Eyes on 3D-Current 3D biomimetic disease concept models and potential applications in age-related macular degeneration

Three dimensional cellular models that mimic disease are being increasingly investigated and have opened an exciting new research area into understanding pathomechanisms. The advantage of 3D in vitro disease models is that they allow systematic and in-depth studies of physiological and pathophysiological processes with less costs and ethical concerns that have arisen with animal models. The purpose of the 3D approach is to allow crosstalk between cells and microenvironment, and with cues from the microenvironment, cells can assemble their niche similar to in vivo conditions. The use of 3D models for mimicking disease processes such as cancer, osteoarthritis etc., is only emerging and allows multidisciplinary teams consisting of tissue engineers, biologist biomaterial scientists and clinicians to work closely together. While in vitro systems require rigorous testing before they can be considered as replicates of the in vivo model, major steps have been made, suggesting that they will become powerful tools for studying physiological and pathophysiological processes. This paper aims to summarize some of the existing 3D models and proposes a novel 3D model of the eye structures that are involved in the most common cause of blindness in the Western World, namely age-related macular degeneration (AMD).

Reasoning about component similarity in building product models from the construction perspective

Identifying the design features that impact construction is essential to developing cost effective and constructible designs. The similarity of building components is a critical design feature that affects method selection, productivity, and ultimately construction cost and schedule performance. However, there is limited understanding of what constitutes similarity in the design of building components and limited computer-based support to identify this feature in a building product model. This paper contributes a feature-based framework for representing and reasoning about component similarity that builds on ontological modelling, model-based reasoning and cluster analysis techniques. It describes the ontology we developed to characterize component similarity in terms of the component attributes, the direction, and the degree of variation. It also describes the generic reasoning process we formalized to identify component similarity in a standard product model based on practitioners' varied preferences. The generic reasoning process evaluates the geometric, topological, and symbolic similarities between components, creates groupings of similar components, and quantifies the degree of similarity. We implemented this reasoning process in a prototype cost estimating application, which creates and maintains cost estimates based on a building product model. Validation studies of the prototype system provide evidence that the framework is general and enables a more accurate and efficient cost estimating process.

Large igneous provinces and silicic large igneous provinces : progress in our understanding over the last 25 years

Large Igneous Provinces are exceptional intraplate igneous events throughout Earth’s history. Their significance and potential global impact is related to the total volume of magma intruded and released during these geologically brief events (peak eruptions are often within 1-5 Myrs duration) where millions to tens of millions of cubic kilometers of magma are produced. In some cases, at least 1% of the Earth’s surface has been directly covered in volcanic rock, being equivalent to the size of small continents with comparable crustal thicknesses. Large Igneous Provinces are thus important, albeit episodic episodes of new crust addition. However, most magmatism is basaltic so that contributions to crustal growth will not always be picked up in zircon geochronology studies that better trace major episodes of extension-related silicic magmatism and the silicic Large Igneous Provinces. Much headway has been made on our understanding of these anomalous igneous events over the last 25 years, driving many new ideas and models. This includes their: 1) global spatial and temporal distribution, with a long-term average of one event approximately every 20 Myrs, but a clear clustering of events at times of supercontinent break-up – Large Igneous Provinces are thus an integral part of the Wilson cycle and are becoming an increasingly important tool in reconnecting dispersed continental fragments; 2) compositional diversity that in part reflects their crustal setting of ocean basins, and continental interiors and margins where in the latter setting, LIP magmatism can be silicicdominant; 3) mineral and energy resources with major PGE and precious metal resources being hosted in these provinces, as well as magmatism impacting on the hydrocarbon potential of volcanic basins and rifted margins through enhancing source rock maturation, providing fluid migration pathways, and trap formation; 4) biospheric, hydrospheric and atmospheric impacts, with Large Igneous Provinces now widely regarded as a key trigger mechanism for mass extinctions, although the exact kill mechanism(s) are still being resolved; 5) role in mantle geodynamics and thermal evolution of the Earth, by potentially recording the transport of material from the lower mantle or core-mantle boundary to the Earth's surface and being a fundamental component in whole mantle convection models; and 6) recognition on the inner planets where the lack of plate tectonics and erosional processes and planetary antiquity means that the very earliest record of LIP events during planetary evolution may be better preserved than on Earth.

Prediction of IBD based on population history for fine gene mapping

A novel multiple regression method (RM) is developed to predict identity-by-descent probabilities at a locus L (IBDL), among individuals without pedigree, given information on surrounding markers and population history. These IBDL probabilities are a function of the increase in linkage disequilibrium (LD) generated by drift in a homogeneous population over generations. Three parameters are sufficient to describe population history: effective population size (Ne), number of generations since foundation (T), and marker allele frequencies among founders (p). IBD L are used in a simulation study to map a quantitative trait locus (QTL) via variance component estimation. RM is compared to a coalescent method (CM) in terms of power and robustness of QTL detection. Differences between RM and CM are small but significant. For example, RM is more powerful than CM in dioecious populations, but not in monoecious populations. Moreover, RM is more robust than CM when marker phases are unknown or when there is complete LD among founders or Ne is wrong, and less robust when p is wrong. CM utilises all marker haplotype information, whereas RM utilises information contained in each individual marker and all possible marker pairs but not in higher order interactions. RM consists of a family of models encompassing four different population structures, and two ways of using marker information, which contrasts with the single model that must cater for all possible evolutionary scenarios in CM.

Candidate gene analysis for quantitative traits using the transmission disequilibrium test : the example of the melanocortin 4-receptor in pigs

Population-wide associations between loci due to linkage disequilibrium can be used to map quantitative trait loci (QTL) with high resolution. However, spurious associations between markers and QTL can also arise as a consequence of population stratification. Statistical methods that cannot differentiate between loci associations due to linkage disequilibria from those caused in other ways can render false-positive results. The transmission-disequilibrium test (TDT) is a robust test for detecting QTL. The TDT exploits within-family associations that are not affected by population stratification. However, some TDTs are formulated in a rigid-form, with reduced potential applications. In this study we generalize TDT using mixed linear models to allow greater statistical flexibility. Allelic effects are estimated with two independent parameters: one exploiting the robust within-family information and the other the potentially biased between-family information. A significant difference between these two parameters can be used as evidence for spurious association. This methodology was then used to test the effects of the fourth melanocortin receptor (MC4R) on production traits in the pig. The new analyses supported the previously reported results; i.e., the studied polymorphism is either causal of in very strong linkage disequilibrium with the causal mutation, and provided no evidence for spurious association.

Sources of ultrafine particles and chemical species along a traffic corridor : comparison of the results from two receptor models

Particulate matter is common in our environment and has been linked to human health problems particularly in the ultrafine size range. A range of chemical species have been associated with particulate matter and of special concern are the hazardous chemicals that can accentuate health problems. If the sources of such particles can be identified then strategies can be developed for the reduction of air pollution and consequently, the improvement of the quality of life. In this investigation, particle number size distribution data and the concentrations of chemical species were obtained at two sites in Brisbane, Australia. Source apportionment was used to determine the sources (or factors) responsible for the particle size distribution data. The apportionment was performed by Positive Matrix Factorisation (PMF) and Principal Component Analysis/Absolute Principal Component Scores (PCA/APCS), and the results were compared with information from the gaseous chemical composition analysis. Although PCA/APCS resolved more sources, the results of the PMF analysis appear to be more reliable. Six common sources identified by both methods include: traffic 1, traffic 2, local traffic, biomass burning, and two unassigned factors. Thus motor vehicle related activities had the most impact on the data with the average contribution from nearly all sources to the measured concentrations higher during peak traffic hours and weekdays. Further analyses incorporated the meteorological measurements into the PMF results to determine the direction of the sources relative to the measurement sites, and this indicated that traffic on the nearby road and intersection was responsible for most of the factors. The described methodology which utilised a combination of three types of data related to particulate matter to determine the sources could assist future development of particle emission control and reduction strategies.

Logan Basin Water Resource Plan : environmental assessment of the southern Moreton Bay islands. Technical Advisory Panel Report: Stage 1.

This report is a technical assessment of the hydrological environment of the southern Moreton Bay islands and follows the terms of reference supplied by the then Queensland Department of Natural Resources and Water. The terms of reference describe stage 1 as a condition assessment and stage 2 as an assessment of the implications of water planning scenarios on future condition. This report is the first stage of a two-stage investigation whose primary purpose is to identify and assess groundwater dependent ecosystems (GDEs) and the groundwater flow regimes necessary to support them. Within this context, the groundwaters themselves are also considered and comment made on their condition. Information provided in this report will inform an amendment to the Logan Basin Water Resource Plan to incorporate the southern Moreton Bay islands. The study area is the water resource plan amendment area, which includes North and South Stradbroke islands and the smaller islands between these and the mainland, including the inhabited smaller rocky islands—namely, Macleay, Russell, Karragarra, Lamb and Coochiemudlo islands. This assessment is largely a desktop study based on existing information, but incorporates some field observations, input from experts in specific areas and community representatives, and the professional experience and knowledge of the authors. This report reviews existing research and information on the southern Moreton Bay area with an emphasis on North Stradbroke Island, as it represents the largest and most regionally significant groundwater resource in southern Moreton Bay. The report provides an assessment of key waterrelated environmental features, their condition and their degree of dependence on groundwater. This report also assesses the condition and status of ecosystems within this region. In addition, the report identifies information gaps, uncertainties and potential impacts; reviews groundwater models that have been developed for North Stradbroke Island; and makes recommendations on monitoring and research needs.

Experimental and modelling investigation of monolayer development with clustering

Standard differential equation–based models of collective cell behaviour, such as the logistic growth model, invoke a mean–field assumption which is equivalent to assuming that individuals within the population interact with each other in proportion to the average population density. Implementing such assumptions implies that the dynamics of the system are unaffected by spatial structure, such as the formation of patches or clusters within the population. Recent theoretical developments have introduced a class of models, known as moment dynamics models, which aim to account for the dynamics of individuals, pairs of individuals, triplets of individuals and so on. Such models enable us to describe the dynamics of populations with clustering, however, little progress has been made with regard to applying moment dynamics models to experimental data. Here, we report new experimental results describing the formation of a monolayer of cells using two different cell types: 3T3 fibroblast cells and MDA MB 231 breast cancer cells. Our analysis indicates that the 3T3 fibroblast cells are relatively motile and we observe that the 3T3 fibroblast monolayer forms without clustering. Alternatively, the MDA MB 231 cells are less motile and we observe that the MDA MB 231 monolayer formation is associated with significant clustering. We calibrate a moment dynamics model and a standard mean–field model to both data sets. Our results indicate that the mean–field and moment dynamics models provide similar descriptions of the 3T3 fibroblast monolayer formation whereas these two models give very different predictions for the MDA MD 231 monolayer formation. These outcomes indicate that standard mean–field models of collective cell behaviour are not always appropriate and that care ought to be exercised when implementing such a model.

Comparative study of analytical rental model and statistical models for predicting house rental levels

The need for a house rental model in Townsville, Australia is addressed. Models developed for predicting house rental levels are described. An analytical model is built upon a priori selected variables and parameters of rental levels. Regression models are generated to provide a comparison to the analytical model. Issues in model development and performance evaluation are discussed. A comparison of the models indicates that the analytical model performs better than the regression models.

Slice, mine and dice : complexity-aware automated discovery of business process models

Automated process discovery techniques aim at extracting models from information system logs in order to shed light into the business processes supported by these systems. Existing techniques in this space are effective when applied to relatively small or regular logs, but otherwise generate large and spaghetti-like models. In previous work, trace clustering has been applied in an attempt to reduce the size and complexity of automatically discovered process models. The idea is to split the log into clusters and to discover one model per cluster. The result is a collection of process models -- each one representing a variant of the business process -- as opposed to an all-encompassing model. Still, models produced in this way may exhibit unacceptably high complexity. In this setting, this paper presents a two-way divide-and-conquer process discovery technique, wherein the discovered process models are split on the one hand by variants and on the other hand hierarchically by means of subprocess extraction. The proposed technique allows users to set a desired bound for the complexity of the produced models. Experiments on real-life logs show that the technique produces collections of models that are up to 64% smaller than those extracted under the same complexity bounds by applying existing trace clustering techniques.

Experimental and computer simulation validation of ultrasound phase interference created by lateral inhomogeneity of transit time in replica bone marrow composite models

Purpose: The measurement of broadband ultrasonic attenuation (BUA) in cancellous bone for the assessment of osteoporosis follows a parabolic-type dependence with bone volume fraction; having minima values corresponding to both entire bone and entire marrow. Langton has recently proposed that the primary BUA mechanism may be significant phase interference due to variations in propagation transit time through the test sample as detected over the phase-sensitive surface of the receive ultrasound transducer. This fundamentally simple concept assumes that the propagation of ultrasound through a complex solid : liquid composite sample such as cancellous bone may be considered by an array of parallel ‘sonic rays’. The transit time of each ray is defined by the proportion of bone and marrow propagated, being a minimum (tmin) solely through bone and a maximum (tmax) solely through marrow. A Transit Time Spectrum (TTS), ranging from tmin to tmax, may be defined describing the proportion of sonic rays having a particular transit time, effectively describing lateral inhomogeneity of transit time over the surface of the receive ultrasound transducer. Phase interference may result from interaction of ‘sonic rays’ of differing transit times. The aim of this study was to test the hypothesis that there is a dependence of phase interference upon the lateral inhomogenity of transit time by comparing experimental measurements and computer simulation predictions of ultrasound propagation through a range of relatively simplistic solid:liquid models exhibiting a range of lateral inhomogeneities. Methods: A range of test models was manufactured using acrylic and water as surrogates for bone and marrow respectively. The models varied in thickness in one dimension normal to the direction of propagation, hence exhibiting a range of transit time lateral inhomogeneities, ranging from minimal (single transit time) to maximal (wedge; ultimately the limiting case where each sonic ray has a unique transit time). For the experimental component of the study, two unfocused 1 MHz ¾” broadband diameter transducers were utilized in transmission mode; ultrasound signals were recorded for each of the models. The computer simulation was performed with Matlab, where the transit time and relative amplitude of each sonic ray was calculated. The transit time for each sonic ray was defined as the sum of transit times through acrylic and water components. The relative amplitude considered the reception area for each sonic ray along with absorption in the acrylic. To replicate phase-sensitive detection, all sonic rays were summed and the output signal plotted in comparison with the experimentally derived output signal. Results: From qualtitative and quantitative comparison of the experimental and computer simulation results, there is an extremely high degree of agreement of 94.2% to 99.0% between the two approaches, supporting the concept that propagation of an ultrasound wave, for the models considered, may be approximated by a parallel sonic ray model where the transit time of each ray is defined by the proportion of ‘bone’ and ‘marrow’. Conclusions: This combined experimental and computer simulation study has successfully demonstrated that lateral inhomogeneity of transit time has significant potential for phase interference to occur if a phase-sensitive ultrasound receive transducer is implemented as in most commercial ultrasound bone analysis devices.

Modelling word activation in semantic networks : three scaled entanglement models compared

Modelling how a word is activated in human memory is an important requirement for determining the probability of recall of a word in an extra-list cueing experiment. Previous research assumed a quantum-like model in which the semantic network was modelled as entangled qubits, however the level of activation was clearly being over-estimated. This paper explores three variations of this model, each of which are distinguished by a scaling factor designed to compensate the overestimation.