Multilevel modelling for inference of genetic regulatory networks

Time-course experiments with microarrays are often used to study dynamic biological systems and genetic regulatory networks (GRNs) that model how genes influence each other in cell-level development of organisms. The inference for GRNs provides important insights into the fundamental biological processes such as growth and is useful in disease diagnosis and genomic drug design. Due to the experimental design, multilevel data hierarchies are often present in time-course gene expression data. Most existing methods, however, ignore the dependency of the expression measurements over time and the correlation among gene expression profiles. Such independence assumptions violate regulatory interactions and can result in overlooking certain important subject effects and lead to spurious inference for regulatory networks or mechanisms. In this paper, a multilevel mixed-effects model is adopted to incorporate data hierarchies in the analysis of time-course data, where temporal and subject effects are both assumed to be random. The method starts with the clustering of genes by fitting the mixture model within the multilevel random-effects model framework using the expectation-maximization (EM) algorithm. The network of regulatory interactions is then determined by searching for regulatory control elements (activators and inhibitors) shared by the clusters of co-expressed genes, based on a time-lagged correlation coefficients measurement. The method is applied to two real time-course datasets from the budding yeast (Saccharomyces cerevisiae) genome. It is shown that the proposed method provides clusters of cell-cycle regulated genes that are supported by existing gene function annotations, and hence enables inference on regulatory interactions for the genetic network.

Socio-economic inequalities in women's fruit and vegetable intakes: a multilevel study of individual, social and environmental mediators

Objective: This study employed a multilevel design to test the contribution of individual, social and environmental factors to mediating socio-economic status (SES) inequalities in fruit and vegetable consumption among women. Design: A cross-sectional survey was linked with objective environmental data. Setting: A community sample involving 45 neighbourhoods. Subjects: In total, 1347 women from 45 neighbourhoods provided survey data on their SES (highest education level), nutrition knowledge, health considerations related to food purchasing, and social support for healthy eating. These data were linked with objective environmental data on the density of supermarkets and fruit and vegetable outlets in local neighbourhoods. Results: Multilevel modelling showed that individual and social factors partly mediated, but did not completely explain, SES variations in fruit and vegetable consumption. Store density did not mediate the relationship of SES with fruit or vegetable consumption. Conclusions: Nutrition promotion interventions should focus on enhancing nutrition knowledge and health considerations underlying food purchasing in order to promote healthy eating, particularly among those who are socio-economically disadvantaged. Further investigation is required to identify additional potential mediators of SES-diet relationships, particularly at the environmental level. © The Authors 2006.

Adolescent depressive symptomatology: Improve schools or help students?

Despite the increasing interest in programs designed to improve the social ecology of schools, surprisingly little is known about whether differences between schools influence student mental health. This 3-year prospective, naturalistic study examines the school effect on adolescent depressive symptomatology (measured by the Center for Epidemiological Studies Depression Scale, CES-D) among 2,489 students from 25 Australian high schools. Multilevel modelling techniques (HLM) formed the basis of the statistical analyses, There were statistically significant school effects on students' depressive symptomatology; however, these were much smaller than expected. Nearly all of the variation in CES-D depression scores was found to be at the student level, indicating that the potential mental health gains from reducing risk factors in school social environments may be extremely limited and have little effect on student depressive symptomatology.

The role of team identification in the dissimilarity-conflict relationship

This study examined the role of team identification in the dissimilarity and conflict relationship. We tested competing predictions that team identification would either mediate or moderate the positive associations between visible (age, gender and ethnic background), professional (background) and value dissimilarity and task and relationship conflict. Data was collected from 27 MBA student teams twice during a semester. Multilevel modelling and a longitudinal design were used. Results showed that value dissimilarity was positively associated with task and relationship conflict at Time 2. Its effects on relationship conflict at Time 1 were moderated by team identification. Team identification also moderated the effects of gender, age and ethnic dissimilarity on task conflict at Time 2, and the effects of gender and professional dissimilarity on relationship conflict at Time 2. No support was obtained for the mediating role of team identification on the associations between dissimilarity and conflict, or for changes in the effects of dissimilarity over time.

Weibull model selection for reliability modelling

A large number of models have been derived from the two-parameter Weibull distribution and are referred to as Weibull models. They exhibit a wide range of shapes for the density and hazard functions, which makes them suitable for modelling complex failure data sets. The WPP and IWPP plot allows one to determine in a systematic manner if one or more of these models are suitable for modelling a given data set. This paper deals with this topic.

Variants of temporal defeasible logics for modelling norm modifications

This paper proposes some variants of Temporal Defeasible Logic (TDL) to reason about normative modifications. These variants make it possible to differentiate cases in which, for example, modifications at some time change legal rules but their conclusions persist afterwards from cases where also their conclusions are blocked.

Air Bubble Entrainment in Hydraulic Jumps: Physical Modelling and Scale Effects

A hydraulic jump is characterised by strong energy dissipation and air entrainment. In the present study, new air-water flow measurements were performed in hydraulic jumps with partially-developed flow conditions in relatively large-size facilities with phase-detection probes. The experiments were conducted with identical Froude numbers, but a range of Reynolds numbers and relative channel widths. The results showed drastic scale effects at small Reynolds numbers in terms of void fraction and bubble count rate distributions. The void fraction distributions implied comparatively greater detrainment at low Reynolds numbers leading to a lesser overall aeration of the jump roller, while dimensionless bubble count rates were drastically lower especially in the mixing layer. The experimental results suggested also that the relative channel width had little effect on the air-water flow properties for identical inflow Froude and Reynolds numbers.

Modelling fungal growth on surfaces

Fungal growth in time and space at the substrate surface was modelled for a simple system mimicking solid-state fermentation, using a polycarbonate Nucleopore membrane laid over a glucose solution. Biomass production depends on both tip density and the diffusion of glucose within the fungal hyphae. The model predicts early increases in both height and concentration, followed by a period in which the biomass profile moves with a constant wavefront. The rate of increase in height increases as tip diffusivity increases or as the Monod saturation constant for glucose decreases.

Erosion/productivity modelling of maize farming in the Philippine uplands part II: Simulation of alternative farming methods

A version of the Agricultural Production Systems Simulator (APSIM) capable of simulating the key agronomic aspects of intercropping maize between legume shrub hedgerows was described and parameterised in the first paper of this series (Nelson et al., this issue). In this paper, APSIM is used to simulate maize yields and soil erosion from traditional open-field farming and hedgerow intercropping in the Philippine uplands. Two variants of open-field farming were simulated using APSIM, continuous and fallow, for comparison with intercropping maize between leguminous shrub hedgerows. Continuous open-field maize farming was predicted to be unsustainable in the long term, while fallow open-field farming was predicted to slow productivity decline by spreading the effect of erosion over a larger cropping area. Hedgerow intercropping was predicted to reduce erosion by maintaining soil surface cover during periods of intense rainfall, contributing to sustainable production of maize in the long term. In the third paper in this series, Nelson et al. (this issue) use cost-benefit analysis to compare the economic viability of hedgerow intercropping relative to traditional open-field farming of maize in relatively inaccessible upland areas. (C) 1998 Elsevier Science Ltd. All rights reserved.

Erosion/productivity modelling of maize farming in the Philippine uplands part III: Economic analysis of alternative farming methods

Two previous papers in this series (Nelson et al., this issue) described the use of the Agricultural Production Systems Simulator (APSIM) to simulate the effect of erosion on maize yields from open-field farming and hedgerow intercropping in the Philippine uplands. In this paper, maize yields simulated with APSIM are used to compare the economic viability of intercropping maize between leguminous shrub hedgerows with that of continuous and fallow open-field farming of maize. The analysis focuses on the economic incentives of upland farmers to adopt hedgerow intercropping, discussing farmers' planning horizons, access to credit and security of land tenure, as well as maize pricing in the Philippines. Insecure land tenure has limited the planning horizons of upland farmers, and high establishment costs reduce the economic viability of hedgerow intercropping relative to continuous and fallow open-field farming in the short term, In the long term, high discount rates and share-tenancy arrangements in which landlords do not contribute to establishment costs reduce the economic viability of hedgerow intercropping relative to fallow open-field farming, (C) 1998 Elsevier Science Ltd. All rights reserved.

Finite element modelling of temperature gradient driven rock alteration and mineralization in porous rock masses

We present finite element simulations of temperature gradient driven rock alteration and mineralization in fluid saturated porous rock masses. In particular, we explore the significance of production/annihilation terms in the mass balance equations and the dependence of the spatial patterns of rock alteration upon the ratio of the roll over time of large scale convection cells to the relaxation time of the chemical reactions. Special concepts such as the gradient reaction criterion or rock alteration index (RAI) are discussed in light of the present, more general theory. In order to validate the finite element simulation, we derive an analytical solution for the rock alteration index of a benchmark problem on a two-dimensional rectangular domain. Since the geometry and boundary conditions of the benchmark problem can be easily and exactly modelled, the analytical solution is also useful for validating other numerical methods, such as the finite difference method and the boundary element method, when they are used to dear with this kind of problem. Finally, the potential of the theory is illustrated by means of finite element studies related to coupled flow problems in materially homogeneous and inhomogeneous porous rock masses. (C) 1998 Elsevier Science S.A. All rights reserved.

Modelling dispersal behaviour on a fractal landscape

We use a spatially explicit population model to explore the population consequences of different habitat selection mechanisms on landscapes with fractal variation in habitat quality. We consider dispersal strategies ranging from random walks to perfect habitat selectors for two species of arboreal marsupial, the greater glider (Petauroides volans) and the mountain brushtail possum (Trichosurus caninus). In this model increasing habitat selection means individuals obtain higher quality territories, but experience increased mortality during dispersal. The net effect is that population sizes are smaller when individuals actively select habitat. We find positive relationships between habitat quality and population size can occur when individuals do not use information about the entire landscape when habitat quality is spatially autocorrelated. We also find that individual behaviour can mitigate the negative effects of spatial variation on population average survival and fecundity. (C) 1998 Elsevier Science Ltd. All rights reserved.

Bandwidth considerations for multilevel converters

Multilevel converters can achieve an overall effective switch frequency multiplication and consequent ripple reduction through the cancellation of the lowest order switch frequency terms. This paper investigates the harmonic content and the frequency response of these multimodulator converters. It is shown that the transfer function of uniformly sampled modulators is a bessel function associated with the inherent sampling process. Naturally sampled modulators have a flat transfer function, but multiple switchings per switch cycle will occur unless the input is slew-rate limited. Lower sideband harmonics of the effective carrier frequency and, in uniform converters, harmonics of the input signal also limit the useful bandwidth. Observations about the effect of the number of converters, their type (naturally or uniformly sampled), and the ratio of modulating frequency and switch frequency are made.