Estimates on the coverage of parameter space using populations of models

In this paper we provide estimates for the coverage of parameter space when using Latin Hypercube Sampling, which forms the basis of building so-called populations of models. The estimates are obtained using combinatorial counting arguments to determine how many trials, k, are needed in order to obtain specified parameter space coverage for a given value of the discretisation size n. In the case of two dimensions, we show that if the ratio (Ø) of trials to discretisation size is greater than 1, then as n becomes moderately large the fractional coverage behaves as 1-exp-ø. We compare these estimates with simulation results obtained from an implementation of Latin Hypercube Sampling using MATLAB.

Populations of models, experimental designs and coverage of parameter space by Latin Hypercube and Orthogonal Sampling

In this paper we have used simulations to make a conjecture about the coverage of a t-dimensional subspace of a d-dimensional parameter space of size n when performing k trials of Latin Hypercube sampling. This takes the form P(k,n,d,t) = 1 - e^(-k/n^(t-1)). We suggest that this coverage formula is independent of d and this allows us to make connections between building Populations of Models and Experimental Designs. We also show that Orthogonal sampling is superior to Latin Hypercube sampling in terms of allowing a more uniform coverage of the t-dimensional subspace at the sub-block size level. These ideas have particular relevance when attempting to perform uncertainty quantification and sensitivity analyses.

Sampling Methods for Exploring Between Subject Variability in Cardiac Electrophysiology Experiments

Between-subject and within-subject variability is ubiquitous in biology and physiology and understanding and dealing with this is one of the biggest challenges in medicine. At the same time it is difficult to investigate this variability by experiments alone. A recent modelling and simulation approach, known as population of models (POM), allows this exploration to take place by building a mathematical model consisting of multiple parameter sets calibrated against experimental data. However, finding such sets within a high-dimensional parameter space of complex electrophysiological models is computationally challenging. By placing the POM approach within a statistical framework, we develop a novel and efficient algorithm based on sequential Monte Carlo (SMC). We compare the SMC approach with Latin hypercube sampling (LHS), a method commonly adopted in the literature for obtaining the POM, in terms of efficiency and output variability in the presence of a drug block through an in-depth investigation via the Beeler-Reuter cardiac electrophysiological model. We show improved efficiency via SMC and that it produces similar responses to LHS when making out-of-sample predictions in the presence of a simulated drug block.

Inter-and Intra-Site Genetic Diversity of Natural Field Populations of Rice Tungro Bacilliform Virus in the Philippines

The genetic structure of rice tungro bacilliform virus (RTBV) populations within and between growing sites was analyzed in a collection of natural field isolates from different rice varieties grown in eight tungro-endemic sites of the Philippines. Total DNA extracts from 345 isolates were digested with EcoRV restriction enzyme and hybridized with a full-length probe of RTBV, a procedure shown in preliminary experiments capable of revealing high levels of polymorphism in RTBV field isolates. In the total population, 17 distinct EcoRV-based genome profiles (genotypes) were identified and used as indicators for virus diversity. Distinct sets of genotypes occurred in Isabela and North Cotabato provinces suggesting a geographic isolation of virus populations. However, among the sites in each province, there were few significant differences in the genotype compositions of virus populations. The number of genotypes detected at a site varied from two to nine with a few genotypes dominating. In general the isolates at a site persisted from season to season indicating a genetic stability for the local virus population. Over the sampling time, IRRI rice varieties, which have green leafhopper resistance genes, supported similar virus populations to those supported by other varieties, indicating that the variety of the host exerted no apparent selection pressures. Insect transmission experiments on selected RTBV field isolates showed that dramatic shifts in genotype and phenotype distributions can occur in response to host /environmental shifts.

Spatially stratified sampling using auxiliary information for geostatistical mapping

This paper presents a method of spatial sampling based on stratification by Local Moran’s I i calculated using auxiliary information. The sampling technique is compared to other design-based approaches including simple random sampling, systematic sampling on a regular grid, conditional Latin Hypercube sampling and stratified sampling based on auxiliary information, and is illustrated using two different spatial data sets. Each of the samples for the two data sets is interpolated using regression kriging to form a geostatistical map for their respective areas. The proposed technique is shown to be competitive in reproducing specific areas of interest with high accuracy.

Ratcheting and wear behavior of Australian rail steel: Experimental investigation of material properties and sampling method

To The ratcheting behavior of high-strength rail steel (Australian Standard AS1085.1) is studied in this work for the purpose of predicting wear and damage to the rail surface. Historically, researchers have used circular test coupons obtained from the rail head to conduct cyclic load tests, but according to hardness profile data, considerable variation exists across the rail head section. For example, the induction-hardened rail (AS1085.1) shows high hardness (400-430 HV100) up to four-millimeters into the rail head’s surface, but then drops considerably beyond that. Given that cyclic test coupons five millimeters in diameter at the gauge area are usually taken from the rail sample, there is a high probability that the original surface properties of the rail do not apply across the entire test coupon and, therefore, data representing only average material properties are obtained. In the literature, disks (47 mm in diameter) for a twin-disk rolling contact test machine have been obtained directly from the rail sample and used to validate rolling contact fatigue wear models. The question arises: How accurate are such predictions? In this research paper, the effect of rail sampling position on the ratcheting behavior of AS1085.1 rail steel was investigated using rectangular shaped specimens. Uniaxial stress-controlled tests were conducted with samples obtained at four different depths to observe the ratcheting behaviour of each. Micro-hardness measurements of the test coupons were carried out to obtain a constitutive relationship to predict the effect of depth on the ratcheting behaviour of the rail material. This work ultimately assists the selection of valid material parameters for constitutive models in the study of rail surface ratcheting.

A review of models of spatial innovation infrastructures in support of high growth SMEs

This Paper first provides a review and analysis of the recent trends on innovation infrastructures developed in industrialised countries to promote innovation and competitiveness for high growth SMEs. It specifically aims to examine various spatial models developed to support provision of innovation infrastructure for high growth sector.

Stem cell–related gene expression in clonal populations of mesenchymal stromal cells from bone marrow

Decline in the frequency of potent mesenchymal stem cells (MSCs) has been implicated in ageing and degenerative diseases. Increasing the circulating stem cell population can lead to renewed recruitment of these potent cells at sites of damage. Therefore, identifying the ideal cells for ex vivo expansion will form a major pursuit of clinical applications. This study is a follow-up of previous work that demonstrated the occurrence of fast-growing multipotential cells from the bone marrow samples. To investigate the molecular processes involved in the existence of such varying populations, gene expression studies were performed between fast- and slow-growing clonal populations to identify potential genetic markers associated with stemness using the quantitative real-time polymerase chain reaction comprising a series of 84 genes related to stem cell pathways. A group of 10 genes were commonly overrepresented in the fast-growing stem cell clones. These included genes that encode proteins involved in the maintenance of embryonic and neural stem cell renewal (sex-determining region Y-box 2, notch homolog 1, and delta-like 3), proteins associated with chondrogenesis (aggrecan and collagen 2 A1), growth factors (bone morphogenetic protein 2 and insulin-like growth factor 1), an endodermal organogenesis protein (forkhead box a2), and proteins associated with cell-fate specification (fibroblast growth factor 2 and cell division cycle 2). Expression of diverse differentiation genes in MSC clones suggests that these commonly expressed genes may confer the maintenance of multipotentiality and self-renewal of MSCs.

A review of models and model usage scenarios for an airport complex system

Airports represent the epitome of complex systems with multiple stakeholders, multiple jurisdictions and complex interactions between many actors. The large number of existing models that capture different aspects of the airport are a testament to this. However, these existing models do not consider in a systematic sense modelling requirements nor how stakeholders such as airport operators or airlines would make use of these models. This can detrimentally impact on the verification and validation of models and makes the development of extensible and reusable modelling tools difficult. This paper develops from the Concept of Operations (CONOPS) framework a methodology to help structure the review and development of modelling capabilities and usage scenarios. The method is applied to the review of existing airport terminal passenger models. It is found that existing models can be broadly categorised according to four usage scenarios: capacity planning, operational planning and design, security policy and planning, and airport performance review. The models, the performance metrics that they evaluate and their usage scenarios are discussed. It is found that capacity and operational planning models predominantly focus on performance metrics such as waiting time, service time and congestion whereas performance review models attempt to link those to passenger satisfaction outcomes. Security policy models on the other hand focus on probabilistic risk assessment. However, there is an emerging focus on the need to be able to capture trade-offs between multiple criteria such as security and processing time. Based on the CONOPS framework and literature findings, guidance is provided for the development of future airport terminal models.

Persistence of multiple genetic lineages within intra-host populations of Ross River virus

We examined the structure and extent of genetic diversity in intrahost populations of Ross River virus (RRV) in samples from six human patients, focusing on the nonstructural (nsP3) and structural (E2) protein genes. Strikingly, although the samples were collected from contrasting ecological settings 3,000 kilometers apart in Australia, we observed multiple viral lineages in four of the six individuals, which is indicative of widespread mixed infections. In addition, a comparison with previously published RRV sequences revealed that these distinct lineages have been in circulation for at least 5 years, and we were able to document their long-term persistence over extensive geographical distances

Polyandry and paternity skew in natural and experimental populations of Drosophila serrata

Many species engage in polyandry, resulting in the potential for sexual selection to continue post-copulation through sperm competition and/or cryptic female choice. The relative importance of pre- vs. post-copulatory processes remains unknown for most species despite this information being fundamental for understanding the evolutionary consequences of sexual selection. The Australian fruit fly Drosophila serrata has become a prominent model system for studying precopulatory sexual selection, such as mating preferences and their influence on the evolution of sexually selected traits. Here, we investigated polyandry and the potential for post-copulatory sexual selection in this species using indirect paternity analysis. We genotyped 21 wild-caught and 19 laboratory-reared mothers and their offspring (a total of 787 flies) at six microsatellite loci and found extensive polyandry, with all broods surveyed having at least two sires. Female remating rates were higher than in other Drosophila surveyed to date and no significant differences were found between laboratory and field populations. Additionally, we found evidence for biased sperm usage in several broods of D. serrata. Paternity skew occurred more frequently in broods from the field population than the laboratory one, suggesting differences between the two environments in the level of post-copulatory sexual selection. Our data suggest that D. serrata represents a promising system for studying the interaction between pre- and post-copulatory sexual selection in driving the evolution of sexually selected phenotypes.

Genetic diversity of cultured and wild populations of the giant freshwater prawn Macrobrachium rosenbergii (de Man, 1879) based on microsatellite analysis

Freshwater prawn (Macrobrachium rosenbergii) culture in the Western Hemisphere is primarily, if not entirely, derived from 36 individual prawns originally introduced to Hawaii from Malaysia in 1965 and 1966. Little information is available regarding genetic variation within and among cultured prawn stocks worldwide. The goal of the current study was to characterize genetic diversity in various prawn populations with emphasis on those cultured in North America. Five microsatellite loci were screened to estimate genetic diversity in two wild (Myanmar and India-wild) and seven cultured (Hawaii-1, Hawaii-2, India-cultured, Israel, Kentucky, Mississippi and Texas) populations. Average allelic richness ranged from 3.96 (Israel) to 20.45 (Myanmar). Average expected heterozygosity ranged from 0.580 (Israel) to 0.935 (Myanmar). Many of the cultured populations exhibited reduced genetic diversity when compared with the Myanmar and the India-cultured populations. Significant deficiency in heterozygotes was detected in the India-cultured, Mississippi and Kentucky populations (overall Fis estimated of 0.053, 0.067 and 0.108 respectively) reflecting moderate levels of inbreeding. Overall estimate of fixation index (Fst = 0.1569) revealed moderately high levels of differentiation among the populations. Outcome of this study provide a baseline assessment of genetic diversity in some available strains that will be useful for the development of breeding programmes.

An assessment of the geographical scale of recurrent gene flow in wild populations of two species of Mekong River carps (Henicorhynchus spp.)

The Mekong is the most productive river fishery in the world, and such as, the Mekong River Basin (MRB) is very important to very large human populations across the region as a source of revenue (through fishing and marketing of aquatic resources products) and as the major source for local animal protein. Threats to biodiversity in the MRB, either to the fishery sector itself or to other sectors are a major concern, even though currently, fisheries across this region are still very productive. If not managed properly however, fish population declines will cause significant economic impact and affect livelihoods of local people and will have a major impact on food security and nutrition. Biodiversity declines will undoubtedly affect food security, income and socio-economic status of people in the MRB that depend on aquatic resources. This is an indicator of unsustainable development and hence should be avoided. Genetic diversity (biodiversity) that can be measured using techniques based on DNA markers; refers to variation within and among populations within the same species or reproductive units. In a population, new genetic variation is generated by sexual recombination contributed by individuals with mutations in genes and chromosomes. Over time, populations of a species that are not reproducing together will diverge as differential impacts of selection and genetic drift change their genetic attributes. For mud carp (Henicorhynchus spp.), understanding the status of breeding units in the MRB will be important for their long term persistence, sustainability and for implementing effective management strategies. Earlier analysis of stock structure in two economically important mud carp species (Henicorhynchus siamensis and H. lobatus) in the MRB completed with mtDNA markers identified a number of populations of both species where gene flow had apparently been interrupted or reduced but applying these data directly to management unit identification is potentially compromised because information was only available about female dispersal patterns. The current study aimed to address this problem and to fully assess the extent of current gene flow (nDNA) and reproductive exchange among selected wild populations of two species of carp (Henicorhynchus spp.) of high economic importance in the MRB using combined mtDNA and nDNA markers. In combination, the data can be used to define effective management units for each species. In general, nDNA diversity for H. lobatus (with average allelic richness (A) 7.56 and average heterozygosity (Ho) 0.61) was very similar to that identified for H. siamensis (A = 6.81 and Ho = 0.75). Both mud carp species show significant but low FST estimates among populations as a result of lower genetic diversity among sampled populations compared with genetic diversity within populations that may potentially mask any 'real' population structure. Overall, population genetic structure patterns from mtDNA and nDNA in both Henicorhynchus species were largely congruent. Different population structures however, were identified for the two Henicorhynchus species across the same geographical area. Apparent co-similarity in morphology and co-distribution of these two relatively closely related species does not apparently imply parallel evolutionary histories. Differences in each species population structure likely reflect historical drainage rearrangement of the Mekong River. The data indicate that H. siamensis is likely to have occupied the Mekong system for much longer than has H. lobatus in the past. Two divergent stocks were identified for H. lobatus in the MRB below the Khone Falls while a single stock had been evident in the earlier mtDNA study. This suggests that the two Henicorhynchus species may possess different life history traits and that different patterns of gene flow has likely influenced modern genetic structure in these close congeners. In combination, results of the earlier mtDNA and the current study have implications for effective management of both Henicorhynchus species across the MRB. Currently, both species are essentially treated as a single management unit in this region. This strategy may be appropriate for H. lobatus as a single stock was evident in the main stream of the MRB, but may not be appropriate for H. siamensis as more than a single stock was identified across the same range for this species. Management strategies should consider this difference to conserve overall biodiversity (local discrete populations) and this will include maintaining natural habitat and migration pathways, provision of fish sanctuaries (refuges) and may also require close monitoring of any stock declines, a signal that may require effective recovery strategies.