Multi-site Models Research Articles

One-dimensional mapping, modulated phases and Lyapunov exponent for the antiferromagnetic [formula omitted]-state Potts and multi-site exchange interaction Ising models

We describe the bifurcation structure, period doubling and chaos for the antiferromagnetic Q -state Potts model on the Bethe lattice and three-site interaction Ising model on Husimi one in a magnetic field, by using the recursion relation technique. A chaotic behavior of the magnetic susceptibility for the models is observed at low temperatures. The resulting one-dimensional rational mapping has a positive Lyapunov exponent in the region of the chaotic regime for the antiferromagnetic Q -state Potts ( Q < 2 ) and three-site interaction Ising models. We discuss modulated phases for the antiferromagnetic Q -state Potts ( Q < 2 and Q ≥ 2 ) and three-site interaction Ising model. At low temperatures the Q-state Potts model ( Q ≥ 2 ) has only one modulated phase with 1 2 pinching corresponding to the 2 -cycle. The Q -state Potts ( Q < 2 ) and three-site interaction Ising models have an infinite number of modulated phases with different pinching numbers; we construct the first modulated phase after the first bifurcation point.

Solvation of glucose, trehalose, and sucrose by the soft-sticky dipole–quadrupole–octupole water model

Water structure around sugars modeled by partial charges is compared for soft-sticky dipole–quadrupole–octupole (SSDQO), a fast single-site multipole model, and commonly used multi-site models in Monte Carlo simulations. Radial distribution functions and coordination numbers of all the models indicate similar hydration by hydrogen-bond donor and acceptor waters. However, the new optimized SSDQO1 parameters as well as TIP4P-Ew and TIP5P predict a ‘lone-pair’ orientation for the water accepting the sugar hydroxyl hydrogen bond that is more consistent with the limited experimental data than the ‘dipole’ orientation in SPC/E, which has important implications for studies of the cryoprotectant properties of sugars.

Site Disorder in Ice VII Arising from Hydrogen Bond Fluctuations

Recently, multisite models used for the refinement of neutron diffraction data have suggested that the structure of ice VII is quite unlike that of its ordered counterpart, ice VIII. We investigate the oxygen site disorder by modeling the site displacement, obtained from periodic DFT calculations, as a function of the local hydrogen bond network. Then, using graph invariants to describe hydrogen bond fluctuations in the thermodynamic limit, we perform statistical mechanical calculations using the oxygen site displacement model developed here. We find that the probability distribution of the oxygen atom about its perfect lattice site more closely resembles the 100 model rather than the recently suggested 111 model, although both models represent a simplification of the actual site distribution. We also find a unimodel distribution for the hydrogen bonded oxygen-oxygen distance and a trimodel distribution for the nearest nonbonded oxygen-oxygen distance with a peak separation of approximately 0.1 A.

A nested multisite daily rainfall stochastic generation model

Summary This paper describes a nested multisite daily rainfall generation model which preserves the statistics at daily, monthly and annual levels of aggregation. A multisite two-part daily model is nested in multisite monthly, then annual models. A multivariate set of fourth order Markov chains is used to model the daily occurrence of rainfall; the daily spatial correlation in the occurrence process is handled by using suitably correlated uniformly distributed variates via a Normal Scores Transform (NST) obtained from a set of matched multinormal pseudo-random variates, following Wilks [Wilks, D.S., 1998. Multisite generalisation of a daily stochastic precipitation generation model. Journal of Hydrology 210, 178–191]; we call it a hidden covariance model. A spatially correlated two parameter gamma distribution is used to obtain the rainfall depths; these values are also correlated via a specially matched hidden multinormal process. For nesting, the generated daily rainfall sequences at all the sites are aggregated to monthly rainfall values and these values are modified by a set of lag-1 autoregressive multisite monthly rainfall models. The modified monthly rainfall values are aggregated to annual rainfall and these are then modified by a lag-1 autoregressive multisite annual model. This nesting process ensures that the daily, monthly and annual means and covariances are preserved. The model was applied to a region with 30 rainfall sites, one of the five sets reported by Srikanthan [Srikanthan, R., 2005. Stochastic Generation of Daily Rainfall Data at a Number of Sites. Technical Report 05/7, CRC for Catchment Hydrology. Monash University, 66p]. A comparison of the historical and generated statistics shows that the model preserves all the important characteristics of rainfall at the daily, monthly and annual time scales, including the spatial structure. There are some outstanding features that need to be improved: depths of rainfall on isolated wet days and sequences of wet days do not depend on the duration of the wet spell as well as they should; the remedy is not trivial, but will be addressed in a follow-up study. The skewness of monthly rainfall was not preserved well which appears to be a deficiency, but this is not considered important, because nearly all other validation statistics are well captured by the model and comparative cumulative frequency distribution plots of the daily depths show satisfactory matches.

Kinetic Modeling of the Interactions between 4-Methylumbelliferone, 1-Naphthol, and Zidovudine Glucuronidation by UDP-Glucuronosyltransferase 2B7 (UGT2B7) Provides Evidence for Multiple Substrate Binding and Effector Sites

Interactions between the UGT2B7-catalyzed glucuronidation of zidovudine (AZT), 4-methylumbelliferone (4MU), and 1-naphthol (1NP) were analyzed using multisite and empirical kinetic models to explore the existence of multiple substrate and effector binding sites within this important drug metabolizing enzyme. 4MU and 1NP glucuronidation by UGT2B7 exhibit sigmoidal kinetics characteristic of homotropic cooperativity (autoactivation), which may be modeled assuming the existence of two equivalent, interacting substrate binding sites. In contrast, UGT2B7-catalyzed AZT glucuronidation follows hyperbolic (Michaelis-Menten) kinetics. Although 4MU and 1NP decreased the binding affinity of AZT, the kinetics of AZT glucuronidation changed from hyperbolic to sigmoidal in the presence of both modifiers. Data were well described by a generic two-substrate binding site model in which there is no interaction between the sites in the absence of 4MU or 1NP, but heterotropic cooperativity results from the binding of modifier. Inhibition of 4MU and 1NP glucuronidation by AZT and interactions between 4MU and 1NP required more complex three-site models, where the modifier acts via a distinct effector site to alter either substrate binding affinity or Vmax without affecting the homotropic cooperativity characteristic of 4MU and 1NP glucuronidation. It is noteworthy that 1NP inhibited 4MU glucuronidation, whereas 4MU activated 1NP glucuronidation. The results are consistent with the existence of two "catalytic" sites for each substrate within the UGT2B7 active site, along with multiple effector sites. The multiplicity of binding and effector sites results in complex kinetic interactions between UGT2B7 substrates, which potentially complicates inhibition screening studies.

IC-P1-021: A novel web-based system for automated computer classification in Alzheimer's dementia

Background: Automated computer classification (ACC) techniques based on routine MRI provide aid to diagnostic information in an objective and reproducible fashion without being resource-intensive. To ensure simple yet reliable access, we propose a web-based ACC prototype tailored to the task of differentiating probable AD from normal aging. Methods: Input The system is based on anonymized T1weighted MR scans. Image quality control (QC) is performed manually on an 11-point scale. Processing The comparative ACC methodology exploits the differences in covariant patterns of Jacobian determinants and scaled grey-level intensity between subjects within a limited volume of interest centered on the medial temporal lobe. The classification result is obtained by comparing the resulting projection coordinates on relevant axes against a linear discriminant function. The nonlinear deformation field is also used to extract volumetric measures of specific temporal structures. Training data In the current instantiation the normative reference space for data projection was created using intensity and determinant features from 150 young controls. The linear discriminant function was obtained via forward stepwise linear discriminant analysis of a training set composed of 150 subjects: 75 patients with a diagnosis of probable AD and 75 age-matched controls without neurological or neuropsychological deficit. The AD subjects were individuals with mild to moderate probable AD recruited among outpatients seen at the IRCC Fatebenefratelli (Brescia, Italy). Longitudinal clinical assessment of all patients supported the diagnostic used as ground truth for the evaluation of the classification function. The final function is composed of 12 intensity and determinant features. Results: Reporting The report consists in three parts: a) QC information; b) quantitative information (e.g. Z-score of amygdalae and hippocampi with respect to retrospective data on age-matched CTRL); and c) summary classification information in support of clinical diagnosis. Conclusions: This web-based prototype interface is ready for routine clinical use for physicians working at the training site. Multi-site models will be made available in the next generation. The proposed technique is completely automated, requires no external expertise, and is completely objective. Acknowledgments: ICBM project, G. B. Frisoni (Brescia, Italy) for the data.

Modelling dissolution of multi-component non-aqueous phase liquids using Pareto distributions

A distributed-site non-aqueous phase liquid (NAPL) dissolution model that can capture the physical process of dissolution is presented. The model uses a Pareto distribution of effective interfacial area and a correlation for the mass transfer. Model parameters are obtained using a formal constrained non-linear optimisation technique. The model is applied on effluent data from two soil column experiments. The results of the Pareto distributed site model, with only two parameters to fit, were compared to two-site and multi-site models as well as the beta distributed-site model. The Pareto distributed-site model produces equal or smaller error estimates than the other models.

Developing daily precipitation scenarios for climate change impact studies in the Guadiana and the Tejo basins

Abstract. Hydrological models to evaluate the impacts of climate change in the water resources sector require spatially correlated daily precipitation scenarios as model inputs. This paper presents a practical procedure for developing such precipitation scenarios using multisite stochastic weather models or generators conditional on large-scale daily circulation patterns, based on GCM-simulated future mean sea level pressure (MSLP) fields. The procedure is demonstrated on the basis of HadCM3 and HadAM3H simulations with an example for two river basins in the Iberian Peninsula. Changes in daily precipitation scenarios for the region generated by stochastic models are consistent with large-scale precipitation scenarios from direct GCM outputs; however, more localised characteristics have to be found from downscaled precipitation scenarios rather than from direct GCM outputs. This may imply that possible changes in downscaled precipitation reflect the underlying physics in GCMs, so that downscaled daily precipitation scenarios may be more suitable for impact models than the coarse GCM outputs.

Molecular simulation of liquid crystals: progress towards a better understanding of bulk structure and the prediction of material properties

This tutorial review covers recent progress in the field of computer simulation of liquid crystals. The development of the main "molecular-based" models for liquid crystals is described. These include lattice models, coarse-grained single site models based on hard and soft interaction potentials, atomistic models and multi-site coarse-grained models. A brief historical review is followed by an assessment of some of the new areas in this field, with an emphasis on understanding of molecular structure in liquid crystal phases and the prediction of bulk material properties. The article also looks to link the field of liquid crystal simulation with important developments in areas such as polymer simulation, lyotropic liquid crystals and model membranes.

Multisite co-allocation scheduling algorithms for parallel jobs in computing grid environments

Cooperation of multi-domain massively parallel processor systems in com- puting grid environment provides new opportunities for multisite job scheduling. At the same time, in the area of co-allocation, heterogeneity, network adaptability and scalability raise the challenge for the international design of multisite job scheduling models and algorithms. It presents multisite job scheduling schema through the introduction of mul- tisite job scheduling model and the performance model under the grid environment. It introduces two job multisite and cooperative scheduling models and algorithms with the core of the optimal and greedy-heuristic resource selection strategies. Meanwhile, com- pared with single and multisite cooperative scheduling models and algorithms introduced by Sabin, Yahyapour and other persons, the validity and advance of the scheduling model and the performance model herein are proved.

Characterization and selectivity for methane and carbon dioxide adsorption on the all-silica DD3R zeolite

Clathrasil Deca-dodecasil 3R (DD3R) zeolite was synthesized in this study. Then, adsorption properties of carbon dioxide and methane were examined on the all-silica DD3R zeolite. Pure component adsorption isotherms are reported at temperatures of 273–348 K and pressures as high as 3 MPa. The isotherms follow a typical Type-I shape according to the Brunauer classification. They are well described using Langmuir and multi-site Langmuir models. Isosteric heats of adsorption and Henry’s Law constants of all adsorbates were determined. High selectivity of adsorption for carbon dioxide over methane suggests that the all-silica DD3R is an effective adsorbent or zeolite membrane material that can separate carbon dioxide and methane gaseous mixtures.

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

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

Multi-site downscaling of heavy daily precipitation occurrence and amounts

This paper compares three statistical models for downscaling heavy daily precipitation occurrence and amounts at multiple sites given lagged and contemporaneous large-scale climate predictors (such as atmospheric circulation, thickness, and moisture content at the surface, 850 and 500 hPa). Three models (a Radial Basis Function (RBF) Artificial Neural Network (ANN), Multi Layer Perceptron (MLP) ANN and a Conditional Resampling Method (SDSM)) were applied to area-average and station daily precipitation amounts in northwest (NWE) and southeast (SEE) England. Predictor selection via both stepwise multiple linear regression and compositing confirmed vorticity and humidity as important downscaling variables. Model skill was evaluated using indices of heavy precipitation for area averages, individual sites and inter-site behaviour. When tested against independent data (1979–1993), multi-site ANN models correctly simulated precipitation occurrence 80% of the time. The ANNs tended to over-estimate inter-site correlations for amounts due to their fully deterministic forcing, but performance was marginally better than SDSM for most seasonal-series of heavy precipitation indices. Conversely, SDSM yielded better inter-site correlation and representation of daily precipitation quantiles than the ANNs. All models had greatest skill for indices reflecting persistence of large-scale winter precipitation (such as maximum 5-day totals) or dry-spell duration in summer. Overall, predictability of daily precipitation was greater in NWE than SEE.

CYP3A4 Substrate Selection and Substitution in the Prediction of Potential Drug-Drug Interactions

The complexity of in vitro kinetic phenomena observed for CYP3A4 substrates (homo- or heterotropic cooperativity) confounds the prediction of drug-drug interactions, and an evaluation of alternative and/or pragmatic approaches and substrates is needed. The current study focused on the utility of the three most commonly used CYP3A4 in vitro probes for the prediction of 26 reported in vivo interactions with azole inhibitors (increase in area under the curve ranged from 1.2 to 24, 50% in the range of potent inhibition). In addition to midazolam, testosterone, and nifedipine, quinidine was explored as a more "pragmatic" substrate due to its kinetic properties and specificity toward CYP3A4 in comparison with CYP3A5. Ki estimates obtained in human liver microsomes under standardized in vitro conditions for each of the four probes were used to determine the validity of substrate substitution in CYP3A4 drug-drug interaction prediction. Detailed inhibitor-related (microsomal binding, depletion over incubation time) and substrate-related factors (cooperativity, contribution of other metabolic pathways, or renal excretion) were incorporated in the assessment of the interaction potential. All four CYP3A4 probes predicted 69 to 81% of the interactions with azoles within 2-fold of the mean in vivo value. Comparison of simple and multisite mechanistic models and interaction prediction accuracy for each of the in vitro probes indicated that midazolam and quinidine in vitro data provided the best assessment of a potential interaction, with the lowest bias and the highest precision of the prediction. Further investigations with a wider range of inhibitors are required to substantiate these findings.

Modelling atypical CYP3A4 kinetics: principles and pragmatism

The Michaelis–Menten model, and the existence of a single active site for the interaction of substrate with drug metabolizing enzyme, adequately describes a substantial number of in vitro metabolite kinetic data sets for both clearance and inhibition determination. However, in an increasing number of cases (involving most notably, but not exclusively, CYP3A4), atypical kinetic features are observed, e.g., auto- and heteroactivation; partial, cooperative, and substrate inhibition; concentration-dependent effector responses (activation/inhibition); limited substrate substitution and inhibitory reciprocity necessitating sub-group classification. The phenomena listed above cannot be readily interpreted using single active site models and the literature indicates that three types of approaches have been adopted. First the ‘naı¨ve’ approach of using the Michaelis–Menten model regardless of the kinetic behaviour, second the ‘empirical’ approach (e.g., employing the Hill or uncompetitive inhibition equations to model homotropic phenomena of sigmoidicity and substrate inhibition, respectively) and finally, the ‘mechanistic’ approach. The later includes multisite kinetic models derived using the same rapid equilibrium/steady-state assumptions as the single-site model. These models indicate that 2 or 3 binding sites exist for a given CYP3A4 substrate and/or effector. Multisite kinetic models share common features, depending on the substrate kinetics and the nature of the effector response observed in vitro, which allow a generic model to be proposed. Thus although more complex than the other two approaches, they show more utility and can be comprehensively applied in relatively simple versions that can be readily generated from generic model. Multisite kinetic features, observed in isolated hepatocytes as well as in microsomes from hepatic tissue and heterologous expression systems, may be evident in substrate depletion–time profiles as well as in metabolite formation rates. Failure to adequately account for multisite kinetic phenomena will compromise any attempts to predict human drug clearance and drug–drug interaction potential from in vitro data.

A proposal for a goodness-of-fit test to the Arnason-Schwarz multisite capture-recapture model.

In an analysis of capture-recapture data, the identification of a model that fits is a critical step. For the multisite (also called multistate) models used to analyze data gathered at several sites, no reliable test for assessing fit is currently available. We propose a test for the JMV model, a simple generalization of the Arnason-Schwarz (AS) model, in the form of interpretable contingency tables. For the AS model, we suggest complementing the test for the JMV model with a likelihood ratio test of AS vs. JMV. The examination of an example leads us to propose further a partitioning that emphasizes the role of the memory model of Brownie et al. (1993 Biometrics 49, 1173-1187) as a biologically more plausible alternative to the AS model.

Quinidine and haloperidol as modifiers of CYP3A4 activity: multisite kinetic model approach.

The selection of appropriate substrates for investigating the potential inhibition of CYP3A4 is critical as the magnitude of effect is often substrate-dependent, and a weak correlation is often observed among different CYP3A4 substrates. This feature has been attributed to the existence of multiple binding sites and, therefore, relatively complex in vitro data modeling is required to avoid erroneous evaluation and to allow prediction of drug-drug interactions. This study, performed in lymphoblast-expressed CYP3A4 with oxidoreductase, provides a systematic comparison of the effects of quinidine (QUI) and haloperidol (HAL) as modifiers of CYP3A4 activity using a selection of CYP3A4 substrates: testosterone (TST), midazolam (MDZ), nifedipine (NIF), felodipine (FEL), and simvastatin (SV). The effect of QUI and HAL on CYP3A4-mediated pathways was substrate-dependent, ranging from potent inhibition of NIF (K(i) = 0.25 and 5.3 micro M for HAL and QUI, respectively), weak inhibition (TST), minimal effect (HAL on MDZ/SV) to QUI activation of FEL and SV metabolism. Inhibition of TST metabolite formation occurred but its autoactivation properties were maintained, indicating binding of a QUI/HAL molecule to a distinct effector site. Various multisite kinetic models have been applied to elucidate the mechanism of the drug-drug interactions observed. Kinetic models with two substrate-binding sites have been found to be appropriate to a number of interactions, provided the substrates show hyperbolic (MDZ, FEL, and SV) or substrate inhibition kinetic properties (NIF). In contrast, a three-site model approach is required for TST, a substrate showing positive cooperativity in its binding to CYP3A4.

Population genetics and dynamics at short spatial scale in Bulinus truncatus, the intermediate host of Schistosoma haematobium, in Morocco.

The population biology of the schistosome-vector snail Bulinus truncatus was studied in an irrigation system near Marrakech, Morocco using both genetic and demographic approaches. The population genetic survey was conducted in 4 sites, 2 sites being sampled on 2 separate occasions. Individuals were genotyped at 6 microsatellite loci. No variability was found at 4 loci, and the 2 other loci had less than 4 alleles. The differentiation, both spatial and temporal, among populations was extremely weak. The demographic survey was conducted using 2 capture-mark-recapture analyses in 2 separate sites, the first in 1999 and the second in 2000. The second analysis permitted the estimation of parameters based on recent methodological developments (multisite models). Although these studies provided information on several traits, we report here on dispersal only. Both analyses showed that individual dispersal is of the order of a few hundreds of metres per reproductive life, that is the scale of the whole irrigation area. Both the genetic and demographic studies indicated that this area harbours a single--or no more than a few--populations of B. truncatus. This has implications for our understanding of the coevolutionary process between snails and flukes.

Multisite stochastic weather models for impact studies

AbstractStochastic weather models have been developed for simultaneous simulations of daily precipitation, and daily maximum and minimum temperatures at multiple sites in a river basin in order to reproduce the interstation correlations and self‐consistency in weather series. The basic structure of the stochastic weather models was adopted from Wilks (1999. Agricultural and Forest Meteorology 96: 85–101), but an extension was made to condition the model parameters on daily circulation patterns. Model parameters were also estimated without conditioning on daily circulation patterns, so that both conditional and unconditional simulations were conducted and compared. Statistical analyses on the synthetic weather data imply a better performance of the conditional simulations, on most aspects of the required statistics. In addition, the conditional weather models on daily circulation patterns can be applied directly in impact studies, for the purpose of downscaling climate scenarios from climate model simulations, and some related aspects are also discussed. Copyright © 2002 Royal Meteorological Society.

Cation competition in a natural subsurface material: Prediction of transport behavior

Predicting the transport of reactive chemicals in subsurface porous media requires accurate adsorption models. This study compares the ability of various cation exchange models to quantitatively capture the transport behavior of major cations (i.e., calcium and sodium) in soil laboratory columns over a wide range of pore water composition. Experimental breakthrough curves were compared with model predictions without adjustable parameters. Various one‐site and multisite cation exchange models were independently calibrated with batch adsorption data. Our results show that a one‐site cation exchange model based on the well‐known Gaines‐Thomas convention yields good predictions of cation transport behavior, although some deviations from experimental data remain. The most reliable predictions were obtained with multisite cation exchange models with a distribution of various types of exchange sites.