Repair of calvarial defects with customized tissue-engineered bone grafts - I. Evaluation of osteogenesis in a three-dimensional culture system

Bone generation by autogenous cell transplantation in combination with a biodegradable scaffold is one of the most promising techniques being developed in craniofacial surgery. The objective of this combined in vitro and in vivo study was to evaluate the morphology and osteogenic differentiation of bone marrow derived mesenchymal progenitor cells and calvarial osteoblasts in a two-dimensional (2-D) and three-dimensional (3-D) culture environment (Part I of this study) and their potential in combination with a biodegradable scaffold to reconstruct critical-size calvarial defects in an autologous animal model [Part II of this study; see Schantz, J.T., et al. Tissue Eng. 2003;9(Suppl. 1):S-127-S-139; this issue]. New Zealand White rabbits were used to isolate osteoblasts from calvarial bone chips and bone marrow stromal cells from iliac crest bone marrow aspirates. Multilineage differentiation potential was evaluated in a 2-D culture setting. After amplification, the cells were seeded within a fibrin matrix into a 3-D polycaprolactone (PCL) scaffold system. The constructs were cultured for up to 3 weeks in vitro and assayed for cell attachment and proliferation using phase-contrast light, confocal laser, and scanning electron microscopy and the MTS cell metabolic assay. Osteogenic differentiation was analyzed by determining the expression of alkaline phosphatase (ALP) and osteocalcin. The bone marrow-derived progenitor cells demonstrated the potential to be induced to the osteogenic, adipogenic, and chondrogenic pathways. In a 3-D environment, cell-seeded PCL scaffolds evaluated by confocal laser microscopy revealed continuous cell proliferation and homogeneous cell distribution within the PCL scaffolds. On osteogenic induction mesenchymal progenitor cells (12 U/L) produce significantly higher (p < 0.05) ALP activity than do osteoblasts (2 U/L); however, no significant differences were found in osteocalcin expression. In conclusion, this study showed that the combination of a mechanically stable synthetic framework (PCL scaffolds) and a biomimetic hydrogel (fibrin glue) provides a potential matrix for bone tissue-engineering applications. Comparison of osteogenic differentiation between the two mesenchymal cell sources revealed a similar pattern.

Interactions between human osteoblasts and prostate cancer cells in a novel 3D in vitro model

Cell-cell and cell-matrix interactions play a major role in tumor morphogenesis and cancer metastasis. Therefore, it is crucial to create a model with a biomimetic microenvironment that allows such interactions to fully represent the pathophysiology of a disease for an in vitro study. This is achievable by using three-dimensional (3D) models instead of conventional two-dimensional (2D) cultures with the aid of tissue engineering technology. We are now able to better address the complex intercellular interactions underlying prostate cancer (CaP) bone metastasis through such models. In this study, we assessed the interaction of CaP cells and human osteoblasts (hOBs) within a tissue engineered bone (TEB) construct. Consistent with other in vivo studies, our findings show that intercellular and CaP cell-bone matrix interactions lead to elevated levels of matrix metalloproteinases, steroidogenic enzymes and the CaP biomarker, prostate specific antigen (PSA); all associated with CaP metastasis. Hence, it highlights the physiological relevance of this model. We believe that this model will provide new insights for understanding of the previously poorly understood molecular mechanisms of bone metastasis, which will foster further translational studies, and ultimately offer a potential tool for drug screening. © 2010 Landes Bioscience.

Model interoperability in building information modelling

The exchange of design models in the design and construction industry is evolving away from 2-dimensional computer-aided design (CAD) and paper towards semantically-rich 3-dimensional digital models. This approach, known as Building Information Modelling (BIM), is anticipated to become the primary means of information exchange between the various parties involved in construction projects. From a technical perspective, the domain represents an interesting study in model-based interoperability, since the models are large and complex, and the industry is one in which collaboration is a vital part of business. In this paper, we present our experiences with issues of model-based interoperability in exchanging building information models between various tools, and in implementing tools which consume BIM models, particularly using the industry standard IFC data modelling format. We report on the successes and challenges in these endeavours, as the industry endeavours to move further towards fully digitised information exchange.

A two-Dimensional finite volume method for variable density flow and solute transport through saturated-unsaturated media

Extensive groundwater withdrawal has resulted in a severe seawater intrusion problem in the Gooburrum aquifers at Bundaberg, Queensland, Australia. Better management strategies can be implemented by understanding the seawater intrusion processes in those aquifers. To study the seawater intrusion process in the region, a two-dimensional density-dependent, saturated and unsaturated flow and transport computational model is used. The model consists of a coupled system of two non-linear partial differential equations. The first equation describes the flow of a variable-density fluid, and the second equation describes the transport of dissolved salt. A two-dimensional control volume finite element model is developed for simulating the seawater intrusion into the heterogeneous aquifer system at Gooburrum. The simulation results provide a realistic mechanism by which to study the convoluted transport phenomena evolving in this complex heterogeneous coastal aquifer.

Modulation of depth-dependent properties in tissue-engineered cartilage with a semi-permeable membrane and perfusion : a continuum model of matrix metabolism and transport

The functional properties of cartilaginous tissues are determined predominantly by the content, distribution, and organization of proteoglycan and collagen in the extracellular matrix. Extracellular matrix accumulates in tissue-engineered cartilage constructs by metabolism and transport of matrix molecules, processes that are modulated by physical and chemical factors. Constructs incubated under free-swelling conditions with freely permeable or highly permeable membranes exhibit symmetric surface regions of soft tissue. The variation in tissue properties with depth from the surfaces suggests the hypothesis that the transport processes mediated by the boundary conditions govern the distribution of proteoglycan in such constructs. A continuum model (DiMicco and Sah in Transport Porus Med 50:57-73, 2003) was extended to test the effects of membrane permeability and perfusion on proteoglycan accumulation in tissue-engineered cartilage. The concentrations of soluble, bound, and degraded proteoglycan were analyzed as functions of time, space, and non-dimensional parameters for several experimental configurations. The results of the model suggest that the boundary condition at the membrane surface and the rate of perfusion, described by non-dimensional parameters, are important determinants of the pattern of proteoglycan accumulation. With perfusion, the proteoglycan profile is skewed, and decreases or increases in magnitude depending on the level of flow-based stimulation. Utilization of a semi-permeable membrane with or without unidirectional flow may lead to tissues with depth-increasing proteoglycan content, resembling native articular cartilage.

Practical stability of approximating discrete-time filters with respect to model mismatch using relative entropy concepts

This paper establishes practical stability results for an important range of approximate discrete-time filtering problems involving mismatch between the true system and the approximating filter model. Using local consistency assumption, the practical stability established is in the sense of an asymptotic bound on the amount of bias introduced by the model approximation. Significantly, these practical stability results do not require the approximating model to be of the same model type as the true system. Our analysis applies to a wide range of estimation problems and justifies the common practice of approximating intractable infinite dimensional nonlinear filters by simpler computationally tractable filters.

Theorising a model for teaching and assessing reflective learning in higher education

The importance of reflection in higher education, and across disciplinary fields is widely recognised; it is generally included in university graduate attributes, professional standards and program objectives. Furthermore, reflection is commonly embedded into assessment requirements in higher education subjects, often without necessary scaffolding or clear expectations for students. Despite the rhetoric around the importance of reflection for ongoing learning, there is scant literature on any systematic, developmental approach to teaching reflective learning across higher education programs/courses. Given that professional or academic reflection is not intuitive, and requires specific pedagogic intervention to do well, a program/course-wide approach is essential. This paper draws on current literature to theorise a new, transferable and customisable model for teaching and assessing reflective learning across higher education, which foregrounds and explains the pedagogic field of higher education as a multi-dimensional space. We argue that explicit and strategic pedagogic intervention, supported by dynamic resources, is necessary for successful, broad-scale approaches to reflection in higher education.

User behaviour modelling in a multi-dimensional environment for personalization and recommendation

Handling information overload online, from the user's point of view is a big challenge, especially when the number of websites is growing rapidly due to growth in e-commerce and other related activities. Personalization based on user needs is the key to solving the problem of information overload. Personalization methods help in identifying relevant information, which may be liked by a user. User profile and object profile are the important elements of a personalization system. When creating user and object profiles, most of the existing methods adopt two-dimensional similarity methods based on vector or matrix models in order to find inter-user and inter-object similarity. Moreover, for recommending similar objects to users, personalization systems use the users-users, items-items and users-items similarity measures. In most cases similarity measures such as Euclidian, Manhattan, cosine and many others based on vector or matrix methods are used to find the similarities. Web logs are high-dimensional datasets, consisting of multiple users, multiple searches with many attributes to each. Two-dimensional data analysis methods may often overlook latent relationships that may exist between users and items. In contrast to other studies, this thesis utilises tensors, the high-dimensional data models, to build user and object profiles and to find the inter-relationships between users-users and users-items. To create an improved personalized Web system, this thesis proposes to build three types of profiles: individual user, group users and object profiles utilising decomposition factors of tensor data models. A hybrid recommendation approach utilising group profiles (forming the basis of a collaborative filtering method) and object profiles (forming the basis of a content-based method) in conjunction with individual user profiles (forming the basis of a model based approach) is proposed for making effective recommendations. A tensor-based clustering method is proposed that utilises the outcomes of popular tensor decomposition techniques such as PARAFAC, Tucker and HOSVD to group similar instances. An individual user profile, showing the user's highest interest, is represented by the top dimension values, extracted from the component matrix obtained after tensor decomposition. A group profile, showing similar users and their highest interest, is built by clustering similar users based on tensor decomposed values. A group profile is represented by the top association rules (containing various unique object combinations) that are derived from the searches made by the users of the cluster. An object profile is created to represent similar objects clustered on the basis of their similarity of features. Depending on the category of a user (known, anonymous or frequent visitor to the website), any of the profiles or their combinations is used for making personalized recommendations. A ranking algorithm is also proposed that utilizes the personalized information to order and rank the recommendations. The proposed methodology is evaluated on data collected from a real life car website. Empirical analysis confirms the effectiveness of recommendations made by the proposed approach over other collaborative filtering and content-based recommendation approaches based on two-dimensional data analysis methods.

Comparison of three-dimensional profiles over time

In this paper, we describe an analysis for data collected on a three-dimensional spatial lattice with treatments applied at the horizontal lattice points. Spatial correlation is accounted for using a conditional autoregressive model. Observations are defined as neighbours only if they are at the same depth. This allows the corresponding variance components to vary by depth. We use the Markov chain Monte Carlo method with block updating, together with Krylov subspace methods, for efficient estimation of the model. The method is applicable to both regular and irregular horizontal lattices and hence to data collected at any set of horizontal sites for a set of depths or heights, for example, water column or soil profile data. The model for the three-dimensional data is applied to agricultural trial data for five separate days taken roughly six months apart in order to determine possible relationships over time. The purpose of the trial is to determine a form of cropping that leads to less moist soils in the root zone and beyond.We estimate moisture for each date, depth and treatment accounting for spatial correlation and determine relationships of these and other parameters over time.

Towards an accurate biomechanical model of the ankle

When compared with similar joint arthroplasties, the prognosis of Total Ankle Replacement (TAR) is not satisfactory although it shows promising results post surgery. To date, most models do not provide the full anatomical functionality and biomechanical range of motion of the healthy ankle joint. This has sparked additional research and evaluation of clinical outcomes in order to enhance ankle prosthesis design. However, the limited biomechanical data that exist in literature are based upon two-dimensional, discrete and outdated techniques1 and may be inaccurate. Since accurate force estimations are crucial to prosthesis design, a paper based on a new biomechanical modeling approach, providing three dimensional forces acting on the ankle joint and the surrounding tissues was published recently, but the identified forces were suspected of being under-estimated, while muscles were . The present paper reports an attempt to improve the accuracy of the analysis by means of novel methods for kinematic processing of gait data, provided in release 4.1 of the AnyBody Modeling System (AnyBody Technology, Aalborg, Denmark) Results from the new method are shown and remaining issues are discussed.

Three-dimensional geological modelling and multivariate statistical analysis of water chemistry data to analyse and visualise aquifer structure and groundwater composition in the Wairau Plain, Marlborough District, New Zealand

Concerns regarding groundwater contamination with nitrate and the long-term sustainability of groundwater resources have prompted the development of a multi-layered three dimensional (3D) geological model to characterise the aquifer geometry of the Wairau Plain, Marlborough District, New Zealand. The 3D geological model which consists of eight litho-stratigraphic units has been subsequently used to synthesise hydrogeological and hydrogeochemical data for different aquifers in an approach that aims to demonstrate how integration of water chemistry data within the physical framework of a 3D geological model can help to better understand and conceptualise groundwater systems in complex geological settings. Multivariate statistical techniques(e.g. Principal Component Analysis and Hierarchical Cluster Analysis) were applied to groundwater chemistry data to identify hydrochemical facies which are characteristic of distinct evolutionary pathways and a common hydrologic history of groundwaters. Principal Component Analysis on hydrochemical data demonstrated that natural water-rock interactions, redox potential and human agricultural impact are the key controls of groundwater quality in the Wairau Plain. Hierarchical Cluster Analysis revealed distinct hydrochemical water quality groups in the Wairau Plain groundwater system. Visualisation of the results of the multivariate statistical analyses and distribution of groundwater nitrate concentrations in the context of aquifer lithology highlighted the link between groundwater chemistry and the lithology of host aquifers. The methodology followed in this study can be applied in a variety of hydrogeological settings to synthesise geological, hydrogeological and hydrochemical data and present them in a format readily understood by a wide range of stakeholders. This enables a more efficient communication of the results of scientific studies to the wider community.

Numerical simulation of a new two-dimensional variable-order fractional percolation equation in non-homogeneous porous media

Percolation flow problems are discussed in many research fields, such as seepage hydraulics, groundwater hydraulics, groundwater dynamics and fluid dynamics in porous media. Many physical processes appear to exhibit fractional-order behavior that may vary with time, or space, or space and time. The theory of pseudodifferential operators and equations has been used to deal with this situation. In this paper we use a fractional Darcys law with variable order Riemann-Liouville fractional derivatives, this leads to a new variable-order fractional percolation equation. In this paper, a new two-dimensional variable-order fractional percolation equation is considered. A new implicit numerical method and an alternating direct method for the two-dimensional variable-order fractional model is proposed. Consistency, stability and convergence of the implicit finite difference method are established. Finally, some numerical examples are given. The numerical results demonstrate the effectiveness of the methods. This technique can be used to simulate a three-dimensional variable-order fractional percolation equation.

Mixed-dimensional consistent coupling by multi-point constraint equations for efficient multi-scale modeling

Finding an appropriate linking method to connect different dimensional element types in a single finite element model is a key issue in the multi-scale modeling. This paper presents a mixed dimensional coupling method using multi-point constraint equations derived by equating the work done on either side of interface connecting beam elements and shell elements for constructing a finite element multiscale model. A typical steel truss frame structure is selected as case example and the reduced scale specimen of this truss section is then studied in the laboratory to measure its dynamic and static behavior in global truss and local welded details while the different analytical models are developed for numerical simulation. Comparison of dynamic and static response of the calculated results among different numerical models as well as the good agreement with those from experimental results indicates that the proposed multi-scale model is efficient and accurate.