could become a solution for this problem. We are studying structures in CFRP with bonded piezoel...

  18. Stable cosmology in chameleon bigravity

    Science.gov (United States)

    De Felice, Antonio; Mukohyama, Shinji; Oliosi, Michele; Watanabe, Yota

    2018-02-01

    The recently proposed chameleonic extension of bigravity theory, by including a scalar field dependence in the graviton potential, avoids several fine-tunings found to be necessary in usual massive bigravity. In particular it ensures that the Higuchi bound is satisfied at all scales, that no Vainshtein mechanism is needed to satisfy Solar System experiments, and that the strong coupling scale is always above the scale of cosmological interest all the way up to the early Universe. This paper extends the previous work by presenting a stable example of cosmology in the chameleon bigravity model. We find a set of initial conditions and parameters such that the derived stability conditions on general flat Friedmann background are satisfied at all times. The evolution goes through radiation-dominated, matter-dominated, and de Sitter eras. We argue that the parameter space allowing for such a stable evolution may be large enough to encompass an observationally viable evolution. We also argue that our model satisfies all known constraints due to gravitational wave observations so far and thus can be considered as a unique testing ground of gravitational wave phenomenologies in bimetric theories of gravity.

  19. Tritiated imipramine binding sites are decreased in the frontal cortex of suicides

    International Nuclear Information System (INIS)

    Stanley, M.; Virgilio, J.; Gershon, S.

    1982-01-01

    Binding characteristics of tritiated imipramine were determined in the frontal cortex of suicides and well-matched controls. Maximal binding was significantly lower in brains from the suicides. This finding is consistent with reports of decreased tritiated imipramine binding in the platelets of patients diagnosed as having a major affective disorder

  20. 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 ...

  1. 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.

  2. 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.

  3. 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.

  4. Stable CSR in Storage Rings: A Model

    International Nuclear Information System (INIS)

    Sannibale, F.

    2005-01-01

    A comprehensive historical view of the work done on coherent synchrotron radiation (CSR) in storage rings is given in reference [1]. Here we want just to point out that even if the issue of CSR in storage rings was already discussed over 50 years ago, it is only recently that a considerable number of observations have been reported. In fact, intense bursts of coherent synchrotron radiation with a stochastic character were measured in the terahertz frequency range, at several synchrotron light source storage rings [2-8]. It has been shown [8-11], that this bursting emission of CSR is associated with a single bunch instability, usually referred as microbunching instability (MBI), driven by the fields of the synchrotron radiation emitted by the bunch itself. Of remarkably different characteristics was the CSR emission observed at BESSY II in Berlin, when the storage ring was tuned into a special low momentum compaction mode [12, 13]. In fact, the emitted radiation was not the quasi-random bursting observed in the other machines, but a powerful and stable flux of broadband CSR in the terahertz range. This was an important result, because it experimentally demonstrated the concrete possibility of constructing a stable broadband source with extremely high power in the terahertz region. Since the publication of the first successful experiment using the ring as a CSR source [14], BESSY II has regular scheduled user's shifts dedicated to CSR experiments. At the present time, several other laboratories are investigating the possibility of a CSR mode of operation [15-17] and a design for a new ring optimized for CSR is at an advanced stage [18]. In what follows, we describe a model that first accounts for the BESSY II observations and then indicates that the special case of BESSY II is actually quite general and typical when relativistic electron storage rings are tuned for short bunches. The model provides a scheme for predicting and optimizing the performance of ring

  5. Stable CSR in storage rings: A model

    International Nuclear Information System (INIS)

    Sannibale, Fernando; Byrd, John M.; Loftsdottir, Agusta; Venturini, Marco; Abo-Bakr, Michael; Feikes, Jorge; Holldack, Karsten; Kuske, Peter; Wustefeld, Godehart; Hubers, Heinz-Willerm; Warnock, Robert

    2005-01-01

    A comprehensive historical view of the work done on coherent synchrotron radiation (CSR) in storage rings is given in reference [1]. Here we want just to point out that even if the issue of CSR in storage rings was already discussed over 50 years ago, it is only recently that a considerable number of observations have been reported. In fact, intense bursts of coherent synchrotron radiation with a stochastic character were measured in the terahertz frequency range, at several synchrotron light source storage rings [2-8]. It has been shown [8-11], that this bursting emission of CSR is associated with a single bunch instability, usually referred as microbunching instability (MBI), driven by the fields of the synchrotron radiation emitted by the bunch itself. Of remarkably different characteristics was the CSR emission observed at BESSY II in Berlin, when the storage ring was tuned into a special low momentum compaction mode [12, 13]. In fact, the emitted radiation was not the quasi-random bursting observed in the other machines, but a powerful and stable flux of broadband CSR in the terahertz range. This was an important result, because it experimentally demonstrated the concrete possibility of constructing a stable broadband source with extremely high power in the terahertz region. Since the publication of the first successful experiment using the ring as a CSR source [14], BESSY II has regular scheduled user s shifts dedicated to CSR experiments. At the present time, several other laboratories are investigating the possibility of a CSR mode of operation [15-17] and a design for a new ring optimized for CSR is at an advanced stage [18]. In what follows, we describe a model that first accounts for the BESSY II observations and then indicates that the special case of BESSY II is actually quite general and typical when relativistic electron storage rings are tuned for short bunches. The model provides a scheme for predicting and optimizing the performance of ring

  6. Stable rotating dipole solitons in nonlocal media

    DEFF Research Database (Denmark)

    Lopez-Aguayo, Servando; Skupin, Stefan; Desyatnikov, Anton S.

    2006-01-01

    We present the first example of stable rotating two-soliton bound states in nonlinear optical media with nonlocal response. We show that, in contrast to media with local response, nonlocality opens possibilities to generate stable azimuthons.......We present the first example of stable rotating two-soliton bound states in nonlinear optical media with nonlocal response. We show that, in contrast to media with local response, nonlocality opens possibilities to generate stable azimuthons....

  7. Selection of medical treatment in stable angina pectoris

    DEFF Research Database (Denmark)

    Ardissino, D; Savonitto, S; Egstrup, K

    1995-01-01

    pectoris. BACKGROUND: The characteristics of anginal symptoms and the results of exercise testing are considered of great importance for selecting medical treatment in patients with chronic stable angina pectoris. However, little information is available on how this first evaluation may be used to select......, the patients were randomly allocated to double-blind treatment for 6 weeks with either metoprolol (Controlled Release, 200 mg once daily) or nifedipine (Retard, 20 mg twice daily) according to a parallel group design. At the end of this period, exercise tests were repeated 1 to 4 h after drug intake. RESULTS....... CONCLUSIONS: The results of a baseline exercise test, but not the characteristics of anginal symptoms, may offer useful information for selecting medical treatment in stable angina pectoris....

  8. Uses of stable isotopes in fish ecology

    Science.gov (United States)

    Analyses of fish tissues (other than otoliths) for stable isotope ratios can provide substantial information on fish ecology, including physiological ecology. Stable isotopes of nitrogen and carbon frequently are used to determine the mix of diet sources for consumers. Stable i...

  9. Stable States of Biological Organisms

    Science.gov (United States)

    Yukalov, V. I.; Sornette, D.; Yukalova, E. P.; Henry, J.-Y.; Cobb, J. P.

    2009-04-01

    A novel model of biological organisms is advanced, treating an organism as a self-consistent system subject to a pathogen flux. The principal novelty of the model is that it describes not some parts, but a biological organism as a whole. The organism is modeled by a five-dimensional dynamical system. The organism homeostasis is described by the evolution equations for five interacting components: healthy cells, ill cells, innate immune cells, specific immune cells, and pathogens. The stability analysis demonstrates that, in a wide domain of the parameter space, the system exhibits robust structural stability. There always exist four stable stationary solutions characterizing four qualitatively differing states of the organism: alive state, boundary state, critical state, and dead state.

  10. Theory of stable allocations II

    Directory of Open Access Journals (Sweden)

    Pantelić Svetlana

    2015-01-01

    Full Text Available The Swedish Royal Academy awarded the 2012 Nobel Prize in Economics to Lloyd Shapley and Alvin Roth, for the theory of stable allocations and the practice of market design. These two American researchers worked independently from each other, combining basic theory and empirical investigations. Through their experiments and practical design they generated a flourishing field of research and improved the performance of many markets. Shapley provided the fundamental theoretical contribution to this field of research, whereas Roth, a professor at the Harvard University in Boston, developed and upgraded these theoretical investigations by applying them to the American market of medical doctors. Namely, their research helps explain the market processes at work, for instance, when doctors are assigned to hospitals, students to schools and human organs for transplant to recipients.

  11. Stable massive particles at colliders

    Energy Technology Data Exchange (ETDEWEB)

    Fairbairn, M.; /Stockholm U.; Kraan, A.C.; /Pennsylvania U.; Milstead, D.A.; /Stockholm U.; Sjostrand, T.; /Lund U.; Skands, P.; /Fermilab; Sloan, T.; /Lancaster U.

    2006-11-01

    We review the theoretical motivations and experimental status of searches for stable massive particles (SMPs) which could be sufficiently long-lived as to be directly detected at collider experiments. The discovery of such particles would address a number of important questions in modern physics including the origin and composition of dark matter in the universe and the unification of the fundamental forces. This review describes the techniques used in SMP-searches at collider experiments and the limits so far obtained on the production of SMPs which possess various colour, electric and magnetic charge quantum numbers. We also describe theoretical scenarios which predict SMPs, the phenomenology needed to model their production at colliders and interactions with matter. In addition, the interplay between collider searches and open questions in cosmology such as dark matter composition are addressed.

  12. Binding, tuning and mechanical function of the 4-hydroxy-cinnamic acid chromophore in photoactive yellow protein

    NARCIS (Netherlands)

    van der Horst, Michael A; Arents, Jos C; Kort, Remco; Hellingwerf, Klaas J

    The bacterial photoreceptor protein photoactive yellow protein (PYP) covalently binds the chromophore 4-hydroxy coumaric acid, tuning (spectral) characteristics of this cofactor. Here, we study this binding and tuning using a combination of pointmutations and chromophore analogs. In all photosensor

  13. Binding, tuning and mechanical function of the 4-hydroxy-cinnamic acid chromophore in photoactive yellow protein

    NARCIS (Netherlands)

    Horst, M.A. van der; Arents, J.C.; Kort, R.; Hellingwerf, K.J.

    2007-01-01

    The bacterial photoreceptor protein photoactive yellow protein (PYP) covalently binds the chromophore 4-hydroxy coumaric acid, tuning (spectral) characteristics of this cofactor. Here, we study this binding and tuning using a combination of pointmutations and chromophore analogs. In all photosensor

  14. Nicotinic Cholinergic Receptor Binding Sites in the Brain: Regulation in vivo

    Science.gov (United States)

    Schwartz, Rochelle D.; Kellar, Kenneth J.

    1983-04-01

    Tritiated acetylcholine was used to measure binding sites with characteristics of nicotinic cholinergic receptors in rat brain. Regulation of the binding sites in vivo was examined by administering two drugs that stimulate nicotinic receptors directly or indirectly. After 10 days of exposure to the cholinesterase inhibitor diisopropyl fluorophosphate, binding of tritiated acetylcholine in the cerebral cortex was decreased. However, after repeated administration of nicotine for 10 days, binding of tritiated acetylcholine in the cortex was increased. Saturation analysis of tritiated acetylcholine binding in the cortices of rats treated with diisopropyl fluorophosphate or nicotine indicated that the number of binding sites decreased and increased, respectively, while the affinity of the sites was unaltered.

  15. Long-term stable surface modification of DLC coatings

    Directory of Open Access Journals (Sweden)

    Gotzmann Gaby

    2017-09-01

    Full Text Available The use of coatings based on diamond like carbon (DLC for medical applications was established during the last years. Main advantages of these coatings are its high hardness, good wear and friction behavior and its biocompatibility. Using low-energy electron-beam treatment, we addressed the surface modification of DLC coatings. The aim was to generate new biofunctional surface characteristics that are long-term stable.

  16. Equalization of Stable Union to Marriage at Property Succession

    OpenAIRE

    Lemos Junior, Eloy Pereira; Barbosa, Grasiele Dias

    2016-01-01

    In this paper will be analyzed the inheritance law of the spouse and partner in the light of the 2002 Civil Code and the 1988 Federal Constitution. First it covers an approach to the legislative history of the spouse's estate succession and partner. Then, analyze the characteristics of inheritance law of marriage and stable union. Furthermore, we analyze the innovations and guarantees brought by the Federal Constitution of 1988, which gave special protection to the family, regardless of their...

  17. End binding proteins are obligatory dimers.

    Directory of Open Access Journals (Sweden)

    Indrani Sen

    Full Text Available End binding (EB proteins are responsible for the recruitment of an array of microtubule plus-end tracking proteins (+TIPs to growing microtubules ends. EBs encompass an N-terminal calponin homology domain that confers microtubule tip tracking activity to the protein. The C-terminal domain of EBs contains a coiled coil that mediates the parallel dimerization of EB monomers. This part of the protein is also responsible for partner binding. While dimerization is not essential for microtubule tip tracking by EBs it is a prerequisite for +TIP partner binding. The concentration of EBs in cells has been estimated to be in the range of hundreds of nanomoles. In contrast, in in vitro single molecule experiments EB concentrations of subnanomoles are employed. From a mechanistic point of view it is important to assess the oligomerization state of EBs at physiologically and experimentally relevant protein concentrations, in particular if the goal of a study is to model the behavior of EB-dependent dynamic +TIP networks. Here we have determined the stability of the EB1 and EB3 dimers using multi-angle light scattering and fluorescence analytical ultracentrifugation. We show that these EBs form stable dimers and do not dissociate even at very low nanomolar concentrations. The dimers remained stable at both room temperature as well as at the physiologically relevant temperature of 37°C. Together, our results reveal that EBs are obligatory dimers, a conclusion that has implications for the mechanistic understanding of these key proteins involved in the orchestration of dynamic protein networks at growing microtubule ends.

  18. Identification of the quinolinedione inhibitor binding site in Cdc25 phosphatase B through docking and molecular dynamics simulations.

    Science.gov (United States)

    Ge, Yushu; van der Kamp, Marc; Malaisree, Maturos; Liu, Dan; Liu, Yi; Mulholland, Adrian J

    2017-11-01

    Cdc25 phosphatase B, a potential target for cancer therapy, is inhibited by a series of quinones. The binding site and mode of quinone inhibitors to Cdc25B remains unclear, whereas this information is important for structure-based drug design. We investigated the potential binding site of NSC663284 [DA3003-1 or 6-chloro-7-(2-morpholin-4-yl-ethylamino)-quinoline-5, 8-dione] through docking and molecular dynamics simulations. Of the two main binding sites suggested by docking, the molecular dynamics simulations only support one site for stable binding of the inhibitor. Binding sites in and near the Cdc25B catalytic site that have been suggested previously do not lead to stable binding in 50 ns molecular dynamics (MD) simulations. In contrast, a shallow pocket between the C-terminal helix and the catalytic site provides a favourable binding site that shows high stability. Two similar binding modes featuring protein-inhibitor interactions involving Tyr428, Arg482, Thr547 and Ser549 are identified by clustering analysis of all stable MD trajectories. The relatively flexible C-terminal region of Cdc25B contributes to inhibitor binding. The binding mode of NSC663284, identified through MD simulation, likely prevents the binding of protein substrates to Cdc25B. The present results provide useful information for the design of quinone inhibitors and their mechanism of inhibition.

  19. Binding Energy and Equilibrium of Compact Objects

    Directory of Open Access Journals (Sweden)

    Germano M.

    2014-04-01

    Full Text Available The theoretical analysis of the existence of a limit mass for compact astronomic ob- jects requires the solution of the Einstein’s equations of g eneral relativity together with an appropriate equation of state. Analytical solutions exi st in some special cases like the spherically symmetric static object without energy sou rces that is here considered. Solutions, i.e. the spacetime metrics, can have a singular m athematical form (the so called Schwarzschild metric due to Hilbert or a nonsingula r form (original work of Schwarzschild. The former predicts a limit mass and, conse quently, the existence of black holes above this limit. Here it is shown that, the origi nal Schwarzschild met- ric permits compact objects, without mass limit, having rea sonable values for central density and pressure. The lack of a limit mass is also demonst rated analytically just imposing reasonable conditions on the energy-matter densi ty, of positivity and decreas- ing with radius. Finally the ratio between proper mass and to tal mass tends to 2 for high values of mass so that the binding energy reaches the lim it m (total mass seen by a distant observer. As it is known the negative binding energ y reduces the gravitational mass of the object; the limit of m for the binding energy provides a mechanism for stable equilibrium of any amount of mass to contrast the gravitatio nal collapse.

  20. RNA binding specificity of Ebola virus transcription factor VP30.

    Science.gov (United States)

    Schlereth, Julia; Grünweller, Arnold; Biedenkopf, Nadine; Becker, Stephan; Hartmann, Roland K

    2016-09-01

    The transcription factor VP30 of the non-segmented RNA negative strand Ebola virus balances viral transcription and replication. Here, we comprehensively studied RNA binding by VP30. Using a novel VP30:RNA electrophoretic mobility shift assay, we tested truncated variants of 2 potential natural RNA substrates of VP30 - the genomic Ebola viral 3'-leader region and its complementary antigenomic counterpart (each ∼155 nt in length) - and a series of other non-viral RNAs. Based on oligonucleotide interference, the major VP30 binding region on the genomic 3'-leader substrate was assigned to the internal expanded single-stranded region (∼ nt 125-80). Best binding to VP30 was obtained with ssRNAs of optimally ∼ 40 nt and mixed base composition; underrepresentation of purines or pyrimidines was tolerated, but homopolymeric sequences impaired binding. A stem-loop structure, particularly at the 3'-end or positioned internally, supports stable binding to VP30. In contrast, dsRNA or RNAs exposing large internal loops flanked by entirely helical arms on both sides are not bound. Introduction of a 5´-Cap(0) structure impaired VP30 binding. Also, ssDNAs bind substantially weaker than isosequential ssRNAs and heparin competes with RNA for binding to VP30, indicating that ribose 2'-hydroxyls and electrostatic contacts of the phosphate groups contribute to the formation of VP30:RNA complexes. Our results indicate a rather relaxed RNA binding specificity of filoviral VP30, which largely differs from that of the functionally related transcription factor of the Paramyxoviridae which binds to ssRNAs as short as 13 nt with a preference for oligo(A) sequences.

  1. 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...

  2. Glucose Sensors Based on Microcapsules Containing an Orange/Red Competitive Binding Resonance Energy Transfer Assay

    Science.gov (United States)

    CHINNAYELKA, SWETHA; McSHANE, and MICHAEL J.

    2015-01-01

    Fluorescent sensing systems offer the potential for noninvasive monitoring with implantable devices, but they require carrier technologies that provide suitable immobilization, accessibility, and biocompatibility while maintaining adequate response characteristics. A recent development towards this goal is a highly specific and sensitive competitive binding assay for glucose using apo-glucose oxidase (apo-GOx) as the recognition element and dextran as the competing ligand; this has been demonstrated as a glucose sensor system by encapsulating the competitive binding assay in semipermeable microcapsule carriers. This paper describes the extension of this sensor design to longer wavelengths in an attempt to increase the applicability to in vivo monitoring. The glucose sensitivity of the tetramethylrhodamine isothiocyanate-dextran (TD) and cyanine Cy5-apo-GOx (CAG) complexes showed five to 10 times greater specificity for β-D-glucose over other sugars. Microcapsules loaded with TD/CAG complexes exhibited a linear, totally reversible response in the range of 0–720 mg/dL, with a sensitivity (percent change in intensity ratio) of 0.06%/(mg/dL). The decrease in sensitivity observed with the use of longer-wavelength dyes is most likely to be compensated with the deeper penetration of light and reduced tissue scattering. These findings imply that the encapsulation of sensing assay elements in microcapsules is a simple and translatable method for the fabrication of stable biosensors, and optimization of resonance energy transfer pairs and assay component preparation will further improve the response to approach clinically relevant performance. PMID:16800748

  3. Air-stable n-type colloidal quantum dot solids

    KAUST Repository

    Ning, Zhijun

    2014-06-08

    Colloidal quantum dots (CQDs) offer promise in flexible electronics, light sensing and energy conversion. These applications rely on rectifying junctions that require the creation of high-quality CQD solids that are controllably n-type (electron-rich) or p-type (hole-rich). Unfortunately, n-type semiconductors made using soft matter are notoriously prone to oxidation within minutes of air exposure. Here we report high-performance, air-stable n-type CQD solids. Using density functional theory we identify inorganic passivants that bind strongly to the CQD surface and repel oxidative attack. A materials processing strategy that wards off strong protic attack by polar solvents enabled the synthesis of an air-stable n-type PbS CQD solid. This material was used to build an air-processed inverted quantum junction device, which shows the highest current density from any CQD solar cell and a solar power conversion efficiency as high as 8%. We also feature the n-type CQD solid in the rapid, sensitive, and specific detection of atmospheric NO2. This work paves the way for new families of electronic devices that leverage air-stable quantum-tuned materials. © 2014 Macmillan Publishers Limited. All rights reserved.

  4. 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...

  5. 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.

  6. Stable Treemaps via Local Moves.

    Science.gov (United States)

    Sondag, Max; Speckmann, Bettina; Verbeek, Kevin

    2018-01-01

    Treemaps are a popular tool to visualize hierarchical data: items are represented by nested rectangles and the area of each rectangle corresponds to the data being visualized for this item. The visual quality of a treemap is commonly measured via the aspect ratio of the rectangles. If the data changes, then a second important quality criterion is the stability of the treemap: how much does the treemap change as the data changes. We present a novel stable treemapping algorithm that has very high visual quality. Whereas existing treemapping algorithms generally recompute the treemap every time the input changes, our algorithm changes the layout of the treemap using only local modifications. This approach not only gives us direct control over stability, but it also allows us to use a larger set of possible layouts, thus provably resulting in treemaps of higher visual quality compared to existing algorithms. We further prove that we can reach all possible treemap layouts using only our local modifications. Furthermore, we introduce a new measure for stability that better captures the relative positions of rectangles. We finally show via experiments on real-world data that our algorithm outperforms existing treemapping algorithms also in practice on either visual quality and/or stability. Our algorithm scores high on stability regardless of whether we use an existing stability measure or our new measure.

  7. Dynamics and control of twisting bi-stable structures

    Science.gov (United States)

    Arrieta, Andres F.; van Gemmeren, Valentin; Anderson, Aaron J.; Weaver, Paul M.

    2018-02-01

    Compliance-based morphing structures have the potential to offer large shape adaptation, high stiffness and low weight, while reducing complexity, friction, and scalability problems of mechanism based systems. A promising class of structure that enables these characteristics are multi-stable structures given their ability to exhibit large deflections and rotations without the expensive need for continuous actuation, with the latter only required intermittently. Furthermore, multi-stable structures exhibit inherently fast response due to the snap-through instability governing changes between stable states, enabling rapid configuration switching between the discrete number of programmed shapes of the structure. In this paper, the design and utilisation of the inherent nonlinear dynamics of bi-stable twisting I-beam structures for actuation with low strain piezoelectric materials is presented. The I-beam structure consists of three compliant components assembled into a monolithic single element, free of moving parts, and showing large deflections between two stable states. Finite element analysis is utilised to uncover the distribution of strain across the width of the flange, guiding the choice of positioning for piezoelectric actuators. In addition, the actuation authority is maximised by calculating the generalised coupling coefficient for different positions of the piezoelectric actuators. The results obtained are employed to tailor and test I-beam designs exhibiting desired large deflection between stable states, while still enabling the activation of snap-through with the low strain piezoelectric actuators. To this end, the dynamic response of the I-beams to piezoelectric excitation is investigated, revealing that resonant excitations are insufficient to dynamically trigger snap-through. A novel bang-bang control strategy, which exploits the nonlinear dynamics of the structure successfully triggers both single and constant snap-through between the stable states

  8. 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

    Full Text Available Abstract Background Various pattern-based methods exist that use in vitro or in silico affinity profiles for classification and functional examination of proteins. Nevertheless, the connection between the protein affinity profiles and the structural characteristics of the binding sites is still unclear. Our aim was to investigate the association between virtual drug screening results (calculated binding free energy values and the geometry of protein binding sites. Molecular Affinity Fingerprints (MAFs were determined for 154 proteins based on their molecular docking energy results for 1,255 FDA-approved drugs. Protein binding site geometries were characterized by 420 PocketPicker descriptors. The basic underlying component structure of MAFs and binding site geometries, respectively, were examined by principal component analysis; association between principal components extracted from these two sets of variables was then investigated by canonical correlation and redundancy analyses. Results PCA analysis of the MAF variables provided 30 factors which explained 71.4% of the total variance of the energy values while 13 factors were obtained from the PocketPicker descriptors which cumulatively explained 94.1% of the total variance. Canonical correlation analysis resulted in 3 statistically significant canonical factor pairs with correlation values of 0.87, 0.84 and 0.77, respectively. Redundancy analysis indicated that PocketPicker descriptor factors explain 6.9% of the variance of the MAF factor set while MAF factors explain 15.9% of the total variance of PocketPicker descriptor factors. Based on the salient structures of the factor pairs, we identified a clear-cut association between the shape and bulkiness of the drug molecules and the protein binding site descriptors. Conclusions This is the first study to investigate complex multivariate associations between affinity profiles and the geometric properties of protein binding sites. We found that

  9. Technological characteristics of meat - viscosity

    OpenAIRE

    DIBĎÁK, Tomáš

    2012-01-01

    This bachelor thesis is focused on the technological characteristics of meat, mainly viscosity of meat. At the beginning I dealt with construction of meat and various types of meat: beef, veal, pork, mutton, rabbit, poultry and venison. Then I described basic chemical composition of meat and it?s characteristic. In detail I dealt with viscosity of meat. Viscosity is the ability of meat to bind water both own and added. I mentioned influences, which effects viscosity and I presented the possib...

  10. Insulin binding to erythrocytes after acute 16-methyleneprednisolone ingestion.

    Science.gov (United States)

    Dwenger, A; Holle, W; Zick, R; Trautschold, I

    1982-10-01

    The binding of [125I]insulin to erythrocytes, glucose and insulin were determined before and 1, 7 and 35 days after ingestion of 2 X 60-methyleneprednisolone. None of two groups of volunteers (7 males, 4 females showed clear alterations of the insulin binding parameters (Ka and R0), or of the fasting cortisol, glucose and insulin concentrations. These results exclude the possibility that the diabetogenic effect of glucocorticoides is accompanied by an alteration of the insulin receptor characteristics of erythrocytes.

  11. 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.

  12. Acanthamoeba castellanii contains a ribosomal RNA enhancer binding protein which stimulates TIF-IB binding and transcription under stringent conditions.

    Science.gov (United States)

    Yang, Q; Radebaugh, C A; Kubaska, W; Geiss, G K; Paule, M R

    1995-01-01

    The intergenic spacer (IGS) of Acanthamoeba castellanii rRNA genes contains repeated elements which are weak enhancers for transcription by RNA polymerase I. A protein, EBF, was identified and partially purified which binds to the enhancers and to several other sequences within the IGS, but not to other DNA fragments, including the rRNA core promoter. No consensus binding sequence could be discerned in these fragments and bound factor is in rapid equilibrium with unbound. EBF has functional characteristics similar to vertebrate upstream binding factors (UBF). Not only does it bind to the enhancer and other IGS elements, but it also stimulates binding of TIF-IB, the fundamental transcription initiation factor, to the core promoter and stimulates transcription from the promoter. Attempts to identify polypeptides with epitopes similar to rat or Xenopus laevis UBF suggest that structurally the protein from A.castellanii is not closely related to vertebrate UBF. Images PMID:7501455

  13. 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

  14. Advanced thermally stable jet fuels

    Energy Technology Data Exchange (ETDEWEB)

    Schobert, H.H.

    1999-01-31

    The Pennsylvania State University program in advanced thermally stable coal-based jet fuels has five broad objectives: (1) Development of mechanisms of degradation and solids formation; (2) Quantitative measurement of growth of sub-micrometer and micrometer-sized particles suspended in fuels during thermal stressing; (3) Characterization of carbonaceous deposits by various instrumental and microscopic methods; (4) Elucidation of the role of additives in retarding the formation of carbonaceous solids; (5) Assessment of the potential of production of high yields of cycloalkanes by direct liquefaction of coal. Future high-Mach aircraft will place severe thermal demands on jet fuels, requiring the development of novel, hybrid fuel mixtures capable of withstanding temperatures in the range of 400--500 C. In the new aircraft, jet fuel will serve as both an energy source and a heat sink for cooling the airframe, engine, and system components. The ultimate development of such advanced fuels requires a thorough understanding of the thermal decomposition behavior of jet fuels under supercritical conditions. Considering that jet fuels consist of hundreds of compounds, this task must begin with a study of the thermal degradation behavior of select model compounds under supercritical conditions. The research performed by The Pennsylvania State University was focused on five major tasks that reflect the objectives stated above: Task 1: Investigation of the Quantitative Degradation of Fuels; Task 2: Investigation of Incipient Deposition; Task 3: Characterization of Solid Gums, Sediments, and Carbonaceous Deposits; Task 4: Coal-Based Fuel Stabilization Studies; and Task 5: Exploratory Studies on the Direct Conversion of Coal to High Quality Jet Fuels. The major findings of each of these tasks are presented in this executive summary. A description of the sub-tasks performed under each of these tasks and the findings of those studies are provided in the remainder of this volume

  15. Characteristics of binding sites of intergenic, intronic and exonic ...

    African Journals Online (AJOL)

    user

    2013-03-06

    2005). DTL. Denticleless homolog (Drosophila). Baraniskin et al. (2012). EBF3. Early B-cell factor 3. Kim and Kim (2007). EGFL7. EGF-like-domain, multiple 7. Díaz et al. (2008). EIF4H. Eukaryotic translation initiation factor 4H.

  16. Biochemical and binding characteristics of boar epididymal fluid proteins

    Czech Academy of Sciences Publication Activity Database

    Maňásková-Postlerová, Pavla; Davidová, Nina; Jonáková, Věra

    2011-01-01

    Roč. 879, č. 1 (2011), s. 100-106 ISSN 1570-0232 R&D Projects: GA ČR(CZ) GA303/09/1285; GA MŠk(CZ) 1M06011; GA ČR(CZ) GD523/08/H064 Institutional research plan: CEZ:AV0Z50520701 Keywords : epididymal proteins * RP HPLC * biotin-labeled ligands Subject RIV: CE - Biochemistry Impact factor: 2.888, year: 2011

  17. Oxygen-binding characteristics of the haemolymph of the freshwater ...

    African Journals Online (AJOL)

    Haemolymph was collected from each snail by me- chanical stimulation of the foot surface. During the retraction response haemolymph is extruded, probably by way of the haemal pore (Lever & Bekius 1965). By means of glass capillaries, 30 - SO ",I of haemolymph could be collected from the vacant last whorl which acts.

  18. Population Games, Stable Games, and Passivity

    Directory of Open Access Journals (Sweden)

    Michael J. Fox

    2013-10-01

    Full Text Available The class of “stable games”, introduced by Hofbauer and Sandholm in 2009, has the attractive property of admitting global convergence to equilibria under many evolutionary dynamics. We show that stable games can be identified as a special case of the feedback-system-theoretic notion of a “passive” dynamical system. Motivated by this observation, we develop a notion of passivity for evolutionary dynamics that complements the definition of the class of stable games. Since interconnections of passive dynamical systems exhibit stable behavior, we can make conclusions about passive evolutionary dynamics coupled with stable games. We show how established evolutionary dynamics qualify as passive dynamical systems. Moreover, we exploit the flexibility of the definition of passive dynamical systems to analyze generalizations of stable games and evolutionary dynamics that include forecasting heuristics as well as certain games with memory.

  19. Stable nuclear transformation of Eudorina elegans

    Directory of Open Access Journals (Sweden)

    Lerche Kai

    2013-02-01

    Full Text Available Abstract Background A fundamental step in evolution was the transition from unicellular to differentiated, multicellular organisms. Volvocine algae have been used for several decades as a model lineage to investigate the evolutionary aspects of multicellularity and cellular differentiation. There are two well-studied volvocine species, a unicellular alga (Chlamydomonas reinhardtii and a multicellular alga with differentiated cell types (Volvox carteri. Species with intermediate characteristics also exist, which blur the boundaries between unicellularity and differentiated multicellularity. These species include the globular alga Eudorina elegans, which is composed of 16–32 cells. However, detailed molecular analyses of E. elegans require genetic manipulation. Unfortunately, genetic engineering has not yet been established for Eudorina, and only limited DNA and/or protein sequence information is available. Results Here, we describe the stable nuclear transformation of E. elegans by particle bombardment using both a chimeric selectable marker and reporter genes from different heterologous sources. Transgenic algae resistant to paromomycin were achieved using the aminoglycoside 3′-phosphotransferase VIII (aphVIII gene of Streptomyces rimosus, an actinobacterium, under the control of an artificial promoter consisting of two V. carteri promoters in tandem. Transformants exhibited an increase in resistance to paromomycin by up to 333-fold. Co-transformation with non-selectable plasmids was achieved with a rate of 50 - 100%. The luciferase (gluc gene from the marine copepod Gaussia princeps, which previously was engineered to match the codon usage of C. reinhardtii, was used as a reporter gene. The expression of gluc was mediated by promoters from C. reinhardtii and V. carteri. Heterologous heat shock promoters induced an increase in luciferase activity (up to 600-fold at elevated temperatures. Long-term stability and both constitutive and

  20. 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.

  1. Receptor concentration and diffusivity control multivalent binding of Sv40 to membrane bilayers.

    Directory of Open Access Journals (Sweden)

    Oliwia M Szklarczyk

    Full Text Available Incoming Simian Virus 40 particles bind to their cellular receptor, the glycolipid GM1, in the plasma membrane and thereby induce membrane deformation beneath the virion leading to endocytosis and infection. Efficient membrane deformation depends on receptor lipid structure and the organization of binding sites on the internalizing particle. To determine the role of receptor diffusion, concentration and the number of receptors required for stable binding in this interaction, we analyze the binding of SV40 to GM1 in supported membrane bilayers by computational modeling based on experimental data. We measure the diffusion rates of SV40 virions in solution by fluorescence correlation spectroscopy and of the receptor in bilayers by single molecule tracking. Quartz-crystal microbalance with dissipation (QCM-D is used to measure binding of SV40 virus-like particles to bilayers containing the viral receptor GM1. We develop a phenomenological stochastic dynamics model calibrated against this data, and use it to investigate the early events of virus attachment to lipid membranes. Our results indicate that SV40 requires at least 4 attached receptors to achieve stable binding. We moreover find that receptor diffusion is essential for the establishment of stable binding over the physiological range of receptor concentrations and that receptor concentration controls the mode of viral motion on the target membrane. Our results provide quantitative insight into the initial events of virus-host interaction at the nanoscopic level.

  2. Discrimination of ginseng cultivation regions using light stable isotope analysis.

    Science.gov (United States)

    Kim, Kiwook; Song, Joo-Hyun; Heo, Sang-Cheol; Lee, Jin-Hee; Jung, In-Woo; Min, Ji-Sook

    2015-10-01

    Korean ginseng is considered to be a precious health food in Asia. Today, thieves frequently compromise ginseng farms by pervasive theft. Thus, studies regarding the characteristics of ginseng according to growth region are required in order to deter ginseng thieves and prevent theft. In this study, 6 regions were selected on the basis of Korea regional criteria (si, gun, gu), and two ginseng-farms were randomly selected from each of the 6 regions. Then 4-6 samples of ginseng were acquired from each ginseng farm. The stable isotopic compositions of H, O, C, and N of the collected ginseng samples were analyzed. As a result, differences in the hydrogen isotope ratios could be used to distinguish regional differences, and differences in the nitrogen isotope ratios yielded characteristic information regarding the farms from which the samples were obtained. Thus, stable isotope values could be used to differentiate samples according to regional differences. Therefore, stable isotope analysis serves as a powerful tool to discriminate the regional origin of Korean ginseng samples from across Korea. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Comparison of Transcription Factor Binding Site Models

    KAUST Repository

    Bhuyan, Sharifulislam

    2012-05-01

    Modeling of transcription factor binding sites (TFBSs) and TFBS prediction on genomic sequences are important steps to elucidate transcription regulatory mechanism. Dependency of transcription regulation on a great number of factors such as chemical specificity, molecular structure, genomic and epigenetic characteristics, long distance interaction, makes this a challenging problem. Different experimental procedures generate evidence that DNA-binding domains of transcription factors show considerable DNA sequence specificity. Probabilistic modeling of TFBSs has been moderately successful in identifying patterns from a family of sequences. In this study, we compare performances of different probabilistic models and try to estimate their efficacy over experimental TFBSs data. We build a pipeline to calculate sensitivity and specificity from aligned TFBS sequences for several probabilistic models, such as Markov chains, hidden Markov models, Bayesian networks. Our work, containing relevant statistics and evaluation for the models, can help researchers to choose the most appropriate model for the problem at hand.

  4. Treatment of stable COPD: antioxidants

    Directory of Open Access Journals (Sweden)

    W. MacNee

    2005-09-01

    Full Text Available There is considerable evidence that an increased oxidative burden occurs in the lungs of patients with chronic obstructive pulmonary disease (COPD and this results in an imbalance between oxidants/antioxidants or oxidative stress, which may play a role in many of the processes involved in the pathogenesis of COPD. These include enhanced proteolytic activity, mucus hypersecretion and the enhanced inflammatory response in the lungs to inhaling tobacco smoke, which is characteristic of COPD. COPD is now recognised to have multiple systemic consequences, such as weight loss and skeletal muscle dysfunction. It is now thought that oxidative stress may extend beyond the lungs and is involved in these systemic effects. Antioxidant therapy therefore would seem to be a logical therapeutic approach in chronic obstructive pulmonary disease. There is a need for more potent antioxidant therapies to test the hypothesis that antioxidant drugs may be a new therapeutic strategy for the prevention and treatment of chronic obstructive pulmonary disease.

  5. Characterization of stable fly (Diptera: Muscidae) larval developmental habitat at round hay bale feeding sites.

    Science.gov (United States)

    Talley, Justin; Broce, Alberto; Zurek, Ludek

    2009-11-01

    In this study, we examined the stable fly, Stomoxys calcitrans (L.) (Diptera: Muscidae), larval developmental habitat within the round hay bale feeding sites on cattle pastures, and we identified three zones with distinct characteristics around two types of hay feeders (ring and cone). The parameters monitored in each zone included stable fly emergence, substrate temperature, moisture, pH, thickness of hay-manure layer, and concentration of fecal coliform bacteria (Escherichia coli and Klebsiella oxytoca) as indicators of fecal material. All measurements were conducted during the period of high stable fly prevalence (HSF) in May-June and low stable fly prevalence (LSF) in July-August to better understand the environmental factors influencing stable fly seasonality. Substrate temperature and fecal coliform concentration were the only two significantly different factors between HSF and LSF. Temperatures ranged from 21 to 25 degrees C during HSF versus 25-30 degrees C in LSF but all were within the range for successful stable fly development. Fecal coliform concentrations ranged from 4.2 x 10(3) to 4.1 x 10(4) colony-forming units (CFU)/g of the substrate during HSF and from undetectable (stable fly development (egg to adult). Temperature was significantly higher and stable fly developmental time significantly shorter in all substrates containing hay when compared with that of manure alone, but no significant differences were detected in stable fly emergence among the substrates. These results strongly indicate that the fecal microbial community plays an important role in stable fly larval development in hay feeding sites and that it is the main factor behind stable fly developmental seasonality on pastures. Our results also demonstrate that animal manure mixed with hay provides conditions for faster stable fly development than manure alone; however, hay does not significantly affect overall stable fly emergence.

  6. Species A rotavirus NSP3 acquires its translation inhibitory function prior to stable dimer formation.

    Directory of Open Access Journals (Sweden)

    Hugo I Contreras-Treviño

    Full Text Available Species A rotavirus non-structural protein 3 (NSP3 is a translational regulator that inhibits or, under some conditions, enhances host cell translation. NSP3 binds to the translation initiation factor eIF4G1 and evicts poly-(A binding protein (PABP from eIF4G1, thus inhibiting translation of polyadenylated mRNAs, presumably by disrupting the effect of PABP bound to their 3'-ends. NSP3 has a long coiled-coil region involved in dimerization that includes a chaperone Hsp90-binding domain (HS90BD. We aimed to study the role in NSP3 dimerization of a segment of the coiled-coil region adjoining the HS90BD. We used a vaccinia virus system to express NSP3 with point mutations in conserved amino acids in the coiled-coil region and determined the effects of these mutations on translation by metabolic labeling of proteins as well as on accumulation of stable NSP3 dimers by non-dissociating Western blot, a method that separates stable NSP3 dimers from the monomer/dimerization intermediate forms of the protein. Four of five mutations reduced the total yield of NSP3 and the formation of stable dimers (W170A, K171E, R173E and R187E:K191E, whereas one mutation had the opposite effects (Y192A. Treatment with the proteasome inhibitor MG132 revealed that stable NSP3 dimers and monomers/dimerization intermediates are susceptible to proteasome degradation. Surprisingly, mutants severely impaired in the formation of stable dimers were still able to inhibit host cell translation, suggesting that NSP3 dimerization intermediates are functional. Our results demonstrate that rotavirus NSP3 acquires its function prior to stable dimer formation and remain as a proteasome target throughout dimerization.

  7. Phosphorus Binding Sites in Proteins: Structural Preorganization and Coordination

    DEFF Research Database (Denmark)

    Gruber, Mathias Felix; Greisen, Per Junior; Junker, Märta Caroline

    2014-01-01

    to individual structures that bind to phosphate groups; here, we investigate a total of 8307 structures obtained from the RCSB Protein Data Bank (PDB). An analysis of the binding site amino acid propensities reveals very characteristic first shell residue distributions, which are found to be influenced...... by the characteristics of the phosphorus compound and by the presence of cobound cations. The second shell, which supports the coordinating residues in the first shell, is found to consist mainly of protein backbone groups. Our results show how the second shell residue distribution is dictated mainly by the first shell...

  8. Substance P and substance K receptor binding sites in the human gastrointestinal tract: localization by autoradiography

    International Nuclear Information System (INIS)

    Gates, T.S.; Zimmerman, R.P.; Mantyh, C.R.; Vigna, S.R.; Maggio, J.E.; Welton, M.L.; Passaro, E.P. Jr.; Mantyh, P.W.

    1988-01-01

    Quantitative receptor autoradiography was used to localize and quantify the distribution of binding sites for 125 I-radiolabeled substance P (SP), substance K (SK) and neuromedin K (NK) in the human GI tract using histologically normal tissue obtained from uninvolved margins of resections for carcinoma. The distribution of SP and SK binding sites is different for each gastrointestinal (GI) segment examined. Specific SP binding sites are expressed by arterioles and venules, myenteric plexus, external circular muscle, external longitudinal muscle, muscularis mucosa, epithelial cells of the mucosa, and the germinal centers of lymph nodules. SK binding sites are distributed in a pattern distinct from SP binding sites and are localized to the external circular muscle, external longitudinal muscle, and the muscularis mucosa. Binding sites for NK were not detected in any part of the human GI tract. These results demonstrate that: (1) surgical specimens from the human GI tract can be effectively processed for quantitative receptor autoradiography; (2) of the three mammalian tachykinins tested, SP and SK, but not NK binding sites are expressed in detectable levels in the human GI tract; (3) whereas SK receptor binding sites are expressed almost exclusively by smooth muscle, SP binding sites are expressed by smooth muscle cells, arterioles, venules, epithelial cells of the mucosa and cells associated with lymph nodules; and (4) both SP and SK binding sites expressed by smooth muscle are more stable than SP binding sites expressed by blood vessels, lymph nodules, and mucosal cells

  9. Binding of Plasmodium falciparum to CD36 can be shielded by the glycocalyx

    DEFF Research Database (Denmark)

    Hempel, Casper; Wang, Christian William; Kurtzhals, Jorgen Anders Lindholm

    2017-01-01

    FCR3/IT) was selected on Chinese hamster ovary (CHO) cells transfected with human CD36. Cytoadhesion to CHO CD36 at 1-4 days after seeding was quantified by using a static binding assay. Results: The glycocalyx thickness of CHO cells increased during 4 days in culture as assessed by metabolic...... labelling of glycans with azido sugars and with electron microscopy studying the binding of cationized ferritin to cell surfaces. The functional importance of this process was addressed in binding assays by using CHO cells transfected with CD36. In parallel with the maturation of the glycocalyx, antibody......-binding to CD36 was inhibited, despite stable expression of CD36. P. falciparum selected for CD36-binding recognized CD36 on CHO cells on the first day in culture, but the binding was lost after 2-4 days. Conclusion: The endothelial glycocalyx affects parasite cytoadhesion in vitro, an effect that has...

  10. PRIORITY DIRECTIONS OF PROVISION OF STABLE LAND USE

    Directory of Open Access Journals (Sweden)

    L. Hun’ko

    2016-10-01

    Full Text Available The conditions of stable land use are highlighted in this article. The question of the territory of agricultural enterprises is considered as well. The characteristic of the type of land use is given here. The recommendations are shown on the formation of ecologically safe types of land use. In the terms of new land relations is important to resolve the issue of land use regulation to with stand landscapes against adverse natural and anthropogenic influences. The main instrument of the state, which aims to provide an ecologically permissible and economically effective land use, land use is as an important component of land relations. Planning should include a system of legal, technical, economic and environmental activities that will ensure the preservation, restoration and rational use of land and other natural resources for the benefit of the whole society. Keywords: land use, land management, stable development, landscape, soil erosion, protection of land.

  11. On the stable Mg-Zn-Y quasicrystals

    Science.gov (United States)

    Luo, Z. P.; Sui, H. X.; Zhang, S. Q.

    1996-07-01

    By the conventional air-cooled casting method, bulk ingots with a large fraction of stable Mg-Zn-Y icosahedral quasicrystals, both simple and face-centered, were obtained. The quasicrystal structures were directly confirmed by high-resolution electron microscopy (HREM) observations. The electron diffraction patterns from the quasicrystals were studied by computer simulations. A coexisting crys-talline phase of the quasicrystals was identified as the Mg7Zn3 phase, which was proved to be the (1/1) approximant of the quasicrystals. The quasicrystals were stable during a continuous heating process. However, at high temperature, oxidation occurred, and thus, Y2O3 and MgO products were formed. Oxidation at high temperatures is characteristic for the Mg-Zn-Y alloys and differs from Al-base alloys.

  12. Gas phase thermal diffusion of stable isotopes

    International Nuclear Information System (INIS)

    Eck, C.F.

    1979-01-01

    The separation of stable isotopes at Mound Facility is reviewed from a historical perspective. The historical development of thermal diffusion from a laboratory process to a separation facility that handles all the noble gases is described. In addition, elementary thermal diffusion theory and elementary cascade theory are presented along with a brief review of the uses of stable isotopes

  13. physico-chemical and stable isotopes

    African Journals Online (AJOL)

    This paper details the mineralogical, chemical and stable isotope abundances of calcrete in the Letlhakeng fossil valley. The stable isotope abundances (O and C) of calcretes yielded some values which were tested against the nature of the calcretes – pedogenic or groundwater type. The Kgalagadi (Kalahari) is a vast ...

  14. Modelling stable atmospheric boundary layers over snow

    NARCIS (Netherlands)

    Sterk, H.A.M.

    2015-01-01

    Thesis entitled:

    Modelling Stable Atmospheric Boundary Layers over Snow

    H.A.M. Sterk

    Wageningen, 29th of April, 2015

    Summary

    The emphasis of this thesis is on the understanding and forecasting of the Stable Boundary Layer (SBL) over snow-covered surfaces. SBLs

  15. Modelling stable atmospheric boundary layers over snow

    NARCIS (Netherlands)

    Sterk, H.A.M.

    2015-01-01

    Thesis entitled: Modelling Stable Atmospheric Boundary Layers over Snow H.A.M. Sterk Wageningen, 29th of April, 2015 Summary The emphasis of this thesis is on the understanding and forecasting of the Stable Boundary Layer (SBL) over snow-covered surfaces. SBLs typically form at night and in polar

  16. Stable isotopes and biomarkers in microbial ecology

    NARCIS (Netherlands)

    Boschker, H.T.S.; Middelburg, J.J.

    2002-01-01

    The use of biomarkers in combination with stable isotope analysis is a new approach in microbial ecology and a number of papers on a variety of subjects have appeared. We will first discuss the techniques for analysing stable isotopes in biomarkers, primarily gas chromatography-combustion-isotope

  17. Stable Agrobacterium -mediated transformation of the halophytic ...

    African Journals Online (AJOL)

    Stable Agrobacterium-mediated transformation of the halophytic Leymus chinensis (Trin.) Yan-Lin Sun, Soon-Kwan Hong. Abstract. In this study, an efficient procedure for stable Agrobacterium-mediated transformation of Leymus chinensis (Trin.) was established. Agrobacterium tumefaciens strain EHA105, harboring a ...

  18. Cow hair allergen concentrations in dairy farms with automatic and conventional milking systems: From stable to bedroom.

    Science.gov (United States)

    Böhlandt, A; Schierl, R; Heizinger, J; Dietrich-Gümperlein, G; Zahradnik, E; Bruckmaier, L; Sültz, J; Raulf, M; Nowak, D

    2016-01-01

    Bovine hair and dander are considered to be a notable risk factor for sensitization and allergic symptoms in occupationally exposed cattle farmers due to various IgE binding proteins. Farmers are suspected not only to be exposed during their work inside the stables but also inside their homes as allergens could be transferred via hair and clothes resulting in continued bovine allergen exposure in private areas. In recent years a new sensitive sandwich ELISA (enzyme linked immunosorbent assay) test has been developed to measure the cow hair allergen (CHA) concentration in dust. The aim of the present study was to determine the CHA concentration in airborne and settled dust samples in stables and private rooms of dairy cattle farms with automatic milking systems (AM) and conventional milking systems (CM), also with respect to questionnaire data on farming characteristics. For this purpose different sampling techniques were applied, and results and practicability of the techniques were compared. Dust sampling was performed in the stable, computer room (only AM), changing room, living room and bedroom (mattress) of 12 dairy farms with automatic milking systems (AM group) and eight dairy farms with conventional milking systems (CM group). Altogether, 90 samples were taken by ALK filter dust collectors from all locations, while 32 samples were collected by an ion charging device (ICD) and 24 samples by an electronic dust fall collector (EDC) in computer rooms (AM) and/or changing and living rooms (not stables). The dust samples were extracted and analyzed for CHA content with a sandwich ELISA. At all investigated locations, CHA concentrations were above the limit of detection (LOD) of 0.1 ng/ml dust extract. The median CHA concentrations in dust collected by ALK filters ranged from 63 to 7154 μg/g dust in AM farms and from 121 to 5627 μg/g dust in CM farms with a steep concentration gradient from stables to bedrooms. ICD sampling revealed median CHA contents of 112

  19. Stable Continental Region Earthquakes in South China

    Science.gov (United States)

    Liu, L.

    This paper reviews some remarkable characteristics of earthquakes in a Stable Continental Region (SCR) of the South China Block (SCB). The kernel of the SCB is the Yangtze platform solidified in late Proterozoic time, with continental growth to the southeast by a series of fold belts in Paleozoic time. The facts that the deviatoric stress is low, the orientations of the major tectonic features in the SCB are substantially normal to the maximum horizontal principal stress, and a relatively uniform crust, seem to be the major reasons for lack of significant seismicity in most regions of the SCB. Earthquakes in this region are mainly associated with three seismic zones: (1) the Southeast China Coast seismic zone related to Guangdong-Fujian coastal folding belt (associated with Eurasia-Philippine Sea plate collision); (2) the Southern Yellow Sea seismic zone associated with continental shelf rifts and basins; and (3) the Downstream Yangtze River seismic zone spatially coinciding with Tertiary rifts and basin development. All three seismic zones are close to one or two major economic and population centers in the SCB so that they pose significant seismic hazards. Earthquake focal mechanisms in the SCB are consistent with strike-slip to normal faulting stress regimes. Because of the global and national economic significance of the SCB and its dense population, the seismic hazard of the region is of outstanding importance. Comparing the SCB with another less developed region, a pending earthquake with the same size and tectonic setting would cause substantially more severe social and economic losses in the SCB. This paper also compiles an inventory of historic moderate to great earthquakes in the SCB; most of the data are not widely available in English literature.

  20. Structure of acid-stable carmine.

    Science.gov (United States)

    Sugimoto, Naoki; Kawasaki, Yoko; Sato, Kyoko; Aoki, Hiromitsu; Ichi, Takahito; Koda, Takatoshi; Yamazaki, Takeshi; Maitani, Tamio

    2002-02-01

    Acid-stable carmine has recently been distributed in the U.S. market because of its good acid stability, but it is not permitted in Japan. We analyzed and determined the structure of the major pigment in acid-stable carmine, in order to establish an analytical method for it. Carminic acid was transformed into a different type of pigment, named acid-stable carmine, through amination when heated in ammonia solution. The features of the structure were clarified using a model compound, purpurin, in which the orientation of hydroxyl groups on the A ring of the anthraquinone skeleton is the same as that of carminic acid. By spectroscopic means and the synthesis of acid-stable carmine and purpurin derivatives, the structure of the major pigment in acid-stable carmine was established as 4-aminocarminic acid, a novel compound.

  1. Stable Fly, (L., Dispersal and Governing Factors

    Directory of Open Access Journals (Sweden)

    Allan T. Showler

    2015-01-01

    Full Text Available Although the movement of stable fly, Stomoxys calcitrans (L., has been studied, its extent and significance has been uncertain. On a local scale (13 km is mainly wind-driven by weather fronts that carry stable flies from inland farm areas for up to 225 km to beaches of northwestern Florida and Lake Superior. Stable flies can reproduce for a short time each year in washed-up sea grass, but the beaches are not conducive to establishment. Such movement is passive and does not appear to be advantageous to stable fly's survival. On a regional scale, stable flies exhibit little genetic differentiation, and on the global scale, while there might be more than one “lineage”, the species is nevertheless considered to be panmictic. Population expansion across much of the globe likely occurred from the late Pleistocene to the early Holocene in association with the spread of domesticated nomad livestock and particularly with more sedentary, penned livestock.

  2. Protein-folding location can regulate manganese-binding versus copper- or zinc-binding.

    Science.gov (United States)

    Tottey, Steve; Waldron, Kevin J; Firbank, Susan J; Reale, Brian; Bessant, Conrad; Sato, Katsuko; Cheek, Timothy R; Gray, Joe; Banfield, Mark J; Dennison, Christopher; Robinson, Nigel J

    2008-10-23

    Metals are needed by at least one-quarter of all proteins. Although metallochaperones insert the correct metal into some proteins, they have not been found for the vast majority, and the view is that most metalloproteins acquire their metals directly from cellular pools. However, some metals form more stable complexes with proteins than do others. For instance, as described in the Irving-Williams series, Cu(2+) and Zn(2+) typically form more stable complexes than Mn(2+). Thus it is unclear what cellular mechanisms manage metal acquisition by most nascent proteins. To investigate this question, we identified the most abundant Cu(2+)-protein, CucA (Cu(2+)-cupin A), and the most abundant Mn(2+)-protein, MncA (Mn(2+)-cupin A), in the periplasm of the cyanobacterium Synechocystis PCC 6803. Each of these newly identified proteins binds its respective metal via identical ligands within a cupin fold. Consistent with the Irving-Williams series, MncA only binds Mn(2+) after folding in solutions containing at least a 10(4) times molar excess of Mn(2+) over Cu(2+) or Zn(2+). However once MncA has bound Mn(2+), the metal does not exchange with Cu(2+). MncA and CucA have signal peptides for different export pathways into the periplasm, Tat and Sec respectively. Export by the Tat pathway allows MncA to fold in the cytoplasm, which contains only tightly bound copper or Zn(2+) (refs 10-12) but micromolar Mn(2+) (ref. 13). In contrast, CucA folds in the periplasm to acquire Cu(2+). These results reveal a mechanism whereby the compartment in which a protein folds overrides its binding preference to control its metal content. They explain why the cytoplasm must contain only tightly bound and buffered copper and Zn(2+).

  3. Structural analysis and binding properties of isoforms of tarin, the GNA-related lectin from Colocasia esculenta.

    Science.gov (United States)

    Pereira, Patrícia R; Winter, Harry C; Verícimo, Mauricio A; Meagher, Jennifer L; Stuckey, Jeanne A; Goldstein, Irwin J; Paschoalin, Vânia M F; Silva, Joab T

    2015-01-01

    The lectins, a class of proteins that occur widely in animals, plants, fungi, lichens and microorganisms, are known for their ability to specifically bind to carbohydrates. Plant lectins can be classified into 12 families including the Galanthus nivalis agglutinin (GNA)-related lectin superfamily, which is widespread among monocotyledonous plants and binds specifically to mannose, a behavior that confers remarkable anti-tumor, anti-viral and insecticidal properties on these proteins. The present study characterized a mitogenic lectin from this family, called tarin, which was purified from the crude extract from taro (Colocasia esculenta). The results showed that tarin is a glycoprotein with 2-3% carbohydrate content, composed of least 10 isoforms with pIs ranging from 5.5 to 9.5. The intact protein is a heterotetramer of 47kDa composed of two non-identical and non-covalently associated polypeptides, with small subunits of 11.9kDa and large subunits of 12.6kDa. The tarin structure is stable and recovers or maintains its functional structure following treatments at different temperatures and pH. Tarin showed a complex carbohydrate specificity, binding with high affinity to high-mannose and complex N-glycans. Many of these ligands can be found in viruses, tumor cells and insects, as well as in hematopoietic progenitor cells. Chemical modifications confirmed that both conserved and non-conserved amino acids participate in this interaction. This study determined the structural and ligand binding characteristics of a GNA-related lectin that can be exploited for several different purposes, particularly as a proliferative therapeutic molecule that is able to enhance the immunological response. Copyright © 2014. Published by Elsevier B.V.

  4. Binding Properties of General Odorant Binding Proteins from the Oriental Fruit Moth, Grapholita molesta (Busck (Lepidoptera: Tortricidae.

    Directory of Open Access Journals (Sweden)

    Guangwei Li

    Full Text Available The oriental fruit moth Grapholita molesta is a host-switching pest species. The adults highly depend on olfactory cues in locating optimal host plants and oviposition sites. Odorant binding proteins (OBPs are thought to be responsible for recognizing and transporting hydrophobic odorants across the aqueous sensillum lymph to stimulate the odorant receptors (ORs within the antennal sensilla and activate the olfactory signal transduction pathway. Exploring the physiological function of these OBPs could facilitate understanding insect chemical communications.Two antennae-specific general OBPs (GOBPs of G. molesta were expressed and purified in vitro. The binding affinities of G. molesta GOBP1 and 2 (GmolGOBP1 and 2 for sex pheromone components and host plant volatiles were measured by fluorescence ligand-binding assays. The distribution of GmolGOBP1 and 2 in the antennal sensillum were defined by whole mount fluorescence immunohistochemistry (WM-FIHC experiments. The binding sites of GmolGOBP2 were predicted using homology modeling, molecular docking and site-directed mutagenesis. Both GmolGOBP1 and 2 are housing in sensilla basiconica and with no differences in male and female antennae. Recombinant GmolGOBP1 (rGmolGOBP1 exhibited broad binding properties towards host plant volatiles and sex pheromone components; rGmolGOBP2 could not effectively bind host plant volatiles but showed specific binding affinity with a minor sex pheromone component dodecanol. We chose GmolGOBP2 and dodecanol for further homology modeling, molecular docking, and site-directed mutagenesis. Binding affinities of mutants demonstrated that Thr9 was the key binding site and confirmed dodecanol bonding to protein involves a hydrogen bond. Combined with the pH effect on binding affinities of rGmolGOBP2, ligand binding and release of GmolGOBP2 were related to a pH-dependent conformational transition.Two rGmolGOBPs exhibit different binding characteristics for tested ligands. r

  5. Binding Properties of General Odorant Binding Proteins from the Oriental Fruit Moth, Grapholita molesta (Busck) (Lepidoptera: Tortricidae).

    Science.gov (United States)

    Li, Guangwei; Chen, Xiulin; Li, Boliao; Zhang, Guohui; Li, Yiping; Wu, Junxiang

    2016-01-01

    The oriental fruit moth Grapholita molesta is a host-switching pest species. The adults highly depend on olfactory cues in locating optimal host plants and oviposition sites. Odorant binding proteins (OBPs) are thought to be responsible for recognizing and transporting hydrophobic odorants across the aqueous sensillum lymph to stimulate the odorant receptors (ORs) within the antennal sensilla and activate the olfactory signal transduction pathway. Exploring the physiological function of these OBPs could facilitate understanding insect chemical communications. Two antennae-specific general OBPs (GOBPs) of G. molesta were expressed and purified in vitro. The binding affinities of G. molesta GOBP1 and 2 (GmolGOBP1 and 2) for sex pheromone components and host plant volatiles were measured by fluorescence ligand-binding assays. The distribution of GmolGOBP1 and 2 in the antennal sensillum were defined by whole mount fluorescence immunohistochemistry (WM-FIHC) experiments. The binding sites of GmolGOBP2 were predicted using homology modeling, molecular docking and site-directed mutagenesis. Both GmolGOBP1 and 2 are housing in sensilla basiconica and with no differences in male and female antennae. Recombinant GmolGOBP1 (rGmolGOBP1) exhibited broad binding properties towards host plant volatiles and sex pheromone components; rGmolGOBP2 could not effectively bind host plant volatiles but showed specific binding affinity with a minor sex pheromone component dodecanol. We chose GmolGOBP2 and dodecanol for further homology modeling, molecular docking, and site-directed mutagenesis. Binding affinities of mutants demonstrated that Thr9 was the key binding site and confirmed dodecanol bonding to protein involves a hydrogen bond. Combined with the pH effect on binding affinities of rGmolGOBP2, ligand binding and release of GmolGOBP2 were related to a pH-dependent conformational transition. Two rGmolGOBPs exhibit different binding characteristics for tested ligands. rGmolGOBP1 has

  6. Binding Properties of General Odorant Binding Proteins from the Oriental Fruit Moth, Grapholita molesta (Busck) (Lepidoptera: Tortricidae)

    Science.gov (United States)

    Li, Guangwei; Chen, Xiulin; Li, Boliao; Zhang, Guohui; Li, Yiping; Wu, Junxiang

    2016-01-01

    binding characteristics for tested ligands. rGmolGOBP1 has dual functions in recognition of host plant volatiles and sex pheromone components, while rGmolGOBP2 is mainly involved in minor sex pheromone component dodecanol perception. This study also provides empirical evidence for the predicted functions of key amino acids in recombinant protein ligand-binding characteristics. PMID:27152703

  7. Microwave generation of stable atmospheric-pressure fireballs in air

    Science.gov (United States)

    Stephan, Karl D.

    2006-11-01

    The generation of stable buoyant fireballs in a microwave cavity in air at atmospheric pressure without the use of vaporized solids is described. These fireballs have some of the characteristics of ball lightning and resemble those reported by Dikhtyar and Jerby [Phys. Rev. Lett. 96, 045002 (2006)], although of a different color, and do not require the presence of molten or vaporized material. Mechanisms of microwave plasma formation and fluid dynamics can account for the observed behavior of the fireballs, which do not appear to meet the accepted definition of dusty plasmas in this case. Relevance to models of ball lightning and industrial applications are discussed.

  8. Iron metabolism study in humans by means of stable tracers

    International Nuclear Information System (INIS)

    Cantone, M.C.; Molho, N.; Pirola, L.; Gambarini, G.; Hansen, C.; Roth, P.; Werner, E.

    1988-01-01

    An investigation of iron metabolism in a female patient volunteer by administration of stable iron isotopes as tracers was performed. The applied methodology had already been tested in rabbits in comparison with radioactive tracer technique. The subject under study was given 58 Fe solution intravenously and about 45 min later 57 Fe solution orally. Ten blood samples were drawn at different times within 522 min from injection. Single iron isotopes content in plasma samples was determined by proton nuclear activation. A Compton suppressor system was utilized to improve the detector limits. The characteristic parameters of iron plasma clearance and of iron intestinal absorption were determined

  9. Stable Organic Neutral Diradical via Reversible Coordination.

    Science.gov (United States)

    Lu, Zhenpin; Quanz, Henrik; Burghaus, Olaf; Hofmann, Jonas; Logemann, Christian; Beeck, Sebastian; Schreiner, Peter R; Wegner, Hermann A

    2017-12-27

    We report the formation of a stable neutral diboron diradical simply by coordination of an aromatic dinitrogen compound to an ortho-phenyldiborane. This process is reversible upon addition of pyridine. The diradical species is stable above 200 °C. Computations are consistent with an open-shell triplet diradical with a very small open-shell singlet-triplet energy gap that is indicative of the electronic disjointness of the two radical sites. This opens a new way of generating stable radicals with fascinating electronic properties useful for a large variety of applications.

  10. 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.

  11. 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

  12. Human chorionic ganodotropin binding sites in the human endometrium

    International Nuclear Information System (INIS)

    Bhattacharya, S.; Banerjee, J.; Sen, S.; Manna, P.R.

    1993-01-01

    The existence of high-affinity and low-capacity specific binding sites for luteinizing hormone/human chorionic gonadotropin (hCG) has been reported in porcine, rabbit and rat uteri. The authors have identified the hCG binding sites in the human endometrium collected from 35-42-year-old ovulatory and anovulatory women. The binding characteristics of hCG to endometrial tissue preparations from ovulatory and anovulatory women showed saturability with high affinity and low capacity. Scatchard plot analysis showed the dissociation constant of specific binding sites in the ovulatory women to be 3.5x10 -10 mol/l and in anovulatory women to be 3.1x10 -10 mol/l. The maximum binding capacity varied considerably between ovulatory and anovulatory endometrium. Among the divalent metal ions tested Zn 2+ effected a remarkable increase in [ 125 I]hCG binding to the endometrium, whereas Mn 2+ showed a marginal increase and other metal ions did not have any effect. Data obtained with human endometrium indicate an influence of the functional state of the ovary on [ 125 I]hCG binding to endometrium. 14 refs., 3 figs

  13. 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...

  14. Stable Isotope Group 1983 progress report

    International Nuclear Information System (INIS)

    Stewart, M.K.

    1984-06-01

    The work of the Stable Isotope Group of the Institute of Nuclear Sciences in the fields of isotope geology, isotope hydrology, geochronology, isotope biology and related fields, and mass spectrometer instrumentation, during 1983, is described

  15. Stable Isotope Group 1982 progress report

    International Nuclear Information System (INIS)

    Stewart, M.K.

    1983-06-01

    The work of the Stable Isotope Group of the Institute of Nuclear Sciences during 1982, in the fields of isotope geology, isotope hydrology, geochronology, isotope biology and mass spectrometer instrumentation, is described

  16. Bartolome Island, Galapagos Stable Oxygen Calibration Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Galapagos Coral Stable Oxygen Calibration Data. Sites: Bartolome Island: 0 deg, 17'S, 90 deg 33' W. Champion Island: 1 deg, 15'S, 90 deg, 05' W. Urvina Bay (Isabela...

  17. Allan Hills Stable Water Isotopes, Version 1

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set includes stable water isotope values at 10 m resolution along an approximately 5 km transect through the main icefield of the Allan Hills Blue Ice...

  18. Applications of stable isotopes in clinical pharmacology

    Science.gov (United States)

    Schellekens, Reinout C A; Stellaard, Frans; Woerdenbag, Herman J; Frijlink, Henderik W; Kosterink, Jos G W

    2011-01-01

    This review aims to present an overview of the application of stable isotope technology in clinical pharmacology. Three main categories of stable isotope technology can be distinguished in clinical pharmacology. Firstly, it is applied in the assessment of drug pharmacology to determine the pharmacokinetic profile or mode of action of a drug substance. Secondly, stable isotopes may be used for the assessment of drug products or drug delivery systems by determination of parameters such as the bioavailability or the release profile. Thirdly, patients may be assessed in relation to patient-specific drug treatment; this concept is often called personalized medicine. In this article, the application of stable isotope technology in the aforementioned three areas is reviewed, with emphasis on developments over the past 25 years. The applications are illustrated with examples from clinical studies in humans. PMID:21801197

  19. On Stable Marriages and Greedy Matchings

    Energy Technology Data Exchange (ETDEWEB)

    Manne, Fredrik; Naim, Md; Lerring, Hakon; Halappanavar, Mahantesh

    2016-12-11

    Research on stable marriage problems has a long and mathematically rigorous history, while that of exploiting greedy matchings in combinatorial scientific computing is a younger and less developed research field. In this paper we consider the relationships between these two areas. In particular we show that several problems related to computing greedy matchings can be formulated as stable marriage problems and as a consequence several recently proposed algorithms for computing greedy matchings are in fact special cases of well known algorithms for the stable marriage problem. However, in terms of implementations and practical scalable solutions on modern hardware, the greedy matching community has made considerable progress. We show that due to the strong relationship between these two fields many of these results are also applicable for solving stable marriage problems.

  20. 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

  1. Dataset on the absorption of PCDTBT:PC70BM layers and the electro-optical characteristics of air-stable, large-area PCDTBT:PC70BM-based polymer solar cell modules, deposited with a custom built slot-die coater

    Directory of Open Access Journals (Sweden)

    Dimitar I. Kutsarov

    2017-04-01

    Full Text Available The data presented in this article is related to the research article entitled “Fabrication of air-stable, large-area, PCDTBT:PC70BM polymer solar cell modules using a custom built slot-die coater” (D.I. Kutsarov, E. New, F. Bausi, A. Zoladek-Lemanczyk, F.A. Castro, S.R.P. Silva, 2016 [1]. The repository name and reference number for the raw data from the abovementioned publication can be found under: https://doi.org/10.15126/surreydata.00813106. In this data in brief article, additional information about the absorption properties of PCDTBT:PC70BM layers deposited from a 12.5 mg/ml and 15 mg/ml photoactive layer dispersion are shown. Additionally, the best and average J-V curves of single cells, fabricated from the 10 and 15 mg/ml dispersions, are presented.

  2. The Reactivity of Stable Metallacyclobutenes and Vinylcarbenes

    OpenAIRE

    Holland, Ryan Lynn

    2016-01-01

    Chapter 1. Historical Development of Stable Metallacyclobutenes Fred Tebbe and co-workers synthesized the first stable metallacyclobutene complexes in the late 1970’s by treatment of an intermediate titanium methylene species – later popularized as the “Tebbe reagent” – with acetylenes. Robert Grubbs at Caltech further studied this system, using it to detail a degenerate metathesis reaction and to isolate a metallacyclobutane complex – which was implicated in the emerging field of alkene meta...

  3. Stable atomic hydrogen: Polarized atomic beam source

    International Nuclear Information System (INIS)

    Niinikoski, T.O.; Penttilae, S.; Rieubland, J.M.; Rijllart, A.

    1984-01-01

    We have carried out experiments with stable atomic hydrogen with a view to possible applications in polarized targets or polarized atomic beam sources. Recent results from the stabilization apparatus are described. The first stable atomic hydrogen beam source based on the microwave extraction method (which is being tested ) is presented. The effect of the stabilized hydrogen gas density on the properties of the source is discussed. (orig.)

  4. On the joint statistics of stable random processes

    International Nuclear Information System (INIS)

    Hopcraft, K I; Jakeman, E

    2011-01-01

    A utilitarian continuous bi-variate random process whose first-order probability density function is a stable random variable is constructed. Results paralleling some of those familiar from the theory of Gaussian noise are derived. In addition to the joint-probability density for the process, these include fractional moments and structure functions. Although the correlation functions for stable processes other than Gaussian do not exist, we show that there is coherence between values adopted by the process at different times, which identifies a characteristic evolution with time. The distribution of the derivative of the process, and the joint-density function of the value of the process and its derivative measured at the same time are evaluated. These enable properties to be calculated analytically such as level crossing statistics and those related to the random telegraph wave. When the stable process is fractal, the proportion of time it spends at zero is finite and some properties of this quantity are evaluated, an optical interpretation for which is provided. (paper)

  5. Residues of the UL25 Protein of Herpes Simplex Virus That Are Required for Its Stable Interaction with Capsids ▿

    Science.gov (United States)

    Cockrell, Shelley K.; Huffman, Jamie B.; Toropova, Katerina; Conway, James F.; Homa, Fred L.

    2011-01-01

    The herpes simplex virus 1 (HSV-1) UL25 gene product is a minor capsid component that is required for encapsidation, but not cleavage, of replicated viral DNA. UL25 is located on the capsid surface in a proposed heterodimer with UL17, where five copies of the heterodimer are found at each of the capsid vertices. Previously, we demonstrated that amino acids 1 to 50 of UL25 are essential for its stable interaction with capsids. To further define the UL25 capsid binding domain, we generated recombinant viruses with either small truncations or amino acid substitutions in the UL25 N terminus. Studies of these mutants demonstrated that there are two important regions within the capsid binding domain. The first 27 amino acids are essential for capsid binding of UL25, while residues 26 to 39, which are highly conserved in the UL25 homologues of other alphaherpesviruses, were found to be critical for stable capsid binding. Cryo-electron microscopy reconstructions of capsids containing either a small tag on the N terminus of UL25 or the green fluorescent protein (GFP) fused between amino acids 50 and 51 of UL25 demonstrate that residues 1 to 27 of UL25 contact the hexon adjacent to the penton. A second region, most likely centered on amino acids 26 to 39, contacts the triplex that is one removed from the penton. Importantly, both of these UL25 capsid binding regions are essential for the stable packaging of full-length viral genomes. PMID:21411517

  6. Genome-scale study of the importance of binding site context for transcription factor binding and gene regulation

    Directory of Open Access Journals (Sweden)

    Ronne Hans

    2008-11-01

    Full Text Available Abstract Background The rate of mRNA transcription is controlled by transcription factors that bind to specific DNA motifs in promoter regions upstream of protein coding genes. Recent results indicate that not only the presence of a motif but also motif context (for example the orientation of a motif or its location relative to the coding sequence is important for gene regulation. Results In this study we present ContextFinder, a tool that is specifically aimed at identifying cases where motif context is likely to affect gene regulation. We used ContextFinder to examine the role of motif context in S. cerevisiae both for DNA binding by transcription factors and for effects on gene expression. For DNA binding we found significant patterns of motif location bias, whereas motif orientations did not seem to matter. Motif context appears to affect gene expression even more than it affects DNA binding, as biases in both motif location and orientation were more frequent in promoters of co-expressed genes. We validated our results against data on nucleosome positioning, and found a negative correlation between preferred motif locations and nucleosome occupancy. Conclusion We conclude that the requirement for stable binding of transcription factors to DNA and their subsequent function in gene regulation can impose constraints on motif context.

  7. Stable preparations of tyrosine hydroxylase provide the solution structure of the full-length enzyme

    Science.gov (United States)

    Bezem, Maria T.; Baumann, Anne; Skjærven, Lars; Meyer, Romain; Kursula, Petri; Martinez, Aurora; Flydal, Marte I.

    2016-01-01

    Tyrosine hydroxylase (TH) catalyzes the rate-limiting step in the biosynthesis of catecholamine neurotransmitters. TH is a highly complex enzyme at mechanistic, structural, and regulatory levels, and the preparation of kinetically and conformationally stable enzyme for structural characterization has been challenging. Here, we report on improved protocols for purification of recombinant human TH isoform 1 (TH1), which provide large amounts of pure, stable, active TH1 with an intact N-terminus. TH1 purified through fusion with a His-tagged maltose-binding protein on amylose resin was representative of the iron-bound functional enzyme, showing high activity and stabilization by the natural feedback inhibitor dopamine. TH1 purified through fusion with a His-tagged ZZ domain on TALON is remarkably stable, as it was partially inhibited by resin-derived cobalt. This more stable enzyme preparation provided high-quality small-angle X-ray scattering (SAXS) data and reliable structural models of full-length tetrameric TH1. The SAXS-derived model reveals an elongated conformation (Dmax = 20 nm) for TH1, different arrangement of the catalytic domains compared with the crystal structure of truncated forms, and an N-terminal region with an unstructured tail that hosts the phosphorylation sites and a separated Ala-rich helical motif that may have a role in regulation of TH by interacting with binding partners. PMID:27462005

  8. Mapping of interaction domains of putative telomere-binding proteins AtTRB1 and AtPOT1b from Arabidopsis thaliana.

    Science.gov (United States)

    Schrumpfová, Petra Procházková; Kuchar, Milan; Palecek, Jan; Fajkus, Jirí

    2008-04-30

    We previously searched for interactions between plant telomere-binding proteins and found that AtTRB1, from the single-myb-histone (Smh) family, interacts with the Arabidopsis POT1-like-protein, AtPOT1b, involved in telomere capping. Here we identify domains responsible for that interaction. We also map domains in AtTRB1 responsible for interactions with other Smh-family-members. Our results show that the N-terminal OB-fold-domain of AtPOT1b mediates the interaction with AtTRB1. This domain is characteristic for POT1- proteins and is involved with binding the G-rich-strand of telomeric DNA. AtPOT1b also interacts with AtTRB2 and AtTRB3. The central histone-globular-domain of AtTRB1 is involved with binding to AtTRB2 and 3, as well as to AtPOT1b. AtTRB1-heterodimers with other Smh-family-members are more stable than AtTRB1-homodimers. Our results reveal interaction networks of plant telomeres.

  9. Local Search Approaches in Stable Matching Problems

    Directory of Open Access Journals (Sweden)

    Toby Walsh

    2013-10-01

    Full Text Available The stable marriage (SM problem has a wide variety of practical applications, ranging from matching resident doctors to hospitals, to matching students to schools or, more generally, to any two-sided market. In the classical formulation, n men and n women express their preferences (via a strict total order over the members of the other sex. Solving an SM problem means finding a stable marriage where stability is an envy-free notion: no man and woman who are not married to each other would both prefer each other to their partners or to being single. We consider both the classical stable marriage problem and one of its useful variations (denoted SMTI (Stable Marriage with Ties and Incomplete lists where the men and women express their preferences in the form of an incomplete preference list with ties over a subset of the members of the other sex. Matchings are permitted only with people who appear in these preference lists, and we try to find a stable matching that marries as many people as possible. Whilst the SM problem is polynomial to solve, the SMTI problem is NP-hard. We propose to tackle both problems via a local search approach, which exploits properties of the problems to reduce the size of the neighborhood and to make local moves efficiently. We empirically evaluate our algorithm for SM problems by measuring its runtime behavior and its ability to sample the lattice of all possible stable marriages. We evaluate our algorithm for SMTI problems in terms of both its runtime behavior and its ability to find a maximum cardinality stable marriage. Experimental results suggest that for SM problems, the number of steps of our algorithm grows only as O(n log(n, and that it samples very well the set of all stable marriages. It is thus a fair and efficient approach to generate stable marriages. Furthermore, our approach for SMTI problems is able to solve large problems, quickly returning stable matchings of large and often optimal size, despite the

  10. Kaposi's Sarcoma-Associated Herpesvirus K8 Is an RNA Binding Protein That Regulates Viral DNA Replication in Coordination with a Noncoding RNA.

    Science.gov (United States)

    Liu, Dongcheng; Wang, Yan; Yuan, Yan

    2018-01-10

    KSHV lytic replication and constant primary infection of fresh cells are crucial for viral tumorigenicity. Virus-encoded b-Zip family protein K8 plays an important role in viral DNA replication in both viral reactivation and de novo infection. The mechanism underlying the functional role of K8 in the viral life cycle is elusive. Here we report that K8 is a RNA binding protein, which also associates with many proteins including other RNA binding proteins. Many K8-involved protein-protein interactions are mediated by RNA. Using a c ross l inking and i mmuno p recipitation (CLIP) procedure combined with high-throughput sequencing, RNAs that are associated with K8 in BCBL-1 cells were identified, that include both viral (PAN, T1.4, T0.7 and etc.) and cellular (MALAT-1, MRP, 7SK and etc.) RNAs. An RNA-binding motif in K8 was defined, and mutation of the motif abolished the ability of K8 binding to many noncoding RNAs as well as viral DNA replication during de novo infection, suggesting that the K8 functions in viral replication are carried out through RNA association. The function of K8 and associated T1.4 RNA was investigated in details and results showed that T1.4 mediates the binding of K8 with ori-Lyt DNA. T1.4-K8 complex physically bound to KSHV ori-Lyt DNA and recruited other proteins and cofactors to assemble replication complex. Depletion of T1.4 abolished the DNA replication in primary infection. These findings provide mechanistic insights into the role of K8 in coordination with T1.4 RNA in regulating KSHV DNA replication during de novo infection. Importance Genome wide analyses of the mammalian transcriptome revealed that a large proportion of sequence previously annotated as noncoding region are actually transcribed and give rise to stable RNAs. Emergence of a large number of noncoding RNAs suggests that functional RNA-protein complexes exampled by ribosome or spliceosome are not ancient relics of the last riboorganism but would be well adapted for

  11. 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

  12. Stable blood lubricated hydrodynamic journal bearing with magnetic loading.

    Science.gov (United States)

    Malanoski, S B; Belawski, H; Horvath, D; Smith, W A; Golding, L R

    1998-01-01

    The Cleveland Clinic Foundation's Innovative Ventricular Assist System (IVAS) is distinguished by the use of a special hydrodynamic journal bearing to support the rotating assembly of the blood pump. In a permanently implanted blood pump, this bearing's characteristics of long life and high reliability are of paramount importance. In addition, this bearing's inherent self-pumping flow and the axial through flow caused by an imposed end-to-end pressure difference provides good washing, thus guarding against deposition. The basic computer analysis and preliminary testing results of this bearing were previously presented. This article reports the ongoing studies (both analytic and in vitro tests) on this innovative bearing as a component of the IVAS in general, with particular emphasis on its stable operating characteristics and reliability. The absence of vibration attributable to hydrodynamic instabilities related to the thick fluid film are both calculated and demonstrated during testing. A stable operating center of the rotor is shown to be inherent under magnetic side loads and resulting hydrodynamic bearing forces. A low shear as a result of large fluid-film thicknesses has been calculated, and low hemolysis has been shown by in vitro testing. Several unique design features of the bearing are believed to be responsible for this high level of performance.

  13. Multiple growth hormone-binding proteins are expressed on insulin-producing cells

    DEFF Research Database (Denmark)

    Møldrup, A; Billestrup, N; Thorn, N A

    1989-01-01

    and intracellular organelles are low in GH-binding activity. The plasma membrane-bound activity is soluble in Triton X-100 with intact hormone binding characteristics. The apparent KD in detergent solution is estimated to 18 ng/ml (8 x 10(-10) M). 125I-hGH-affinity cross-linking to intact and detergent...

  14. HemeBIND: a novel method for heme binding residue prediction by combining structural and sequence information

    Directory of Open Access Journals (Sweden)

    Hu Jianjun

    2011-05-01

    Full Text Available Abstract Background Accurate prediction of binding residues involved in the interactions between proteins and small ligands is one of the major challenges in structural bioinformatics. Heme is an essential and commonly used ligand that plays critical roles in electron transfer, catalysis, signal transduction and gene expression. Although much effort has been devoted to the development of various generic algorithms for ligand binding site prediction over the last decade, no algorithm has been specifically designed to complement experimental techniques for identification of heme binding residues. Consequently, an urgent need is to develop a computational method for recognizing these important residues. Results Here we introduced an efficient algorithm HemeBIND for predicting heme binding residues by integrating structural and sequence information. We systematically investigated the characteristics of binding interfaces based on a non-redundant dataset of heme-protein complexes. It was found that several sequence and structural attributes such as evolutionary conservation, solvent accessibility, depth and protrusion clearly illustrate the differences between heme binding and non-binding residues. These features can then be separately used or combined to build the structure-based classifiers using support vector machine (SVM. The results showed that the information contained in these features is largely complementary and their combination achieved the best performance. To further improve the performance, an attempt has been made to develop a post-processing procedure to reduce the number of false positives. In addition, we built a sequence-based classifier based on SVM and sequence profile as an alternative when only sequence information can be used. Finally, we employed a voting method to combine the outputs of structure-based and sequence-based classifiers, which demonstrated remarkably better performance than the individual classifier alone

  15. The thermodynamic landscape of testosterone binding to cytochrome P450 3A4: ligand binding and spin state equilibria.

    Science.gov (United States)

    Roberts, Arthur G; Campbell, A Patricia; Atkins, William M

    2005-02-01

    Human cytochrome P450 (CYP) 3A4 catalyzes the oxygen-dependent metabolism of greater than 60% of known drugs. CYP3A4 binds multiple ligands simultaneously, and this contributes to complex allosteric kinetic behavior. Substrates that bind to this enzyme change the ferric spin state equilibrium of the heme, which can be observed by optical absorbance and electron paramagnetic resonance (EPR) spectroscopy. The ligand-dependent spin state equilibrium has not been quantitatively understood for any ligands that exhibit multiple binding. The CYP3A4 substrate testosterone (TST) has been shown previously by absorbance spectroscopy to induce spin state changes that are characteristic of a low spin to high spin conversion. Here, EPR was used to examine the equilibrium binding of TST to CYP3A4 at [CYP3A4] > K(D), which allows for characterization of the singly occupied state (i.e., CYP3A4.TST). We also have used absorbance spectroscopy to examine equilibrium binding, where [CYP3A4] equations, and modifications of it, reveals that the first equivalent of TST binds with higher affinity than the second equivalent of TST and its binding is positively cooperative with respect to ligand-dependent spin state conversion. Careful analysis of the EPR and absorbance spectral results suggests that the binding of the second TST induces a shift to the high spin state and thus that the second TST binding causes displacement of the bound water. A model involving six thermodynamic states is presented and this model is related to the turnover of the enzyme.

  16. A peek into tropomyosin binding and unfolding on the actin filament.

    Directory of Open Access Journals (Sweden)

    Abhishek Singh

    Full Text Available BACKGROUND: Tropomyosin is a prototypical coiled coil along its length with subtle variations in structure that allow interactions with actin and other proteins. Actin binding globally stabilizes tropomyosin. Tropomyosin-actin interaction occurs periodically along the length of tropomyosin. However, it is not well understood how tropomyosin binds actin. PRINCIPAL FINDINGS: Tropomyosin's periodic binding sites make differential contributions to two components of actin binding, cooperativity and affinity, and can be classified as primary or secondary sites. We show through mutagenesis and analysis of recombinant striated muscle alpha-tropomyosins that primary actin binding sites have a destabilizing coiled-coil interface, typically alanine-rich, embedded within a non-interface recognition sequence. Introduction of an Ala cluster in place of the native, more stable interface in period 2 and/or period 3 sites (of seven increased the affinity or cooperativity of actin binding, analysed by cosedimentation and differential scanning calorimetry. Replacement of period 3 with period 5 sequence, an unstable region of known importance for cooperative actin binding, increased the cooperativity of binding. Introduction of the fluorescent probe, pyrene, near the mutation sites in periods 2 and 3 reported local instability, stabilization by actin binding, and local unfolding before or coincident with dissociation from actin (measured using light scattering, and chain dissociation (analyzed using circular dichroism. CONCLUSIONS: This, and previous work, suggests that regions of tropomyosin involved in binding actin have non-interface residues specific for interaction with actin and an unstable interface that is locally stabilized upon binding. The destabilized interface allows residues on the coiled-coil surface to obtain an optimal conformation for interaction with actin by increasing the number of local substates that the side chains can sample. We suggest

  17. Molecular simulations and Markov state modeling reveal the structural diversity and dynamics of a theophylline-binding RNA aptamer in its unbound state.

    Directory of Open Access Journals (Sweden)

    Becka M Warfield

    Full Text Available RNA aptamers are oligonucleotides that bind with high specificity and affinity to target ligands. In the absence of bound ligand, secondary structures of RNA aptamers are generally stable, but single-stranded and loop regions, including ligand binding sites, lack defined structures and exist as ensembles of conformations. For example, the well-characterized theophylline-binding aptamer forms a highly stable binding site when bound to theophylline, but the binding site is unstable and disordered when theophylline is absent. Experimental methods have not revealed at atomic resolution the conformations that the theophylline aptamer explores in its unbound state. Consequently, in the present study we applied 21 microseconds of molecular dynamics simulations to structurally characterize the ensemble of conformations that the aptamer adopts in the absence of theophylline. Moreover, we apply Markov state modeling to predict the kinetics of transitions between unbound conformational states. Our simulation results agree with experimental observations that the theophylline binding site is found in many distinct binding-incompetent states and show that these states lack a binding pocket that can accommodate theophylline. The binding-incompetent states interconvert with binding-competent states through structural rearrangement of the binding site on the nanosecond to microsecond timescale. Moreover, we have simulated the complete theophylline binding pathway. Our binding simulations supplement prior experimental observations of slow theophylline binding kinetics by showing that the binding site must undergo a large conformational rearrangement after the aptamer and theophylline form an initial complex, most notably, a major rearrangement of the C27 base from a buried to solvent-exposed orientation. Theophylline appears to bind by a combination of conformational selection and induced fit mechanisms. Finally, our modeling indicates that when Mg2+ ions are

  18. SHBG (Sex Hormone Binding Globulin)

    Science.gov (United States)

    ... and Iron-binding Capacity (TIBC, UIBC) Trichomonas Testing Triglycerides Troponin Tryptase Tumor Markers Uric Acid Urinalysis Urine ... Syndrome CME. Medscape From Nature Clinical Practice Endocrinology & Metabolism [On-line information]. Available online at http://www. ...

  19. Stable chaos in fluctuation driven neural circuits

    International Nuclear Information System (INIS)

    Angulo-Garcia, David; Torcini, Alessandro

    2014-01-01

    Highlights: • Nonlinear instabilities in fluctuation driven (balanced) neural circuits are studied. • Balanced networks display chaos and stable phases at different post-synaptic widths. • Linear instabilities coexists with nonlinear ones in the chaotic regime. • Erratic motion appears also in linearly stable phase due to stable chaos. - Abstract: We study the dynamical stability of pulse coupled networks of leaky integrate-and-fire neurons against infinitesimal and finite perturbations. In particular, we compare mean versus fluctuations driven networks, the former (latter) is realized by considering purely excitatory (inhibitory) sparse neural circuits. In the excitatory case the instabilities of the system can be completely captured by an usual linear stability (Lyapunov) analysis, whereas the inhibitory networks can display the coexistence of linear and nonlinear instabilities. The nonlinear effects are associated to finite amplitude instabilities, which have been characterized in terms of suitable indicators. For inhibitory coupling one observes a transition from chaotic to non chaotic dynamics by decreasing the pulse-width. For sufficiently fast synapses the system, despite showing an erratic evolution, is linearly stable, thus representing a prototypical example of stable chaos

  20. Metabolic studies in man using stable isotopes

    International Nuclear Information System (INIS)

    Faust, H.; Jung, K.; Krumbiegel, P.

    1993-01-01

    In this project, stable isotope compounds and stable isotope pharmaceuticals were used (with emphasis on the application of 15 N) to study several aspects of nitrogen metabolism in man. Of the many methods available, the 15 N stable isotope tracer technique holds a special position because the methodology for application and nitrogen isotope analysis is proven and reliable. Valid routine methods using 15 N analysis by emission spectrometry have been demonstrated. Several methods for the preparation of biological material were developed during our participation in the Coordinated Research Programme. In these studies, direct procedures (i.e. use of diluted urine as a samples without chemical preparation) or rapid isolation methods were favoured. Within the scope of the Analytical Quality Control Service (AQCS) enriched stable isotope reference materials for medical and biological studies were prepared and are now available through the International Atomic Energy Agency. The materials are of special importance as the increasing application of stable isotopes as tracers in medical, biological and agricultural studies has focused interest on reliable measurements of biological material of different origin. 24 refs

  1. Asymmetric cation-binding catalysis

    DEFF Research Database (Denmark)

    Oliveira, Maria Teresa; Lee, Jiwoong

    2017-01-01

    solvents, thus increasing their applicability in synthesis. The expansion of this concept to chiral polyethers led to the emergence of asymmetric cation-binding catalysis, where chiral counter anions are generated from metal salts, particularly using BINOL-based polyethers. Alkali metal salts, namely KF...... and KCN, are selectively bound to the catalyst, providing exceptionally high enantioselectivities for kinetic resolutions, elimination reactions (fluoride base), and Strecker synthesis (cyanide nucleophile). Asymmetric cation-binding catalysis was recently expanded to silicon-based reagents, enabling...

  2. A BPTTF-based self-assembled electron-donating triangle capable of C60 binding.

    Science.gov (United States)

    Goeb, Sébastien; Bivaud, Sébastien; Dron, Paul Ionut; Balandier, Jean-Yves; Chas, Marcos; Sallé, Marc

    2012-03-25

    A kinetically stable self-assembled redox-active triangle is isolated. The resulting electron-donating cavity, which incorporates three BPTTF units, exhibits a remarkable binding ability for electron-deficient C(60), supported by a favorable combination of structural and electronic features.

  3. 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.

  4. Temperature and Humidity Control in Livestock Stables

    DEFF Research Database (Denmark)

    Hansen, Michael; Andersen, Palle; Nielsen, Kirsten M.

    2010-01-01

    The paper describes temperature and humidity control of a livestock stable. It is important to have a correct air flow pattern in the livestock stable in order to achieve proper temperature and humidity control as well as to avoid draught. In the investigated livestock stable the air flow...... is controlled using wall mounted ventilation flaps. In the paper an algorithm for air flow control is presented meeting the needs for temperature and humidity while taking the air flow pattern in consideration. To obtain simple and realisable controllers a model based control design method is applied....... In the design dynamic models for temperature and humidity are very important elements and effort is put into deriving and testing the models. It turns out that non-linearities are dominating in both models making feedback linearization the natural design method. The air controller as well as the temperature...

  5. On some topological properties of stable measures

    DEFF Research Database (Denmark)

    Nielsen, Carsten Krabbe

    1996-01-01

    Summary The paper shows that the set of stable probability measures and the set of Rational Beliefs relative to a given stationary measure are closed in the strong topology, but not closed in the topology of weak convergence. However, subsets of the set of stable probability measures which...... are characterized by uniformity of convergence of the empirical distribution are closed in the topology of weak convergence. It is demonstrated that such subsets exist. In particular, there is an increasing sequence of sets of SIDS measures who's union is the set of all SIDS measures generated by a particular...... system and such that each subset consists of stable measures. The uniformity requirement has a natural interpretation in terms of plausibility of Rational Beliefs...

  6. Concentration of stable elements in food products

    Energy Technology Data Exchange (ETDEWEB)

    Montford, M.A.; Shank, K.E.; Hendricks, C.; Oakes, T.W.

    1980-01-01

    Food samples were taken from commercial markets and analyzed for stable element content. The concentrations of most stable elements (Ag, Al, As, Au, Ba, Br, Ca, Ce, Cl, Co, Cr, Cs, Cu, Fe, Hf, I, K, La, Mg, Mn, Mo, Na, Rb, Sb, Sc, Se, Sr, Ta, Th, Ti, V, Zn, Zr) were determined using multiple-element neutron activation analysis, while the concentrations of other elements (Cd, Hg, Ni, Pb) were determined using atomic absorption. The relevance of the concentrations found are noted in relation to other literature values. An earlier study was extended to include the determination of the concentration of stable elements in home-grown products in the vicinity of the Oak Ridge National Laboratory. Comparisons between the commercial and local food-stuff values are discussed.

  7. Clinical presentation and management of stable coronary artery disease in Austria.

    Directory of Open Access Journals (Sweden)

    Otto Pichlhöfer

    Full Text Available Cardiovascular disease is the main cause of death in Austria. However, no systematic information exists regarding characteristics and treatments of contemporary patients with stable coronary artery disease (CAD in Austria. We assembled two retrospective physicians' databases to describe demographics, clinical profiles, and therapeutic strategies in patients with stable CAD. In addition, we compared patient profiles of secondary care internists and hospital-based cardiologists with those of general practitioners in a primary care setting outside of hospital.The study population was identified from retrospective chart review of 1020 patients from 106 primary care physicians in Austria (ProCor II registry, and was merged with a previous similar database of 1280 patients under secondary care (ProCor I registry to yield a total patient number of 2300.Female patients with stable CAD were older, had more angina and/or heart failure symptoms, and more depression than males. Female gender, type 2 diabetes mellitus, higher CCS class and asthma/COPD were predictors of elevated heart rate, while previous coronary events/revascularization predicted a lower heart rate in multivariate analysis. There were no significant differences with regard to characteristics and management of patients of general practitioners in the primary care setting versus internists in secondary care.Characteristics and treatments of unselected patients with stable ischemic heart disease in Austria resemble the pattern of large international registries of stable ischemic heart disease, with the exception that diabetes and systemic hypertension were more prevalent.

  8. Faster and Simpler Approximation of Stable Matchings

    Directory of Open Access Journals (Sweden)

    Katarzyna Paluch

    2014-04-01

    Full Text Available We give a 3 2 -approximation algorithm for finding stable matchings that runs in O(m time. The previous most well-known algorithm, by McDermid, has the same approximation ratio but runs in O(n3/2m time, where n denotes the number of people andm is the total length of the preference lists in a given instance. In addition, the algorithm and the analysis are much simpler. We also give the extension of the algorithm for computing stable many-to-many matchings.

  9. Stable isotopes in Lithuanian bioarcheological material

    Science.gov (United States)

    Skipityte, Raminta; Jankauskas, Rimantas; Remeikis, Vidmantas

    2015-04-01

    Investigation of bioarcheological material of ancient human populations allows us to understand the subsistence behavior associated with various adaptations to the environment. Feeding habits are essential to the survival and growth of ancient populations. Stable isotope analysis is accepted tool in paleodiet (Schutkowski et al, 1999) and paleoenvironmental (Zernitskaya et al, 2014) studies. However, stable isotopes can be useful not only in investigating human feeding habits but also in describing social and cultural structure of the past populations (Le Huray and Schutkowski, 2005). Only few stable isotope investigations have been performed before in Lithuanian region suggesting a quite uniform diet between males and females and protein intake from freshwater fish and animal protein. Previously, stable isotope analysis has only been used to study a Stone Age population however, more recently studies have been conducted on Iron Age and Late medieval samples (Jacobs et al, 2009). Anyway, there was a need for more precise examination. Stable isotope analysis were performed on human bone collagen and apatite samples in this study. Data represented various ages (from 5-7th cent. to 18th cent.). Stable carbon and nitrogen isotope analysis on medieval populations indicated that individuals in studied sites in Lithuania were almost exclusively consuming C3 plants, C3 fed terrestrial animals, and some freshwater resources. Current investigation demonstrated social differences between elites and country people and is promising in paleodietary and daily life reconstruction. Acknowledgement I thank prof. dr. G. Grupe, Director of the Anthropological and Palaeoanatomical State Collection in Munich for providing the opportunity to work in her laboratory. The part of this work was funded by DAAD. Antanaitis-Jacobs, Indre, et al. "Diet in early Lithuanian prehistory and the new stable isotope evidence." Archaeologia Baltica 12 (2009): 12-30. Le Huray, Jonathan D., and Holger

  10. Modelling stable water isotopes: Status and perspectives

    Directory of Open Access Journals (Sweden)

    Werner M.

    2010-12-01

    Full Text Available Modelling of stable water isotopes H2 18O and HDO within various parts of the Earth’s hydrological cycle has clearly improved our understanding of the interplay between climatic variations and related isotope fractionation processes. In this article key principles and major research results of stable water isotope modelling studies are described. Emphasis is put on research work using explicit isotope diagnostics within general circulation models as this highly complex model setup bears many resemblances with studies using simpler isotope modelling approaches.

  11. On the symmetric α-stable distribution with application to symbol error rate calculations

    KAUST Repository

    Soury, Hamza

    2016-12-24

    The probability density function (PDF) of the symmetric α-stable distribution is investigated using the inverse Fourier transform of its characteristic function. For general values of the stable parameter α, it is shown that the PDF and the cumulative distribution function of the symmetric stable distribution can be expressed in terms of the Fox H function as closed-form. As an application, the probability of error of single input single output communication systems using different modulation schemes with an α-stable perturbation is studied. In more details, a generic formula is derived for generalized fading distribution, such as the extended generalized-k distribution. Later, simpler expressions of these error rates are deduced for some selected special cases and compact approximations are derived using asymptotic expansions.

  12. Calorimetric study of binding of some disaccharides with crown ethers

    International Nuclear Information System (INIS)

    Davydova, Olga I.; Lebedeva, Nataliya Sh.; Parfenyuk, Elena V.

    2004-01-01

    Isothermal titration calorimetry has been applied to the determination of the thermodynamic parameters of binding of β-lactose, α,α-trehalose and sucrose with 15-crown-5 and 18-crown-6 in water at 298.15 K. The formation of 1:1 molecular associates has been found for the systems studied except 18-crown-6 and β-lactose. The associates are preferentially or completely entropy stabilized. The most stable associate is formed between α,α-trehalose and 18-crown-6. The obtained values of thermodynamic parameters of binding are discussed from the point of view of solute-solvent interactions as well as conformational and structural peculiarities of the disaccharides (DS) and crown ethers (CE)

  13. Binding mechanisms of intrinsically disordered proteins: theory, simulation, and experiment

    Directory of Open Access Journals (Sweden)

    Luca Mollica

    2016-09-01

    Full Text Available In recent years, protein science has been revolutionized by the discovery of intrinsically disordered proteins (IDPs. In contrast to the classical paradigm that a given protein sequence corresponds to a defined structure and an associated function, we now know that proteins can be functional in the absence of a stable three-dimensional structure. In many cases, disordered proteins or protein regions become structured, at least locally, upon interacting with their physiological partners. Many, sometimes conflicting, hypotheses have been put forward regarding the interaction mechanisms of IDPs and the potential advantages of disorder for protein-protein interactions. Whether disorder may increase, as proposed e.g. in the fly-casting hypothesis, or decrease binding rates, increase or decrease binding specificity, or what role pre-formed structure might play in interactions involving IDPs (conformational selection vs. induced fit, are subjects of intense debate. Experimentally, these questions remain difficult to address. Here, we review experimental studies of binding mechanisms of IDPs using NMR spectroscopy and transient kinetic techniques, as well as the underlying theoretical concepts and numerical methods that can be applied to describe these interactions at the atomic level. The available literature suggests that the kinetic and thermodynamic parameters characterizing interactions involving IDPs can vary widely and that there may be no single common mechanism that can explain the different binding modes observed experimentally. Rather, disordered proteins appear to make combined use of features such as pre-formed structure and flexibility, depending on the individual system and the functional context.

  14. Steric and allosteric factors prevent simultaneous binding of transferrin-binding proteins A and B to transferrin.

    Science.gov (United States)

    Silva, Leslie P; Yu, Rong-hua; Calmettes, Charles; Yang, Xue; Moraes, Trevor F; Schriemer, David C; Schryvers, Anthony B

    2012-06-01

    The ability to acquire iron directly from host Tf (transferrin) is an adaptation common to important bacterial pathogens belonging to the Pasteurellaceae, Moraxellaceae and Neisseriaceae families. A surface receptor comprising an integral outer membrane protein, TbpA (Tf-binding protein A), and a surface-exposed lipoprotein, TbpB (Tf-binding protein B), mediates the iron acquisition process. TbpB is thought to extend from the cell surface for capture of Tf to initiate the process and deliver Tf to TbpA. TbpA functions as a gated channel for the passage of iron into the periplasm. In the present study we have mapped the effect of TbpA from Actinobacillus pleuropneumoniae on pTf (porcine Tf) using H/DX-MS (hydrogen/deuterium exchange coupled to MS) and compare it with a previously determined binding site for TbpB. The proposed TbpA footprint is adjacent to and potentially overlapping the TbpB-binding site, and induces a structural instability in the TbpB site. This suggests that simultaneous binding to pTf by both receptors would be hindered. We demonstrate that a recombinant TbpB lacking a portion of its anchor peptide is unable to form a stable ternary TbpA-pTf-TbpB complex. This truncated TbpB does not bind to a preformed Tf-TbpA complex, and TbpA removes pTf from a preformed Tf-TbpB complex. Thus the results of the present study support a model whereby TbpB 'hands-off' pTf to TbpA, which completes the iron removal and transport process.

  15. Is parricide a stable phenomenon? An analysis of parricide offenders in a forensic hospital

    Directory of Open Access Journals (Sweden)

    Lisieux Elaine de Borba-Telles

    2017-01-01

    Conclusions: Regarding weapon usage and the characteristics of victims and offenders, the observed pattern is consistent with previous researches, which allows concluding that the phenomenon of parricide is relatively stable and homogeneous. A forensic psychiatric evaluation of parricide offenders should be warranted given the high prevalence of mental illness among them.

  16. Stable isotope analysis of dynamic lipidomics.

    Science.gov (United States)

    Brandsma, Joost; Bailey, Andrew P; Koster, Grielof; Gould, Alex P; Postle, Anthony D

    2017-08-01

    Metabolic pathway flux is a fundamental element of biological activity, which can be quantified using a variety of mass spectrometric techniques to monitor incorporation of stable isotope-labelled substrates into metabolic products. This article contrasts developments in electrospray ionisation mass spectrometry (ESI-MS) for the measurement of lipid metabolism with more established gas chromatography mass spectrometry and isotope ratio mass spectrometry methodologies. ESI-MS combined with diagnostic tandem MS/MS scans permits the sensitive and specific analysis of stable isotope-labelled substrates into intact lipid molecular species without the requirement for lipid hydrolysis and derivatisation. Such dynamic lipidomic methodologies using non-toxic stable isotopes can be readily applied to quantify lipid metabolic fluxes in clinical and metabolic studies in vivo. However, a significant current limitation is the absence of appropriate software to generate kinetic models of substrate incorporation into multiple products in the time domain. Finally, we discuss the future potential of stable isotope-mass spectrometry imaging to quantify the location as well as the extent of lipid synthesis. This article is part of a Special Issue entitled: BBALIP_Lipidomics Opinion Articles edited by Sepp Kohlwein. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Substitution of stable isotopes in Chlorella

    Science.gov (United States)

    Flaumenhaft, E.; Katz, J. J.; Uphaus, R. A.

    1969-01-01

    Replacement of biologically important isotopes in the alga Chlorella by corresponding heavier stable isotopes produces increasingly greater deviations from the normal cell size and changes the quality and distribution of certain cellular components. The usefulness of isotopically altered organisms increases interest in the study of such permuted organisms.

  18. Champion Island, Galapagos Stable Oxygen Calibration Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Galapagos Coral Stable Oxygen Calibration Data. Sites: Bartolome Island: 0 deg, 17 min S, 90 deg 33 min W. Champion Island: 1 deg, 15 min S, 90 deg, 05 min W. Urvina...

  19. Stable propagation of 'selfish'genetic elements

    Indian Academy of Sciences (India)

    Unknown

    viruses such as the Epstein-Barr virus (Harris et al 1985;. Kanda et al 2001) and bovine papilloma virus (Lehman and Botchan 1998; Ilves et al 1999), which exist pre- dominantly as extrachromosomal episomes, have been shown to utilize chromosome tethering as a means for stable segregation. The tethering mechanism ...

  20. Unconditionally stable perfectly matched layer boundary conditions

    NARCIS (Netherlands)

    De Raedt, H.; Michielsen, K.

    2007-01-01

    A brief review is given of a systematic, product-formula based approach to construct unconditionally stable algorithms for solving the time-dependent Maxwell equations. The fundamental difficulties that arise when we want to incorporate uniaxial perfectly matched layer boundary conditions into this

  1. Facies, dissolution seams and stable isotope compositions

    Indian Academy of Sciences (India)

    Stable isotope analysis of the limestone shows that 13C and 18O values are compatible with the early Mesoproterozoic open seawater composition. The ribbon limestone facies in the Rohtas Limestone is characterized by micritic beds, each decoupled in a lower band enriched and an upper band depleted in dissolution ...

  2. Connected domination stable graphs upon edge addition ...

    African Journals Online (AJOL)

    A set S of vertices in a graph G is a connected dominating set of G if S dominates G and the subgraph induced by S is connected. We study the graphs for which adding any edge does not change the connected domination number. Keywords: Connected domination, connected domination stable, edge addition ...

  3. Stable magnetic remanence in antiferromagnetic goethite.

    Science.gov (United States)

    Strangway, D W; McMahon, B E; Honea, R M

    1967-11-10

    Goethite, known to be antiferromagnetic, acquires thermoremanent magnetization at its Neel temperature of 120 degrees C. This remanence, extremely stable, is due to the presence of unbalanced spins in the antiferromagnetic structure; the spins may result from grain size, imperfections, or impurities.

  4. Increases thermal stability and cellulose-binding capacity of Cryptococcus sp. S-2 lipase by fusion of cellulose binding domain derived from Trichoderma reesei

    International Nuclear Information System (INIS)

    Thongekkaew, Jantaporn; Ikeda, Hiroko; Iefuji, Haruyuki

    2012-01-01

    Highlights: ► The CSLP and fusion enzyme were successfully expressed in the Pichia pastoris. ► The fusion enzyme was stable at 80 °C for 120-min. ► The fusion enzyme was responsible for cellulose-binding capacity. ► The fusion enzyme has an attractive applicant for enzyme immobilization. -- Abstract: To improve the thermal stability and cellulose-binding capacity of Cryptococcus sp. S-2 lipase (CSLP), the cellulose-binding domain originates from Trichoderma reesei cellobiohydrolase I was engineered into C-terminal region of the CSLP (CSLP-CBD). The CSLP and CSLP-CBD were successfully expressed in the Pichia pastoris using the strong methanol inducible alcohol oxidase 1 (AOX1) promoter and the secretion signal sequence from Saccharomyces cerevisiae (α factor). The recombinant CSLP and CSLP-CBD were secreted into culture medium and estimated by SDS–PAGE to be 22 and 27 kDa, respectively. The fusion enzyme was stable at 80 °C and retained more than 80% of its activity after 120-min incubation at this temperature. Our results also found that the fusion of fungal exoglucanase cellulose-binding domain to CSLP is responsible for cellulose-binding capacity. This attribute should make it an attractive applicant for enzyme immobilization.

  5. Increases thermal stability and cellulose-binding capacity of Cryptococcus sp. S-2 lipase by fusion of cellulose binding domain derived from Trichoderma reesei

    Energy Technology Data Exchange (ETDEWEB)

    Thongekkaew, Jantaporn, E-mail: jantaporn_25@yahoo.com [Department of Biological Science, Faculty of Science, Ubon-Ratchathani University, Warinchumrab, Ubon-Ratchathani 34190 (Thailand); Ikeda, Hiroko; Iefuji, Haruyuki [Application Research Division, National Research Institute of Brewing, 3-7-1 Kagamiyama, Higashi-Hiroshima 739-0046 (Japan)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer The CSLP and fusion enzyme were successfully expressed in the Pichia pastoris. Black-Right-Pointing-Pointer The fusion enzyme was stable at 80 Degree-Sign C for 120-min. Black-Right-Pointing-Pointer The fusion enzyme was responsible for cellulose-binding capacity. Black-Right-Pointing-Pointer The fusion enzyme has an attractive applicant for enzyme immobilization. -- Abstract: To improve the thermal stability and cellulose-binding capacity of Cryptococcus sp. S-2 lipase (CSLP), the cellulose-binding domain originates from Trichoderma reesei cellobiohydrolase I was engineered into C-terminal region of the CSLP (CSLP-CBD). The CSLP and CSLP-CBD were successfully expressed in the Pichia pastoris using the strong methanol inducible alcohol oxidase 1 (AOX1) promoter and the secretion signal sequence from Saccharomyces cerevisiae ({alpha} factor). The recombinant CSLP and CSLP-CBD were secreted into culture medium and estimated by SDS-PAGE to be 22 and 27 kDa, respectively. The fusion enzyme was stable at 80 Degree-Sign C and retained more than 80% of its activity after 120-min incubation at this temperature. Our results also found that the fusion of fungal exoglucanase cellulose-binding domain to CSLP is responsible for cellulose-binding capacity. This attribute should make it an attractive applicant for enzyme immobilization.

  6. Strontium stable isotope behaviour accompanying basalt weathering

    Science.gov (United States)

    Burton, K. W.; Parkinson, I. J.; Gíslason, S. G. R.

    2016-12-01

    The strontium (Sr) stable isotope composition of rivers is strongly controlled by the balance of carbonate to silicate weathering (Krabbenhöft et al. 2010; Pearce et al. 2015). However, rivers draining silicate catchments possess distinctly heavier Sr stable isotope values than their bedrock compositions, pointing to significant fractionation during weathering. Some have argued for preferential release of heavy Sr from primary phases during chemical weathering, others for the formation of secondary weathering minerals that incorporate light isotopes. This study presents high-precision double-spike Sr stable isotope data for soils, rivers, ground waters and estuarine waters from Iceland, reflecting both natural weathering and societal impacts on those environments. The bedrock in Iceland is dominantly basaltic, d88/86Sr ≈ +0.27, extending to lighter values for rhyolites. Geothermal waters range from basaltic Sr stable compositions to those akin to seawater. Soil pore waters reflect a balance of input from primary mineral weathering, precipitation and litter recycling and removal into secondary phases and vegetation. Rivers and ground waters possess a wide range of d88/86Sr compositions from +0.101 to +0.858. Elemental and isotope data indicate that this fractionation primarily results from the formation or dissolution of secondary zeolite (d88/86Sr ≈ +0.10), but also carbonate (d88/86Sr ≈ +0.22) and sometimes anhydrite (d88/86Sr ≈ -0.73), driving the residual waters to heavier or lighter values, respectively. Estuarine waters largely reflect mixing with seawater, but are also be affected by adsorption onto particulates, again driving water to heavy values. Overall, these data indicate that the stability and nature of secondary weathering phases, exerts a strong control on the Sr stable isotope composition of silicate rivers. [1] Krabbenhöft et al. (2010) Geochim. Cosmochim. Acta 74, 4097-4109. [2] Pearce et al. (2015) Geochim. Cosmochim. Acta 157, 125-146.

  7. Development of a Safety Management Web Tool for Horse Stables.

    Science.gov (United States)

    Leppälä, Jarkko; Kolstrup, Christina Lunner; Pinzke, Stefan; Rautiainen, Risto; Saastamoinen, Markku; Särkijärvi, Susanna

    2015-11-12

    Managing a horse stable involves risks, which can have serious consequences for the stable, employees, clients, visitors and horses. Existing industrial or farm production risk management tools are not directly applicable to horse stables and they need to be adapted for use by managers of different types of stables. As a part of the InnoEquine project, an innovative web tool, InnoHorse, was developed to support horse stable managers in business, safety, pasture and manure management. A literature review, empirical horse stable case studies, expert panel workshops and stakeholder interviews were carried out to support the design. The InnoHorse web tool includes a safety section containing a horse stable safety map, stable safety checklists, and examples of good practices in stable safety, horse handling and rescue planning. This new horse stable safety management tool can also help in organizing work processes in horse stables in general.

  8. Pactamycin binding site on archaebacterial and eukaryotic ribosomes

    International Nuclear Information System (INIS)

    Tejedor, F.; Amils, R.; Ballesta, J.P.G.

    1987-01-01

    The presence of a photoreactive acetophenone group in the protein synthesis inhibitor pactamycin and the possibility of obtaining active iodinated derivatives that retain full biological activity allow the antibiotic binding site on Saccharomyces cerevisiae and archaebacterium Sulfolobus solfataricus ribosomes to be photoaffinity labeled. Four major labeled proteins have been identified in the yeast ribosomes, i.e., YS10, YS18, YS21/24, and YS30, while proteins AL1a, AS10/L8, AS18/20, and AS21/22 appeared as radioactive spots in S. solfataricus. There seems to be a correlation between some of the proteins labeled in yeast and those previously reported in Escherichia coli indicating that the pactamycin binding sites of both species, which are in the small subunit close to the initiation factors and mRNA binding sites, must have similar characteristics

  9. Dinitrogen binding and cleavage by multinuclear iron complexes.

    Science.gov (United States)

    McWilliams, Sean F; Holland, Patrick L

    2015-07-21

    The iron-molybdenum cofactor of nitrogenase has unprecedented coordination chemistry, including a high-spin iron cluster called the iron-molybdenum cofactor (FeMoco). Thus, understanding the mechanism of nitrogenase challenges coordination chemists to understand the fundamental N2 chemistry of high-spin iron sites. This Account summarizes a series of studies in which we have synthesized a number of new compounds with multiple iron atoms, characterized them using crystallography and spectroscopy, and studied their reactions in detail. These studies show that formally iron(I) and iron(0) complexes with three- and four-coordinate metal atoms have the ability to weaken and break the triple bond of N2. These reactions occur at or below room temperature, indicating that they are kinetically facile. This in turn implies that iron sites in the FeMoco are chemically reasonable locations for N2 binding and reduction. The careful evaluation of these compounds and their reaction pathways has taught important lessons about what characteristics make iron more effective for N2 activation. Cooperation of two iron atoms can lengthen and weaken the N-N bond, while three working together enables iron atoms to completely cleave the N-N bond to nitrides. Alkali metals (typically introduced into the reaction as part of the reducing agent) are thermodynamically useful because the alkali metal cations stabilize highly reduced complexes, pull electron density into the N2 unit, and make reduced nitride products more stable. Alkali metals can also play a kinetic role, because cation-π interactions with the supporting ligands can hold iron atoms near enough to one another to facilitate the cooperation of multiple iron atoms. Many of these principles may also be relevant to the iron-catalyzed Haber-Bosch process, at which collections of iron atoms (often promoted by the addition of alkali metals) break the N-N bond of N2. The results of these studies teach more general lessons as well. They

  10. Temporal binding within and across events

    Science.gov (United States)

    DuBrow, Sarah; Davachi, Lila

    2016-01-01

    Remembering the order in which events occur is a fundamental component of episodic memory. However, the neural mechanisms supporting serial recall remain unclear. Behaviorally, serial recall is greater for information encountered within the same event compared to across event boundaries, raising the possibility that contextual stability may modulate the cognitive and neural processes supporting serial encoding. In the present study, we used fMRI during the encoding of consecutive face and object stimuli to elucidate the neural encoding signatures supporting subsequent serial recall behavior both within and across events. We found that univariate BOLD activation in both the middle hippocampus and left ventrolateral prefrontal cortex (PFC) was associated with subsequent serial recall of items that occur across event boundaries. By contrast, successful serial encoding within events was associated with increased functional connectivity between the hippocampus and ventromedial PFC, but not with univariate activation in these or other regions. These findings build on evidence implicating hippocampal and PFC processes in encoding temporal aspects of memory. They further suggest that these encoding processes are influenced by whether binding occurs within a stable context or bridges two adjacent but distinct events. PMID:27422018

  11. Design criteria for stable Pt/C fuel cell catalysts

    Directory of Open Access Journals (Sweden)

    Josef C. Meier

    2014-01-01

    Full Text Available Platinum and Pt alloy nanoparticles supported on carbon are the state of the art electrocatalysts in proton exchange membrane fuel cells. To develop a better understanding on how material design can influence the degradation processes on the nanoscale, three specific Pt/C catalysts with different structural characteristics were investigated in depth: a conventional Pt/Vulcan catalyst with a particle size of 3–4 nm and two Pt@HGS catalysts with different particle size, 1–2 nm and 3–4 nm. Specifically, Pt@HGS corresponds to platinum nanoparticles incorporated and confined within the pore structure of the nanostructured carbon support, i.e., hollow graphitic spheres (HGS. All three materials are characterized by the same platinum loading, so that the differences in their performance can be correlated to the structural characteristics of each material. The comparison of the activity and stability behavior of the three catalysts, as obtained from thin film rotating disk electrode measurements and identical location electron microscopy, is also extended to commercial materials and used as a basis for a discussion of general fuel cell catalyst design principles. Namely, the effects of particle size, inter-particle distance, certain support characteristics and thermal treatment on the catalyst performance and in particular the catalyst stability are evaluated. Based on our results, a set of design criteria for more stable and active Pt/C and Pt-alloy/C materials is suggested.

  12. Structure-Based Understanding of Binding Affinity and Mode of Estrogen Receptor α Agonists and Antagonists.

    Directory of Open Access Journals (Sweden)

    Sehan Lee

    Full Text Available The flexible hydrophobic ligand binding pocket (LBP of estrogen receptor α (ERα allows the binding of a wide variety of endocrine disruptors. Upon ligand binding, the LBP reshapes around the contours of the ligand and stabilizes the complex by complementary hydrophobic interactions and specific hydrogen bonds with the ligand. Here we present a framework for quantitative analysis of the steric and electronic features of the human ERα-ligand complex using three dimensional (3D protein-ligand interaction description combined with 3D-QSAR approach. An empirical hydrophobicity density field is applied to account for hydrophobic contacts of ligand within the LBP. The obtained 3D-QSAR model revealed that hydrophobic contacts primarily determine binding affinity and govern binding mode with hydrogen bonds. Several residues of the LBP appear to be quite flexible and adopt a spectrum of conformations in various ERα-ligand complexes, in particular His524. The 3D-QSAR was combined with molecular docking based on three receptor conformations to accommodate receptor flexibility. The model indicates that the dynamic character of the LBP allows accommodation and stable binding of structurally diverse ligands, and proper representation of the protein flexibility is critical for reasonable description of binding of the ligands. Our results provide a quantitative and mechanistic understanding of binding affinity and mode of ERα agonists and antagonists that may be applicable to other nuclear receptors.

  13. On the Fractional Poisson Process and the Discretized Stable Subordinator

    Directory of Open Access Journals (Sweden)

    Rudolf Gorenflo

    2015-08-01

    Full Text Available We consider the renewal counting number process N = N(t as a forward march over the non-negative integers with independent identically distributed waiting times. We embed the values of the counting numbers N in a “pseudo-spatial” non-negative half-line x ≥ 0 and observe that for physical time likewise we have t ≥ 0. Thus we apply the Laplace transform with respect to both variables x and t. Applying then a modification of the Montroll-Weiss-Cox formalism of continuous time random walk we obtain the essential characteristics of a renewal process in the transform domain and, if we are lucky, also in the physical domain. The process t = t(N of accumulation of waiting times is inverse to the counting number process, in honour of the Danish mathematician and telecommunication engineer A.K. Erlang we call it the Erlang process. It yields the probability of exactly n renewal events in the interval (0; t]. We apply our Laplace-Laplace formalism to the fractional Poisson process whose waiting times are of Mittag-Leffler type and to a renewal process whose waiting times are of Wright type. The process of Mittag-Leffler type includes as a limiting case the classical Poisson process, the process of Wright type represents the discretized stable subordinator and a re-scaled version of it was used in our method of parametric subordination of time-space fractional diffusion processes. Properly rescaling the counting number process N(t and the Erlang process t(N yields as diffusion limits the inverse stable and the stable subordinator, respectively.

  14. Binding of heavy metals to derivatives of cholesterol and sodium dodecyl sulfate

    Energy Technology Data Exchange (ETDEWEB)

    Ahmadi, S.; Batchelor, B.; Koseoglu, S.S. [Texas A and M Univ., College Station, TX (United States); Huang, Y.C.

    1995-09-01

    The binding behaviors of five metals (cadmium, copper, nickel, lead, and zinc), individually at pH 6 and collectively at pHs 6 and 3, to deoxycholic acid (DCA) and taurocholic acid (TCA) were compared with those of sodium dodecyl sulfate (SDS) using a continuous diafiltration method. DCA and SDS have been successfully applied in micellar-enhanced ultrafiltration (MEUF) for metal removal from water. In this study, SDS exhibits the strongest binding in the single-component experiments while DCA binds the most in the multicomponent trials. TCA does not show any significant biding compared with DCA and SDS. Overall the molar binding ratios of the mixture at pH 3 were well below those of the other two solutions. This diafiltration technique quantifies the binding characteristics of a surfactant by generating sorption isotherms and determining the intrinsic association constraints with corresponding number of binding sites. These parameters can be useful in designing an efficient MEUF system.

  15. Exploring the binding properties and structural stability of an opsin in the chytrid Spizellomyces punctatus using comparative and molecular modeling

    Directory of Open Access Journals (Sweden)

    Steven R. Ahrendt

    2017-04-01

    Full Text Available Background Opsin proteins are seven transmembrane receptor proteins which detect light. Opsins can be classified into two types and share little sequence identity: type 1, typically found in bacteria, and type 2, primarily characterized in metazoa. The type 2 opsins (Rhodopsins are a subfamily of G-protein coupled receptors (GPCRs, a large and diverse class of seven transmembrane proteins and are generally restricted to metazoan lineages. Fungi use light receptors including opsins to sense the environment and transduce signals for developmental or metabolic changes. Opsins characterized in the Dikarya (Ascomycetes and Basidiomycetes are of the type 1 bacteriorhodopsin family but the early diverging fungal lineages have not been as well surveyed. We identified by sequence similarity a rhodopsin-like GPCR in genomes of early diverging chytrids and examined the structural characteristics of this protein to assess its likelihood to be homologous to animal rhodopsins and bind similar chromophores. Methods We used template-based structure modeling, automated ligand docking, and molecular modeling to assess the structural and binding properties of an identified opsin-like protein found in Spizellomyces punctatus, a unicellular, flagellated species belonging to Chytridiomycota, one of the earliest diverging fungal lineages. We tested if the sequence and inferred structure were consistent with a solved crystal structure of a type 2 rhodopsin from the squid Todarodes pacificus. Results Our results indicate that the Spizellomyces opsin has structural characteristics consistent with functional animal type 2 rhodopsins and is capable of maintaining a stable structure when associated with the retinaldehyde chromophore, specifically the 9-cis-retinal isomer. Together, these results support further the homology of Spizellomyces opsins to animal type 2 rhodopsins. Discussion This represents the first test of structure/function relationship of a type 2 rhodopsin

  16. Synthesis and optical characteristics of ZnO nanocrystals

    Indian Academy of Sciences (India)

    Administrator

    (Johnson et al 2001; Zhang et al 2002). Compared to other semiconductors, ZnO has wide bandgap of 3⋅37 eV and other large excitation binding energy, which makes excitation stable even at room temperature. There are various methods in order to synthesize ZnO nanomaterials viz. solvothermal synthesis, sol–gel (Li ...

  17. Stable lithium electrodeposition in liquid and nanoporous solid electrolytes

    KAUST Repository

    Lu, Yingying

    2014-08-10

    Rechargeable lithium, sodium and aluminium metal-based batteries are among the most versatile platforms for high-energy, cost-effective electrochemical energy storage. Non-uniform metal deposition and dendrite formation on the negative electrode during repeated cycles of charge and discharge are major hurdles to commercialization of energy-storage devices based on each of these chemistries. A long-held view is that unstable electrodeposition is a consequence of inherent characteristics of these metals and their inability to form uniform electrodeposits on surfaces with inevitable defects. We report on electrodeposition of lithium in simple liquid electrolytes and in nanoporous solids infused with liquid electrolytes. We find that simple liquid electrolytes reinforced with halogenated salt blends exhibit stable long-term cycling at room temperature, often with no signs of deposition instabilities over hundreds of cycles of charge and discharge and thousands of operating hours. We rationalize these observations with the help of surface energy data for the electrolyte/lithium interface and impedance analysis of the interface during different stages of cell operation. Our findings provide support for an important recent theoretical prediction that the surface mobility of lithium is significantly enhanced in the presence of lithium halide salts. Our results also show that a high electrolyte modulus is unnecessary for stable electrodeposition of lithium.

  18. Study Tranport Barrier Formation using Bi- Stable Sandpile Model

    International Nuclear Information System (INIS)

    Kitpitak, B.; Kanjanaput, W.; Poolyarat, N.; Picha, R; Onjun, T.

    2014-01-01

    The formation of plasma transport barrier in Tokamak is an important issue for achieving high energy confinement and sufficient fusion performance. The simulation using in this experiment simulates cycles of dropping grains in a sandpile with two stable and two unstable slope regimes which share the same characteristic as the formation of pedestal and there are several parameters used, including stable boundaries, grains in a toppling, relax process iterations per cycle, grains in a drop and number of drops per cycle. By using this simulation, the effects of the relaxation times and number of trooping grain (the number of collapsing grain in the relaxation process) can be investigated. It is found in the simulations that the pedestal region can be observed only when the number of deposited grain exceeds a critical value which is related to number of relaxation times and number of allowed trooping grain. In another words, the pedestal formation occurs when the particle deposition rate is higher than the average diffusion rate. In addition, altering amount of trooping grain can lead to remarkable effects on slope and height of the profiles. In order to achieve better energy confinement, further study of formation of plasma transport barrier is needed.

  19. Shelf-stable food through high dose irradiation

    International Nuclear Information System (INIS)

    Placek, V.; Svobodova, V.; Bartonicek, B.; Rosmus, J.; Camra, M.

    2004-01-01

    Irradiation of food with high doses (radappertization) is a way, how to prepare shelf-stable ready-to-eat food. The radappertization process requires that the food be heated at first to an internal temperature of at least 75 deg. C to inactivate autolytic enzyme, which could cause the spoilage during storage without refrigeration. In order to prevent radiation induced changes in sensory properties (off flavors, odors, undesirable color change, etc.) the food was vacuum packed and irradiated in frozen state at -30 deg. C or less to a minimum dose of 35 kGy. Such products have characteristics of fresh food prepared for eating even if they are stored for long time under tropical conditions. The wholesomeness (safety for consumption) has been confirmed during 40 years of testing. Within the NRI Rez 10 kinds of shelf-stable meat products have been prepared. The meat was cooked, vacuum packed in SiO x -containing pouch, freezed in liquid nitrogen and irradiated with electron beam accelerator. The microbial, chemical, and organoleptic properties have been tested

  20. Dopant designing for thermally stable graded index plastic optical fiber

    Science.gov (United States)

    Yamaki, Y.; Kondo, A.; Koike, Y.

    2009-02-01

    The graded index polymer optical fiber (GI POF) has been proposed as a media for very short reach network because of its high flexibility, low laying cost and excellent transmission characteristics. However, the plasticization efficiency which causes by the high refractive dopant decreases the glass transition temperature (Tg) in the center of the core and deteriorates thermal stability of fibers. In this paper, thermally stable PMMA based GI POF was successfully fabricated for the first time by designing dopant molecule which has little plasticizer effect. Tg at the core region was improved to 104 °C while that of conventional GI POF is 86 °C. Stability of attenuation at 85 °C/dry and 75 °C/85 %RH were clarified to be as high as that of non-doped step index POF.

  1. Fused electron deficient semiconducting polymers for air stable electron transport

    KAUST Repository

    Onwubiko, Ada

    2018-01-23

    Conventional semiconducting polymer synthesis typically involves transition metal-mediated coupling reactions that link aromatic units with single bonds along the backbone. Rotation around these bonds contributes to conformational and energetic disorder and therefore potentially limits charge delocalisation, whereas the use of transition metals presents difficulties for sustainability and application in biological environments. Here we show that a simple aldol condensation reaction can prepare polymers where double bonds lock-in a rigid backbone conformation, thus eliminating free rotation along the conjugated backbone. This polymerisation route requires neither organometallic monomers nor transition metal catalysts and offers a reliable design strategy to facilitate delocalisation of frontier molecular orbitals, elimination of energetic disorder arising from rotational torsion and allowing closer interchain electronic coupling. These characteristics are desirable for high charge carrier mobilities. Our polymers with a high electron affinity display long wavelength NIR absorption with air stable electron transport in solution processed organic thin film transistors.

  2. In silico docking of forchlorfenuron (FCF to septins suggests that FCF interferes with GTP binding.

    Directory of Open Access Journals (Sweden)

    Dimitrios Angelis

    Full Text Available Septins are GTP-binding proteins that form cytoskeleton-like filaments, which are essential for many functions in eukaryotic organisms. Small molecule compounds that disrupt septin filament assembly are valuable tools for dissecting septin functions with high temporal control. To date, forchlorfenuron (FCF is the only compound known to affect septin assembly and functions. FCF dampens the dynamics of septin assembly inducing the formation of enlarged stable polymers, but the underlying mechanism of action is unknown. To investigate how FCF binds and affects septins, we performed in silico simulations of FCF docking to all available crystal structures of septins. Docking of FCF with SEPT2 and SEPT3 indicated that FCF interacts preferentially with the nucleotide-binding pockets of septins. Strikingly, FCF is predicted to form hydrogen bonds with residues involved in GDP-binding, mimicking nucleotide binding. FCF docking with the structure of SEPT2-GppNHp, a nonhydrolyzable GTP analog, and SEPT7 showed that FCF may assume two alternative non-overlapping conformations deeply into and on the outer side of the nucleotide-binding pocket. Surprisingly, FCF was predicted to interact with the P-loop Walker A motif GxxxxGKS/T, which binds the phosphates of GTP, and the GTP specificity motif AKAD, which interacts with the guanine base of GTP, and highly conserved amino acids including a threonine, which is critical for GTP hydrolysis. Thus, in silico FCF exhibits a conserved mechanism of binding, interacting with septin signature motifs and residues involved in GTP binding and hydrolysis. Taken together, our results suggest that FCF stabilizes septins by locking them into a conformation that mimics a nucleotide-bound state, preventing further GTP binding and hydrolysis. Overall, this study provides the first insight into how FCF may bind and stabilize septins, and offers a blueprint for the rational design of FCF derivatives that could target septins with

  3. Fluorescently labeled ribosomes as a tool for analyzing antibiotic binding.

    Science.gov (United States)

    Llano-Sotelo, Beatriz; Hickerson, Robyn P; Lancaster, Laura; Noller, Harry F; Mankin, Alexander S

    2009-08-01

    Measuring the binding of antibiotics and other small-molecular-weight ligands to the 2.5 MDa ribosome often presents formidable challenges. Here, we describe a general method for studying binding of ligands to ribosomes that carry a site-specific fluorescent label covalently attached to one of the ribosomal proteins. As a proof of principle, an environment-sensitive fluorescent group was placed at several specific sites within the ribosomal protein S12. Small ribosomal subunits were reconstituted from native 16S rRNA, individually purified small subunit proteins, and fluorescently labeled S12. The fluorescence characteristics of the reconstituted subunits were affected by several antibiotics, including streptomycin and neomycin, which bind in the vicinity of protein S12. The equilibrium dissociation constants of the drugs obtained using a conventional fluorometer were in good agreement with those observed using previously published methods and with measurements based on the use of radiolabeled streptomycin. The newly developed method is rapid and sensitive, and can be used for determining thermodynamic and kinetic binding characteristics of antibiotics and other small ribosomal ligands. The method can readily be adapted for use in high-throughput screening assays.

  4. Fc-Binding Ligands of Immunoglobulin G: An Overview of High Affinity Proteins and Peptides

    Directory of Open Access Journals (Sweden)

    Weonu Choe

    2016-12-01

    Full Text Available The rapidly increasing application of antibodies has inspired the development of several novel methods to isolate and target antibodies using smart biomaterials that mimic the binding of Fc-receptors to antibodies. The Fc-binding domain of antibodies is the primary binding site for e.g., effector proteins and secondary antibodies, whereas antigens bind to the Fab region. Protein A, G, and L, surface proteins expressed by pathogenic bacteria, are well known to bind immunoglobulin and have been widely exploited in antibody purification strategies. Several difficulties are encountered when bacterial proteins are used in antibody research and application. One of the major obstacles hampering the use of bacterial proteins is sample contamination with trace amounts of these proteins, which can invoke an immune response in the host. Many research groups actively develop synthetic ligands that are able to selectively and strongly bind to antibodies. Among the reported ligands, peptides that bind to the Fc-domain of antibodies are attractive tools in antibody research. Besides their use as high affinity ligands in antibody purification chromatography, Fc-binding peptides are applied e.g., to localize antibodies on nanomaterials and to increase the half-life of proteins in serum. In this review, recent developments of Fc-binding peptides are presented and their binding characteristics and diverse applications are discussed.

  5. The next generation of transcription factor binding site prediction.

    Directory of Open Access Journals (Sweden)

    Anthony Mathelier

    Full Text Available Finding where transcription factors (TFs bind to the DNA is of key importance to decipher gene regulation at a transcriptional level. Classically, computational prediction of TF binding sites (TFBSs is based on basic position weight matrices (PWMs which quantitatively score binding motifs based on the observed nucleotide patterns in a set of TFBSs for the corresponding TF. Such models make the strong assumption that each nucleotide participates independently in the corresponding DNA-protein interaction and do not account for flexible length motifs. We introduce transcription factor flexible models (TFFMs to represent TF binding properties. Based on hidden Markov models, TFFMs are flexible, and can model both position interdependence within TFBSs and variable length motifs within a single dedicated framework. The availability of thousands of experimentally validated DNA-TF interaction sequences from ChIP-seq allows for the generation of models that perform as well as PWMs for stereotypical TFs and can improve performance for TFs with flexible binding characteristics. We present a new graphical representation of the motifs that convey properties of position interdependence. TFFMs have been assessed on ChIP-seq data sets coming from the ENCODE project, revealing that they can perform better than both PWMs and the dinucleotide weight matrix extension in discriminating ChIP-seq from background sequences. Under the assumption that ChIP-seq signal values are correlated with the affinity of the TF-DNA binding, we find that TFFM scores correlate with ChIP-seq peak signals. Moreover, using available TF-DNA affinity measurements for the Max TF, we demonstrate that TFFMs constructed from ChIP-seq data correlate with published experimentally measured DNA-binding affinities. Finally, TFFMs allow for the straightforward computation of an integrated TF occupancy score across a sequence. These results demonstrate the capacity of TFFMs to accurately model DNA

  6. On The Roman Domination Stable Graphs

    Directory of Open Access Journals (Sweden)

    Hajian Majid

    2017-11-01

    Full Text Available A Roman dominating function (or just RDF on a graph G = (V,E is a function f : V → {0, 1, 2} satisfying the condition that every vertex u for which f(u = 0 is adjacent to at least one vertex v for which f(v = 2. The weight of an RDF f is the value f(V (G = Pu2V (G f(u. The Roman domination number of a graph G, denoted by R(G, is the minimum weight of a Roman dominating function on G. A graph G is Roman domination stable if the Roman domination number of G remains unchanged under removal of any vertex. In this paper we present upper bounds for the Roman domination number in the class of Roman domination stable graphs, improving bounds posed in [V. Samodivkin, Roman domination in graphs: the class RUV R, Discrete Math. Algorithms Appl. 8 (2016 1650049].

  7. Design of optically stable image reflector system.

    Science.gov (United States)

    Tsai, Chung-Yu

    2013-08-01

    The design of a partially optically stable (POS) reflector system, in which the exit ray direction and image pose are unchanged as the reflector system rotates about a specific directional vector, was presented in an earlier study by the current group [Appl. Phys. B100, 883-890 (2010)]. The present study further proposes an optically stable image (OSI) reflector system, in which not only is the optical stability property of the POS system retained, but the image position and total ray path length are also fixed. An analytical method is proposed for the design of OSI reflector systems comprising multiple reflectors. The validity of the proposed approach is demonstrated by means of two illustrative examples.

  8. Stable microfluidic flow focusing using hydrostatics.

    Science.gov (United States)

    Gnyawali, Vaskar; Saremi, Mohammadali; Kolios, Michael C; Tsai, Scott S H

    2017-05-01

    We present a simple technique to generate stable hydrodynamically focused flows by driving the flow with hydrostatic pressure from liquid columns connected to the inlets of a microfluidic device. Importantly, we compare the focused flows generated by hydrostatic pressure and classical syringe pump driven flows and find that the stability of the hydrostatic pressure driven technique is significantly better than the stability achieved via syringe pumps, providing fluctuation-free focused flows that are suitable for sensitive microfluidic flow cytometry applications. We show that the degree of flow focusing with the hydrostatic method can be accurately controlled by the simple tuning of the liquid column heights. We anticipate that this approach to stable flow focusing will find many applications in microfluidic cytometry technologies.

  9. Utilization of stable isotopes in medicine

    International Nuclear Information System (INIS)

    1980-11-01

    The ten lectures given at this round table are presented together with a discussion. Five lectures, relating to studies in which deuterium oxide was employed as a tracer of body water, dealt with pulmonary water measurements in man and animals, the total water pool in adipose subjects, and liquid compartments in children undergoing hemodyalisis. The heavy water is analysed by infrared spectrometry and a new double spectrodoser is described. Two studies using 13 C as tracer, described the diagnosis of liver troubles and diabetes respectively. A general review of the perspectives of the application of stable isotopes in clinical medicine is followed by a comparison of the use of stable and radioactive isotopes in France [fr

  10. An angiogenin-binding protein from endothelial cells

    International Nuclear Information System (INIS)

    Hu, Guofu; Chang, Sooik; Riordan, J.F.; Vallee, B.L.

    1991-01-01

    A 42-kDa bovine protein that binds bovine angiogenin [angiogenin binding protein (AngBP)] has been identified as a dissociable cell-surface component of calf pulmonary artery endothelial cells and a transformed bovine endothelial cell line, GM7373. 125 I-Ang can be crosslinked efficiently to AngBP by a water-soluble carbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)carbo-diimide. Bovine ribonuclease A competes with the binding of 125 I-Ang to AngBP, but lysozyme does not. Direct binding to AngBP of 125 I-labeled bovine ribonuclease A is, however, much weaker than that of 125 I-Ang. Two enzymatically active derivatives of angiogenin cleaved at residues 60-61 and 67-68, respectively, fail to induce angiogenesis and also bind to AngBP only weakly. AngBP has been isolated by treatment of cells with heparan sulfate, affinity chromatography on angiogenin-Sepharose of the material dissociated from the cell surface, and gel filtration HPLC. The results suggest that AngBP has the characteristics of a receptor that may likely function in angiogenesis

  11. When is protein binding important?

    Science.gov (United States)

    Heuberger, Jules; Schmidt, Stephan; Derendorf, Hartmut

    2013-09-01

    The present paper is an ode to a classic citation by Benet and Hoener (2002. Clin Pharm Ther 71(3):115-121). The now classic paper had a huge impact on drug development and the way the issue of protein binding is perceived and interpreted. Although the authors very clearly pointed out the limitations and underlying assumptions for their delineations, these are too often overlooked and the classic paper's message is misinterpreted by broadening to cases that were not intended. Some members of the scientific community concluded from the paper that protein binding is not important. This was clearly not intended by the authors, as they finished their paper with a paragraph entitled: "When is protein binding important?" Misinterpretation of the underlying assumptions in the classic work can result in major pitfalls in drug development. Therefore, we revisit the topic of protein binding with the intention of clarifying when clinically relevant changes should be considered during drug development. Copyright © 2013 Wiley Periodicals, Inc.

  12. Thermally Stable, Latent Olefin Metathesis Catalysts

    OpenAIRE

    Thomas, Renee M.; Fedorov, Alexey; Keitz, Benjamin K.; Grubbs, Robert H.

    2011-01-01

    Highly thermally stable N-aryl,N-alkyl N-heterocyclic carbene (NHC) ruthenium catalysts were designed and synthesized for latent olefin metathesis. These catalysts showed excellent latent behavior toward metathesis reactions, whereby the complexes were inactive at ambient temperature and initiated at elevated temperatures, a challenging property to achieve with second generation catalysts. A sterically hindered N-tert-butyl substituent on the NHC ligand of the ruthenium complex was found to i...

  13. A belief-based evolutionarily stable strategy

    OpenAIRE

    Deng, Xinyang; Wang, Zhen; Liu, Qi; Deng, Yong; Mahadevan, Sankaran

    2014-01-01

    As an equilibrium refinement of the Nash equilibrium, evolutionarily stable strategy (ESS) is a key concept in evolutionary game theory and has attracted growing interest. An ESS can be either a pure strategy or a mixed strategy. Even though the randomness is allowed in mixed strategy, the selection probability of pure strategy in a mixed strategy may fluctuate due to the impact of many factors. The fluctuation can lead to more uncertainty. In this paper, such uncertainty involved in mixed st...

  14. Stable iodine prophylaxis. Recommendations of the 2nd UK Working Group on Stable Iodine Prophylaxis

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

    The Working Group reviewed the revised Who guidance and the information published since 1991 on the risks of thyroid cancer in children from radioiodine and the risks of side effects from stable iodine. In particular, it reviewed data compiled on the incidence of thyroid cancers in children following the accident at the Chernobyl nuclear power plant in 1986. It considered whether the NRPB Earls were still appropriate, in the light of the new data. It also reviewed a range of other recommendations given by the 1st Working Group, concerning the chemical form of stable iodine tablets and practical issues concerning implementation of stable iodine prophylaxis. Finally, it reviewed the Patient Information Leaflet that is required, by law, to be included in each box of tablets and provided suggestions for information to be included in a separate information leaflet to be handed out to the public when stable iodine tablets are distributed.

  15. Detonation of Meta-stable Clusters

    Energy Technology Data Exchange (ETDEWEB)

    Kuhl, Allen; Kuhl, Allen L.; Fried, Laurence E.; Howard, W. Michael; Seizew, Michael R.; Bell, John B.; Beckner, Vincent; Grcar, Joseph F.

    2008-05-31

    We consider the energy accumulation in meta-stable clusters. This energy can be much larger than the typical chemical bond energy (~;;1 ev/atom). For example, polymeric nitrogen can accumulate 4 ev/atom in the N8 (fcc) structure, while helium can accumulate 9 ev/atom in the excited triplet state He2* . They release their energy by cluster fission: N8 -> 4N2 and He2* -> 2He. We study the locus of states in thermodynamic state space for the detonation of such meta-stable clusters. In particular, the equilibrium isentrope, starting at the Chapman-Jouguet state, and expanding down to 1 atmosphere was calculated with the Cheetah code. Large detonation pressures (3 and 16 Mbar), temperatures (12 and 34 kilo-K) and velocities (20 and 43 km/s) are a consequence of the large heats of detonation (6.6 and 50 kilo-cal/g) for nitrogen and helium clusters respectively. If such meta-stable clusters could be synthesized, they offer the potential for large increases in the energy density of materials.

  16. The interrelationship between ligand binding and thermal unfolding of the folate binding protein. The role of self-association and pH

    DEFF Research Database (Denmark)

    Holm, Jan; Babol, Linnea N.; Markova, Natalia

    2014-01-01

    increased concentration-dependent self-association of FBP into stable multimers of holo-FBP. DSC of 3.3μM holo-FBP showed Tm (76°C) and molar enthalpy (146kcalM(-1)) values increasing to 78°C and 163kcalM(-1) at 10μM holo-FBP, while those of apo-FBP were 55°C and 105kcalM(-1). Besides ligand binding......-wise rise in temperature to 78°C≈Tm. Stable holo-FBP multimers may protect naturally occurring labile folates against decomposition or bacterial utilization. DSC established an interrelationship between diminished folate binding at pH5, especially in NaCl-free buffers, and low thermostability. Positively...

  17. EPR studies of intermolecular interactions and competitive binding of drugs in a drug-BSA binding model.

    Science.gov (United States)

    Akdogan, Y; Emrullahoglu, M; Tatlidil, D; Ucuncu, M; Cakan-Akdogan, G

    2016-08-10

    Understanding intermolecular interactions between drugs and proteins is very important in drug delivery studies. Here, we studied different binding interactions between salicylic acid and bovine serum albumin (BSA) using electron paramagnetic resonance (EPR) spectroscopy. Salicylic acid was labeled with a stable radical (spin label) in order to monitor its mobilized (free) or immobilized (bound to BSA) states. In addition to spin labeled salicylic acid (SL-salicylic acid), its derivatives including SL-benzoic acid, SL-phenol, SL-benzene, SL-cyclohexane and SL-hexane were synthesized to reveal the effects of various drug binding interactions. EPR results of these SL-molecules showed that hydrophobic interaction is the main driving force. Whereas each of the two functional groups (-COOH and -OH) on the benzene ring has a minute but detectable effect on the drug-protein complex formation. In order to investigate the effect of electrostatic interaction on drug binding, cationic BSA (cBSA) was synthesized, altering the negative net charge of BSA to positive. The salicylic acid loading capacity of cBSA is significantly higher compared to that of BSA, indicating the importance of electrostatic interaction in drug binding. Moreover, the competitive binding properties of salicylic acid, ibuprofen and aspirin to BSA were studied. The combined EPR results of SL-salicylic acid/ibuprofen and SL-ibuprofen/salicylic acid showed that ibuprofen is able to replace up to ∼83% of bound SL-salicylic acid, and salicylic acid can replace only ∼14% of the bound SL-ibuprofen. This indicates that ∼97% of all salicylic acid and ibuprofen binding sites are shared. On the other hand, aspirin replaces only ∼23% of bound SL-salicylic acid, and salicylic acid replaces ∼50% of bound SL-aspirin, indicating that ∼73% of all salicylic acid and aspirin binding sites are shared. These results show that EPR spectroscopy in combination with the spin labeling technique is a very powerful

  18. Mechanism of uranium binding to cellular components of microorganisms. II

    International Nuclear Information System (INIS)

    Jilek, R.; Beranova, E.

    1986-01-01

    Knowledge is summed up of the mechanism of inhibition of carbohydrate metabolism by uranyl ions in yeast and bacteria. The inhibition was found of anaerobic fermentation of glucose by undisturbed yeast cells and by cell-free extract to take place at different uranyl concentrations. The course of time dependence of uranium intake by live yeast cells showed that this process is not controlled by diffusion. It is based on complex binding of uranyl to the cell surface. A more detailed study of the process has shown that even with full saturation of the cell surface with uranyl ions the anaerobic metabolism is only inhibited to 90%, the remaining 10% of the metabolism is apparently provided by a different mechanism. Other centres were discovered on the surface of the yeast cell which do not take part in the anaerobic intake of glucose but form complexes with the uranyl. Mg 2+ , Ca 2+ , Ba 2+ , Mn 2+ , Cu 2+ , Ni 2+ , Co 2+ , Fe 2+ and other bivalent cations can compete with uranyl binding to active cell centres. The most stable complex, however, is formed by the uranyl ion. A more detailed clarification of the chemical character of active centres of the cell surface was made by comparative studies of the stability of the uranyl complex with yeast cells and similar complexes of model compounds. The most stable complex bonds were found to exist in highly polymerated inorganic phosphates. (E.S.)

  19. Two stable steady states in the Hodgkin-Huxley axons

    OpenAIRE

    Aihara, K.; Matsumoto, G.

    1983-01-01

    Two stable steady states were found in the numerical solution of the Hodgkin-Huxley equations for the intact squid axon bathed in potassium-rich sea water with an externally applied inward current. Under the conditions the two stable steady-states exist, the Hodgkin-Huxley equations have a complex bifurcation structure including, in addition to the two stable steady-states, a stable limit cycle, two unstable equilibrium points, and one asymptotically stable equilibrium point. It was also conc...

  20. Stable isotopes (carbon, nitrogen, sulfur), diet, and anthropometry in urban Colombian women: investigating socioeconomic differences.

    Science.gov (United States)

    Bender, Richard L; Dufour, Darna L; Valenzuela, Luciano O; Cerling, Thure E; Sponheimer, Matt; Reina, Julio C; Ehleringer, James R

    2015-01-01

    We conducted stable isotope and dietary analyses of women from higher and lower socioeconomic status (SES) groups in Cali, Colombia. The objectives were to test between-group differences in stable isotope, dietary, and anthropometric characteristics, and to evaluate relationships between diet and stable isotope values. Hair samples from 38 women (mean age 33.4) from higher and lower SES groups were analyzed for δ(13) C, δ(15) N, and δ(34) S values. Dietary intake was assessed via 24-h recalls. Anthropometric variables measured were body mass index, five body circumferences, and six skinfold thicknesses. Mean δ(13) C and δ(15) N values of the higher SES group (-16.4 and 10.3‰) were significantly greater than those of the lower SES group (-17.2 and 9.6‰; P stable isotope values (P Stable isotope values revealed a difference between SES groups that was not explained by the dietary data. The relationship between diet and stable isotope composition is complex. © 2014 Wiley Periodicals, Inc.

  1. Cadmium resistance in Drosophila: a small cadmium binding substance

    International Nuclear Information System (INIS)

    Jacobson, K.B.; Williams, M.W.; Richter, L.J.; Holt, S.E.; Hook, G.J.; Knoop, S.M.; Sloop, F.V.; Faust, J.B.

    1985-01-01

    A small cadmium-binding substance (CdBS) has been observed in adult Drosophila melanogaster that were raised for their entire growth cycle on a diet that contained 0.15 mM CdCl 2 . Induction of CdBS was observed in strains that differed widely in their sensitivity of CdCl 2 . This report describes the induction of CdBS and some of its characteristics. 17 refs., 4 figs., 1 tab

  2. Experimental studies on cycling stable characteristics of inorganic phase change material CaCl2·6H2O-MgCl2·6H2O modified with SrCl2·6H2O and CMC

    Science.gov (United States)

    He, Meizhi; Yang, Luwei; Zhang, Zhentao

    2018-01-01

    By means of mass ratio method, binary eutectic hydrated salts inorganic phase change thermal energy storage system CaCl2·6H2O-20wt% MgCl2·6H2O was prepared, and through adding nucleating agent 1wt% SrCl2·6H2O and thickening agent 0.5wt% carboxy methyl cellulose (CMC), inoganic phase change material (PCM) modified was obtained. With recording cooling-melting curves simultaneously, this PCM was frozen and melted for 100 cycles under programmable temperature control. After per 10 cycles, the PCM was charaterized by differential scanning calorimeter (DSC), X-ray diffraction (XRD) and density meter, then analysing variation characteristics of phase change temperature, supercooling degree, superheat degree, latent heat, crystal structure and density with the increase of cycle index. The results showed that the average values of average phase change temperature for cooling and heating process were 25.70°C and 27.39°C respectively with small changes. The average values of average supercooling and superheat degree were 0.59°C and 0.49°C respectively, and the maximum value was 1.10°C. The average value and standard deviation of latent heat of fusion were 120.62 J/g and 1.90 J/g respectively. Non-molten white solid sediments resulted from phase separation were tachyhydrite (CaMg2Cl6·12H2O), which was characterized by XRD. Measuring density of the PCM after per 10 cycles, and the results suggested that the total mass of tachyhydrite was limited. In summary, such modified inoganic PCM CaCl2·6H2O-20wt% MgCl2·6H2O-1wt% SrCl2·6H2O-0.5wt% CMC could stay excellent circulation stability within 100 cycles, and providing reference value in practical use.

  3. Prognostic Determinants of Coronary Atherosclerosis in Stable Ischemic Heart Disease: Anatomy, Physiology, or Morphology?

    Science.gov (United States)

    Ahmadi, Amir; Stone, Gregg W; Leipsic, Jonathon; Shaw, Leslee J; Villines, Todd C; Kern, Morton J; Hecht, Harvey; Erlinge, David; Ben-Yehuda, Ori; Maehara, Akiko; Arbustini, Eloisa; Serruys, Patrick; Garcia-Garcia, Hector M; Narula, Jagat

    2016-07-08

    Risk stratification in patients with stable ischemic heart disease is essential to guide treatment decisions. In this regard, whether coronary anatomy, physiology, or plaque morphology is the best determinant of prognosis (and driver an effective therapeutic risk reduction) remains one of the greatest ongoing debates in cardiology. In the present report, we review the evidence for each of these characteristics and explore potential algorithms that may enable a practical diagnostic and therapeutic strategy for the management of patients with stable ischemic heart disease. © 2016 American Heart Association, Inc.

  4. Identification of stable normalization genes for quantitative real-time PCR in porcine articular cartilage.

    Science.gov (United States)

    McCulloch, Ryan S; Ashwell, Melissa S; O'Nan, Audrey T; Mente, Peter L

    2012-11-12

    Expression levels for genes of interest must be normalized with an appropriate reference, or housekeeping gene, to make accurate comparisons of quantitative real-time PCR results. The purpose of this study was to identify the most stable housekeeping genes in porcine articular cartilage subjected to a mechanical injury from a panel of 10 candidate genes. Ten candidate housekeeping genes were evaluated in three different treatment groups of mechanically impacted porcine articular cartilage. The genes evaluated were: beta actin, beta-2-microglobulin, glyceraldehyde-3-phosphate dehydrogenase, hydroxymethylbilane synthase, hypoxanthine phosphoribosyl transferase, peptidylprolyl isomerase A (cyclophilin A), ribosomal protein L4, succinate dehydrogenase flavoprotein subunit A, TATA box binding protein, and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein-zeta polypeptide. The stability of the genes was measured using geNorm, BestKeeper, and NormFinder software. The four most stable genes measured via geNorm were (most to least stable) succinate dehydrogenase flavoprotein, subunit A, peptidylprolyl isomerase A, glyceraldehyde-3-phosphate dehydrogenase, beta actin; the four most stable genes measured via BestKeeper were glyceraldehyde-3-phosphate dehydrogenase, peptidylprolyl isomerase A, beta actin, succinate dehydrogenase flavoprotein, subunit A; and the four most stable genes measured via NormFinder were peptidylprolyl isomerase A, succinate dehydrogenase flavoprotein, subunit A, glyceraldehyde-3-phosphate dehydrogenase, beta actin. BestKeeper, geNorm, and NormFinder all generated similar results for the most stable genes in porcine articular cartilage. The use of these appropriate reference genes will facilitate accurate gene expression studies of porcine articular cartilage and suggest appropriate housekeeping genes for articular cartilage studies in other species.

  5. Thermodynamically stable amyloid-β monomers have much lower membrane affinity than the small oligomers

    Directory of Open Access Journals (Sweden)

    Bidyut eSarkar

    2013-04-01

    Full Text Available Amyloid beta (Aβ is an extracellular 39-43 residue long peptide present in the mammalian cerebrospinal fluid, whose aggregation is associated with Alzheimer’s disease. Small oligomers of Aβ are currently thought to be the key to toxicity. However, it is not clear why the monomers of Aβ are non-toxic, and at what stage of aggregation toxicity emerges. Interactions of Aβ with cell membranes is thought to be the initiator of toxicity, but membrane-binding studies with different preparations of monomers and oligomers have not settled this issue. We have earlier found that thermodynamically stable Aβ monomers emerge spontaneously from oligomeric mixtures upon long term incubation in physiological solutions (Nag et al, JBC, 2011. Here we show that the membrane-affinity of these stable Aβ monomers is much lower than that of a mixture of small oligomers (containing dimers to decamers, providing a clue to the emergence of toxicity. Fluorescently labeled Aβ40 monomers show negligible binding to cell membranes of a neuronal cell line (RN46A at physiological concentrations (250 nM, while oligomers at the same concentrations show strong binding within 30 minutes of incubation. The increased affinity most likely does not require any specific neuronal receptor, since this difference in membrane-affinity was also observed in a somatic cell-line (HEK 293T. Similar results are also obtained for Aβ42 monomers and oligomers. Minimal amount of cell death is observed at these concentrations even after 36 hours of incubation. It is likely that membrane binding precedes subsequent slower toxic events induced by Aβ. Our results a provide an explanation for the non-toxic nature of Aβ monomers, b suggest that Aβ toxicity emerges at the initial oligomeric phase, and c provide a quick assay for monitoring the benign-to-toxic transformation of Aβ.

  6. 2[125I]Iodomelatonin binding sites in spleens of guinea pigs

    International Nuclear Information System (INIS)

    Poon, A.M.S.; Pang, S.F.

    1992-01-01

    2-[ 125 I]Iodomelatonin was found to bind specifically to the membrane preparations of the spleens of guinea pigs with high affinity. The binding was rapid, stable, saturable and reversible. Scatchard analysis of the binding assays revealed an equilibrium dissociation constant (Kd) of 49.8±4.12 pmol/l and binding site density (Bmax) of 0.69±0.082 fmol/mg protein at mid-light. There was no significant change in the Kd or the Bmax at mid-dark. Kinetic analysis showed a Kd of 23.13±4.81 pmol/l, in agreement to that derived from the saturation studies. The 2-[ 125 I]iodomelatonin binding sites have the following order of potency: 2-iodomelatonin > melatonin > 6-chloromelatonin much-gt N-acetylserotonin, 6-hydroxymelatonin > 5-methoxytryptamine, 5-methoxytryptophol > serotonin, 5-methoxyindole-3-acetic acid > 5-hydroxytryptophol, 3-acetylindole, 1-acetylindole-3-carboxyaldehyde, L-tryptophan > tryptamine, 5-hydroxyindole-3-acetic acid. Differential centrifugation studies showed that the binding sites are localized mainly in the nuclear fraction, the rest are distributed in the microsomal fraction, mitochondrial fraction and cytosolic fraction. The demonstration of 2-[ 125 I]iodomelatonin binding sites in the spleen suggests the presence of melatonin receptors and a direct mechanism of action of melatonin on the immune system

  7. A microcalorimetry and binding study on interaction of dodecyl trimethylammonium bromide with wigeon hemoglobin

    International Nuclear Information System (INIS)

    Bordbar, A.K.; Moosavi-Movahedi, A.A.; Amini, M.K.

    2003-01-01

    The thermodynamic parameters for the binding of dodecyl trimethylammonium bromide (DTAB) with wigeon hemoglobin (Hb) in aqueous solution at various pH and 27 deg. C have been measured by equilibrium dialysis and titration microcalorimetry techniques. The Scatchard plots represent unusual features at neutral and alkaline pH and specific binding at acidic pH. This leads us to analyze the binding data by fitting the data to the Hill equation for multiclasses of binding sites. The best fit was obtained with the equation for one class at acidic pH and two classes at neutral and alkaline pH. The thermodynamic analysis of the binding process shows that the strength of binding at neutral pH is more than these at other pH values. This can be related to the more accessible hydrophobic surface area of wigeon hemoglobin at this pH. The endothermic enthalpy data which was measured by microcalorimetry confirms the binding data analysis and represents the more regular and stable structure of wigeon hemoglobin at neutral pH

  8. Glucose tolerance, insulin release, and insulin binding to monocytes in kidney transplant recipients

    International Nuclear Information System (INIS)

    Briggs, W.A.; Wielechowski, K.S.; Mahajan, S.K.; Migdal, S.D.; McDonald, F.D.

    1982-01-01

    In order to evaluate glucose tolerance following renal transplantation, intravenous glucose tolerance tests (IVGTT), with evaluation of hormonal responses to the intravenous glucose load and percent specific 125 I-insulin binding to peripheral blood monocytes, were studied in eight clinically stable kidney transplant recipients. For comparison purposes, identical studies were done in eight control subjects and seven clinically stable hemodialysis patients. One transplant recipient was glucose intolerant, with fasting hyperglycemia, elevated HbA1C, and abnormal glucose decay constant. Impaired pancreatic insulin release appeared to be the major factor accounting for his glucose intolerance. The seven glucose-tolerant transplant recipients had significantly increased insulin release during IVGTT compared to control subjects, and significant correlations were found among insulin release, glucose decay constant, and fasting blood sugar in those patients. Insulin binding to monocytes was significantly greater in transplant recipients than control subjects due to an increase in insulin binding capacity per cell. A significant correlation was found between percent specific 125 I-insulin binding and steroid dose, expressed as mg/kg body weight/day, in those patients. Thus, chronic steroid administration does not cause glucose intolerance in transplant recipients who manifest steroid-associated increases in pancreatic insulin release and cellular insulin binding capacity

  9. Microbiological characterization of stable resuspended dust

    Directory of Open Access Journals (Sweden)

    Nora Kováts

    2016-06-01

    Full Text Available Objectives: Air quality in the stables is characterized by elevated level of dust and aeroallergens which are supposed to directly cause or exacerbate several respiratory disorders. The most often recognized problem is recurrent airway obstruction (RAO, previously known as chronic obstructive pulmonary disease (COPD. There is some indication that aeroallergens (among them endotoxins may also cause inflammation in human airways and may exceed safe levels in stables. Monitoring studies have covered mainly the determination of the concentration of respirable particles and of culturable fungi and their toxins. However, these particles do not only directly affect the respiratory system, but might act as a carrier conveying toxic contaminants and biological agents such as bacteria. In a typical, 20-horse Hungarian stable, microbial community of respirable fraction of resuspended dust has been characterized to reveal if these particles convey hazardous pathogenic bacteria, posing risk to either horses or staff. Material and Methods: Resuspended dust was sampled using a mobile instrument. The instrument contains a PARTISOL-FRM model 2000 sampler that was operated at a flow rate of 16.7 l/min and a cyclone separator which collected the particulate matter with an aerodynamic size between 1 μm and 10 μm (PM1–10 fraction. Microbial taxa were identified by culture-independent next generation sequencing (NGS of variable 16S ribosomal ribonucleic acid (rRNA gene regions. Results: In total, 1491 different taxa were identified, of them 384 were identified to species level, 961 to genus level. The sample was dominated by common ubiquitous soil and organic material-dwelling taxa. Conclusions: Pathogens occurred at low abundance, and were represented by mostly facultative human pathogens, with the prevalence of Staphylococcus species.

  10. Stable channel of reclaimed tidal lowland

    Science.gov (United States)

    Syarifudin, Achmad; Imanuddin, Momon S.; Moerwanto, Arie S.; Suryadi, F. X.

    2017-11-01

    This study aimed to develop models of the Operation and Maintenance in the reclaimed tidal marsh area to get a stable channel. The research location is reclaimed tidal delta area Telang I Primary 8 representing land typology A/B and a survey conducted in 13 South Secondary Schemes following existing tertiary Telang I. MIKE - 11 computer models used used to analyze the movement of sediment in the channel in both the Primary channel 8, SPD, SDU and tertiary channels in block 13 South. Calibration model with multiple channels in the field of physical parameters has been performed to obtain results close to the results of measurement modeling sediment movement in the channel. The integration models of MIKE - 11 models with various scenarios are used to model the operation and maintenance of the channel in the tidal marsh area to get a stable channel. According to the scheme P8 - 13S, OM models obtained 75 percent, in which the secondary channel (SPD/SDU) and built flap gate in tertiary channel, get a well prototype model of the stable channel (equilibriums), where the average erosion on P8 at a distance of 3,200 m in the amount of 4,472,049 m3 and the mean sedimentation in the SPD of 963,836 m3 and mean of sedimentation in the tertiary channel of 3,508,213 m3. Similarly, on average erosion P8 by 4,135,649 m3 and the mean sedimentation in the SDU of 681,304 m3 and the mean sedimentation in the tertiary channel of 3,454,345 m3.

  11. Computational exploration of a protein receptor binding space with student proposed peptide ligands.

    Science.gov (United States)

    King, Matthew D; Phillips, Paul; Turner, Matthew W; Katz, Michael; Lew, Sarah; Bradburn, Sarah; Andersen, Tim; McDougal, Owen M

    2016-01-01

    Computational molecular docking is a fast and effective in silico method for the analysis of binding between a protein receptor model and a ligand. The visualization and manipulation of protein to ligand binding in three-dimensional space represents a powerful tool in the biochemistry curriculum to enhance student learning. The DockoMatic tutorial described herein provides a framework by which instructors can guide students through a drug screening exercise. Using receptor models derived from readily available protein crystal structures, docking programs have the ability to predict ligand binding properties, such as preferential binding orientations and binding affinities. The use of computational studies can significantly enhance complimentary wet chemical experimentation by providing insight into the important molecular interactions within the system of interest, as well as guide the design of new candidate ligands based on observed binding motifs and energetics. In this laboratory tutorial, the graphical user interface, DockoMatic, facilitates docking job submissions to the docking engine, AutoDock 4.2. The purpose of this exercise is to successfully dock a 17-amino acid peptide, α-conotoxin TxIA, to the acetylcholine binding protein from Aplysia californica-AChBP to determine the most stable binding configuration. Each student will then propose two specific amino acid substitutions of α-conotoxin TxIA to enhance peptide binding affinity, create the mutant in DockoMatic, and perform docking calculations to compare their results with the class. Students will also compare intermolecular forces, binding energy, and geometric orientation of their prepared analog to their initial α-conotoxin TxIA docking results. © 2015 The International Union of Biochemistry and Molecular Biology.

  12. Aggressive Fibromatosis: Evidence for a Stable Phase

    Directory of Open Access Journals (Sweden)

    Gillian Mitchell

    1998-01-01

    Full Text Available Purpose. Aggressive fibromatosis (AF is an uncommon locally infiltrating benign disease of soft tissue for which treatment comprises complete surgical resection. Radiotherapy can be given postoperatively if the margin is incompletely resected. If the tumour is inoperable radiotherapy provides an alternative treatment. Hormone therapy and cytotoxic chemotherapy have also been used for unresectable or recurrent disease. All treatment modalities carry an associated morbidity. We believe that the natural history of aggressive fibromatosis may include a period of stable disease without progression, during which time, treatment is not always necessary.

  13. Stable isogeometric analysis of trimmed geometries

    Science.gov (United States)

    Marussig, Benjamin; Zechner, Jürgen; Beer, Gernot; Fries, Thomas-Peter

    2017-04-01

    We explore extended B-splines as a stable basis for isogeometric analysis with trimmed parameter spaces. The stabilization is accomplished by an appropriate substitution of B-splines that may lead to ill-conditioned system matrices. The construction for non-uniform knot vectors is presented. The properties of extended B-splines are examined in the context of interpolation, potential, and linear elasticity problems and excellent results are attained. The analysis is performed by an isogeometric boundary element formulation using collocation. It is argued that extended B-splines provide a flexible and simple stabilization scheme which ideally suits the isogeometric paradigm.

  14. 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)

  15. Ligand binding by PDZ domains

    DEFF Research Database (Denmark)

    Chi, Celestine N.; Bach, Anders; Strømgaard, Kristian

    2012-01-01

    The postsynaptic density protein-95/disks large/zonula occludens-1 (PDZ) protein domain family is one of the most common protein-protein interaction modules in mammalian cells, with paralogs present in several hundred human proteins. PDZ domains are found in most cell types, but neuronal proteins...... as pathological conditions have been reviewed recently. In this review, we focus on the molecular details of how PDZ domains bind their protein ligands and their potential as drug targets in this context....

  16. Binding energy of protonium ions

    Science.gov (United States)

    Assad Abdel-Raouf, Mohamed

    2009-11-01

    The goal of the present work is to calculate the binding energy of the protonium ions bar PPe+ and bar PPe- using Rayleigh- Ritz variational method. It is indicated that an employment of 21 components of the trial wavefunction yields -0.08793 eV as the ground state energy of these ions. Our result agrees quite well with recently obtained results based on elaborate Monte Carlo approximations. It confirms the possible formation of these ions in laboratory.

  17. Material Binding Peptides for Nanotechnology

    Directory of Open Access Journals (Sweden)

    Urartu Ozgur Safak Seker

    2011-02-01

    Full Text Available Remarkable progress has been made to date in the discovery of material binding peptides and their utilization in nanotechnology, which has brought new challenges and opportunities. Nowadays phage display is a versatile tool, important for the selection of ligands for proteins and peptides. This combinatorial approach has also been adapted over the past decade to select material-specific peptides. Screening and selection of such phage displayed material binding peptides has attracted great interest, in particular because of their use in nanotechnology. Phage display selected peptides are either synthesized independently or expressed on phage coat protein. Selected phage particles are subsequently utilized in the synthesis of nanoparticles, in the assembly of nanostructures on inorganic surfaces, and oriented protein immobilization as fusion partners of proteins. In this paper, we present an overview on the research conducted on this area. In this review we not only focus on the selection process, but also on molecular binding characterization and utilization of peptides as molecular linkers, molecular assemblers and material synthesizers.

  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. Remarks on stable and quasi-stable k-strings at large N

    International Nuclear Information System (INIS)

    Armoni, A.; Shifman, M.

    2003-01-01

    We discuss k-strings in the large-N Yang-Mills theory and its supersymmetric extension. Whereas the tension of the bona fide (stable) QCD string is expected to depend only on the N-ality of the representation, tensions that depend on specific representation R are often reported in the lattice literature. In particular, adjoint strings are discussed and found in certain simulations. We clarify this issue by systematically exploiting the notion of the quasi-stable strings which becomes well-defined at large N. The quasi-stable strings with representation-dependent tensions decay, but the decay rate (per unit length per unit time) is suppressed as Λ 2 F(N) where F(N) falls off as a function of N. It can be determined on the case-by-case basis. The quasi-stable strings eventually decay into stable strings whose tension indeed depends only on the N-ality. We also briefly review large-N arguments showing why the Casimir formula for the string tension cannot be correct, and present additional arguments in favor of the sine formula. Finally, we comment on the relevance of our estimates to Euclidean lattice measurements

  2. Performance of Alpine Touring Boots When Used in Alpine Ski Bindings.

    Science.gov (United States)

    Campbell, Jeffrey R; Scher, Irving S; Carpenter, David; Jahnke, Bruce L; Ching, Randal P

    2017-10-01

    Alpine touring (AT) equipment is designed for ascending mountains and snow skiing down backcountry terrain. Skiers have been observed using AT boots in alpine (not made for Alpine Touring) ski bindings. We tested the effect on the retention-release characteristics of AT boots used in alpine bindings. Ten AT ski boots and 5 alpine ski boots were tested in 8 models of alpine ski bindings using an ASTM F504-05 (2012) apparatus. Thirty-one percent of the AT boots released appropriately when used in alpine ski bindings. One alpine binding released appropriately for all alpine and AT boots tested; 2 alpine ski bindings did not release appropriately for any AT boots. Altering the visual indicator settings on the bindings (that control the release torque of an alpine system) had little or no effect on the release torque when using AT boots in alpine ski bindings. Many combinations released appropriately in ski shop tests, but did not release appropriately in the more complex loading cases that simulated forward and backward falls; the simple tests performed by ski shops could produce a "false-negative" test result. These results indicate that using AT boots with alpine ski bindings could increase the likelihood of lower leg injuries.

  3. Heavy metals binding properties of esterified lemon

    International Nuclear Information System (INIS)

    Arslanoglu, Hasan; Altundogan, Hamdi Soner; Tumen, Fikret

    2009-01-01

    Sorption of Cd 2+ , Cr 3+ , Cu 2+ , Ni 2+ , Pb 2+ and Zn 2+ onto a carboxyl groups-rich material prepared from lemon was investigated in batch systems. The results revealed that the sorption is highly pH dependent. Sorption kinetic data indicated that the equilibrium was achieved in the range of 30-240 min for different metal ions and sorption kinetics followed the pseudo-second-order model for all metals studied. Relative sorption rate of various metal cations was found to be in the general order of Ni 2+ > Cd 2+ > Cu 2+ > Pb 2+ > Zn 2+ > Cr 3+ . The binding characteristics of the sorbent for heavy metal ions were analyzed under various conditions and isotherm data was accurately fitted to the Langmuir equation. The metal binding capacity order calculated from Langmuir isotherm was Pb 2+ > Cu 2+ > Ni 2+ > Cd 2+ > Zn 2+ > Cr 3+ . The mean free energy of metal sorption process calculated from Dubinin-Radushkevich parameter and the Polanyi potential was found to be in the range of 8-11 kJ mol -1 for the metals studied showing that the main mechanism governing the sorption process seems to be ion exchange. The basic thermodynamic parameters of metals ion sorption process were calculated by using the Langmuir constants obtained from equilibration study. The ΔG o and ΔH o values for metals ion sorption on the lemon sorbent showed the process to be spontaneous and exothermic in nature. Relatively low ΔH o values revealed that physical adsorption significantly contributed to the mechanism.

  4. Heavy metals binding properties of esterified lemon.

    Science.gov (United States)

    Arslanoglu, Hasan; Altundogan, Hamdi Soner; Tumen, Fikret

    2009-05-30

    Sorption of Cd(2+), Cr(3+), Cu(2+), Ni(2+), Pb(2+) and Zn(2+) onto a carboxyl groups-rich material prepared from lemon was investigated in batch systems. The results revealed that the sorption is highly pH dependent. Sorption kinetic data indicated that the equilibrium was achieved in the range of 30-240 min for different metal ions and sorption kinetics followed the pseudo-second-order model for all metals studied. Relative sorption rate of various metal cations was found to be in the general order of Ni(2+)>Cd(2+)>Cu(2+)>Pb(2+)>Zn(2+)>Cr(3+). The binding characteristics of the sorbent for heavy metal ions were analyzed under various conditions and isotherm data was accurately fitted to the Langmuir equation. The metal binding capacity order calculated from Langmuir isotherm was Pb(2+)>Cu(2+)>Ni(2+)>Cd(2+)>Zn(2+)>Cr(3+). The mean free energy of metal sorption process calculated from Dubinin-Radushkevich parameter and the Polanyi potential was found to be in the range of 8-11 kJ mol(-1) for the metals studied showing that the main mechanism governing the sorption process seems to be ion exchange. The basic thermodynamic parameters of metals ion sorption process were calculated by using the Langmuir constants obtained from equilibration study. The DeltaG degrees and DeltaH degrees values for metals ion sorption on the lemon sorbent showed the process to be spontaneous and exothermic in nature. Relatively low DeltaH degrees values revealed that physical adsorption significantly contributed to the mechanism.

  5. Heavy metals binding properties of esterified lemon

    Energy Technology Data Exchange (ETDEWEB)

    Arslanoglu, Hasan; Altundogan, Hamdi Soner [Department of Chemical Engineering, Firat University, 23279 Elazig (Turkey); Tumen, Fikret, E-mail: ftumen@firat.edu.tr [Department of Chemical Engineering, Firat University, 23279 Elazig (Turkey)

    2009-05-30

    Sorption of Cd{sup 2+}, Cr{sup 3+}, Cu{sup 2+}, Ni{sup 2+}, Pb{sup 2+} and Zn{sup 2+} onto a carboxyl groups-rich material prepared from lemon was investigated in batch systems. The results revealed that the sorption is highly pH dependent. Sorption kinetic data indicated that the equilibrium was achieved in the range of 30-240 min for different metal ions and sorption kinetics followed the pseudo-second-order model for all metals studied. Relative sorption rate of various metal cations was found to be in the general order of Ni{sup 2+} > Cd{sup 2+} > Cu{sup 2+} > Pb{sup 2+} > Zn{sup 2+} > Cr{sup 3+}. The binding characteristics of the sorbent for heavy metal ions were analyzed under various conditions and isotherm data was accurately fitted to the Langmuir equation. The metal binding capacity order calculated from Langmuir isotherm was Pb{sup 2+} > Cu{sup 2+} > Ni{sup 2+} > Cd{sup 2+} > Zn{sup 2+} > Cr{sup 3+}. The mean free energy of metal sorption process calculated from Dubinin-Radushkevich parameter and the Polanyi potential was found to be in the range of 8-11 kJ mol{sup -1} for the metals studied showing that the main mechanism governing the sorption process seems to be ion exchange. The basic thermodynamic parameters of metals ion sorption process were calculated by using the Langmuir constants obtained from equilibration study. The {Delta}G{sup o} and {Delta}H{sup o} values for metals ion sorption on the lemon sorbent showed the process to be spontaneous and exothermic in nature. Relatively low {Delta}H{sup o} values revealed that physical adsorption significantly contributed to the mechanism.

  6. Stable nanoconjugates of transferrin with alloyed quaternary nanocrystals Ag-In-Zn-S as a biological entity for tumor recognition.

    Science.gov (United States)

    Matysiak-Brynda, Edyta; Bujak, Piotr; Augustin, Ewa; Kowalczyk, Agata; Mazerska, Zofia; Pron, Adam; Nowicka, Anna M

    2018-01-18

    One way to limit the negative effects of anti-tumor drugs on healthy cells is targeted therapy employing functionalized drug carriers. Here we present a biocompatible and stable nanoconjugate of transferrin anchored to Ag-In-Zn-S quantum dots modified with 11-mercaptoundecanoic acid (Tf-QD) as a drug carrier versus typical anticancer drug, doxorubicin. Detailed investigations of Tf-QD nanoconjugates without and with doxorubicin by fluorescence studies and cytotoxic measurements showed that the biological activity of both the transferrin and doxorubicin was fully retained in the nanoconjugate. In particular, the intercalation capabilities of free doxorubicin versus ctDNA remained essentially intact upon its binding to the nanoconjugate. In order to evaluate these capabilities, we studied the binding constant of doxorubicin attached to Tf-QDs with ctDNA as well as the binding site size on the ctDNA molecule. The binding constant slightly decreased compared to that of free doxorubicin while the binding site size, describing the number of consecutive DNA lattice residues involved in the binding, increased. It was also demonstrated that the QDs alone and in the form of a nanoconjugate with Tf were not cytotoxic towards human non-small cell lung carcinoma (H460 cell line) and the tumor cell sensitivity of the DOX-Tf-QD nanoconjugate was comparable to that of doxorubicin alone.

  7. Multivariate Max-Stable Spatial Processes

    KAUST Repository

    Genton, Marc G.

    2014-01-06

    Analysis of spatial extremes is currently based on univariate processes. Max-stable processes allow the spatial dependence of extremes to be modelled and explicitly quantified, they are therefore widely adopted in applications. For a better understanding of extreme events of real processes, such as environmental phenomena, it may be useful to study several spatial variables simultaneously. To this end, we extend some theoretical results and applications of max-stable processes to the multivariate setting to analyze extreme events of several variables observed across space. In particular, we study the maxima of independent replicates of multivariate processes, both in the Gaussian and Student-t cases. Then, we define a Poisson process construction in the multivariate setting and introduce multivariate versions of the Smith Gaussian extremevalue, the Schlather extremal-Gaussian and extremal-t, and the BrownResnick models. Inferential aspects of those models based on composite likelihoods are developed. We present results of various Monte Carlo simulations and of an application to a dataset of summer daily temperature maxima and minima in Oklahoma, U.S.A., highlighting the utility of working with multivariate models in contrast to the univariate case. Based on joint work with Simone Padoan and Huiyan Sang.

  8. Stable states in a strong IR field

    Science.gov (United States)

    Zhong, Changchun; Robicheaux, Francis

    2015-05-01

    It is found that 10% of atoms stay in the quasi-stable states after being exposed to intense laser or microwave (MW) pulses, even though the pulses' intensity is much stronger than that needed for static fields ionization. The reason why atoms survive those strong pulses has attracted growing attentions. A. Arakelyan et al. have observed the optical spectra of the surviving Lithium atoms after interaction with intense 38-GHz MW fields for more than 1000 cycles, and the spectra exhibit a periodic train of peaks 38 GHz apart. It suggests that those weakly bound Rydberg electrons seldom go back to the ionic core, where the cycle average energy exchange happens. In this study, we are interested in the electron behavior in the presence of intense infrared fields with a much shorter wavelength (1000 nm). By solving the full 3D time dependent Schrodinger equation, we calculate the spectra of the surviving atoms under intense IR fields. Our numerical calculations show atoms survive the intense field in quasi-stable states for a long time, and the optical spectra are obviously modulated by the IR frequency. Through tuning the ponderomotive energy, we see how field parameters affect the behavior of electrons. Different atoms, such as Hydrogen, Helium, Lithium, and Sodium, are tested to see how atom's energy structures influence the results.

  9. Color stable manganese-doped phosphors

    Science.gov (United States)

    Lyons, Robert Joseph [Burnt Hills, NY; Setlur, Anant Achyut [Niskayuna, NY; Deshpande, Anirudha Rajendra [Twinsburg, OH; Grigorov, Ljudmil Slavchev [Sofia, BG

    2012-08-28

    A process for preparing color stable Mn.sup.+4 doped phosphors includes providing a phosphor of formula I; A.sub.x[MF.sub.y]:Mn.sup.+4 I and contacting the phosphor in particulate form with a saturated solution of a composition of formula II in aqueous hydrofluoric acid; A.sub.x[MF.sub.y]; II wherein A is Li, Na, K, Rb, Cs, NR.sub.4 or a combination thereof; M is Si, Ge, Sn, Ti, Zr, Al, Ga, In, Sc, Y, La, Nb, Ta, Bi, Gd, or a combination thereof; R is H, lower alkyl, or a combination thereof; x is the absolute value of the charge of the [MF.sub.y] ion; and y is 5, 6 or 7. In particular embodiments, M is Si, Ge, Sn, Ti, Zr, or a combination thereof. A lighting apparatus capable of emitting white light includes a semiconductor light source; and a phosphor composition radiationally coupled to the light source, and which includes a color stable Mn.sup.+4 doped phosphor.

  10. Binding, tuning and mechanical function of the 4-hydroxy-cinnamic acid chromophore in photoactive yellow protein.

    NARCIS (Netherlands)

    van der Horst, M.A.; Arents, J.C.; Kort, R.; Hellingwerf, K.J.

    2007-01-01

    The bacterial photoreceptor protein photoactive yellow protein (PYP) covalently binds the chromophore 4-hydroxy-cinnamic acid, tuning (spectral) characteristics of this cofactor. Here, we study this binding and tuning using a combination of pointmutations and chromophore analogs. In all photosensor

  11. 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

  12. Lactoferrin binding molecules in human seminal plasma.

    Science.gov (United States)

    Thaler, C J; Vanderpuye, O A; McIntyre, J A; Faulk, W P

    1990-10-01

    During ejaculation, the iron binding protein lactoferrin binds to sperm and forms a major component of sperm-coating antigens. Physicochemical properties of lactoferrin in seminal plasma (SP) and on sperm differ from those of purified lactoferrin. These differences have been attributed to the binding of unknown seminal macromolecules to lactoferrin. We have studied lactoferrin binding molecules in SP. The SP samples were coated onto microtiter plates and tested for binding of biotinylated lactoferrin. SP was found to specifically bind biotinylated lactoferrin. This binding was competitively inhibited by coincubation with unlabeled lactoferrin but was not affected by control incubations done with human IgG or transferrin. Lactoferrin binding molecules in SP were biochemically characterized by using SDS-PAGE and ligand blotting. Biotinylated lactoferrin bound to SP molecules of approximately 120, 60 and 30 kDa. No binding was observed with biotinylated transferrin. The presence of molecules that associate with lactoferrin in SP was further studied by using crossed immunoelectrophoresis. Lactoferrin in SP immunoprecipitated as two peaks, one of which corresponded to purified lactoferrin. These results suggest that some lactoferrin molecules in SP are free and that others are associated with lactoferrin binding molecules. Binding of lactoferrin to lactoferrin binding molecules appears to change its physicochemical properties and thus could influence its biologic activity and its affinity to sperm.

  13. Acyl-coenzyme A binding protein (ACBP)

    DEFF Research Database (Denmark)

    Kragelund, B B; Knudsen, J; Poulsen, F M

    1999-01-01

    Acyl-coenzyme A binding proteins are known from a large group of eukaryote species and to bind a long chain length acyl-CoA ester with very high affinity. Detailed biochemical mapping of ligand binding properties has been obtained as well as in-depth structural studies on the bovine apo-protein a...

  14. Polymeric competitive protein binding adsorbents for radioassay

    International Nuclear Information System (INIS)

    Adams, R.J.

    1976-01-01

    Serum protein comprising specific binding proteins such as antibodies, B 12 intrinsic factor, thyroxin binding globulin and the like may be copolymerized with globulin constituents of serum by the action of ethylchloroformate to form readily packed insoluble precipitates which, following purification as by washing, are eminently suited for employment as competitive binding protein absorbents in radioassay procedures. 10 claims, no drawings

  15. The Production of a Stable Infliximab Powder: The Evaluation of Spray and Freeze-Drying for Production

    Science.gov (United States)

    Kanojia, Gaurav; Have, Rimko ten; Bakker, Arjen; Wagner, Koen; Frijlink, Henderik W.; Kersten, Gideon F. A.; Amorij, Jean-Pierre

    2016-01-01

    In prospect of developing an oral dosage form of Infliximab, for treatment of Crohn’s disease and rheumatoid arthritis, freeze-drying (vial vs Lyoguard trays) and spray-drying were investigated as production method for stable powders. Dextran and inulin were used in combination with sucrose as stabilizing excipients. The drying processes did not affect Infliximab in these formulations, i.e. both the physical integrity and biological activity (TNF binding) were retained. Accelerated stability studies (1 month at 60°C) showed that the TNF binding ability of Infliximab was conserved in the freeze-dried formulations, whereas the liquid counterpart lost all TNF binding. After thermal treatment, the dried formulations showed some chemical modification of the IgG in the dextran-sucrose formulation, probably due to Maillard reaction products. This study indicates that, with the appropriate formulation, both spray-drying and freeze-drying may be useful for (bulk) powder production of Infliximab. PMID:27706175

  16. The 5'HS2 of the globin locus control region enhances transcription through the interaction of a multimeric complex binding at two functionally distinct NF-E2 binding sites.

    NARCIS (Netherlands)

    D. Talbot; F.G. Grosveld (Frank)

    1991-01-01

    textabstractThe locus control region (LCR) of the human beta-globin locus consists of four hypersensitive regions (5'HS 1-4). One of these sites, 5'HS2, is active in both transient and stable transfection assays and transgenic mice. It has previously been shown that the jun/fos consensus binding

  17. Poor correspondence between predicted and experimental binding of peptides to class I MHC molecules

    DEFF Research Database (Denmark)

    Andersen, Mads Hald; Tan, L.; Søndergaard, Ib

    2000-01-01

    Naturally processed peptides presented by class I major histocompatibility complex (MHC) molecules display a characteristic allele specific motif of two or more essential amino acid side chains, the so-called peptide anchor residues, in the context of an 8-10 amino acid long peptide. Knowledge...... of the peptide binding motif of individual class I MHC molecules permits the selection of potential peptide antigens from proteins of infectious organisms that could induce protective T-cell-mediated immunity. Several methods have been developed for the prediction of potential class I MHC binding peptides. One...... of peptide binding motifs for individual class I MHC molecules. The actual binding was compared with the results obtained when analyzing the same peptides by two well-known, publicly available computer algorithms. We conclude that there is no strong correlation between actual and predicted binding when using...

  18. Binding and thermodynamics of REV peptide-ctDNA interaction.

    Science.gov (United States)

    Upadhyay, Santosh Kumar

    2017-03-01

    The thermodynamics of DNA-ligand binding is important as it provides useful information to understand the details of binding processes. HIV-1 REV response element (RRE) located in the env coding region of the viral genome is reported to be well conserved across different HIV-1 isolates. In this study, the binding characteristics of Calf thymus DNA (ctDNA) and REV peptide from HIV-1 were investigated using spectroscopic (UV-visible, fluorescence, and circular dichroism (CD)) and isothermal titration calorimetric (ITC) techniques. Thermal stability and ligand binding properties of the ctDNA revealed that native ctDNA had a T m of 75.5 °C, whereas the ctDNA-REV peptide complex exhibited an incremental shift in the T m by 8 °C, indicating thermal stability of the complex. CD data indicated increased ellipticity due to large conformational changes in ctDNA molecule upon binding with REV peptide and two binding stoichiometric modes are apparent. The ctDNA experienced condensation due to large conformational changes in the presence of REV peptide and positive B→Ψ transition was observed at higher molar charge ratios. Fluorescence studies performed at several ligand concentrations revealed a gradual decrease in the fluorescence intensity of EtBr-bound ctDNA in response to increasing ligand concentrations. The fluorescence data further confirmed two stoichiometric modes of binding for ctDNA-REV peptide complex as previously observed with CD studies. The binding enthalpies were determined using ITC in the temperature range of 293 K-308 K. The ITC binding isotherm was exothermic at all temperatures examined, with low ΔH values indicating that the ctDNA-REV peptide interaction is driven largely by entropy. The heat capacity change (ΔC p ) was insignificant, an unusual finding in the area of DNA-peptide interaction studies. The variation in the values obtained for ΔH, ΔS, and ΔG with temperature further suggests that ctDNA-REV peptide interaction is entropically

  19. Mathematical description of drug-target interactions: application to biologics that bind to targets with two binding sites.

    Science.gov (United States)

    Gibiansky, Leonid; Gibiansky, Ekaterina

    2018-02-01

    The emerging discipline of mathematical pharmacology occupies the space between advanced pharmacometrics and systems biology. A characteristic feature of the approach is application of advance mathematical methods to study the behavior of biological systems as described by mathematical (most often differential) equations. One of the early application of mathematical pharmacology (that was not called this name at the time) was formulation and investigation of the target-mediated drug disposition (TMDD) model and its approximations. The model was shown to be remarkably successful, not only in describing the observed data for drug-target interactions, but also in advancing the qualitative and quantitative understanding of those interactions and their role in pharmacokinetic and pharmacodynamic properties of biologics. The TMDD model in its original formulation describes the interaction of the drug that has one binding site with the target that also has only one binding site. Following the framework developed earlier for drugs with one-to-one binding, this work aims to describe a rigorous approach for working with similar systems and to apply it to drugs that bind to targets with two binding sites. The quasi-steady-state, quasi-equilibrium, irreversible binding, and Michaelis-Menten approximations of the model are also derived. These equations can be used, in particular, to predict concentrations of the partially bound target (RC). This could be clinically important if RC remains active and has slow internalization rate. In this case, introduction of the drug aimed to suppress target activity may lead to the opposite effect due to RC accumulation.

  20. Estimation of Time-Varying Autoregressive Symmetric Alpha Stable

    Data.gov (United States)

    National Aeronautics and Space Administration — In the last decade alpha-stable distributions have become a standard model for impulsive data. Especially the linear symmetric alpha-stable processes have found...

  1. Synthesis and characterization of DNA minor groove binding alkylating agents.

    Science.gov (United States)

    Iyer, Prema; Srinivasan, Ajay; Singh, Sreelekha K; Mascara, Gerard P; Zayitova, Sevara; Sidone, Brian; Fouquerel, Elise; Svilar, David; Sobol, Robert W; Bobola, Michael S; Silber, John R; Gold, Barry

    2013-01-18

    Derivatives of methyl 3-(1-methyl-5-(1-methyl-5-(propylcarbamoyl)-1H-pyrrol-3-ylcarbamoyl)-1H-pyrrol-3-ylamino)-3-oxopropane-1-sulfonate (1), a peptide-based DNA minor groove binding methylating agent, were synthesized and characterized. In all cases, the N-terminus was appended with an O-methyl sulfonate ester, while the C-terminus group was varied with nonpolar and polar side chains. In addition, the number of pyrrole rings was varied from 2 (dipeptide) to 3 (tripeptide). The ability of the different analogues to efficiently generate N3-methyladenine was demonstrated as was their selectivity for minor groove (N3-methyladenine) versus major groove (N7-methylguanine) methylation. Induced circular dichroism studies were used to measure the DNA equilibrium binding properties of the stable sulfone analogues; the tripeptide binds with affinity that is >10-fold higher than that of the dipeptide. The toxicities of the compounds were evaluated in alkA/tag glycosylase mutant E. coli and in human WT glioma cells and in cells overexpressing and under-expressing N-methylpurine-DNA glycosylase, which excises N3-methyladenine from DNA. The results show that equilibrium binding correlates with the levels of N3-methyladenine produced and cellular toxicity. The toxicity of 1 was inversely related to the expression of MPG in both the bacterial and mammalian cell lines. The enhanced toxicity parallels the reduced activation of PARP and the diminished rate of formation of aldehyde reactive sites observed in the MPG knockdown cells. It is proposed that unrepaired N3-methyladenine is toxic due to its ability to directly block DNA polymerization.

  2. Direct observation of the influence of cardiolipin and antibiotics on lipid II binding to MurJ

    Science.gov (United States)

    Bolla, Jani Reddy; Sauer, Joshua B.; Wu, Di; Mehmood, Shahid; Allison, Timothy M.; Robinson, Carol V.

    2018-03-01

    Translocation of lipid II across the cytoplasmic membrane is essential in peptidoglycan biogenesis. Although most steps are understood, identifying the lipid II flippase has yielded conflicting results, and the lipid II binding properties of two candidate flippases—MurJ and FtsW—remain largely unknown. Here we apply native mass spectrometry to both proteins and characterize lipid II binding. We observed lower levels of lipid II binding to FtsW compared to MurJ, consistent with MurJ having a higher affinity. Site-directed mutagenesis of MurJ suggests that mutations at A29 and D269 attenuate lipid II binding to MurJ, whereas chemical modification of A29 eliminates binding. The antibiotic ramoplanin dissociates lipid II from MurJ, whereas vancomycin binds to form a stable complex with MurJ:lipid II. Furthermore, we reveal cardiolipins associate with MurJ but not FtsW, and exogenous cardiolipins reduce lipid II binding to MurJ. These observations provide insights into determinants of lipid II binding to MurJ and suggest roles for endogenous lipids in regulating substrate binding.

  3. Chance and stability stable distributions and their applications

    CERN Document Server

    Uchaikin, Vladimir V

    1999-01-01

    An introduction to the theory of stable distributions and their applications. It contains a modern outlook on the mathematical aspects of the theory. The authors explain numerous peculiarities of stable distributions and describe the principle concept of probability theory and function analysis. A significant part of the book is devoted to applications of stable distributions. Another notable feature is the material on the interconnection of stable laws with fractals, chaos and anomalous transport processes.

  4. Semisynthetic Lipopeptides Derived from Nisin Display Antibacterial Activity and Lipid II Binding on Par with That of the Parent Compound

    NARCIS (Netherlands)

    Koopmans, Timo; Wood, Thomas M.; 't Hart, Peter; Kleijn, Laurens H. J.; Hendrickx, Antoni P. A.; Willems, Rob J. L.; Breukink, Eefjan; Martin, Nathaniel I.

    2015-01-01

    The lipid II-binding N-terminus of nisin, comprising the so-called A/B ring system, was synthetically modified to provide antibacterially active and proteolytically stable derivatives. A variety of lipids were coupled to the C-terminus of the nisin A/B ring system to generate semisynthetic

  5. Nanostructured Basaltfiberconcrete Exploitational Characteristics

    Science.gov (United States)

    Saraykina, K. A.; Shamanov, V. A.

    2017-11-01

    The article demonstrates that the mass use of basalt fiber concrete (BFC) is constrained by insufficient study of their durability and serviceability in a variety of environments. This research is aimed at the study of the basalt fiber corrosion processes in the cement stone of BFC, the control of the new products structure formation in order to protect the reinforcing fiber from alkaline destruction and thereby improve the exploitational characteristics of the composite. The research result revealed that the modification of basaltfiber concrete by the dispersion of MWNTs contributes to the directional formation of new products in the cement matrix. The HAM additive in basaltfiberconcrete provides for the binding of portlandite to low-basic calcium hydroaluminosilicates, thus reducing the aggressive effect of the cement environment on the reinforcing fibers properties. The complex modification of BFC with nanostructured additives provides for an increase in its durability and exploitational properties (strength, frost resistance and water resistance) due to basalt fiber protection from alkali corrosion on account of the compacting of the contact zone “basalt fiber - cement stone” and designing of the new products structure and morphology of cement matrix over the fiber surface.

  6. A Note on Interpolation of Stable Processes | Nassiuma | Journal of ...

    African Journals Online (AJOL)

    Interpolation procedures tailored for gaussian processes may not be applied to infinite variance stable processes. Alternative techniques suitable for a limited set of stable case with index α∈(1,2] were initially studied by Pourahmadi (1984) for harmonizable processes. This was later extended to the ARMA stable process ...

  7. Respiratory depression by stable xenon in goats

    International Nuclear Information System (INIS)

    Winkler, S.S.

    1986-01-01

    Regional cerebral blood flow (rCBF) studies with stable xenon have recently become practical. Xenon pharmacology is thus a more than academic interest. The authors studied the respiratory response of three trained goats to a mixture of 70% xenon, 30% oxygen. The relatively high xenon concentration was used because of the animals' resistance to anesthetic effects. Two other goats were treated with equivalent anesthetic concentration of nitrous oxide and halothane. The xenon-treated animals showed respiratory depression, in contrast to the stimulating effects observed with halothane and nitrous oxide. Elevation of PaCO/sub 2/ was significant and would substantially increase cRBF. Their findings emphasize the need to monitor ventilation and respond appropriately if necessary

  8. The production of stable isotopes in Spain

    Energy Technology Data Exchange (ETDEWEB)

    Urgel, M.; Iglesias, J.; Casas, J.; Saviron, J. M.; Quintanilla, M.

    1965-07-01

    The activities developed in the field of the production of stable isotopes by means of ion-exchange chromatography and thermal diffusion techniques are reported. The first method was used to study the separation of the nitrogen and boron isotopes, whereby the separation factor was determined by the break through method. Values ranging from 1,028 to 1,022 were obtained for the separation factor of nitrogen by using ammonium hydroxide solutions while the corresponding values as obtained for boron amounted to 1,035-1,027 using boric acid solutions. Using ammonium chloride or acetate and sodium borate, respectively, resulted in the obtention of values for the separation factor approaching unity. The isotopic separation has been carried out according to the method of development by displacement. The separation of the isotopes of the noble gases, oxygen, nitrogen and carbon has been accomplished resorting to the method of thermal diffusion. (Author) 16 refs.

  9. The uniqueness of stable crack growth data

    International Nuclear Information System (INIS)

    Smith, E.

    1981-01-01

    The paper addresses the uniqueness of the stable crack growth relation, with particular reference to creep crack growth and stress corrosion crack growth, where it is the pattern to use laboratory data which relates the stress intensity K to the crack growth rate dc/dt. Simple models are used to define the conditions under which the K versus dc/dt data is unique. Extensive use is made of the Dugdale-Bilby-Cottrell-Swinden (DBCS) model, in which the yield accompanying crack growth is assumed to be confined to an infinitesimal thin strip coplanar with the growing crack. The DBCS model can be modified to give an incremental growth criterion, which is in the form of a differential equation relating the stress intensity to crack length. The conditions under which this equation gives a unique relation between stress intensity and crack length are then investigated. (orig./HP)

  10. The production of stable isotopes in Spain

    International Nuclear Information System (INIS)

    Urgel, M.; Iglesias, J.; Casas, J.; Saviron, J. M.; Quintanilla, M.

    1965-01-01

    The activities developed in the field of the production of stable isotopes by means of ion-exchange chromatography and thermal diffusion techniques are reported. The first method was used to study the separation of the nitrogen and boron isotopes, whereby the separation factor was determined by the break through method. Values ranging from 1,028 to 1,022 were obtained for the separation factor of nitrogen by using ammonium hydroxide solutions while the corresponding values as obtained for boron amounted to 1,035-1,027 using boric acid solutions. Using ammonium chloride or acetate and sodium borate, respectively, resulted in the obtention of values for the separation factor approaching unity. The isotopic separation has been carried out according to the method of development by displacement. The separation of the isotopes of the noble gases, oxygen, nitrogen and carbon has been accomplished resorting to the method of thermal diffusion. (Author) 16 refs

  11. The Search for Stable, Massive, Elementary Particles

    International Nuclear Information System (INIS)

    Kim, Peter C.

    2001-01-01

    In this paper we review the experimental and observational searches for stable, massive, elementary particles other than the electron and proton. The particles may be neutral, may have unit charge or may have fractional charge. They may interact through the strong, electromagnetic, weak or gravitational forces or through some unknown force. The purpose of this review is to provide a guide for future searches--what is known, what is not known, and what appear to be the most fruitful areas for new searches. A variety of experimental and observational methods such as accelerator experiments, cosmic ray studies, searches for exotic particles in bulk matter and searches using astrophysical observations is included in this review

  12. Multivariate max-stable spatial processes

    KAUST Repository

    Genton, Marc G.

    2015-02-11

    Max-stable processes allow the spatial dependence of extremes to be modelled and quantified, so they are widely adopted in applications. For a better understanding of extremes, it may be useful to study several variables simultaneously. To this end, we study the maxima of independent replicates of multivariate processes, both in the Gaussian and Student-t cases. We define a Poisson process construction and introduce multivariate versions of the Smith Gaussian extreme-value, the Schlather extremal-Gaussian and extremal-t, and the Brown–Resnick models. We develop inference for the models based on composite likelihoods. We present results of Monte Carlo simulations and an application to daily maximum wind speed and wind gust.

  13. Stable computation of generalized singular values

    Energy Technology Data Exchange (ETDEWEB)

    Drmac, Z.; Jessup, E.R. [Univ. of Colorado, Boulder, CO (United States)

    1996-12-31

    We study floating-point computation of the generalized singular value decomposition (GSVD) of a general matrix pair (A, B), where A and B are real matrices with the same numbers of columns. The GSVD is a powerful analytical and computational tool. For instance, the GSVD is an implicit way to solve the generalized symmetric eigenvalue problem Kx = {lambda}Mx, where K = A{sup {tau}}A and M = B{sup {tau}}B. Our goal is to develop stable numerical algorithms for the GSVD that are capable of computing the singular value approximations with the high relative accuracy that the perturbation theory says is possible. We assume that the singular values are well-determined by the data, i.e., that small relative perturbations {delta}A and {delta}B (pointwise rounding errors, for example) cause in each singular value {sigma} of (A, B) only a small relative perturbation {vert_bar}{delta}{sigma}{vert_bar}/{sigma}.

  14. Stable Oxygen-18 and Deuterium Isotopes

    DEFF Research Database (Denmark)

    Müller, Sascha

    The application of stable Oxygen-18 (18O) and Deuterium (2H) isotopes, as a tracer for fluxes between different compartments of the water cycle was subject of the present PhD-thesis. During a three year period, temporal data from a wide range of water cycle constituents was collected from...... the Skjern River catchment, Denmark. The presented applications focused on studying the isotopic 'input signal' to the hydrosphere in the form of precipitation, the isotopic 'output signal' with its related dynamic processes at a coastal saltwater-freshwater interface (groundwater isotopes) and the temporal...... development within a given lowland headwater catchment (stream water isotopes). Based on our investigations on the precipitation isotopic composition a local meteoric water line (LMWL) was constructed and expressed as: δ2H=7.4 δ18O + 5.36‰. Moreover, we showed that under maritime temperature climate influence...

  15. A belief-based evolutionarily stable strategy.

    Science.gov (United States)

    Deng, Xinyang; Wang, Zhen; Liu, Qi; Deng, Yong; Mahadevan, Sankaran

    2014-11-21

    As an equilibrium refinement of the Nash equilibrium, evolutionarily stable strategy (ESS) is a key concept in evolutionary game theory and has attracted growing interest. An ESS can be either a pure strategy or a mixed strategy. Even though the randomness is allowed in mixed strategy, the selection probability of pure strategy in a mixed strategy may fluctuate due to the impact of many factors. The fluctuation can lead to more uncertainty. In this paper, such uncertainty involved in mixed strategy has been further taken into consideration: a belief strategy is proposed in terms of Dempster-Shafer evidence theory. Furthermore, based on the proposed belief strategy, a belief-based ESS has been developed. The belief strategy and belief-based ESS can reduce to the mixed strategy and mixed ESS, which provide more realistic and powerful tools to describe interactions among agents. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Stable orbits for lunar landing assistance

    Science.gov (United States)

    Condoleo, Ennio; Cinelli, Marco; Ortore, Emiliano; Circi, Christian

    2017-10-01

    To improve lunar landing performances in terms of mission costs, trajectory determination and visibility the use of a single probe located over an assistance orbit around the Moon has been taken into consideration. To this end, the properties of two quasi-circular orbits characterised by a stable behaviour of semi-major axis, eccentricity and inclination have been investigated. The analysis has demonstrated the possibility of using an assistance probe, located over one of these orbits, as a relay satellite between lander and Earth, even in the case of landings on the far side of the Moon. A comparison about the accuracy in retrieving the lander's state with respect to the use of a probe located in the Lagrangian point L2 of the Earth-Moon system has also been carried out.

  17. Stable glomerular filtration rate in normotensive IDDM patients with stable microalbuminuria. A 5-year prospective study

    DEFF Research Database (Denmark)

    Mathiesen, E R; Feldt-Rasmussen, B; Hommel, E

    1997-01-01

    OBJECTIVE: To investigate the long-term course of glomerular filtration rate (GFR) in IDDM patients with microalbuminuria in order to identify patients with stable or declining kidney function over a 5-year study. RESEARCH DESIGN AND METHODS: Forty normotensive (129 +/- 11/80 +/- 8 mmHg) IDDM...

  18. [Lectin-binding patterns and cell kinetics of head and neck squamous cell carcinomas].

    Science.gov (United States)

    Gotoh, T

    1991-01-01

    In order to elucidate the cell characteristics of head and neck squamous cell carcinomas, the cell kinetics and lectin binding patterns were compared with the histological classification and staging of the tumors, using surgically resected materials (maxillary sinus 10, oral cavity 21, pharynx 8, larynx 11). Eight biotinylated lectins (WGA, 1-PHA, ConA, UEA1, RCA1, SBA, DBA, PNA) were applied to the paraffin-embedded sections, and were visualized histochemically by the streptavidin-alkaline phosphatase method. The DNA contents of the isolated carcinoma cells obtained from the adjacent thick sections were evaluated using an epi-illumination cytofluorometer after propidium iodide staining. On lectin histochemistry, the binding pattern of WGA lectin was similar between carcinoma tissues and normal tissues, but the binding was more intense in well differentiated than less differentiated carcinomas. Lymph node metastasis was found to be related to the presence of cells with poor WGA-binding. In the binding patterns of the other lectins, RCA1, SBA and ConA were related to the differentiation of carcinomas, but they were not related to the TNM-classification. DNA cytofluorometry exhibited marked polyploidization, which progressed with the advancement of the clinical and pathological staging of carcinomas. However, the DNA ploidy pattern was not associated with the cell characteristics such as the degree of histological differentiation and the lectin-binding pattern, except that the appearance of aneuploidy had some relationship with the binding-patterns of UEA1 and 1-PHA.

  19. Stable carbides in transition metal alloys

    International Nuclear Information System (INIS)

    Piotrkowski, R.

    1991-01-01

    In the present work different techniques were employed for the identification of stable carbides in two sets of transition metal alloys of wide technological application: a set of three high alloy M2 type steels in which W and/or Mo were total or partially replaced by Nb, and a Zr-2.5 Nb alloy. The M2 steel is a high speed steel worldwide used and the Zr-2.5 Nb alloy is the base material for the pressure tubes in the CANDU type nuclear reactors. The stability of carbide was studied in the frame of Goldschmidt's theory of interstitial alloys. The identification of stable carbides in steels was performed by determining their metallic composition with an energy analyzer attached to the scanning electron microscope (SEM). By these means typical carbides of the M2 steel, MC and M 6 C, were found. Moreover, the spatial and size distribution of carbide particles were determined after different heat treatments, and both microstructure and microhardness were correlated with the appearance of the secondary hardening phenomenon. In the Zr-Nb alloy a study of the α and β phases present after different heat treatments was performed with optical and SEM metallographic techniques, with the guide of Abriata and Bolcich phase diagram. The α-β interphase boundaries were characterized as short circuits for diffusion with radiotracer techniques and applying Fisher-Bondy-Martin model. The precipitation of carbides was promoted by heat treatments that produced first the C diffusion into the samples at high temperatures (β phase), and then the precipitation of carbide particles at lower temperature (α phase or (α+β)) two phase field. The precipitated carbides were identified as (Zr, Nb)C 1-x with SEM, electron microprobe and X-ray diffraction techniques. (Author) [es

  20. Stable isotopes as tracers for radionuclides

    International Nuclear Information System (INIS)

    Giussani, A.; Bartolo, D. de; Cantone, M.C.; Zilker, T.; Greim, H.; Roth, P.; Werner, E.

    2000-01-01

    The assessment of internal dose after incorporation of radionuclides requires as input data the knowledge of the uptake into the systemic circulation, the distribution and retention in selected organs, the excretion pathways. Realistic biokinetic models are needed for reliable estimates, correct interpretation of bioassay measurements, appropriate decision-making in radiological emergencies. For many radionuclides, however, the biokinetic models currently recommended are often generic, with very few specific parameters, due to the lack of experimental human data. The use of stable isotopes as tracers enables to determine important biokinetic parameters such as the fractional uptake, the clearance from the transfer compartment, the excretion patterns under experimentally controlled conditions. The subjects investigated are not exposed to any radiation risk, so this technique enables to obtain biokinetic information also for sensitive groups of the population, such as children or pregnant women, and to determine age- and gender-specific model parameters. Sophisticated analytical method, able to discriminate and quantitate different isotopes of the same element in complex matrices such as biological fluids, have to be purposely developed and optimized. Activation analysis and mass spectrometry are the most proper techniques of choice. Experiments were conducted with molybdenum, tellurium, ruthenium and zirconium. Activation analysis with protons, thermal ionization mass spectrometry and inductively coupled mass spectrometry were employed for the determination of stable isotopes of these elements in blood plasma and urine samples. Several deviations from the predictions of the ICRP models were observed. For example, modifications to the current model for molybdenum have been suggested on the basis of these results. The dose coefficients to the target regions calculated with this proposed model are even of one order of magnitude different than the ICRP estimates

  1. Addiction treatment and stable housing among a cohort of injection drug users.

    Directory of Open Access Journals (Sweden)

    Anita Palepu

    Full Text Available Unstable housing and homelessness is prevalent among injection drug users (IDU. We sought to examine whether accessing addiction treatment was associated with attaining stable housing in a prospective cohort of IDU in Vancouver, Canada.We used data collected via the Vancouver Injection Drug User Study (VIDUS between December 2005 and April 2010. Attaining stable housing was defined as two consecutive "stable housing" designations (i.e., living in an apartment or house during the follow-up period. We assessed exposure to addiction treatment in the interview prior to the attainment of stable housing among participants who were homeless or living in single room occupancy (SRO hotels at baseline. Bivariate and multivariate associations between the baseline and time-updated characteristics and attaining stable housing were examined using Cox proportional hazard regression models.Of the 992 IDU eligible for this analysis, 495 (49.9% reported being homeless, 497 (50.1% resided in SRO hotels, and 380 (38.3% were enrolled in addiction treatment at the baseline interview. Only 211 (21.3% attained stable housing during the follow-up period and of this group, 69 (32.7% had addiction treatment exposure prior to achieving stable housing. Addiction treatment was inversely associated with attaining stable housing in a multivariate model (adjusted hazard ratio [AHR]=0.71; 95% CI: 0.52-0.96. Being in a partnered relationship was positively associated with the primary outcome (AHR=1.39; 95% CI: 1.02-1.88. Receipt of income assistance (AHR=0.65; 95% CI: 0.44-0.96, daily crack use (AHR=0.69; 95% CI: 0.51-0.93 and daily heroin use (AHR=0.63; 95% CI: 0.43-0.92 were negatively associated with attaining stable housing.Exposure to addiction treatment in our study was negatively associated with attaining stable housing and may have represented a marker of instability among this sample of IDU. Efforts to stably house this vulnerable group may be occurring in contexts

  2. Slowing of oscillatory brain activity is a stable characteristic of Parkinson's disease without dementia

    NARCIS (Netherlands)

    Stoffers, D.; Bosboom, JL; Deijen, J.B.; Wolters, E.C.M.J.; Berendse, H.W.; Stam, L.

    2007-01-01

    Extensive changes in resting-state oscillatory brain activity have recently been demonstrated using magnetoencephalography (MEG) in moderately advanced, non-demented Parkinson's disease patients relative to age-matched controls. The aim of the present study was to determine the onset and evolution

  3. Ecological characteristics and polyphasic taxonomic classification of stable pigment-types of the genus Chroococcus (Cyanobacteria)

    Czech Academy of Sciences Publication Activity Database

    Kováčik, L.; Jezberová, Jitka; Komárková, Jaroslava; Kopecký, Jiří; Komárek, Jiří

    2011-01-01

    Roč. 83, č. 1 (2011), s. 145-166 ISSN 0032-7786 R&D Projects: GA ČR(CZ) GA525/07/0338; GA AV ČR(CZ) IAA600050704 Institutional research plan: CEZ:AV0Z60170517; CEZ:AV0Z50200510; CEZ:AV0Z60050516 Keywords : chromatic adaptation * Chroococcus * cyanobacteria * ecology * phylogeny * pigment content * pigment mutants * Slovakia * taxonomy * ultrastructure Subject RIV: EF - Botanics Impact factor: 2.521, year: 2011

  4. A microscopic insight from conformational thermodynamics to functional ligand binding in proteins.

    Science.gov (United States)

    Sikdar, Samapan; Chakrabarti, J; Ghosh, Mahua

    2014-12-01

    We show that the thermodynamics of metal ion-induced conformational changes aid to understand the functions of protein complexes. This is illustrated in the case of a metalloprotein, alpha-lactalbumin (aLA), a divalent metal ion binding protein. We use the histograms of dihedral angles of the protein, generated from all-atom molecular dynamics simulations, to calculate conformational thermodynamics. The thermodynamically destabilized and disordered residues in different conformational states of a protein are proposed to serve as binding sites for ligands. This is tested for β-1,4-galactosyltransferase (β4GalT) binding to the Ca(2+)-aLA complex, in which the binding residues are known. Among the binding residues, the C-terminal residues like aspartate (D) 116, glutamine (Q) 117, tryptophan (W) 118 and leucine (L) 119 are destabilized and disordered and can dock β4GalT onto Ca(2+)-aLA. No such thermodynamically favourable binding residues can be identified in the case of the Mg(2+)-aLA complex. We apply similar analysis to oleic acid binding and predict that the Ca(2+)-aLA complex can bind to oleic acid through the basic histidine (H) 32 of the A2 helix and the hydrophobic residues, namely, isoleucine (I) 59, W60 and I95, of the interfacial cleft. However, the number of destabilized and disordered residues in Mg(2+)-aLA are few, and hence, the oleic acid binding to Mg(2+)-bound aLA is less stable than that to the Ca(2+)-aLA complex. Our analysis can be generalized to understand the functionality of other ligand bound proteins.

  5. Drug binding properties of neonatal albumin

    DEFF Research Database (Denmark)

    Brodersen, R; Honoré, B

    1989-01-01

    Neonatal and adult albumin was isolated by gel chromatography on Sephacryl S-300, from adult and umbilical cord serum, respectively. Binding of monoacetyl-diamino-diphenyl sulfone, warfarin, sulfamethizole, and diazepam was studied by means of equilibrium dialysis and the binding data were analyzed...... by the method of several acceptable fitted curves. It was found that the binding affinity to neonatal albumin is less than to adult albumin for monoacetyl-diamino-diphenyl sulfone and warfarin. Sulfamethizole binding to the neonatal protein is similarly reduced when more than one molecule of the drug is bound...... per albumin molecule, and binding of the first sulfamethizole molecule is possibly reduced as well. Diazepam binds with equal affinity to the fetal and adult proteins. Among the two main albumin drug-binding functions, for warfarin and diazepam, the former is thus compromised in the newborn infant...

  6. Studies on folate binding and a radioassay for serum and whole-blood folate using goat milk as binding agent

    International Nuclear Information System (INIS)

    Piyasena, R.D.; Weerasekera, D.A.; Hettiaratchi, N.; Wikramanayake, T.W.

    1978-01-01

    Preparations of cow, goat, buffalo and human milk in addition to pig plasma were tested for folate binding properties. Of these, only pig plasma and goat milk showed sufficient binding to enable them to be used as binding agents in a radioassay for serum and whole-blood folate. The binding of folate by cow milk preparations in particular was found to be very poor. Goat milk was preferred to pig plasma as a binder for folate radioassay for reasons of convenience, economy and greater stability, and because pteroylglutamic acid (PGA) can be used both as tracer and standard. Where pig plasma is used with the inclusion of folate-free serum in the standard tubes, differences were observed between the standard and serum blanks which themselves varied from sample to sample. By contrast, with goat milk, all blank readings were normally 3% or less. Five out of eight samples of goat milk were seen to contain 'releasing factor' necessary to liberate folate from endogenous binder (FABP). Where present, the factor was found to be stable for at least three months when the partially purified milk was stored freeze dried at 4 0 C. Goat milk binder was found unable to distinguish between PGA and methyltetrahydrofolic acid (MTFA) at pH9.3. This enabled PGA rather than the more unstable MTFA to be used as tracer and standard. The assay employs a one-step incubation procedure at room temperature. It is sensitive to about 0.1 ng of PGA and is reproducible to less than 5% variation. The mean % recovery of inactive added folate was 101+-4%. (author)

  7. The human HIP gene, overexpressed in primary liver cancer encodes for a C-type carbohydrate binding protein with lactose binding activity.

    Science.gov (United States)

    Christa, L; Felin, M; Morali, O; Simon, M T; Lasserre, C; Brechot, C; Sève, A P

    1994-01-03

    HIP was originally identified as a gene expression in primary liver cancers, and in normal tissues such as pancreas and small intestine. Based on gene data base homologies, the HIP protein should consist of a signal peptide linked to a single carbohydrate recognition domain. To test this hypothesis HIP and the putative carbohydrate recognition domain encoded by the last 138 C-terminal amino acids, were expressed as glutathione-S-transferase proteins (GST-HIP and GST-HIP-142, respectively). Both recombinant proteins were purified by a single affinity purification step from bacterial lysates and their ability to bind saccharides coupled to trisacryl GF 2000M were tested. Our results show that HIP and HIP-142 proteins bind to lactose, moreover the binding requires divalent cations. Thus the HIP protein is a lactose-binding lectin with the characteristics of a C-type carbohydrate recognition domain of 138 amino acids in the C-terminal region.

  8. Insulin binding to individual rat skeletal muscles

    International Nuclear Information System (INIS)

    Koerker, D.J.; Sweet, I.R.; Baskin, D.G.

    1990-01-01

    Studies of insulin binding to skeletal muscle, performed using sarcolemmal membrane preparations or whole muscle incubations of mixed muscle or typical red (soleus, psoas) or white [extensor digitorum longus (EDL), gastrocnemius] muscle, have suggested that red muscle binds more insulin than white muscle. We have evaluated this hypothesis using cryostat sections of unfixed tissue to measure insulin binding in a broad range of skeletal muscles; many were of similar fiber-type profiles. Insulin binding per square millimeter of skeletal muscle slice was measured by autoradiography and computer-assisted densitometry. We found a 4.5-fold range in specific insulin tracer binding, with heart and predominantly slow-twitch oxidative muscles (SO) at the high end and the predominantly fast-twitch glycolytic (FG) muscles at the low end of the range. This pattern reflects insulin sensitivity. Evaluation of displacement curves for insulin binding yielded linear Scatchard plots. The dissociation constants varied over a ninefold range (0.26-2.06 nM). Binding capacity varied from 12.2 to 82.7 fmol/mm2. Neither binding parameter was correlated with fiber type or insulin sensitivity; e.g., among three muscles of similar fiber-type profile, the EDL had high numbers of low-affinity binding sites, whereas the quadriceps had low numbers of high-affinity sites. In summary, considerable heterogeneity in insulin binding was found among hindlimb muscles of the rat, which can be attributed to heterogeneity in binding affinities and the numbers of binding sites. It can be concluded that a given fiber type is not uniquely associated with a set of insulin binding parameters that result in high or low binding

  9. Insulin binding to individual rat skeletal muscles

    Energy Technology Data Exchange (ETDEWEB)

    Koerker, D.J.; Sweet, I.R.; Baskin, D.G. (Univ. of Washington, Seattle (USA))

    1990-10-01

    Studies of insulin binding to skeletal muscle, performed using sarcolemmal membrane preparations or whole muscle incubations of mixed muscle or typical red (soleus, psoas) or white (extensor digitorum longus (EDL), gastrocnemius) muscle, have suggested that red muscle binds more insulin than white muscle. We have evaluated this hypothesis using cryostat sections of unfixed tissue to measure insulin binding in a broad range of skeletal muscles; many were of similar fiber-type profiles. Insulin binding per square millimeter of skeletal muscle slice was measured by autoradiography and computer-assisted densitometry. We found a 4.5-fold range in specific insulin tracer binding, with heart and predominantly slow-twitch oxidative muscles (SO) at the high end and the predominantly fast-twitch glycolytic (FG) muscles at the low end of the range. This pattern reflects insulin sensitivity. Evaluation of displacement curves for insulin binding yielded linear Scatchard plots. The dissociation constants varied over a ninefold range (0.26-2.06 nM). Binding capacity varied from 12.2 to 82.7 fmol/mm2. Neither binding parameter was correlated with fiber type or insulin sensitivity; e.g., among three muscles of similar fiber-type profile, the EDL had high numbers of low-affinity binding sites, whereas the quadriceps had low numbers of high-affinity sites. In summary, considerable heterogeneity in insulin binding was found among hindlimb muscles of the rat, which can be attributed to heterogeneity in binding affinities and the numbers of binding sites. It can be concluded that a given fiber type is not uniquely associated with a set of insulin binding parameters that result in high or low binding.

  10. Human plasminogen binding protein tetranectin

    DEFF Research Database (Denmark)

    Kastrup, J S; Rasmussen, H; Nielsen, B B

    1997-01-01

    The recombinant human plasminogen binding protein tetranectin (TN) and the C-type lectin CRD of this protein (TN3) have been crystallized. TN3 crystallizes in the tetragonal space group P4(2)2(1)2 with cell dimensions a = b = 64.0, c = 75.7 A and with one molecule per asymmetric unit. The crystals...... to at least 2.5 A. A full data set has been collected to 3.0 A. The asymmetric unit contains one monomer of TN. Molecular replacement solutions for TN3 and TN have been obtained using the structure of the C-type lectin CRD of rat mannose-binding protein as search model. The rhombohedral space group indicates...... diffract X-rays to at least 2.0 A resolution. A complete diffraction data set has been collected to 2.7 A resolution. The crystals of TN, obtained by the vapour-diffusion reverse salting-in method at 280 K, are rhombohedral, space group R3, with the hexagonal axes a = b = 89.1, c = 75.8 A, and diffract...

  11. NMR structure of a biologically active peptide containing the RNA-binding domain of human immunodeficiency virus type 1 Tat.

    Science.gov (United States)

    Mujeeb, A; Bishop, K; Peterlin, B M; Turck, C; Parslow, T G; James, T L

    1994-01-01

    The Tat protein of human immunodeficiency virus type 1 enhances transcription by binding to a specific RNA element on nascent viral transcripts. Binding is mediated by a 10-amino acid basic domain that is rich in arginines and lysines. Here we report the three-dimensional peptide backbone structure of a biologically active 25-mer peptide that contains the human immunodeficiency virus type 1 Tat basic domain linked to the core regulatory domain of another lentiviral Tat--i.e., that from equine infectious anemia virus. Circular dichroism and two-dimensional proton NMR studies of this hybrid peptide indicate that the Tat basic domain forms a stable alpha-helix, whereas the adjacent regulatory sequence is mostly in extended form. These findings suggest that the tendency to form stable alpha-helices may be a common property of arginine- and lysine-rich RNA-binding domains. Images PMID:8058789

  12. Diagnostic models of the pre-test probability of stable coronary artery disease: A systematic review

    Directory of Open Access Journals (Sweden)

    Ting He

    Full Text Available A comprehensive search of PubMed and Embase was performed in January 2015 to examine the available literature on validated diagnostic models of the pre-test probability of stable coronary artery disease and to describe the characteristics of the models. Studies that were designed to develop and validate diagnostic models of pre-test probability for stable coronary artery disease were included. Data regarding baseline patient characteristics, procedural characteristics, modeling methods, metrics of model performance, risk of bias, and clinical usefulness were extracted. Ten studies involving the development of 12 models and two studies focusing on external validation were identified. Seven models were validated internally, and seven models were validated externally. Discrimination varied between studies that were validated internally (C statistic 0.66-0.81 and externally (0.49-0.87. Only one study presented reclassification indices. The majority of better performing models included sex, age, symptoms, diabetes, smoking, and hyperlipidemia as variables. Only two diagnostic models evaluated the effects on clinical decision making processes or patient outcomes. Most diagnostic models of the pre-test probability of stable coronary artery disease have had modest success, and very few present data regarding the effects of these models on clinical decision making processes or patient outcomes.

  13. Stability properties of nonlinear dynamical systems and evolutionary stable states

    Energy Technology Data Exchange (ETDEWEB)

    Gleria, Iram, E-mail: iram@fis.ufal.br [Instituto de Física, Universidade Federal de Alagoas, 57072-970 Maceió-AL (Brazil); Brenig, Leon [Faculté des Sciences, Université Libre de Bruxelles, 1050 Brussels (Belgium); Rocha Filho, Tarcísio M.; Figueiredo, Annibal [Instituto de Física and International Center for Condensed Matter Physics, Universidade de Brasília, 70919-970 Brasília-DF (Brazil)

    2017-03-18

    Highlights: • We address the problem of equilibrium stability in a general class of non-linear systems. • We link Evolutionary Stable States (ESS) to stable fixed points of square quasi-polynomial (QP) systems. • We show that an interior ES point may be related to stable interior fixed points of QP systems. - Abstract: In this paper we address the problem of stability in a general class of non-linear systems. We establish a link between the concepts of asymptotic stable interior fixed points of square Quasi-Polynomial systems and evolutionary stable states, a property of some payoff matrices arising from evolutionary games.

  14. Influence of horse stable environment on human airways

    Directory of Open Access Journals (Sweden)

    Pringle John

    2009-05-01

    Full Text Available Abstract Background Many people spend considerable amount of time each day in equine stable environments either as employees in the care and training of horses or in leisure activity. However, there are few studies available on how the stable environment affects human airways. This study examined in one horse stable qualitative differences in indoor air during winter and late summer conditions and assessed whether air quality was associated with clinically detectable respiratory signs or alterations to selected biomarkers of inflammation and lung function in stable personnel. Methods The horse stable environment and stable-workers (n = 13 in one stable were investigated three times; first in the winter, second in the interjacent late summer and the third time in the following winter stabling period. The stable measurements included levels of ammonia, hydrogen sulphide, total and respirable dust, airborne horse allergen, microorganisms, endotoxin and glucan. The stable-workers completed a questionnaire on respiratory symptoms, underwent nasal lavage with subsequent analysis of inflammation markers, and performed repeated measurements of pulmonary function. Results Measurements in the horse stable showed low organic dust levels and high horse allergen levels. Increased viable level of fungi in the air indicated a growing source in the stable. Air particle load as well as 1,3-β-glucan was higher at the two winter time-points, whereas endotoxin levels were higher at the summer time-point. Two stable-workers showed signs of bronchial obstruction with increased PEF-variability, increased inflammation biomarkers relating to reported allergy, cold or smoking and reported partly work-related symptoms. Furthermore, two other stable-workers reported work-related airway symptoms, of which one had doctor's diagnosed asthma which was well treated. Conclusion Biomarkers involved in the development of airway diseases have been studied in relation to

  15. Specific binding of lactoferrin to Escherichia coli isolated from human intestinal infections

    Energy Technology Data Exchange (ETDEWEB)

    Naidu, S.S.; Erdei, J.; Forsgren, A.; Naidu, A.S. (Departments of Medical Microbiology, Malmoe General Hospital (Sweden)); Czirok, E.; Gado, I. (National Institute of Hygiene, Budapest (Hungary)); Kalfas, S. (School of Dentistry, University of Lund, Malmoe (Sweden)); Thoren, A. (Infectious Diseases, Malmoe General Hospital (Sweden))

    1991-01-01

    The degrees of human lactoferrin (HLf) and bovine lactoferrin (BLf) binding in 169 Escherichia coli strains isolated from human intestinal infections, and in an additional 68 strains isolated from healthy individuals, were examined in a {sup 125}I-labelled protein binding assay. The binding was expressed as a percentage calculated from the total labelled ligand added to bacteria. The HLf and BLf binding to E. coli was in the range 3.7 to 73.4% and 4.8 to 61.6%, respectively. Enterotoxigenic strains demonstrated a significantly higher HLf binding (median = 19%) than enteropathogenic, enteroinvasive, enterohaemorrhagic strains or normal intestinal E. coli isolates (medians 6 to 9). Enteropathogenic strains belonging to serotypes O44 and O127 demonstrated significantly higher HLf binding compared to O26, O55, O111, O119 and O126. No significant differences in the degree of HLf or BLf binding were found between aerobactin-producing and non-producing strains. The interaction was further characterized in a high Lf-binging EPEC strain, E34663 (serotype O127). The binding was stable in the pH range 4.0 to 7.5, did not dissociate in the presence of 2M NaCl or 2M urea, and reached saturation within two h. Unlabelled HLf and BLf displaced the {sup 125}I-HLf binding to E34663 in a dose-dependent manner. Apo- and iron-saturated forms of Lf demonstrated similar binding to E34663. Among various unlabelled subephithelial matrix proteins and carbohydrates tested (in 10{sup 4}-fold excess) only fibronectin and fibrinogen caused a moderate inhibition of {sup 125}I-HLf binding. According to Scatchard plot analysis, 5,400 HLf-binding sites/cell, with an affinity constant (K{sub a}) of 1.4 x 10{sup -7} M, were estimated in strain E34663. These data establish the presence of a specific Lf-binding mechanism in E. coli. (au).

  16. Characterization of binding specificities of bovine leucocyte class I molecules: impacts for rational epitope discovery

    DEFF Research Database (Denmark)

    Hansen, Andreas M.; Rasmussen, Michael; Svitek, Nicholas

    2014-01-01

    The binding of peptides to classical major histocompatibility complex (MHC) class I proteins is the single most selective step in antigen presentation. However, the peptide-binding specificity of cattle MHC (bovine leucocyte antigen, BoLA) class I (BoLA-I) molecules remains poorly characterized....... Using this strategy, we characterized eight BoLA-I molecules, and found the peptide specificity to resemble that of human MHC-I molecules with primary anchors most often at P2 and P9, and occasional auxiliary P1/P3/P5/P6 anchors. We analyzed nine reported CTL epitopes from Theileria parva, and in eight...... cases, stable and high affinity binding was confirmed. A set of peptides were tested for binding affinity to the eight BoLA proteins and used to refine the predictors of peptide-MHC binding NetMHC and NetMHCpan. The inclusion of BoLA-specific peptide-binding data led to a significant improvement...

  17. An Unusual Dimeric Inhibitor of Acetylcholinesterase: Cooperative Binding of Crystal Violet

    Directory of Open Access Journals (Sweden)

    Anders Allgardsson

    2017-08-01

    Full Text Available Acetylcholinesterase (AChE is an essential enzyme that terminates cholinergic transmission by a rapid hydrolysis of the neurotransmitter acetylcholine. AChE is an important target for treatment of various cholinergic deficiencies, including Alzheimer’s disease and myasthenia gravis. In a previous high throughput screening campaign, we identified the dye crystal violet (CV as an inhibitor of AChE. Herein, we show that CV displays a significant cooperativity for binding to AChE, and the molecular basis for this observation has been investigated by X-ray crystallography. Two monomers of CV bind to residues at the entrance of the active site gorge of the enzyme. Notably, the two CV molecules have extensive intermolecular contacts with each other and with AChE. Computational analyses show that the observed CV dimer is not stable in solution, suggesting the sequential binding of two monomers. Guided by the structural analysis, we designed a set of single site substitutions, and investigated their effect on the binding of CV. Only moderate effects on the binding and the cooperativity were observed, suggesting a robustness in the interaction between CV and AChE. Taken together, we propose that the dimeric cooperative binding is due to a rare combination of chemical and structural properties of both CV and the AChE molecule itself.

  18. Evaluation of galectin binding by frontal affinity chromatography (FAC).

    Science.gov (United States)

    Iwaki, Jun; Hirabayashi, Jun

    2015-01-01

    Frontal affinity chromatography (FAC) is a simple and versatile procedure enabling quantitative determination of diverse biological interactions in terms of dissociation constants (K d), even though these interactions are relatively weak. The method is best applied to glycans and their binding proteins, with the analytical system operating on the basis of highly reproducible isocratic elution by liquid chromatography. Its application to galectins has been successfully developed to characterize their binding specificities in detail. As a result, their minimal requirements for recognition of disaccharides, i.e., β-galactosides, as well as characteristic features of individual galectins, have been elucidated. In this chapter, we describe standard procedures to determine the K d's for interactions between a series of standard glycans and various galectins.

  19. Oxygen binding properties of non-mammalian nerve globins

    DEFF Research Database (Denmark)

    Hundahl, Christian; Fago, Angela; Dewilde, Sylvia

    2006-01-01

    Oxygen-binding globins occur in the nervous systems of both invertebrates and vertebrates. While the function of invertebrate nerve haemoglobins as oxygen stores that extend neural excitability under hypoxia has been convincingly demonstrated, the physiological role of vertebrate neuroglobins...... is less well understood. Here we provide a detailed analysis of the oxygenation characteristics of nerve haemoglobins from an annelid (Aphrodite aculeata), a nemertean (Cerebratulus lacteus) and a bivalve (Spisula solidissima) and of neuroglobin from zebrafish (Danio rerio). The functional differences...... temperatures investigated and exhibited large enthalpies of oxygenation, the hexacoordinate globins showed reverse Bohr effects (at least at low temperature) and approximately twofold lower oxygenation enthalpies. Only S. solidissima nerve haemoglobin showed apparent cooperativity in oxygen binding, suggesting...

  20. Zinc-Binding Cysteines: Diverse Functions and Structural Motifs

    Science.gov (United States)

    Pace, Nicholas J.; Weerapana, Eranthie

    2014-01-01

    Cysteine residues are known to perform essential functions within proteins, including binding to various metal ions. In particular, cysteine residues can display high affinity toward zinc ions (Zn2+), and these resulting Zn2+-cysteine complexes are critical mediators of protein structure, catalysis and regulation. Recent advances in both experimental and theoretical platforms have accelerated the identification and functional characterization of Zn2+-bound cysteines. Zn2+-cysteine complexes have been observed across diverse protein classes and are known to facilitate a variety of cellular processes. Here, we highlight the structural characteristics and diverse functional roles of Zn2+-cysteine complexes in proteins and describe structural, computational and chemical proteomic technologies that have enabled the global discovery of novel Zn2+-binding cysteines. PMID:24970223

  1. Multifunctionality and mechanism of ligand binding in a mosquito antiinflammatory protein

    Energy Technology Data Exchange (ETDEWEB)

    Calvo, Eric; Mans, Ben J.; Ribeiro, José M.C.; Andersen, John F.; (NIH)

    2009-04-07

    The mosquito D7 salivary proteins are encoded by a multigene family related to the arthropod odorant-binding protein (OBP) superfamily. Forms having either one or two OBP domains are found in mosquito saliva. Four single-domain and one two-domain D7 proteins from Anopheles gambiae and Aedes aegypti (AeD7), respectively, were shown to bind biogenic amines with high affinity and with a stoichiometry of one ligand per protein molecule. Sequence comparisons indicated that only the C-terminal domain of AeD7 is homologous to the single-domain proteins from A. gambiae, suggesting that the N-terminal domain may bind a different class of ligands. Here, we describe the 3D structure of AeD7 and examine the ligand-binding characteristics of the N- and C-terminal domains. Isothermal titration calorimetry and ligand complex crystal structures show that the N-terminal domain binds cysteinyl leukotrienes (cysLTs) with high affinities (50-60 nM) whereas the C-terminal domain binds biogenic amines. The lipid chain of the cysLT binds in a hydrophobic pocket of the N-terminal domain, whereas binding of norepinephrine leads to an ordering of the C-terminal portion of the C-terminal domain into an alpha-helix that, along with rotations of Arg-176 and Glu-268 side chains, acts to bury the bound ligand.

  2. Serotonin transporter binding as a possible predictor of one-year remission in major depressive disorder.

    Science.gov (United States)

    Miller, Jeffrey M; Oquendo, Maria A; Ogden, R Todd; Mann, J John; Parsey, Ramin V

    2008-10-01

    Lower serotonin transporter (5-HTT) binding (BP(P)=f(P)B(avail)/K(D)) is reported during a major depressive episode (MDE) compared to healthy controls. Higher 5-HTT binding in the diencephalon has previously been associated with acute response to antidepressant treatment. We assessed baseline 5-HTT binding as a predictor of one-year remission from a MDE, examining binding in brain regions implicated in the pathophysiology of major depressive disorder (MDD). 5-HTT binding was quantified using positron emission tomography (PET) with [(11)C]McN5652 in 19 currently depressed subjects with MDD and 41 healthy controls. Depressed subjects received open, naturalistic antidepressant treatment. Remission status was determined one year after PET scan and treatment initiation. Significant differences in 5-HTT binding among the three groups (healthy controls, remitters, and non-remitters) were observed in a linear mixed-effects model. Post hoc, non-remitters had lower 5-HTT binding than controls in midbrain, amygdala, and anterior cingulate. Remitters did not differ significantly from controls or non-remitters in 5-HTT binding. Remitters did not differ from non-remitters in clinical characteristics apart from greater family history of depression among non-remitters. A logistic regression model fit to determine the capacity of baseline 5-HTT binding to predict remission status at one year yielded a coefficient that was suggestive but not significant (p=0.057). The small sample size and heterogeneous treatments received reduced statistical power to detect differences in binding based on clinical outcome. Lower pretreatment 5-HTT binding may be predictive of non-remission from major depression following one year of naturalistic antidepressant treatment. Future studies using standardized treatment are warranted.

  3. Stable isotope analysis in primatology: a critical review.

    Science.gov (United States)

    Sandberg, Paul A; Loudon, James E; Sponheimer, Matt

    2012-11-01

    Stable isotope analysis has become an important tool in ecology over the last 25 years. A wealth of ecological information is stored in animal tissues in the relative abundances of the stable isotopes of several elements, particularly carbon and nitrogen, because these isotopes navigate through ecological processes in predictable ways. Stable carbon and nitrogen isotopes have been measured in most primate taxonomic groups and have yielded information about dietary content, dietary variability, and habitat use. Stable isotopes have recently proven useful for addressing more fine-grained questions about niche dynamics and anthropogenic effects on feeding ecology. Here, we discuss stable carbon and nitrogen isotope systematics and critically review the published stable carbon and nitrogen isotope data for modern primates with a focus on the problems and prospects for future stable isotope applications in primatology. © 2012 Wiley Periodicals, Inc.

  4. Stable non-covalent labeling of layered silicate nanoparticles for biological imaging.

    Science.gov (United States)

    Mortimer, Gysell M; Jack, Kevin S; Musumeci, Anthony W; Martin, Darren J; Minchin, Rodney F

    2016-04-01

    Layered silicate nanoparticles (LSN) are widely used in industrial applications and consumer products. They also have potential benefits in biomedical applications such as implantable devices and for drug delivery. To study how nanomaterials interact with cells and tissues, techniques to track and quantify their movement through different biological compartments are essential. While radiolabels can be very sensitive, particularly for in vivo studies, fluorescent labeling has been preferred in recent years because of the array of methods available to image and quantify fluorescent nanoparticles. However, labeling can be problematic, especially if it alters the physical properties of the nanomaterial. Herein is described a novel non-covalent labeling technique for LSN using readily available fluorescent dimeric cyanine dyes without the need to use excess amounts of dye to achieve labeling, or the need for removal of unbound dye. The approach utilizes the cationic binding properties of layered silicate clays and the multiple quaternary nitrogens associated with the dyes. Preparation of YOYO-1 labeled LSN with optimal dispersion in aqueous media is presented. The utilization of the labeled particles is then demonstrated in cell binding and uptake studies using flow cytometry and confocal microscopy. The labeled LSN are highly fluorescent, stable and exhibit identical physical properties with respect to the unlabeled nanoparticles. The general approach described here is applicable to other cyanine dyes and may be utilized more widely for labeling nanoparticles that comprise a crystalline plate structure with a high binding capacity. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  5. Identification of stable housekeeping genes in response to ionizing radiation in cancer research

    Science.gov (United States)

    Iyer, Gopal; Wang, Albert R.; Brennan, Sean R.; Bourgeois, Shay; Armstrong, Eric; Shah, Pari; Harari, Paul M.

    2017-01-01

    Housekeeping genes (HKGs) are essential for basic maintenance of a variety of cellular processes. They ideally maintain uniform expression independent of experimental conditions. However, the effects of ionizing radiation (IR) on HKG expression is unclear. Statistical algorithms, geNorm and Normfinder were used for estimating the stability of HKGs as raw quantification cycle (Cq) values were not a reliable factor for normalization. Head and neck, non-small lung and pancreas cells were exposed to 2, 4 and 6 Gy IR doses and expression of fourteen HKGs was measured at 5 min to 48 h post-irradiation within a given tissue. Paired and single cell line analyses under these experimental conditions identified TATA-Box Binding Protein (TBP) and Importin 8 (IPO8) to be stable in non-small cell lung cancer. In addition to these two genes, Ubiquitin C (UBC) in head and neck cancer and Transferrin receptor (TFRC) and β-Glucuronidase (GUSB) in pancreatic cancer were identified to be stable as well. In summary we present a resource for top ranked five stable HKGs and their transcriptional behavior in commonly used cancer model cell lines and suggest the use of multiple HKGs under radiation treatment conditions is a reliable metric for quantifying gene expression. PMID:28262749

  6. Tau can switch microtubule network organizations: from random networks to dynamic and stable bundles.

    Science.gov (United States)

    Prezel, Elea; Elie, Auréliane; Delaroche, Julie; Stoppin-Mellet, Virginie; Bosc, Christophe; Serre, Laurence; Fourest-Lieuvin, Anne; Andrieux, Annie; Vantard, Marylin; Arnal, Isabelle

    2018-01-15

    In neurons, microtubule networks alternate between single filaments and bundled arrays under the influence of effectors controlling their dynamics and organization. Tau is a microtubule bundler that stabilizes microtubules by stimulating growth and inhibiting shrinkage. The mechanisms by which tau organizes microtubule networks remain poorly understood. Here, we studied the self-organization of microtubules growing in the presence of tau isoforms and mutants. The results show that tau's ability to induce stable microtubule bundles requires two hexapeptides located in its microtubule-binding domain and is modulated by its projection domain. Site-specific pseudophosphorylation of tau promotes distinct microtubule organizations: stable single microtubules, stable bundles, or dynamic bundles. Disease-related tau mutations increase the formation of highly dynamic bundles. Finally, cryo-electron microscopy experiments indicate that tau and its variants similarly change the microtubule lattice structure by increasing both the protofilament number and lattice defects. Overall, our results uncover novel phosphodependent mechanisms governing tau's ability to trigger microtubule organization and reveal that disease-related modifications of tau promote specific microtubule organizations that may have a deleterious impact during neurodegeneration. © 2018 Prezel, Elie, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  7. Tungsten Stable Isotope Compositions of Ferromanganese Crusts

    Science.gov (United States)

    Abraham, K.; Barling, J.; Hein, J. R.; Schauble, E. A.; Halliday, A. N.

    2014-12-01

    We report the first accurate and precise data for mass-dependent fractionation of tungsten (W) stable isotopes, using a double spike technique and MC-ICPMS. Results are expressed relative to the NIST 3136 W isotope standard as per mil deviations in 186W/184W (δ186W). Although heavy element mass-dependent fractionations are expected to be small, Tl and U both display significant low temperature isotopic fractionations. Theoretical calculations indicate that W nuclear volume isotopic effects should be smaller than mass-dependent fractionations at low temperatures. Hydrogenetic ferromanganese (Fe-Mn) crusts precipitate directly from seawater and have been used as paleoceanographic recorders of temporal changes in seawater chemistry. Crusts are strongly enriched in W and other metals, and are a promising medium for exploring W isotopic variability. Tungsten has a relatively long residence time in seawater of ~61,000 years, mainly as the tungstate ion (WO42-). Water depth profiles show conservative behaviour. During adsorption on Fe-Mn crusts, W species form inner-sphere complexes in the hexavalent (W6+) state. The major host phase is thought to be Mn oxides and the lighter W isotope is expected to be absorbed preferentially. Surface scrapings of 13 globally distributed hydrogenetic Fe-Mn crusts display δ186W from -0.08 to -0.22‰ (±0.03‰, 2sd). A trend toward lighter W isotope composition exists with increasing water depth (~1500 to ~5200m) and W concentration. One hydrothermal Mn-oxide sample is anomalously light and Mn nodules are both heavy and light relative to Fe-Mn crusts. Tungsten speciation depends on concentration, pH, and time in solution and is not well understood because of the extremely slow kinetics of the reactions. In addition, speciation of aqueous and/or adsorbed species might be sensitive to pressure, showing similar thermodynamic stability but different effective volumes. Thus, W stable isotopes might be used as a water-depth barometer in

  8. Iron-binding properties of sugar cane yeast peptides.

    Science.gov (United States)

    de la Hoz, Lucia; Ponezi, Alexandre N; Milani, Raquel F; Nunes da Silva, Vera S; Sonia de Souza, A; Bertoldo-Pacheco, Maria Teresa

    2014-01-01

    The extract of sugar-cane yeast (Saccharomyces cerevisiae) was enzymatically hydrolysed by Alcalase, Protex or Viscozyme. Hydrolysates were fractionated using a membrane ultrafiltration system and peptides smaller than 5kDa were evaluated for iron chelating ability through measurements of iron solubility, binding capacity and dialyzability. Iron-chelating peptides were isolated using immobilized metal affinity chromatography (IMAC). They showed higher content of His, Lys, and Arg than the original hydrolysates. In spite of poor iron solubility, hydrolysates of Viscozyme provided higher iron dialyzability than those of other enzymes. This means that more chelates of iron or complexes were formed and these kept the iron stable during simulated gastro-intestinal digestion in vitro, improving its dialyzability. Published by Elsevier Ltd.

  9. 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...

  10. Factors responsible for a stable biosphere of silicon utilizing organisms

    Science.gov (United States)

    Mitra, D.; Das, S.

    2012-12-01

    -Pg boundary. All these evidences support the role of the unique characteristics of silicon utilizing organisms in maintaining their stable biosphere on earth.

  11. Actin binding proteins and spermiogenesis

    Science.gov (United States)

    Mruk, Dolores D

    2011-01-01

    Drebrin E, an actin-binding protein lacking intrinsic activity in the regulation of actin dynamics (e.g., polymerization, capping, nucleation, branching, cross-linking, bundling and severing), is known to recruit actin regulatory proteins to a specific cellular site. Herein, we critically evaluate recent findings in the field which illustrate that drebrin E works together with two other actin-binding proteins, namely Arp3 (actin-related protein 3, a component of the Arp2/3 complex that simultaneously controls actin nucleation for polymerization and branching of actin filaments) and Eps8 (epidermal growth factor receptor pathway substrate 8 that controls capping of the barbed ends of actin filaments, as well as actin filament bundling) to regulate the homeostasis of F-actin filament bundles at the ectoplasmic specialization (ES), a testis-specific atypical adherens junction (AJ) in the seminiferous epithelium. This is mediated by the strict temporal and spatial expression of these three actin-binding proteins at the apical and basal ES at the Sertoli cell-spermatid (step 8–19) and Sertoli-Sertoli cell interface, respectively, during the seminiferous epithelial cycle of spermatogenesis. In this Commentary, we put forth a possible model by which drebrin E may be acting as a platform upon which proteins (e.g., Arp3) that are needed to alter the conformation of actin filament bundles at the ES can be recruited to the site, thus facilitating changes in cell shape and cell position in the epithelium during spermiogenesis and spermiation. In short, drebrin E may be acting as a “logistic” distribution center to manage different regulatory proteins at the apical ES, thereby regulating the dynamics of actin filament bundles and modulating the plasticity of the apical ES. This would allow adhesion to be altered continuously throughout the epithelial cycle to accommodate spermatid movement in the seminiferous epithelium during spermiogenesis and spermiation. We also

  12. Stable isotope, site-specific mass tagging for protein identification

    Science.gov (United States)

    Chen, Xian

    2006-10-24

    Proteolytic peptide mass mapping as measured by mass spectrometry provides an important method for the identification of proteins, which are usually identified by matching the measured and calculated m/z values of the proteolytic peptides. A unique identification is, however, heavily dependent upon the mass accuracy and sequence coverage of the fragment ions generated by peptide ionization. The present invention describes a method for increasing the specificity, accuracy and efficiency of the assignments of particular proteolytic peptides and consequent protein identification, by the incorporation of selected amino acid residue(s) enriched with stable isotope(s) into the protein sequence without the need for ultrahigh instrumental accuracy. Selected amino acid(s) are labeled with .sup.13C/.sup.15N/.sup.2H and incorporated into proteins in a sequence-specific manner during cell culturing. Each of these labeled amino acids carries a defined mass change encoded in its monoisotopic distribution pattern. Through their characteristic patterns, the peptides with mass tag(s) can then be readily distinguished from other peptides in mass spectra. The present method of identifying unique proteins can also be extended to protein complexes and will significantly increase data search specificity, efficiency and accuracy for protein identifications.

  13. 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

  14. Introducing Stable Radicals into Molecular Machines.

    Science.gov (United States)

    Wang, Yuping; Frasconi, Marco; Stoddart, J Fraser

    2017-09-27

    Ever since their discovery, stable organic radicals have received considerable attention from chemists because of their unique optical, electronic, and magnetic properties. Currently, one of the most appealing challenges for the chemical community is to develop sophisticated artificial molecular machines that can do work by consuming external energy, after the manner of motor proteins. In this context, radical-pairing interactions are important in addressing the challenge: they not only provide supramolecular assistance in the synthesis of molecular machines but also open the door to developing multifunctional systems relying on the various properties of the radical species. In this Outlook, by taking the radical cationic state of 1,1'-dialkyl-4,4'-bipyridinium (BIPY •+ ) as an example, we highlight our research on the art and science of introducing radical-pairing interactions into functional systems, from prototypical molecular switches to complex molecular machines, followed by a discussion of the (i) limitations of the current systems and (ii) future research directions for designing BIPY •+ -based molecular machines with useful functions.

  15. Canonical, stable, general mapping using context schemes.

    Science.gov (United States)

    Novak, Adam M; Rosen, Yohei; Haussler, David; Paten, Benedict

    2015-11-15

    Sequence mapping is the cornerstone of modern genomics. However, most existing sequence mapping algorithms are insufficiently general. We introduce context schemes: a method that allows the unambiguous recognition of a reference base in a query sequence by testing the query for substrings from an algorithmically defined set. Context schemes only map when there is a unique best mapping, and define this criterion uniformly for all reference bases. Mappings under context schemes can also be made stable, so that extension of the query string (e.g. by increasing read length) will not alter the mapping of previously mapped positions. Context schemes are general in several senses. They natively support the detection of arbitrary complex, novel rearrangements relative to the reference. They can scale over orders of magnitude in query sequence length. Finally, they are trivially extensible to more complex reference structures, such as graphs, that incorporate additional variation. We demonstrate empirically the existence of high-performance context schemes, and present efficient context scheme mapping algorithms. The software test framework created for this study is available from https://registry.hub.docker.com/u/adamnovak/sequence-graphs/. anovak@soe.ucsc.edu Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Chemically Stable Lipids for Membrane Protein Crystallization

    Energy Technology Data Exchange (ETDEWEB)

    Ishchenko, Andrii; Peng, Lingling; Zinovev, Egor; Vlasov, Alexey; Lee, Sung Chang; Kuklin, Alexander; Mishin, Alexey; Borshchevskiy, Valentin; Zhang, Qinghai; Cherezov, Vadim (MIPT); (USC); (Scripps)

    2017-05-01

    The lipidic cubic phase (LCP) has been widely recognized as a promising membrane-mimicking matrix for biophysical studies of membrane proteins and their crystallization in a lipidic environment. Application of this material to a wide variety of membrane proteins, however, is hindered due to a limited number of available host lipids, mostly monoacylglycerols (MAGs). Here, we designed, synthesized, and characterized a series of chemically stable lipids resistant to hydrolysis, with properties complementary to the widely used MAGs. In order to assess their potential to serve as host lipids for crystallization, we characterized the phase properties and lattice parameters of mesophases made of two most promising lipids at a variety of different conditions by polarized light microscopy and small-angle X-ray scattering. Both lipids showed remarkable chemical stability and an extended LCP region in the phase diagram covering a wide range of temperatures down to 4 °C. One of these lipids has been used for crystallization and structure determination of a prototypical membrane protein bacteriorhodopsin at 4 and 20 °C.

  17. Migration, fertility, and aging in stable populations.

    Science.gov (United States)

    Alho, Juha M

    2008-08-01

    Fertility is below replacement level in all European countries, and population growth is expected to decline in the coming decades. Increasing life expectancy will accentuate concomitant aging of the population. Migration has been seen as a possible means to decelerate aging. In this article, I introduce a stable, open-population model in which cohort net migration is proportional to births. In this case, the migration-fertility trade-off can be studied with particular ease. I show that although migration can increase the growth rate, which tends to make the age distribution younger, it also has an opposite effect because of its typical age pattern. I capture the effect of the age pattern of net migration in a migration-survivor function. The effect of net migration on growth is quantified with data from 17 European countries. I show that some countries already have a level of migration that will lead to stationarity. For other countries with asymptotically declining population, migration still provides opportunities for slowing down aging of the population as a whole.

  18. Shelf-stable foods through irradiation processing

    International Nuclear Information System (INIS)

    1995-11-01

    This survey has been produced from a database on analytical reference materials of biological and environmental origin, which is maintained at the International Atomic Energy Agency. It is an updated version of earlier reports, the last published in 1990. The information presented refers mostly to reference materials for trace element constituents; however, information is also included on a number of other selected measurands of relevance to IAEA programmes, i.e. radionuclides, stable isotopes, anions, cations, organometallic compounds and organic contaminants. The database presently contains over 10,000 analyte values for 455 measurands in 650 reference materials produced by 30 different suppliers. Additional information on the cost of the materials, the unit size supplied, and recommended minimum weight of material for analysis is also provided, if this information is available to the authors. It is expected that this survey will help analysts to select reference materials for quality assurance purposes that match as closely as possible, with respect to matrix type and concentrations of the measurands of interest, their samples to be analyzed. 22 refs, 2 tabs

  19. STABLE ISOTOPE GEOCHEMISTRY OF MASSIVE ICE

    Directory of Open Access Journals (Sweden)

    Yurij K. Vasil’chuk

    2016-01-01

    Full Text Available The paper summarises stable-isotope research on massive ice in the Russian and North American Arctic, and includes the latest understanding of massive-ice formation. A new classification of massive-ice complexes is proposed, encompassing the range and variabilityof massive ice. It distinguishes two new categories of massive-ice complexes: homogeneousmassive-ice complexes have a similar structure, properties and genesis throughout, whereasheterogeneous massive-ice complexes vary spatially (in their structure and properties andgenetically within a locality and consist of two or more homogeneous massive-ice bodies.Analysis of pollen and spores in massive ice from Subarctic regions and from ice and snow cover of Arctic ice caps assists with interpretation of the origin of massive ice. Radiocarbon ages of massive ice and host sediments are considered together with isotope values of heavy oxygen and deuterium from massive ice plotted at a uniform scale in order to assist interpretation and correlation of the ice.

  20. LHC Report: Towards stable beams and collisions

    CERN Multimedia

    CERN Bulletin

    2011-01-01

    Over the past two weeks, the LHC re-commissioning with beam has continued at a brisk pace. The first collisions of 2011 were produced on 2 March, with stable beams and collisions for physics planned for the coming days. Low intensity beams with just a few bunches of particles were used to test the energy ramp to 3.5 TeV and the squeeze. The results were successful and, as a by-product, the first collisions of 2011 were recorded 2 March. One of the main activities carried out by the operation teams has been the careful set-up of the collimation system, and the injection and beam dump protection devices. The collimation system provides essential beam cleaning, preventing stray particles from impacting other elements of the machine, particularly the superconducting magnets. In addition to the collimation system, also the injection and beam dump protection devices perform a vital machine protection role, as they detect any beam that might be mis-directed during rare, but not totally unavoidable, hardware hiccups...

  1. Stable Isotope Group 1984 progress report

    International Nuclear Information System (INIS)

    Lyon, G.L.

    1985-04-01

    The work of the group in 1984 is described and includes studies in isotope geology, isotope hydrology, geochronology, isotope biology and mass spectrometer instrumentation. Geothermal studies have decreased compared to other years, but major data summaries were made for Wairakei and Ngawha. The hydrology of Whakarewarewa and Rotorua is being elucidated using water isotopes. Models of the subsurface flows at Kawerau and Ngawha are being made to relate fluid to mineral isotope compositions. A study of the δ 13 C and δ 34 S compositions of New Zealand oils has been started. Groups of oils of related origin are being defined, and compositions will be compared with those of potential source rocks. A method was developed for isotope analysis of sulphur in rocks. The isotopic composition of water is being used to identify and characterise groundwater aquifers in the Wairarapa and at Poverty Bay. Stable carbon isotopes have been used to identify food sources for invertebrates, and to show biochemical pathways in lactation by cows. The geochronology group is involved in major studies in Antarctica, using U-Pb, Rb-Sr and K-Ar methods. Rocks from North Victoria Land, Marie Byrd Land and the USARP mountains are being compared with possible correlatives in New Zealand and Argentina. Strontium isotope data is being applied to the origin of magmas in several regions of New Zealand. The K-Ar data is being stored on computer files. Fission track measurements are being applied to unravel uplift histories in Westland and Taranaki

  2. An Sp1/Sp3 binding polymorphism confers methylation protection.

    Directory of Open Access Journals (Sweden)

    Yanis A Boumber

    2008-08-01

    Full Text Available Hundreds of genes show aberrant DNA hypermethylation in cancer, yet little is known about the causes of this hypermethylation. We identified RIL as a frequent methylation target in cancer. In search for factors that influence RIL hypermethylation, we found a 12-bp polymorphic sequence around its transcription start site that creates a long allele. Pyrosequencing of homozygous tumors revealed a 2.1-fold higher methylation for the short alleles (P<0.001. Bisulfite sequencing of cancers heterozygous for RIL showed that the short alleles are 3.1-fold more methylated than the long (P<0.001. The comparison of expression levels between unmethylated long and short EBV-transformed cell lines showed no difference in expression in vivo. Electrophorectic mobility shift assay showed that the inserted region of the long allele binds Sp1 and Sp3 transcription factors, a binding that is absent in the short allele. Transient transfection of RIL allele-specific transgenes showed no effects of the additional Sp1 site on transcription early on. However, stable transfection of methylation-seeded constructs showed gradually decreasing transcription levels from the short allele with eventual spreading of de novo methylation. In contrast, the long allele showed stable levels of expression over time as measured by luciferase and approximately 2-3-fold lower levels of methylation by bisulfite sequencing (P<0.001, suggesting that the polymorphic Sp1 site protects against time-dependent silencing. Our finding demonstrates that, in some genes, hypermethylation in cancer is dictated by protein-DNA interactions at the promoters and provides a novel mechanism by which genetic polymorphisms can influence an epigenetic state.

  3. Potential uses of stable isotope ratios of Sr, Nd, and Pb in geological materials for environmental studies.

    Science.gov (United States)

    Nakano, Takanori

    2016-01-01

    The ratios of stable isotopes of certain elements in rocks and minerals have strong regional characteristics that are reflected in atmospheric components, in water, and in the living organisms that form Earth's surface environment as well as in agricultural and fishery products. Geologically derived stable isotope ratios can be used as a tracer for the source of many kinds of substances, with current geochemical techniques allowing the precise determination of numerous stable isotope ratios in both natural and manmade objects. This review presents examples of the use of stable isotopes as tracers within diverse dynamic ecosystems, focusing on Sr isotopes but also including examples of Nd and Pb isotopic analysis, and reviewing the potential of this technique for a wide range of environmental research, including determining the geographic origin of food and archeological materials.

  4. Potential uses of stable isotope ratios of Sr, Nd, and Pb in geological materials for environmental studies

    Science.gov (United States)

    NAKANO, Takanori

    2016-01-01

    The ratios of stable isotopes of certain elements in rocks and minerals have strong regional characteristics that are reflected in atmospheric components, in water, and in the living organisms that form Earth’s surface environment as well as in agricultural and fishery products. Geologically derived stable isotope ratios can be used as a tracer for the source of many kinds of substances, with current geochemical techniques allowing the precise determination of numerous stable isotope ratios in both natural and manmade objects. This review presents examples of the use of stable isotopes as tracers within diverse dynamic ecosystems, focusing on Sr isotopes but also including examples of Nd and Pb isotopic analysis, and reviewing the potential of this technique for a wide range of environmental research, including determining the geographic origin of food and archeological materials. PMID:27302069

  5. Sex hormone binding globulin phenotypes

    DEFF Research Database (Denmark)

    Cornelisse, M M; Bennett, Patrick; Christiansen, M

    1994-01-01

    Human sex hormone binding globulin (SHBG) is encoded by a normal and a variant allele. The resulting SHBG phenotypes (the homozygous normal SHBG, the heterozygous SHBG and the homozygous variant SHBG phenotype) can be distinguished by their electrophoretic patterns. We developed a novel detection....... This method of detection was used to determine the distribution of SHBG phenotypes in healthy controls of both sexes and in five different pathological conditions characterized by changes in the SHBG level or endocrine disturbances (malignant and benign ovarian neoplasms, hirsutism, liver cirrhosis...... on the experimental values. Differences in SHBG phenotypes do not appear to have any clinical significance and no sex difference was found in the SHBG phenotype distribution....

  6. Non-canonical binding interactions of the RNA recognition motif (RRM domains of P34 protein modulate binding within the 5S ribonucleoprotein particle (5S RNP.

    Directory of Open Access Journals (Sweden)

    Anyango D Kamina

    Full Text Available RNA binding proteins are involved in many aspects of RNA metabolism. In Trypanosoma brucei, our laboratory has identified two trypanosome-specific RNA binding proteins P34 and P37 that are involved in the maturation of the 60S subunit during ribosome biogenesis. These proteins are part of the T. brucei 5S ribonucleoprotein particle (5S RNP and P34 binds to 5S ribosomal RNA (rRNA and ribosomal protein L5 through its N-terminus and its RNA recognition motif (RRM domains. We generated truncated P34 proteins to determine these domains' interactions with 5S rRNA and L5. Our analyses demonstrate that RRM1 of P34 mediates the majority of binding with 5S rRNA and the N-terminus together with RRM1 contribute the most to binding with L5. We determined that the consensus ribonucleoprotein (RNP 1 and 2 sequences, characteristic of canonical RRM domains, are not fully conserved in the RRM domains of P34. However, the aromatic amino acids previously described to mediate base stacking interactions with their RNA target are conserved in both of the RRM domains of P34. Surprisingly, mutation of these aromatic residues did not disrupt but instead enhanced 5S rRNA binding. However, we identified four arginine residues located in RRM1 of P34 that strongly impact L5 binding. These mutational analyses of P34 suggest that the binding site for 5S rRNA and L5 are near each other and specific residues within P34 regulate the formation of the 5S RNP. These studies show the unique way that the domains of P34 mediate binding with the T. brucei 5S RNP.

  7. First Passage Time for Tempered Stable Process and Its Application to Perpetual American Option and Barrier Option Pricing

    OpenAIRE

    Kim, Young Shin

    2018-01-01

    In this paper, we will discuss an approximation of the characteristic function of the first passage time for a Levy process using the martingale approach. The characteristic function of the first passage time of the tempered stable process is provided explicitly or by an indirect numerical method. This will be applied to the perpetual American option pricing and the barrier option pricing. Numerical illustrations are provided for the calibrated parameters using the market call and put prices.

  8. Reshaping the Energy Landscape Transforms the Mechanism and Binding Kinetics of DNA Threading Intercalation.

    Science.gov (United States)

    Clark, Andrew G; Naufer, M Nabuan; Westerlund, Fredrik; Lincoln, Per; Rouzina, Ioulia; Paramanathan, Thayaparan; Williams, Mark C

    2018-02-06

    Molecules that bind DNA via threading intercalation show high binding affinity as well as slow dissociation kinetics, properties ideal for the development of anticancer drugs. To this end, it is critical to identify the specific molecular characteristics of threading intercalators that result in optimal DNA interactions. Using single-molecule techniques, we quantify the binding of a small metal-organic ruthenium threading intercalator (Δ,Δ-B) and compare its binding characteristics to a similar molecule with significantly larger threading moieties (Δ,Δ-P). The binding affinities of the two molecules are the same, while comparison of the binding kinetics reveals significantly faster kinetics for Δ,Δ-B. However, the kinetics is still much slower than that observed for conventional intercalators. Comparison of the two threading intercalators shows that the binding affinity is modulated independently by the intercalating section and the binding kinetics is modulated by the threading moiety. In order to thread DNA, Δ,Δ-P requires a "lock mechanism", in which a large length increase of the DNA duplex is required for both association and dissociation. In contrast, measurements of the force-dependent binding kinetics show that Δ,Δ-B requires a large DNA length increase for association but no length increase for dissociation from DNA. This contrasts strongly with conventional intercalators, for which almost no DNA length change is required for association but a large DNA length change must occur for dissociation. This result illustrates the fundamentally different mechanism of threading intercalation compared with conventional intercalation and will pave the way for the rational design of therapeutic drugs based on DNA threading intercalation.

  9. Embryotoxicity of stable isotopes and use of stable isotopes in studies of teratogenetic mechanisms

    International Nuclear Information System (INIS)

    Spielmann, H.; Nau, H.

    1986-01-01

    Experiments on teratogenic effects of stable isotopes from our own and other laboratories are evaluated. In the first series of investigations, the enrichment of the stable isotope 13 C derived from U- 13 C-glucose was studied in mouse embryos at various stages of development, including limb buds in organ culture. Preimplantation mouse embryos incubated in vitro in 13 C-enriched medium for 48 hours showed normal development during subsequent differentiation in vitro and also in vivo after embryo transfer to faster mothers. These embryos were 15% to 20% enriched in 13 C. Administration of U-13-C-glucose to pregnant mice during organogenesis led to an increase of the absolute 13 C content of the embryo for several days after the end of isotope administration, whereas the enrichment in maternal tissue decreased. No alterations of embryonic development were detected due to stable isotope enrichment. Development of cultured mouse limb buds was unaffected by incubation with 82 mol% U- 13 C-glucose as judged from morphologic and biochemical criteria. The second part of the article describes the value of deuterium-labeled drugs as probes into the mechanism of activation of teratogenic metabolites. A comparison of the pharmacokinetics as well as the teratogenicity between cyclophosphamide and some specific deuterium-labeled analogues showed that the isotope effect observed can be related to a particular metabolic pathway crucial for teratogenic activation by this drug

  10. Binding thermodynamics of a glutamate transporter homologue

    Science.gov (United States)

    Reyes, Nicolas; Oh, SeCheol; Boudker, Olga

    2013-01-01

    Glutamate transporters catalyze concentrative uptake of the neurotransmitter into glial cells and neurons. Their transport cycle involves binding and release of the substrate on the extra- and intracellular sides of the plasma membranes, and translocation of the substrate-binding site across the lipid bilayers. The energy of the ionic gradients, mainly sodium, fuels the cycle. Here, we used a cross-linking approach to trap a glutamate transporter homologue from Pyrococcus horikoshii in key conformational states with substrate-binding site facing either the extracellular or intracellular sides of the membrane to study their binding thermodynamics. We show that the chemical potential of sodium ions in solution is exclusively coupled to substrate binding and release, and not to substrate translocation. Despite the structural symmetry, the binding mechanisms are distinct on the opposite sides of the membrane and more complex than the current models suggest. PMID:23563139

  11. An Aromatic Cap Seals the Substrate Binding Site in an ECF-Type S Subunit for Riboflavin

    Energy Technology Data Exchange (ETDEWEB)

    Karpowich, Nathan K.; Song, Jinmei; Wang, Da-Neng

    2016-06-13

    ECF transporters are a family of active membrane transporters for essential micronutrients, such as vitamins and trace metals. Found exclusively in archaea and bacteria, these transporters are composed of four subunits: an integral membrane substrate-binding subunit (EcfS), a transmembrane coupling subunit (EcfT), and two ATP-binding cassette ATPases (EcfA and EcfA'). We have characterized the structural basis of substrate binding by the EcfS subunit for riboflavin from Thermotoga maritima, TmRibU. TmRibU binds riboflavin with high affinity, and the protein–substrate complex is exceptionally stable in solution. The crystal structure of riboflavin-bound TmRibU reveals an electronegative binding pocket at the extracellular surface in which the substrate is completely buried. Analysis of the intermolecular contacts indicates that nearly every available substrate hydrogen bond is satisfied. A conserved aromatic residue at the extracellular end of TM5, Tyr130, caps the binding site to generate a substrate-bound, occluded state, and non-conservative mutation of Tyr130 reduces the stability of this conformation. Using a novel fluorescence binding assay, we find that an aromatic residue at this position is essential for high-affinity substrate binding. Comparison with other S subunit structures suggests that TM5 and Loop5-6 contain a dynamic, conserved motif that plays a key role in gating substrate entry and release by S subunits of ECF transporters.

  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 conformational state of the nucleosome entry–exit site modulates TATA box-specific TBP binding

    Science.gov (United States)

    Hieb, Aaron R.; Gansen, Alexander; Böhm, Vera; Langowski, Jörg

    2014-01-01

    The TATA binding protein (TBP) is a critical transcription factor used for nucleating assembly of the RNA polymerase II machinery. TBP binds TATA box elements with high affinity and kinetic stability and in vivo is correlated with high levels of transcription activation. However, since most promoters use less stable TATA-less or TATA-like elements, while also competing with nucleosome occupancy, further mechanistic insight into TBP's DNA binding properties and ability to access chromatin is needed. Using bulk and single-molecule FRET, we find that TBP binds a minimal consensus TATA box as a two-state equilibrium process, showing no evidence for intermediate states. However, upon addition of flanking DNA sequence, we observe non-specific cooperative binding to multiple DNA sites that compete for TATA-box specificity. Thus, we conclude that TBP binding is defined by a branched pathway, wherein TBP initially binds with little sequence specificity and is thermodynamically positioned by its kinetic stability to the TATA box. Furthermore, we observed the real-time access of TBP binding to TATA box DNA located within the DNA entry–exit site of the nucleosome. From these data, we determined salt-dependent changes in the nucleosome conformation regulate TBP's access to the TATA box, where access is highly constrained under physiological conditions, but is alleviated by histone acetylation and TFIIA. PMID:24829456

  14. The conformational state of the nucleosome entry-exit site modulates TATA box-specific TBP binding.

    Science.gov (United States)

    Hieb, Aaron R; Gansen, Alexander; Böhm, Vera; Langowski, Jörg

    2014-07-01

    The TATA binding protein (TBP) is a critical transcription factor used for nucleating assembly of the RNA polymerase II machinery. TBP binds TATA box elements with high affinity and kinetic stability and in vivo is correlated with high levels of transcription activation. However, since most promoters use less stable TATA-less or TATA-like elements, while also competing with nucleosome occupancy, further mechanistic insight into TBP's DNA binding properties and ability to access chromatin is needed. Using bulk and single-molecule FRET, we find that TBP binds a minimal consensus TATA box as a two-state equilibrium process, showing no evidence for intermediate states. However, upon addition of flanking DNA sequence, we observe non-specific cooperative binding to multiple DNA sites that compete for TATA-box specificity. Thus, we conclude that TBP binding is defined by a branched pathway, wherein TBP initially binds with little sequence specificity and is thermodynamically positioned by its kinetic stability to the TATA box. Furthermore, we observed the real-time access of TBP binding to TATA box DNA located within the DNA entry-exit site of the nucleosome. From these data, we determined salt-dependent changes in the nucleosome conformation regulate TBP's access to the TATA box, where access is highly constrained under physiological conditions, but is alleviated by histone acetylation and TFIIA. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. 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.

  16. Binding energy of the barbell exciton

    Science.gov (United States)

    Peeters, F. M.; Golub, J. E.

    1991-02-01

    The exciton binding energy in asymmetric coupled double quantum wells is calculated. As the system is electrically tuned from type I to type II, the exciton binding energy decreases from that of a two-dimensional exciton to the binding energy of a spatially separated electron-hole pair, i.e., the barbell exciton.$-- We compare our theoretical results with a recent experiment and find good agreement.

  17. CAP binding proteins associated with the nucleus.

    OpenAIRE

    Patzelt, E; Blaas, D; Kuechler, E

    1983-01-01

    Cap binding proteins of HeLa cells were identified by photo-affinity labelling using the cap analogue gamma-[32P]-[4-(benzoyl-phenyl)methylamido]-7-methylguanosine-5'- triphosphate. Photoreaction with whole cell homogenates resulted in specific labelling of five major polypeptides. The small molecular weight polypeptide appeared to be identical to the 24 000 to 26 000 dalton cap binding protein previously identified in initiation factors. A cap binding protein of 37 000 dalton was found in in...

  18. Evaluation of Cu(i) binding to the E2 domain of the amyloid precursor protein - a lesson in quantification of metal binding to proteins via ligand competition.

    Science.gov (United States)

    Young, Tessa R; Wedd, Anthony G; Xiao, Zhiguang

    2018-01-24

    The extracellular domain E2 of the amyloid precursor protein (APP) features a His-rich metal-binding site (denoted as the M1 site). In conjunction with surrounding basic residues, the site participates in interactions with components of the extracellular matrix including heparins, a class of negatively charged polysaccharide molecules of varying length. This work studied the chemistry of Cu(i) binding to APP E2 with the probe ligands Bcs, Bca, Fz and Fs. APP E2 forms a stable Cu(i)-mediated ternary complex with each of these anionic ligands. The complex with Bca was selected for isolation and characterization and was demonstrated, by native ESI-MS analysis, to have the stoichiometry E2 : Cu(i) : Bca = 1 : 1 : 1. Formation of these ternary complexes is specific for the APP E2 domain and requires Cu(i) coordination to the M1 site. Mutation of the M1 site was consistent with the His ligands being part of the E2 ligand set. It is likely that interactions between the negatively charged probe ligands and a positively charged patch on the surface of APP E2 are one aspect of the generation of the stable ternary complexes. Their formation prevented meaningful quantification of the affinity of Cu(i) binding to the M1 site with these probe ligands. However, the ternary complexes are disrupted by heparin, allowing reliable determination of a picomolar Cu(i) affinity for the E2/heparin complex with the Fz or Bca probe ligands. This is the first documented example of the formation of stable ternary complexes between a Cu(i) binding protein and a probe ligand. The ready disruption of the complexes by heparin identified clear 'tell-tale' signs for diagnosis of ternary complex formation and allowed a systematic review of conditions and criteria for reliable determination of affinities for metal binding via ligand competition. This study also provides new insights into a potential correlation of APP functions regulated by copper binding and heparin interaction.

  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.