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At least 19 recordsLinked to original sources

Model-fitting approaches to the analysis of human behaviour.

Model-fitting methods are now prominent in the analysis of human behavioural variation. Various ways of specifying models have been proposed. These are identical in their simplest form but differ in the emphasis given to more subtle sources of variation. The biometrical genetical approach allows flexibility in the specification of non-additive factors. Given additivity, the approach of path analysis may be used to specify several environmental models in the presence of assortative mating. In many cases the methods should yield identical conclusions. Several statistical methods have been proposed for parameter estimation and hypothesis testing. The most suitable rely on the method of maximum likelihood for the estimation of variance and covariance components. Any multifactorial model can be formulated in these terms. The choice of method will depend chiefly on the design of the experiment and the ease with which a data summary can be obtained without significant loss of information. Examples are given in which the causes of variation show different degrees of detectable complexity. A variety of experimental designs yield behavioural data which illustrate the contribution of additive and non-additive genetical effects, the mating system, sibling and cultural effects, the interaction of genetical effects with age and sex. The discrimination between alternative hypotheses is often difficult. The extension of the approach to the analysis of multiple measurements and discontinuous traits is considered.

Adoption

A gene-based model of fitness and its implications for genetic variation: Linkage disequilibrium.

A widely used model of the effects of mutations on fitness (the "sites" model) assumes that heterozygous recessive or partially recessive deleterious mutations at different sites in a gene complement each other, similarly to mutations in different genes. However, the general lack of complementation between major effect allelic mutations suggests an alternative possibility, which we term the "gene" model. This assumes that a pair of heterozygous deleterious mutations in trans behave effectively as homozygotes, so that the fitnesses of trans heterozygotes are lower than those of cis heterozygotes. We examine the properties of the two different models, using both analytical and simulation methods. We show that the gene model predicts positive linkage disequilibrium (LD) between deleterious variants within the coding sequence, under conditions when the sites model predicts zero or slightly negative LD. We also show that focussing on rare variants when examining patterns of LD, especially with Lewontin's´ measure, is likely to produce misleading results with respect to inferences concerning the causes of the sign of LD. Synergistic epistasis between pairs of mutations was also modeled; it is less likely to produce negative LD under the gene model than the sites model. The theoretical results are discussed in relation to patterns of LD in natural populations of several species.

complementation

Some applications of categorical data analysis to epidemiological studies.

Several examples of categorized data from epidemiological studies are analyzed to illustrate that more informative analysis than tests of independence can be performed by fitting models. All of the analyses fit into a unified conceptual framework that can be performed by weighted least squares. The methods presented show how to calculate point estimate of parameters, asymptotic variances, and asymptotically valid chi 2 tests. The examples presented are analysis of relative risks estimated from several 2 x 2 tables, analysis of selected features of life tables, construction of synthetic life tables from cross-sectional studies, and analysis of dose-response curves.

Actuarial Analysis

A fully coupled transient excited state model for the sodium channel. I. Conductance in the voltage clamped case.

The behavior under voltage clamp conditions of a coupled kinetic scheme for the sodium channel is examined. The scheme is given diagrammatically by: Numerical simulations are presented which show that this model fits the voltage clamp data which are well described by the Hodgkin-Huxley equations, but also gives the sorts of behavior anomalous to the Hodgkin-Huxley model which have been seen experimentally. Further, straightforward changes in parameter values are shown to be capable of mimicking the ways in which some axonal preparations differ from others. Detailed, but admittedly heuristic, arguments are presented for the propositions that: 1) the model is minimal; i.e. no simpler kinetic model will fit the array of data simulated, and: 2) the transient excited state is necessary; i.e. no model of comparable simplicity with pure voltage dependent kinetics will fit the array of data simulated.

Animals

Cation permeation of the amphibian motor end-plate.

Measurements of acetylcholine-induced single-channel conductance and null potentials at the amphibian motor end-plate in solutions containing Na, K, Li and Cs ions (Gage & Van Helden, 1979; J. Physiol. (London) (in press) were analyzed in terms of three models. Two of these models, the "neutral" site channel model and the "charged" site channel model were developed to cater for three cations. Both were shown to be able to explain the dependence of single-channel conductance on membrane potential and gave the following sequences of equilibrium constants and mobilities. KLi/KNa/KK/KCs = 7:1.1:1:0.9 and UCs/UK/UNa/ULi = 1.4:1:0.58:0.13 at 8 degrees C. Similar sequences were obtained at 20 degrees C. Although the neutral model fitted the data for relative conductances in Li-, Cs- and Na-solutions slightly better than the charged model, experiments done in normal [NaCl] and [NaCl]/2 solutions could only be fitted by the neutral model. In contrast, the third model, the Constant Field Equation, was unable to fit the conductance data in any of the above situations. The data available suggests that permeation is through "long" neutral channels, lined with high field-strength negative polar groups and including one or possibly more high resistance barriers for anions.

Amphibians

Determination of dose-response curves by quantitative ionophoresis at the frog neuromuscular junction.

1. Quantitative ionophoresis at the neuromuscular junction is possible when (a) the drug is released from appropriate distances (15--20 micrometer for most drugs), (b) the topology of receptors is known and (c) high resistance drug pipettes (100--200 M omega) are sued. 2. With this method, drug concentration-endplate conductance relations were determined in voltage-clamped end-plates of the frog for the agonists ACh, carbamylcholine (CCh) and suberyldicholine (SubCh). 3. Based on the co-operative and independent model, theoretical dose-response curves were computed using as parameters the Hill coefficient nH, maximum conductance gmax., and apparent dissociation constant K. It was found that the co-operative model fitted the data much better than the independent model. 4. Based on the co-operative model, the mean maximum conductance for ACh was gmax. = 169 nS/micrometer, equivalent to 9000 ionic channels/micrometer length of a nerve terminal which can be opened at high drug concentrations. 5. The maximum conductance for CCh at--80 mV membrane potential was, on the average, 78% of that for ACh measured at the same end-plates. This value is termed the relative efficacy of CCh. 6. The mean values for the apparent dissociation constant K were 27.8 micrometer for ACh, 336 micrometer for CCh and 18 micrometer for SubCh. 7. The inhibition of the acetylcholinesterase activity by edrophonium (3--10 micrometer) affected only the local ACh concentration at the receptor sites, but not gmax. and nH. 8. Dose-response curves measured before and after removal of single nerve terminals in collagenase-treated muscle fibres showed no change in the nH, gmax. and K. A slight increase in gmax. to a value of 218 nS/micrometer observed comparing collagenase-treated and untreated end-plate. 9. Desensitization of receptors may occur in the range of several tens of milli-seconds.

Acetylcholine

Mechanism of generation and regulation of photopotential by bacteriorhodopsin in bimolecular lipid membrane.

Photoelectric properties of bacteriorhodopsin incorporated into a bimolecular lipid membrane were investigated with special regard to the mechanism of photoelectric field generation. It was shown that besides its proton pump and electric generator functions bacteriorhodopsin works as a possible molecular regulator of the light-induced membrane potential. When a bimolecular lipid membrane containing bacteriorhodopsin is continuously illuminated in its main visible absorption band, and afterwards by superimposed blue light matching the absorption band of the long-living photobleached bacteriorhodopsin (M412) as well, the latter either enhances or decreases the steady-state photoresponse, depending upon the intensity of the green light. Thus, the additional blue-light illumination tends to cause the resultant photoelectric membrane potential to become stabilized. Two alternative schemes are tentatively proposed for the photochemical cycle of bacteriorhodopsin whereby blue light can control photovoltage generation. A kinetic model of the proton pump and the regulation of the photoelectric membrane potential is presented. This model fits all the experimental findings, even quantitatively. From the model some kinetic and physical parameters of this light-driven pump could be determined.

Bacteriorhodopsins

Phylogenomics reveals persistent gene-tree discordance in the Chenopodium album aggregate.

BACKGROUND AND AIMS: Complex genomic histories shaped by hybridisation and polyploidy can influence traits related to plant defence, stress tolerance and toxicity, particularly in Amaranthaceae, which includes crops such as quinoa and spinach. Within this family, white goosefoot (Chenopodium album), a widespread agricultural weed and traditional food resource, belongs to a diploid-polyploid aggregate with extensive phylogenetic discordance. Clarifying its evolutionary history provides context for interpreting ecologically and agronomically relevant trait variation across the aggregate. Building on the established genome-lineage framework, we tested whether discordance persists when constituent genome-lineage components are represented separately and whether the remaining signal is compatible with reticulate evolution. METHODS: We analysed 2,298 conserved nuclear BUSCO families across 27 assembly-level terminals using tree- and network-based approaches. Genome-lineage-aware analyses used 2,156 families after separating polyploid Chenopodium into A-H components, with Dysphania ambrosioides as outgroup. HyDe tested site-pattern asymmetry under global false-discovery-rate correction. KEY RESULTS: Assembly-level analyses grouped the Danish C. album aggregate accession Ca6-1 with hexaploid C. album sensu stricto dcCheAlbu1.1, whereas relationships among surrounding Chenopodium taxa were less stable. Genome-lineage-aware analyses recovered the expected B-, C- and D-affinity relationships, but substantial gene-family heterogeneity persisted. Reticulate network models fitted the assembly-level data better than bifurcating models, although inferred patterns differed between methods. HyDe detected significant site-pattern asymmetry in a small subset of loci, with most retained signal shared between the focal assemblies. CONCLUSIONS: Gene-tree discordance persists in the C. album aggregate after genome-lineage separation. The established genome-lineage framework captures the dominant phylogenomic structure, while residual heterogeneity is compatible with both tree-like and reticulate processes without identifying direct progenitors or a unique hybridisation history. This framework supports future analyses of lineage-specific and trait-associated loci related to plant defence, food quality and toxicity in C. album and related Amaranthaceae.

Chenopodium album

A useful method for the analysis of growth studies.

A group of parsimonious models for the analysis of animal growth curves is presented. The effects of correlations between the successive weights are reduced by analyzing the weight gained between the different weighing times. A model is developed for the resulting two-way table of group average gain curves (group by periods), using the two-way table modeling techniques proposed by Mandel. The coefficients in the fitted model are examined to determine what functions of the weight gain measurements will summarize the characteristics of the curves. In the second part of the analysis these statistics are computed for each animal and analyzed to determine the effects of the design variables on the growth of the animals. Experience has shown that in many instances total weight gain summarizes all the information in the curve. The conditions under which total gain provides an adequate summary are discussed. The model has been used in the analysis of rat, dog, hamster, guinea pig and swine growth curves. An example is included to illustrate the utility of the proposed approach.

Analysis of Variance

A theoretical model for lipid mixtures, phase transitions, and phase diagrams.

We present a new model for the thermodynamic properties of lipid bilayers. The model consists of a system of hard cylinders of varying radii that correspond to the different molecular radii of lipids having different numbers of gauche rotations in their chains. Scaled particle theory is used to provide an accurate estimate of the entropy of packing of the cylinders. To apply the model to bilayers we introduce a semiempirical attractive potential energy. Once the form of this potential is chosen, we adjust one parameter, the interaction strength, so that the model fits the transition temperatures and entropies for various phospholipids. The model then agrees quite well with other published data for these systems. We also directly generalize our model to lipid mixtures, and we obtain phase diagrams that we compare to existing data for these systems. We use the model to describe lipid protein interactions in bilayers as well.

Lipid Bilayers

Ethylmorphine-N-demethylation by liver homogenate of newborn and adult rats; Enzyme kinetics and age course of Vmax and Km1.

Optimum incubation conditions for determination of ethylmorphine-N-demethylation with newborn and adult rat liver homogenate have been determined: 1 ml 1:20 liver homogenate in 1.15% KCl, 1 ml 0.1 M phosphate buffer with ethylmorphine, NADP, and glucose-6-P, final concentrations 10, 0.33 and 5 mM, respectively, no nicotinamide, no MgCl2, 1 ml 0.5 M phosphate buffer; 3 ml final volume, 20 min incubation time. With both age groups NADH increases the activity to the same extent. With NADPH, saturation could be achieved only with newborn liver, but not with adult liver homogenate. Postnatally, the activity increases about fivefold, with a break at the 10th day of life. The Lineweaver-Burk plot was linear with newborn liver homogenate, whereas for all other age groups the graphs showed an angle. Statistical analysis pointed out that a two-enzyme model fits the experimental data only insignificantly better than a one-enzyme model. From other experimental evidence and manifold reproduction without any exception of these results, however, it may be concluded that there are different monooxygenases which show different affinities towards one substrate (ethylmorphine) and which show different developmental patterns.

Age Factors