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PubMed1990

Divorce in contemporary Japan.

Data from the 1985-86 Japanese census are analysed to explore the determinants of the divorce rates in Japan's forty-seven prefectures, using two theoretical models: (a) the social integration model, which is shown to have a greater utility in predicting Japanese divorce levels than (b), the human capital model. Female emigration patterns play a significant role in affecting the divorce rate. Population increase and net household income are also important predictors of the Japanese divorce rate and urbanization has a great influence in modern Japan. Demographic and aggregate variables such as migration, urbanization, and socioeconomic factors are useful when organized under a social integration model.

Divorce↗

PubMed1977

Air exchange through doorways. The effect of temperature difference, turbulence and ventilation flow.

Analytical expressions have been derived for the exchange of air across doorways or similar apertures, in terms of the temperature difference between the spaces on both sides of the opening and the net volume of air flowing through this as a result of unbalanced air supply or extract. A simple allowance for turbulence which gives reasonable correspondence with observation is included. The formulae, which assume complete air mixing on both sides of the doorway up to the plane of the aperture, predict outflows from the warmer side, when there is an excess air supply to this side, which are progressively smaller than those observed as the temperature difference rises above 2-3 degrees C and the volume of excess air supply increases to produce an averaged outflow velocity greater than 0-1-0-15 m/s. This seems to be due to lack of mixing of the warm outflowing air with the cooler air mass. A correction factor for this can be deduced as a function of the pressure difference due to the excess air supply. The limiting magnitude and general form of this function are compatible with a simple theoretical model of the air flow patterns involved.

Air Movements↗

PubMed2001

Costs of sexual traits: a mismatch between theoretical considerations and empirical evidence.

Costs of sexual traits are of central importance to the theory of sexual selection. To qualify as a cost in line with theoretical models, empirical studies must demonstrate that sexual traits cause negative effects on one component of fitness of the trait bearer. Moreover, it must be demonstrated that the costs are differential such that negative effects on fitness are more severe for individuals in poor condition than for individuals in good condition. However, in the current literature, there is confusion over what qualifies as a cost, and costs are often anticipated based on findings of increased expenditure. Consequently, it seems that the generally accepted notion that sexual traits are costly is in fact based almost exclusively on indirect evidence and that direct empirical evidence is very scarce.

Amphibians↗

PubMed1996

Laser-excited atomic fluorescence spectrometry in a pressure-controlled electrothermal atomizer.

A theoretical model was developed to describe the loss of analyte atoms in graphite furnaces during atomization. The model was based on two functions, one that described the supply of analyte by vaporization, and another that described the removal of the analyte by diffusion. Variation in working pressure was shown to affect the competition between these two processes. Optimal atomization efficiency was predicted to occur at a pressure where the supply of the analyte was maximized, and gas phase interactions between the analyte and matrix were minimized. Experiments to test the model included the direct determination of phosphorus and tellurium in nickel alloys and of cobalt in glass. In all cases, reduction in working pressure from atmospheric pressure to 7 Pa decreased sensitivity by 2 orders of magnitude, but improved temporal peak shape. For the atomization of tellurium directly from a solid nickel alloy, and the atomization of cobalt from an aqueous solution, no change in sensitivity was observed as the working pressure was reduced from atmospheric pressure to approximately 70 kPa. If a reduction in working pressure affected only the diffusion of the analyte, poorer sensitivity should have been obtained. Only a commensurate increase in analyte vaporization could account for maintained sensitivity at lower working pressures. Overall, analyte vaporization was not dramatically improved at reduced working pressures, and maximum atomization efficiency was found to occur near atmospheric pressure.

Fluorescence↗

PubMed1998

HSA-solute interactions, enantioselectivity, and binding site geometrical characteristics.

Recently, a theoretical model was proposed to study the existence of pockets of acetonitrile (ACN) called clusters in a hydroorganic mixture. The proposal used ACN as an interaction organic modifier between D,L-dansyl amino acids and their binding site in human serum albumin at site II. This solute binding is governed by primary and secondary interactions. The primary interactions are under the dependence of the solute solvation by ACN clusters and electrostatic interactions. Following this first step, the solute engages strong short-range interactions with the residues of site II. Using a biochromatographic approach, the solute binding, i.e., the solute retention, was divided into two dielectric constant (epsilon) ranges. In the first range, epsilon > epsilon c (epsilon c is the critical dielectric constant); the primary and secondary nonstereoselective electrostatic interactions were the major contributions to the variation in the solute binding with the ACN fraction in the mixture. In the second range, epsilon < epsilon c, the solute retention variation with the ACN fraction was governed by its solvation by the ACN clusters and also by the secondary hydrophobic stereoselective interaction. The mathematical model developed provided the determination of the surface charge density of site II as well as the cluster number that solvates each solute.

Acetonitriles↗

PubMed1987

Oligomerization and ring closure of immunoglobulin E class antibodies by divalent haptens.

Cross-linking of antibodies constitutes a widespread initiation signal for their respective effector functions. Cross-linking IgE-class antibodies provide the triggering signal to mast cells for their degranulation process. To obtain a quantitative insight into these cross-linking processes, the interactions between a DNP-specific monoclonal antibody of the IgE class and a series of divalent DNP haptens with spacers of different length and flexibility have been studied by fluorescence titration experiments. These were analyzed by employing the theoretical model developed by Dembo and Goldstein [Dembo, M., & Goldstein, B. (1978) J. Immunol. 121, 345-353] in a fitting procedure. Equilibrium constants that describe the aggregation and ring-closure processes caused by divalent hapten binding have been used as free parameters. The intrinsic binding constants were determined by fluorescence titrations with corresponding monovalent haptens. The main results are the following: (1) The divalent haptens with a short and flexible spacer [i.e., N alpha, N epsilon-di-(DNP)-L-lysine,meso-bis[(DNP-beta-Ala)amino]succinate, and bis[(DNP-tri-D-Ala)amino]heptane, having a maximal DNP-DNP distance of gamma = 14, 21, and 45 A, respectively] effect aggregation of the antibodies mainly into closed dimers. (2) The divalent hapten family with long and rigid oligoproline spacers di(DNP)-Ahx-Asp-(Pro)n-Lys with n = 24, 27, and 33 (i.e., gamma = 100, 110, and 130 A) causes aggregation of the antibodies predominantly into closed dimers and trimers. The corresponding equilibrium constants of the respective ring-closure processes decrease significantly with longer spacer length. (3) Evidence was found that intramolecularly monomeric ring closure of the IgE antibodies is caused by haptens containing oligoproline spacers with n = 37 or 42 (gamma = 130-150 A). The equilibrium constant of the ring-closure process increases with spacer length. This increase in stability indicates a difference in the imposed strain. Furthermore, the latter results imply that the distance between the two binding sites of the IgE molecule lies in the range dictated by the rigid oligoproline part of the respective hapten's spacer, i.e., 115-130 A. (4) Nearly all oligomeric ring-closure processes proceed relatively slowly with an approximate lower limit of a half-life of 5-10 s. This slowing down of the aggregation and ring-closure processes most probably reflects steric factors.

Calorimetry↗

PubMed2006

Prediction of folding rates of small proteins: empirical relations based on length, secondary structure content, residue type, and stability.

Delineating the determinants of folding of small proteins is essential for decoding the folding code. By considering the literature data for the folding of 45 two-state proteins that differ widely in sequence, structure, and function, this work suggests two empirical relations for the prediction of the folding rate. One relation is based on the content of secondary structure elements, and the other uses the number of residues of each of the following types: hydrophobic, positively charged, and negatively charged. Both relations incorporate the chain length as an indirect descriptor. The correlation between experimental values for folding rates and free energy is poor, providing little support to the "stability gap" hypothesis based on the folding of simple lattice and off-lattice polymers. The average rate-determining barrier height for these two-state proteins is much larger than the small barriers for the transition-state ensemble envisaged by theoretical models.

Animals↗

PubMed1996

The determinants of pKas in proteins.

Although validation studies show that theoretical models for predicting the pKas of ionizable groups in proteins are increasingly accurate, a number of important questions remain: (1) What factors limit the accuracy of current models? (2) How can conformational flexibility of proteins best be accounted for? (3) Will use of solution structures in the calculations, rather than crystal structures, improve the accuracy of the computed pKas? and (4) Why does accurate prediction of protein pKas seem to require that a high dielectric constant be assigned to the protein interior? This paper addresses these and related issues. Among the conclusions are the following: (1) computed pKas averaged over NMR structure sets are more accurate than those based upon single crystal structures; (2) use of atomic parameters optimized to reproduce hydration energies of small molecules improves agreement with experiment when a low protein dielectric constant is assumed; (3) despite use of NMR structures and optimized atomic parameters, pKas computed with a protein dielectric constant of 20 are more accurate than those computed with a low protein dielectric constant; (4) the pKa shifts in ribonuclease A that result from phosphate binding are reproduced reasonably well by calculations; (5) the substantial pKa shifts observed in turkey ovomucoid third domain result largely from interactions among ionized groups; and (6) both experimental data and calculations indicate that proteins tend to lower the pKas of Asp side chains but have little overall effect upon the pKas of other ionizable groups.

Amino Acid Sequence↗

PubMedDate not supplied

Small angle X-ray scattering of resistant starch type III.

Starch fraction, which is resistant to enzymatic digestion, is produced during retrogradation. This fraction, termed resistant starch type III (RSIII), has health benefits such as pre-biotic effects, improving lipid and cholesterol metabolism, and reducing the risk of colon cancer. The work presented in this paper is aimed at investigating the colloidal structure of native high amylose corn starch (HACS) and the RSIII polymorphs produced from it using small angle X-ray scattering. Experimental scattering curves were fitted with appropriate theoretical models such as the "modified lamellar model". Our results show that retrogradation at low temperature leads to formation of polymorph B with crystallinity much lower than that of the granular form, but the lamellas are arranged in long-range periodicity. Conversely, retrogradation at high temperature leads to formation of polymorphs A and V with no defined periodicity. The degree of crystallinity is very low, and the system is better described as a dilute particulate system.

Amylose↗

PubMedDate not supplied

Interactions of two amphiphilic penicillins with myoglobin in aqueous buffered solutions: a thermodynamic and spectroscopy study.

The interactions and complexation process of the amphiphilic penicillins sodium cloxacillin and sodium dicloxacillin with horse myoglobin in aqueous buffered solutions of pH 4.5 and 7.4 have been examined by equilibrium dialysis, zeta-potential, isothermal titration calorimetry (ITC) and UV-Vis absorbance techniques. A more opened structure of the protein molecules is detected as a consequence of the reduction of pH from 7.4 to 4.5. Binding isotherms and derived Hill coefficients reflect a cooperative binding behavior. Gibbs energies of binding per mole of drug were obtained from equilibrium dialysis data and compared with those derived from the zeta potential taking into account cooperativity. DeltaGads degrees values so obtained are large and negative at low concentrations where binding to the "high-energy" sites occurs and decreases with the drug concentration. The enthalpies of binding have been obtained from ITC and are small and exothermic so that the Gibbs energies of binding are dominated by large increases in entropy consistent with hydrophobic interactions. Other thermodynamic quantities of the binding mechanism, that is, entropy, DeltaSITCi, Gibbs energy, DeltaGITCi, the binding constant, KITCi, and the number of binding sites, ni, were also obtained, confirming the above results. From ITC data and following a theoretical model, the number of bound and free penicillin molecules was calculated, being higher at pH 4.5 than at pH 7.4. The binding of penicillin causes a conformational transition on protein structure as a consequence of the resulting intramolecular repulsion between the penicillin molecules bound to the protein. Thermodynamic quantites (the Gibbs energy of the transition in water, DeltaGw degrees , and in a hydrophobic environment, DeltaGhc degrees) of the denaturation process were calculated, indicating that at pH 4.5 some of the histidine residues are protonated, becoming accessible to solvent and giving rise to a more opened protein structure.

Animals↗

PubMedDate not supplied

The influence of pH upon the kinetic parameters of the enzymatic hydrolysis of cellobiose with Novozym 188.

We have studied experimentally within the pH range of 3.65-5.5 at 50 degrees C the hydrolysis of cellobiose with Novozym 188, a commercial product with high beta-1,4-glucosidase activity derived from Aspergillus niger. We used wide variations in the conversion to be able to apply the integral method and thus determine that there is substrate and mixed product inhibition. Whether the SES triple compound contributes to the formation of glucose does not influence the fitting of the experimental results to the theoretical model to any significant extent. We have established how pH affects the kinetic parameters and ascertained that pH 4.3 is the optimum for the conversion of cellobiose into glucose.

Cellobiose↗

PubMedDate not supplied

Relationships between Molecular Complexity, Biological Activity, and Structural Diversity.

Following the theoretical model by Hann et al. moderately complex structures are preferable lead compounds since they lead to specific binding events involving the complete ligand molecule. To make this concept usable in practice for library design, we studied several complexity measures on the biological activity of ligand molecules. We applied the historical IC50/EC50 summary data of 160 assays run at Novartis covering a diverse range of targets, among them kinases, proteases, GPCRs, and protein-protein interactions, and compared this to the background of "inactive" compounds which have been screened for 2 years but have never shown any activity in any primary screen. As complexity measures we used the number of structural features present in various molecular fingerprints and descriptors. We found generally that with increasing activity of the ligands, their average complexity also increased, and we could therefore establish a minimum number of structural features in each descriptor needed for biological activity. Especially well suited in this context were the Similog keys and circular substructure fingerprints. These are those descriptors, which also perform especially well in the identification of bioactive compounds by similarity search, suggesting that structural features encoded in these descriptors have a high relevance for bioactivity. Since the number of features correlates with the number of atoms present in the molecule, also the number of atoms serves as a reasonable complexity measure and larger molecules have, in general, higher activities. Due to the relationship between feature counts and densities on one hand and biological activity on the other, the size bias present in almost all similarity coefficients becomes especially important. Diversity selections using these coefficients can influence the overall complexity of the resulting set of molecules, which has an impact on the biological activity that they exhibit. Using sphere-exclusion based diversity selection methods, such as OptiSim together with the Tanimoto dissimilarity, the average feature count distribution of the resulting selections is shifted toward lower complexity than that of the original set, particularly when applying tight diversity constraints. This size bias reduces the fraction of molecules in the subsets having the complexity required for a high, submicromolar activity. None of the diversity selection methods studied, namely OptiSim, divisive K-means clustering, and self-organizing maps, yielded subsets covering the activity space of the IC50 summary data set better than subsets selected randomly.

Drug Design↗

PubMed2003

Reduction of uranium(VI) by mixed iron(II)/iron(III) hydroxide (green rust): formation of UO2 nanoparticles.

Green rusts, which are mixed ferrous/ferric hydroxides, are found in many suboxic environments and are believed to play a central role in the biogeochemistry of Fe. Analysis by U LIII-edge X-ray absorption near edge spectroscopy of aqueous green rust suspensions spiked with uranyl (U(VI)) showed that U(VI) was readily reduced to U(IV) by green rust The extended X-ray absorption fine structure (EXAFS) date for uranium reduced by green rust indicate the formation of a UO2 phase. A theoretical model based on the crystal structure of UO2 was generated by using FEFF7 and fitted to the data for the UO2 standard and the uranium in the green rust samples. The model fits indicate that the number of nearest-neighbor uranium atoms decreases from 12 for the UO2 structure to 5.4 forthe uranium-green rust sample. With an assumed four near-neighbor uranium atoms per uranium atom on the surface of UO2, the best-fit value for the average number of uranium atoms indicates UO2 particles with an average diameter of 1.7 +/- 0.6 nm. The formation of nanometer-scale particles of UO2, suggested by the modeling of the EXAFS data, was confirmed by high-resolution transmission electron microscopy, which showed discrete particles (approximately 2-9 nm in diameter) of crystalline UO2. Our results clearly indicate that U(VI) (as soluble uranyl ion) is readily reduced by green rust to U(IV) in the form of relatively insoluble UO2 nanoparticles, suggesting that the presence of green rusts in the subsurface may have significant effects on the mobility of uranium, particularly under iron-reducing conditions.

Ferric Compounds↗

PubMed2004

Stream-subsurface exchange of zinc in the presence of silica and kaolinite colloids.

The mobility of sorbing contaminants in surface waters often depends strongly on associations with sediments, including both fine suspended particles and stationary bed sediments. Hydrodynamic flow coupling causes an exchange of dissolved and suspended substances between streams and underlying pore waters (hyporheic exchange). As a result, the fate of many pollutants is expected to be greatly influenced bythe flux of colloids and contaminants across the stream-subsurface interface and the interactions of both types of substances with the bed sediments. Herein, we present experimental results on the stream-subsurface exchange of zinc in the presence of colloidal silica and kaolinite in a laboratory flume. We also apply a process-based theoretical model to predict the coupled transport of colloids and reactive solutes. Model input parameters were obtained using independent batch and column experiments. Zinc immobilization in the bed was found to be significantly greater in the presence of kaolinite than in the presence of colloidal silica. Model predictions indicated that there were two distinct reasons for the greater zinc immobilization in the presence of kaolinite: zinc sorbed more strongly to kaolinite than to silica, and kaolinite particles also deposited more readily in the streambed than did silica colloids. Model simulations were found to be highly dependent on the colloid size distribution. When the colloids had a bimodal distribution, colloidal-phase contaminant transport occurred primarily on the finer fraction, but bulk colloid deposition was dominated by removal of the coarser fraction.

Adsorption↗

PubMed2006

Determination of NAPL-water interfacial areas in well-characterized porous media.

The nonaqueous-phase liquid (NAPL)-water interfacial area is an important parameter which influences the rate of NAPL dissolution in porous media. The aim of this study was to generate a set of baseline data for specific interfacial area for a two-phase-entrapped NAPL-water system in well-characterized porous media and subsequently use these data to evaluate two current theoretical models. The first model tested distributes entrapped NAPL over the pore classes based on Land's algorithm and assumes the resulting blobs to be spherical. The other model is thermodynamically based, assuming that reversible work done on the system results in an increase in interfacial area, such that the area between drainage and imbibition retention curves can be related to the interfacial area. Interfacial tracer tests (IFTT) were used to measure specific entrapped NAPL (hexadecane)-water interfacial areas in columns packed with four grades (12/20, 20/30, 30/40, 40/50) of silica sand. By use of the anionic surfactant dihexylsulfosuccinate (Aerosol MA80), IFTT gave specific interfacial areas between 58 cm(-1) for the finest sand and 16 cm(-1) for the coarsest, compared to values of between 33 and 7 cm(-1) for the first model and between 19 and 5 cm(-1) for the thermodynamic model. Results from the literature suggest that nonspherical blobs shapes occur relatively frequently; hence it is reasonable to suggest that the assumption of spherical NAPL blobs may explain the underprediction by the first model. The thermodynamic model underestimates the interfacial area because it assumes that entrapment occurs only within the largest pores. A modified version of the latter model, allowing entrapment across all pore classes, yielded values between 58 and 13 cm(-1). Of the models tested the modified thermodynamic model best predicts the interfacial area.

Forecasting↗

PubMed2006

Chemically controlled self-assembly of protein nanorings.

The exploitation of biological macromolecules, such as nucleic acids, for the fabrication of advanced materials is a promising area of research. Although a greater variety of structural and functional uses can be envisioned for protein-based materials, systematic approaches for their construction have yet to emerge. Consistent with theoretical models of polymer macrocyclization, we have demonstrated that, in the presence of dimeric methotrexate (bisMTX), wild-type Escherichia coli dihydrofolate reductase (DHFR) molecules tethered together by a flexible peptide linker (ecDHFR(2)) are capable of spontaneously forming highly stable cyclic structures with diameters ranging from 8 to 20 nm. The nanoring size is dependent on the length and composition of the peptide linker, on the affinity and conformational state of the dimerizer, and on induced protein-protein interactions. Delineation of these and other rules for the control of protein oligomer assembly by chemical induction provides an avenue to the future design of protein-based materials and nanostructures.

Binding Sites↗

PubMed2006

Collective dynamics of lysozyme in water: terahertz absorption spectroscopy and comparison with theory.

To directly measure the low-frequency vibrational modes of proteins in biologically relevant water environment rather than previously explored dry or slightly hydrated phase, we have developed a broadband terahertz spectrometer suitable for strongly attenuating protein solutions. Radiation is provided by harmonic multipliers (up to 0.21 THz), a Gunn oscillator (at 0.139 THz), and the UCSB free-electron lasers (up to 4.8 THz). Our spectrometer combines these intense sources with a sensitive cryogenic detector and a variable path length sample cell to detect radiation after it is attenuated by more than 7 orders of magnitudes by the aqueous sample. Using this spectrometer, we have measured the molar extinction of solvated lysozyme between 0.075 and 3.72 THz (2.5-124 cm(-1)), and we made direct comparison to several published theoretical models based on molecular dynamics simulations and normal-mode analysis. We confirm the existence of dense, overlapping normal modes in the terahertz frequency range. Our observed spectrum, while in rough qualitative agreement with these models, differs in detail. Further, we observe a low-frequency cutoff in terahertz dynamics between 0.2 and 0.3 THz, and we see no evidence of a predicted normal mode at approximately 0.09 THz for the protein.

Binding Sites↗

PubMed2004

Protein folding and evolution are driven by the Maxwell Demon activity of proteins.

In this paper we propose a theoretical model of protein folding and protein evolution in which a polypeptide (sequence/structure) is assumed to behave as a Maxwell Demon or Information Gathering and Using System (IGUS) that performs measurements aiming at the construction of the native structure. Our model proposes that a physical meaning to Shannon information (H) and Chaitin's algorithmic information (K) parameters can be both defined and referred from the IGUS standpoint. Our hypothesis accounts for the interdependence of protein folding and protein evolution through mutual influencing relationships mediated by the IGUS. In brief, IGUS activity in protein folding determines long term tendencies that emerge at the evolutionary time-scale.Thus, protein evolution is a consequence of measurements executed by proteins at the cellular level, where the IGUS imposes a tendency to attain a highly unique stable native form that promotes the updating of the information content. The folding kinetics observed is, thus, the outcome of an evolutionary process where the polypeptide-IGUS drives the evolution of its linear sequence. Finally, we describe protein evolution as an entropic process that tends to increase the content of mutual algorithmic information between the sequence and the structure. This model enables one: 1. To comprehend that full determination of the three-dimensional structure by the linear sequence is a tendency where satisfaction is only possible at thermodynamic equilibrium.2. To account for the observed randomness of the amino acid sequences. 3. To predict an alternation of periods of selection and neutral diffusion during protein evolutionary time.

Algorithms↗