Single-site Model Research Articles

Surface complexation modeling of Co(II) adsorption on mixtures of hydrous ferric oxide, quartz and kaolinite

Co sorption was measured as a function of pH, ionic strength (0.001–0.1 M NaNO 3) and sorbate/sorbent ratio on pure quartz, HFO and kaolinite and on binary and ternary mixtures of the three solids. Sorption data measured for the pure solids were used to derive internally-consistent diffuse layer surface complexation model (DLM) stability constants for Co sorption. Co sorption on HFO could be adequately modeled over a broad range of ionic strengths and sorbate/sorbent ratios with a two variable-charge site model. Fits based on a single variable-charge site model were reasonable, but were improved by using ionic-strength dependent stability constants. A single variable-charge site model with an additional permanent ion exchange site produced the best fit to Co edges measured on kaolinite over a range of ionic strength and sorbate/sorbent ratios. These DLM fits were also improved by using ionic-strength dependent stability constants. The DLM approach could not adequately describe the slope of Co sorption edges on quartz. This study demonstrates that for accurate prediction of Co sorption over wide ranges of ionic strength and sorbate/sorbent ratio, the DLM may require ionic-strength dependent stability constants. DLM stability constants for Co sorption derived for the pure solids were used to predict sorption as a function of pH and solid concentration on binary and ternary mixtures of the three solids. Discrepancies between predictions and measurements were quantitatively similar to those observed for the pure mineral systems. Thus, a simple component additivity approach provides useful predictions of metal sorption in the mixed solid systems.

Model Discrimination in Chemical Kinetics

In studies on chemical kinetics, generally after the rate data have been taken, a mechanism and an associated rate law model are proposed based on the data taken. Frequently, more than one mechanism and rate law may be consis- tent with data. In order to find the correct rate law, regression techniques (model discrimination) are applied to indentify which model equation best fits the data by choosing the one with the smaller sum of squares. With this non-linear regres- sion technique, rate parameters with 95% confidence limits are calculated along with residues. Of course, model parame- ters must be realistic. For example, reaction rate constants, activation energies or adsorption equilibrium constants must be positive by comparing the calculated value of parameters with 95% confidence limits, one can judge about the validity of the model. In this paper, model discrimination will be applied to certain data from the literature along with the suggested heterogene- ous catalytic models such as Langmuir-Hinshelwood Kinetic Model or Rideal-Eley Model. A reaction of A + B C + D type have been selected (like methanation) with the rate laws given below: rA = kPAPB /1 + KAPA + KBPB + KCPC + KDPD () 2 dual-site Langmuir-Hinshelwood Model r A = kP A P B /1 + K A P A + K B P B + K C P C + K D P D () single-site Langmuir-Hinshelwood Model

Regulation of the Xylan-degrading Apparatus of Cellvibrio japonicus by a Novel Two-component System

The microbial degradation of lignocellulose biomass is not only an important biological process but is of increasing industrial significance in the bioenergy sector. The mechanism by which the plant cell wall, an insoluble composite structure, activates the extensive repertoire of microbial hydrolytic enzymes required to catalyze its degradation is poorly understood. Here we have used a transposon mutagenesis strategy to identify a genetic locus, consisting of two genes that modulate the expression of xylan side chain-degrading enzymes in the saprophytic bacterium Cellvibrio japonicus. Significantly, the locus encodes a two-component signaling system, designated AbfS (sensor histidine kinase) and AbfR (response regulator). The AbfR/S two-component system is required to activate the expression of the suite of enzymes that remove the numerous side chains from xylan, but not the xylanases that hydrolyze the beta1,4-linked xylose polymeric backbone of this polysaccharide. Studies on the recombinant sensor domain of AbfS (AbfS(SD)) showed that it bound to decorated xylans and arabinoxylo-oligosaccharides, but not to undecorated xylo-oligosaccharides or other plant structural polysaccharides/oligosaccharides. The crystal structure of AbfS(SD) was determined to a resolution of 2.6A(.) The overall fold of AbfS(SD) is that of a classical Per Arndt Sim domain with a central antiparallel four-stranded beta-sheet flanked by alpha-helices. Our data expand the number of molecules known to bind to the sensor domain of two-component histidine kinases to include complex carbohydrates. The biological rationale for a regulatory system that induces enzymes that remove the side chains of xylan, but not the hydrolases that cleave the backbone of the polysaccharide, is discussed.

A Catalytic Role of Heparin within the Extracellular Matrix

We investigated the mechanism by which heparin enhances the binding of vascular endothelial growth factor (VEGF) to the extracellular matrix protein fibronectin. In contrast to other systems, where heparin acts as a protein scaffold, we found that heparin functions catalytically to modulate VEGF binding site availability on fibronectin. By measuring the binding of VEGF and heparin to surface-immobilized fibronectin, we show that substoichiometric amounts of heparin exposed cryptic VEGF binding sites within fibronectin that remain available after heparin removal. Measurement of association and dissociation kinetics for heparin binding to fibronectin indicated that the interaction is rapid and transient. We localized the heparin-responsive element to the C-terminal 40-kDa Hep2 domain of fibronectin. A mathematical model of this catalytic process was constructed that supports a mechanism whereby the heparin-induced conformational change in fibronectin is accompanied by release of heparin. Experiments with endothelial extracellular matrix suggest that this process may also occur within biological matrices. These results indicate a novel mechanism whereby heparin catalyzes the conversion of fibronectin to an open conformation by transiently interacting with fibronectin and progressively hopping from molecule to molecule. Catalytic activation of the extracellular matrix might be an important mechanism for heparin to regulate function during normal and disease states.

Carbohydrate Binding Mechanism of the Macrophage Galactose-type C-type Lectin 1 Revealed by Saturation Transfer Experiments

Macrophage galactose-type C-type lectins 1 and 2 (MGL1/2) are expressed on the surfaces of macrophages and immature dendritic cells. Despite the high similarity between the primary sequences of MGL1 and MGL2, they display different ligand specificities. MGL1 shows high affinity for the LewisX trisaccharide, whereas MGL2 shows affinity for N-acetylgalactosamine. To elucidate the structural basis for the ligand specificities of the MGLs, we performed NMR analyses of the MGL1-LewisX complex. To identify the LewisX binding site on MGL1, a saturation transfer experiment for the MGL1-LewisX complex where sugar-CH/CH2-selective saturation was applied was carried out. To obtain sugar moiety-specific information on the interface between MGL1 and the LewisX trisaccharide, saturation transfer experiments where each of galactose-H5-, fucose-CH3-, and N-acetylglucosamine-CH3-selective saturations was applied to the MGL1-LewisX complex were performed. Based on these results, we present a LewisX binding mode on MGL1 where the galactose moiety is bound to the primary sugar binding site, including Asp-94, Trp-96, and Asp-118, and the fucose moiety interacts with the secondary sugar binding site, including Ala-89 and Thr-111. Ala-89 and Thr-111 in MGL1 are replaced with arginine and serine in MGL2, respectively. The hydrophobic environment formed by a small side chain of Ala-89 and a methyl group of Thr-111 is a requisite for the accommodation of the fucose moiety of the LewisX trisaccharide within the sugar binding site of MGL1.

Assembly of Oligomeric Death Domain Complexes during Toll Receptor Signaling

The Drosophila Toll receptor is activated by the endogenous protein ligand Spätzle in response to microbial stimuli in immunity and spatial cues during embryonic development. Downstream signaling is mediated by the adaptor proteins Tube, the kinase Pelle, and the Drosophila homologue of myeloid differentiation primary response protein (dMyD88). Here we have characterized heterodimeric (dMyD88-Tube) and heterotrimeric (dMyD88-Tube-Pelle) death domain complexes. We show that both the heterodimeric and heterotrimeric complexes form kidney-shaped structures and that Tube is bivalent and has separate high affinity binding sites for dMyD88 and Pelle. Additionally we found no interaction between the isolated death domains of Pelle and dMyD88. These results indicate that the mode of assembly of the heterotrimeric dMyD88-Tube-Pelle complex downstream of the activated Toll receptor is unique. The measured dissociation constants for the interaction between the death domains of dMyD88 and Tube and of Pelle and a preformed dMyD88-Tube complex are used to propose a model of the early postreceptor events in Drosophila Toll receptor signaling.

Crystal Structure and NMR Binding Reveal That Two Small Molecule Antagonists Target the High Affinity Ephrin-binding Channel of the EphA4 Receptor

The Eph receptor tyrosine kinases regulate a variety of physiological and pathological processes not only during development but also in adult organs, and therefore they represent a promising class of drug targets. The EphA4 receptor plays important roles in the inhibition of the regeneration of injured axons, synaptic plasticity, platelet aggregation, and likely in certain types of cancer. Here we report the first crystal structure of the EphA4 ligand-binding domain, which adopts the same jellyroll beta-sandwich architecture as shown previously for EphB2 and EphB4. The similarity with EphB receptors is high in the core beta-stranded regions, whereas large variations exist in the loops, particularly the D-E and J-K loops, which form the high affinity ephrin binding channel. We also used isothermal titration calorimetry, NMR spectroscopy, and computational docking to characterize the binding to EphA4 of two small molecules, 4- and 5-(2,5 dimethyl-pyrrol-1-yl)-2-hydroxybenzoic acid which antagonize ephrin-induced effects in EphA4-expressing cells. We show that the two molecules bind to the EphA4 ligand-binding domain with K(d) values of 20.4 and 26.4 microm, respectively. NMR heteronuclear single quantum coherence titrations revealed that upon binding, both molecules significantly perturb EphA4 residues Ile(31)-Met(32) in the D-E loop, Gln(43) in the E beta-strand, and Ile(131)-Gly(132) in the J-K loop. Molecular docking shows that they can occupy a cavity in the high affinity ephrin binding channel of EphA4 in a similar manner, by interacting mainly with the EphA4 residues in the E strand and D-E and J-K loops. However, many of the interactions observed in Eph receptor-ephrin complexes are absent, which is consistent with the small size of the two molecules and may account for their relatively weak binding affinity. Thus, our studies provide the first published structure of the ligand-binding domain of an EphA receptor of the A subclass. Furthermore, the results demonstrate that the high affinity ephrin binding channel of the Eph receptors is amenable to targeting with small molecule antagonists and suggest avenues for further optimization.

Crystal Structures of NADH:FMN Oxidoreductase (EmoB) at Different Stages of Catalysis

EDTA has become a major organic pollutant in the environment because of its extreme usage and resistance to biodegradation. Recently, two critical enzymes, EDTA monooxygenase (EmoA) and NADH:FMN oxidoreductase (EmoB), belonging to the newly established two-component flavin-diffusible monooxygenase family, were identified in the EDTA degradation pathway in Mesorhizobium sp. BNC1. EmoA is an FMNH2-dependent enzyme that requires EmoB to provide FMNH2 for the conversion of EDTA to ethylenediaminediacetate. To understand the molecular basis of this FMN-mediated reaction, the crystal structures of the apo-form, FMN.FMN complex, and FMN.NADH complex of EmoB were determined at 2.5 angstroms resolution. The structure of EmoB is a homotetramer consisting of four alpha/beta-single-domain monomers of five parallel beta-strands flanked by five alpha-helices, which is quite different from those of other known two-component flavin-diffusible monooxygenase family members, such as PheA2 and HpaC, in terms of both tertiary and quaternary structures. For the first time, the crystal structures of both the FMN.FMN and FMN.NADH complexes of an NADH:FMN oxidoreductase were determined. Two stacked isoalloxazine rings and nicotinamide/isoalloxazine rings were at a proper distance for hydride transfer. The structures indicated a ping-pong reaction mechanism, which was confirmed by activity assays. Thus, the structural data offer detailed mechanistic information for hydride transfer between NADH to an enzyme-bound FMN and between the bound FMNH2 and a diffusible FMN.

Welfare Measurement Convergence Through Bias Adjustments in General Population and On-Site Surveys: An Application to Water-based Recreation at Lake Sevan, Armenia

This paper compares household survey with on-site survey data for estimating the access value of a unique natural resource using a single-site travel cost model. The household survey model is adjusted for inflated zero observations for respondents who would not visit the site at any observable positive price. The on-site survey model is corrected for truncation and endogenous stratification, the latter being an adjustment for avidity bias. In an application to recreation at Lake Sevan (Armenia), consumer surplus estimates were not statistically different between the household model and the on-site model when zero-inflation and truncation and endogenous stratification are corrected In the respective models. This leads us to believe that either method can be used to derive a consistent welfare measure of access to a recreational site after appropriate adjustments and corrections are made. These results are somewhat reassuring as the choice between household and on-site surveys is often dictated by time and resource availability.

Inelastic effects in electron transport studied with wave packet propagation

A time-dependent approach is used to explore inelastic effects during electron transport through few-level systems. We study a tight-binding chain with one and two sites connected to vibrations. This simple but transparent model gives insight about inelastic effects, their meaning, and the approximations currently used to treat them. Our time-dependent approach allows us to trace back the time sequence of vibrational excitation and electronic interference, the vibrationally introduced time delay, and the electronic phase shift. We explore a full range of parameters going from weak to strong electron-vibration coupling, from tunneling to contact, and from one-vibration description to the need of including all vibrations for a correct description of inelastic effects in transport. We explore the validity of single-site resonant models as well as its extension to more sites via molecular orbitals and the conditions under which multiorbital and multivibrational descriptions cannot be simplified. We explain the physical meaning of the spectral features in the second derivative of the electron current with respect to the bias voltage. This permits us to nuance the meaning of the energy value of dips and peaks. Finally, we show that finite-band effects lead to electron backscattering off the molecular vibrations in the regime of high-conductance, although the drop in conductance at the vibrational threshold is rather due to the rapid variation of the vibronic density of states.

Hydrogenation of Benzaldehyde over Palladium Intercalated Bentonite Catalysts: Kinetic Studies

Bentonite, a 2:1 type swellable phyllosilicate clay mineral having exchangeable inorganic cations in the interlamellar space to nullify their charge deficiency was used to generate palladium nanoparticles. It was found that 1% w/w palladium nanoparticles were generated in the interlamellar space using adsorption excess technique. The synthesized catalysts were characterized by using XRD, TEM, BET surface area analysis, and AAS. The modified clay catalysts were tested for their catalytic activity towards the hydrogenation of benzaldehyde to benzyl alcohol in liquid phase using a high-pressure reactor at various temperatures and pressures. High selectivity (100%) towards the desired product of benzyl alcohol was achieved with conversion over 80% in all cases. These results showed different hydrogen dependency for the reaction at various temperatures. The kinetics of the reaction was studied using Langmuir Hinshelwood single site model. The rate constant was determined using pseudo first-order kinetics and activation energy for benzaldehyde hydrogenation was calculated at various temperatures using Arrhenius equation and was found to decrease with increase in temperature.

Rate equations and isotherms for two adsorption models

The rate equations and isotherms for two adsorption models have been formulated and discussed. The rate equations obtained have been compared to those of pseudo-first-order model and pseudo-second-order model, respectively. Calculated results indicated that the rate equations of single site model and dual site model could be approximated by those of pseudo-first-order model and pseudo-second-order model, respectively, in a limited ranges of the values of C A ⋅ Se ∗ ( or C A ⋅ S 2 e ∗ ) , K*and t*. The adsorption isotherm of single site model has been found to be the same as that of Langmuir type.

Enhanced dopamine D2 receptor function in hypothalamus and corpus striatum: their role in liver, plasma and in vitro hepatocyte ALDH regulation in ethahol treated rats

Dopamine D(2) receptors are involved in ethanol self- administration behavior and also suggested to mediate the onset and offset of ethanol drinking. In the present study, we investigated dopamine (DA) content and Dopamine D(2) (DA D(2)) receptors in the hypothalamus and corpus striatum of ethanol treated rats and aldehyde dehydrogenase (ALDH) activity in the liver and plasma of ethanol treated rats and in vitro hepatocyte cultures. Hypothalamic and corpus striatal DA content decreased significantly (P < 0.05, P < 0.001 respectively) and homovanillic acid/dopamine (HVA/DA) ratio increased significantly (P < 0.001) in ethanol treated rats when compared to control. Scatchard analysis of [(3)H] YM-09151-2 binding to DA D(2) receptors in hypothalamus showed a significant increase (P < 0.001) in B(max) without any change in K(d) in ethanol treated rats compared to control. The K(d) of DA D(2) receptors significantly decreased (P < 0.05) in the corpus striatum of ethanol treated rats when compared to control. DA D(2) receptor affinity in the hypothalamus and corpus striatum of control and ethanol treated rats fitted to a single site model with unity as Hill slope value. The in vitro studies on hepatocyte cultures showed that 10(-5) M and 10(-7) M DA can reverse the increased ALDH activity in 10% ethanol treated cells to near control level. Sulpiride, an antagonist of DA D(2), reversed the effect of dopamine on 10% ethanol induced ALDH activity in hepatocytes. Our results showed a decreased dopamine concentration with enhanced DA D(2) receptors in the hypothalamus and corpus striatum of ethanol treated rats. Also, increased ALDH was observed in the plasma and liver of ethanol treated rats and in vitro hepatocyte cultures with 10% ethanol as a compensatory mechanism for increased aldehyde production due to increased dopamine metabolism. A decrease in dopamine concentration in major brain regions is coupled with an increase in ALDH activity in liver and plasma, which contributes to the tendency for alcoholism. Since the administration of 10(-5) M and 10(-7) M DA can reverse the increased ALDH activity in ethanol treated cells to near control level, this has therapeutic application to correct ethanol addicts from addiction due to allergic reaction observed in aldehyde accumulation.

Metrics and isospectral partners for the most generic cubic -symmetric non-Hermitian Hamiltonian

We investigate properties of the most general -symmetric non-Hermitian Hamiltonian of cubic order in the annihilation and creation operators as a ten-parameter family. For various choices of the parameters we systematically construct an exact expression for a metric operator and an isospectral Hermitian counterpart in the same similarity class by exploiting the isomorphism between operator and Moyal products. We elaborate on the subtleties of this approach. For special choices of the ten parameters the Hamiltonian reduces to various models previously studied, such as to the complex cubic potential, the so-called Swanson Hamiltonian or the transformed version of the from below unbounded quartic −x4-potential. In addition, it also reduces to various models not considered in the present context, namely the single-site lattice Reggeon model and a transformed version of the massive sextic ±x6-potential, which plays an important role as a toy model to identify theories with vanishing cosmological constant.

Analysis of Nucleotide Binding to P97 Reveals the Properties of a Tandem AAA Hexameric ATPase

p97, an essential chaperone in endoplasmic reticulum-associated degradation and organelle biogenesis, contains two AAA domains (D1 and D2) and assembles as a stable hexamer. We present a quantitative analysis of nucleotide binding to both D1 and D2 domains of p97, the first detailed study of nucleotide binding to both AAA domains for this type of AAA+ ATPase. We report that adenosine 5′-O-(thiotriphosphate) (ATPγS) binds with similar affinity to D1 and D2, but ADP binds with higher affinity to D1 than D2, offering an explanation for the higher ATPase activity in D2. Stoichiometric measurements suggest that although both ADP and ATPγS can saturate all 6 nucleotide binding sites in D1, only 3–4 of the 6 D2 sites can bind ATPγS simultaneously. ATPγS binding triggers a downstream cooperative conformational change of at least three monomers, which involves conserved arginine fingers and is necessary for ATP hydrolysis.

Liquid phase hydrogenation of citral and intermediaries over Ir/TiO 2/SiO 2 catalysts: Kinetic study

Kinetics of the hydrogenation of citral and its intermediates over Ir/TiO 2/SiO 2 catalysts has been studied. The effect of various parameters such as the initial concentration, H 2 pressure partial, temperature and weight of catalyst were examined. A high selectivity towards unsaturated alcohols using this catalyst was demonstrated. The initial rates increased linearly with the catalyst weight. The reaction rate obeys a kinetics represented by the Langmuir–Hinshelwood model. A single site model suggesting the surface reaction as the rate determining step provided the best fit of the experimental data for the hydrogenation of citral and alcohols (geraniol, nerol and citronellol), while a dual site represent the best kinetics for the hydrogenation of citronellal.

Characterization of the Essential Activities of Saccharomyces cerevisiae Mtr4p, a 3′→5′ Helicase Partner of the Nuclear Exosome

Mtr4p belongs to the Ski2p family of DEVH-box containing proteins and is required for processing and degradation of a variety of RNA substrates in the nucleus. In particular, Mtr4p is required for creating the 5.8 S ribosomal RNA from its 7 S precursor, proper 3'-end processing of the U4 small nuclear RNA and some small nucleolar RNAs, and degradation of aberrant mRNAs and tRNAs. In these studies we have shown that Mtr4p has RNA-dependent ATPase (or dATPase) activity that is stimulated effectively by likely substrates (e.g. tRNA) but surprisingly weakly by poly(A). Using an RNA strand-displacement assay, we have demonstrated that Mtr4p can, in the presence of ATP or dATP, unwind the duplex region of a partial duplex RNA substrate in the 3'-->5' direction. We have examined the ability of Mtr4p to bind model RNA substrates in the presence of nucleotides that mimic the stages (i.e. ATP-bound, ADP-bound, and nucleotide-free) of the unwinding reaction. Our results demonstrate that the presence of a non-hydrolyzable ATP analog allows Mtr4p to discriminate between partial duplex RNA substrates, binding a 3'-tailed substrate with 5-fold higher affinity than a 5'-tailed substrate. In addition, Mtr4p displays a marked preference for binding to poly(A) RNA relative to an oligoribonucleotide of the same length and a random sequence. This binding exhibits apparent cooperativity and different dynamic behavior from binding to the random single-stranded RNA. This unique binding mode might be employed primarily for degradation.

How Can We Reduce the Errors from Benefits Transfer? An Investigation Using the Choice Experiment Method

Policymakers are increasingly making use of benefits transfer in benefit-cost assessments of environmental policy. An important question is how big the resultant errors are, and how sensitive errors are to how the transfer is conducted. We employ a choice experiment focusing on landscape attributes to investigate the sensitivity of transfer error to procedures. The main findings are that errors depend on the choice of study site at which original valuations are sought, on whether a single site or pooled model is used; and that adding more information by pooling sites does not always seem to be economically desirable.

Simulation and spatio-temporal disaggregation of multi-site rainfall data for urban drainage applications

For urban drainage and urban flood modelling applications, fine spatial and temporal rainfall resolution is required. Simulation methods are developed to overcome the problem of data limitations. Although temporal resolution higher than 10–20 minutes is not well suited for detailed rainfall—runoff modelling for urban drainage networks, in the absence of monitored data, longer time intervals can be used for master planning or similar purposes. A methodology is presented for temporal disaggregation and spatial distribution of hourly rainfall fields, tested on observations for a 10-year period at 16 raingauges in the urban catchment of Dalmuir (UK). Daily rainfall time series are simulated with a generalized linear model (GLM). Next, using a single-site disaggregation model, the daily data of the central gauge in the catchment are downscaled to an hourly time scale. This hourly pattern is then applied linearly in space to disaggregate the daily data into hourly rainfall at all sites. Finally, the spatial rainfall field is obtained using inverse distance weighting (IDW) to interpolate the data over the whole catchment. Results are satisfactory: at individual sites within the region the simulated data preserve properties that match the observed statistics to an acceptable level for practical purposes.

Allosteric Transinhibition by Specific Antagonists in CCR2/CXCR4 Heterodimers

Chemokine receptors are presently used as targets for candidate drugs in the frame of inflammatory diseases and human immunodeficiency virus infection. They were shown to dimerize, but the functional relevance of dimerization in terms of drug action remains poorly understood. We reported previously the existence of negative binding cooperativity between the subunits of CCR2/CCR5 heterodimers. In the present study, we extend these observations to heterodimers formed by CCR2 and CXCR4, which are more distantly related. We also show that specific antagonists of one receptor inhibit the binding of chemokines to the other receptor as a consequence of their heterodimerization, both in recombinant cell lines and primary leukocytes. This resulted in a significant functional cross-inhibition in terms of calcium mobilization and chemotaxis. These data demonstrate that chemokine receptor antagonists regulate allosterically the functional properties of receptors on which they do not bind directly, with important implications on the effects of these potential therapeutic agents.