Bending the Rules of Cell Protrusions : Molecular Mechanisms and Biological Roles of Inverse-BAR Proteins in Cell Morphogenesis

Plasma membrane adopts myriad of different shapes to carry out essential cellular processes such as nutrient uptake, immunological defence mechanisms and cell migration. Therefore, the details how different plasma membrane structures are made and remodelled are of the upmost importance. Bending of plasma membrane into different shapes requires substantial amount of force, which can be provided by the actin cytoskeleton, however, the molecules that regulate the interplay between the actin cytoskeleton and plasma membrane have remained elusive. Recent findings have placed new types of effectors at sites of plasma membrane remodelling, including BAR proteins, which can directly bind and deform plasma membrane into different shapes. In addition to their membrane-bending abilities, BAR proteins also harbor protein domains that intimately link them to the actin cytoskeleton. The ancient BAR domain fold has evolved into at least three structurally and functionally different sub-groups: the BAR, F-BAR and I-BAR domains. This thesis work describes the discovery and functional characterization of the Inverse-BAR domains (I-BARs). Using synthetic model membranes, we have shown that I-BAR domains bind and deform membranes into tubular structures through a binding-surface composed of positively charged amino acids. Importantly, the membrane-binding surface of I-BAR domains displays an inverse geometry to that of the BAR and F-BAR domains, and these structural differences explain why I-BAR domains induce cell protrusions whereas BAR and most F-BAR domains induce cell invaginations. In addition, our results indicate that the binding of I-BAR domains to membranes can alter the spatial organization of phosphoinositides within membranes. Intriguingly, we also found that some I-BAR domains can insert helical motifs into the membrane bilayer, which has important consequences for their membrane binding/bending functions. In mammals there are five I-BAR domain containing proteins. Cell biological studies on ABBA revealed that it is highly expressed in radial glial cells during the development of the central nervous system and plays an important role in the extension process of radial glia-like C6R cells by regulating lamellipodial dynamics through its I-BAR domain. To reveal the role of these proteins in the context of animals, we analyzed MIM knockout mice and found that MIM is required for proper renal functions in adult mice. MIM deficient mice displayed a severe urine concentration defect due to defective intercellular junctions of the kidney epithelia. Consistently, MIM localized to adherens junctions in cultured kidney epithelial cells, where it promoted actin assembly through its I-BAR andWH2 domains. In summary, this thesis describes the mechanism how I-BAR proteins deform membranes and provides information about the biological role of these proteins, which to our knowledge are the first proteins that have been shown to directly deform plasma membrane to make cell protrusions.

Integrating urban ecosystem sustainability assessment into policy-making: Insights from the Gold Coast City

This paper introduces a policy-making support tool called ‘Micro-level Urban ecosystem Sustainability IndeX (MUSIX)’. The index serves as a sustainability assessment model that monitors six aspects of urban ecosystems, hydrology, ecology, pollution, location, design, and efficiency based on parcel-scale indicators. This index is applied in a case study investigation in the Gold Coast City, Queensland, Australia. The outcomes reveal that there are major environmental problems caused by increased impervious surfaces from growing urban development in the study area. The findings suggest that increased impervious surfaces are linked to increased surface runoff, car dependency, transport-related pollution, poor public transport accessibility, and unsustainable built environment. This paper presents how the MUSIX outputs can be used to guide policy-making through the evaluation of existing policies.

Pseudo-time marching schemes for inverse problems in structural health assessment and medical imaging

We propose a self-regularized pseudo-time marching strategy for ill-posed, nonlinear inverse problems involving recovery of system parameters given partial and noisy measurements of system response. While various regularized Newton methods are popularly employed to solve these problems, resulting solutions are known to sensitively depend upon the noise intensity in the data and on regularization parameters, an optimal choice for which remains a tricky issue. Through limited numerical experiments on a couple of parameter re-construction problems, one involving the identification of a truss bridge and the other related to imaging soft-tissue organs for early detection of cancer, we demonstrate the superior features of the pseudo-time marching schemes.

A model eliciting framework for integrating mathematics and robotics learning

Robotics is taught in many Australian ICT classrooms, in both primary and secondary schools. Robotics activities, including those developed using the LEGO Mindstorms NXT technology, are mathematics-rich and provide a fertile round for learners to develop and extend their mathematical thinking. However, this context for learning mathematics is often under-exploited. In this paper a variant of the model construction sequence (Lesh, Cramer, Doerr, Post, & Zawojewski, 2003) is proposed, with the purpose of explicitly integrating robotics and mathematics teaching and learning. Lesh et al.’s model construction sequence and the model eliciting activities it embeds were initially researched in primary mathematics classrooms and more recently in university engineering courses. The model construction sequence involves learners working collaboratively upon product-focussed tasks, through which they develop and expose their conceptual understanding. The integrating model proposed in this paper has been used to design and analyse a sequence of activities in an Australian Year 4 classroom. In that sequence more traditional classroom learning was complemented by the programming of LEGO-based robots to ‘act out’ the addition and subtraction of simple fractions (tenths) on a number-line. The framework was found to be useful for planning the sequence of learning and, more importantly, provided the participating teacher with the ability to critically reflect upon robotics technology as a tool to scaffold the learning of mathematics.

Accurate Parameter Estimation of Contaminant Transport Inverse Problem using Particle Swarm Optimization

Swarm Intelligence techniques such as particle swarm optimization (PSO) are shown to be incompetent for an accurate estimation of global solutions in several engineering applications. This problem is more severe in case of inverse optimization problems where fitness calculations are computationally expensive. In this work, a novel strategy is introduced to alleviate this problem. The proposed inverse model based on modified particle swarm optimization algorithm is applied for a contaminant transport inverse model. The inverse models based on standard-PSO and proposed-PSO are validated to estimate the accuracy of the models. The proposed model is shown to be out performing the standard one in terms of accuracy in parameter estimation. The preliminary results obtained using the proposed model is presented in this work.

Agents Based Algorithms for Design Parameter Estimation in Contaminant Transport Inverse Problems

A considerable amount of work has been dedicated on the development of analytical solutions for flow of chemical contaminants through soils. Most of the analytical solutions for complex transport problems are closed-form series solutions. The convergence of these solutions depends on the eigen values obtained from a corresponding transcendental equation. Thus, the difficulty in obtaining exact solutions from analytical models encourages the use of numerical solutions for the parameter estimation even though, the later models are computationally expensive. In this paper a combination of two swarm intelligence based algorithms are used for accurate estimation of design transport parameters from the closed-form analytical solutions. Estimation of eigen values from a transcendental equation is treated as a multimodal discontinuous function optimization problem. The eigen values are estimated using an algorithm derived based on glowworm swarm strategy. Parameter estimation of the inverse problem is handled using standard PSO algorithm. Integration of these two algorithms enables an accurate estimation of design parameters using closed-form analytical solutions. The present solver is applied to a real world inverse problem in environmental engineering. The inverse model based on swarm intelligence techniques is validated and the accuracy in parameter estimation is shown. The proposed solver quickly estimates the design parameters with a great precision.

Optimum design of cantilever sheet pile walls in sandy soils using inverse reliability approach

In this paper an approach for obtaining depth and section modulus of the cantilever sheet pile wall using inverse reliability method is described. The proposed procedure employs inverse first order reliability method to obtain the design penetration depth and section modulus of the steel sheet pile wall in order that the reliability of the wall against failure modes must meet a desired level of safety. Sensitivity analysis is conducted to assess the effect of uncertainties in design parameters on the reliability of cantilever sheet pile walls. The analysis is performed by treating back fill soil properties, depth of the water table from the top of the sheet pile wall, yield strength of steel and section modulus of steel pile as random variables. Two limit states, viz., rotational and flexural failure of sheet pile wall are considered. The results using this approach are used to develop a set of reliability based design charts for different coefficients of variation of friction angle of the backfill (5%, 10% and 15%). System reliability considerations in terms of series and parallel systems are also studied.

Direct and Inverse Scattering for Beltrami Fields

We consider an obstacle scattering problem for linear Beltrami fields. A vector field is a linear Beltrami field if the curl of the field is a constant times itself. We study the obstacles that are of Neumann type, that is, the normal component of the total field vanishes on the boundary of the obstacle. We prove the unique solvability for the corresponding exterior boundary value problem, in other words, the direct obstacle scattering model. For the inverse obstacle scattering problem, we deduce the formulas that are needed to apply the singular sources method. The numerical examples are computed for the direct scattering problem and for the inverse scattering problem.

A model Integrating the Facilities Management Process with the Building End User’s Business Process (ProFacil)

The ProFacil model is a generic process model defined as a framework model showing the links between the facilities management process and the building end user’s business process. The purpose of using the model is to support more detailed process modelling. The model has been developed using the IDEF0 modelling method. The ProFacil model describes business activities from the generalized point of view as management-, support-, and core processes and their relations. The model defines basic activities in the provision of a facility. Examples of these activities are “operate facilities”, “provide new facilities”, “provide re-build facilities”, “provide maintained facilities” and “perform dispose of facilities”. These are all generic activities providing a basis for a further specialisation of company specific FM activities and their tasks. A facilitator can establish a specialized process model using the ProFacil model and interacting with company experts to describe their company’s specific processes. These modelling seminars or interviews will be done in an informal way, supported by the high-level process model as a common reference.

Developing and Integrating HRM Practices in MNC Subsidiaries in China

Whilst previous research on Human Resource Management (HRM) in subsidiaries of multinational companies (MNCs) has focused extensively on the HRM practices that exist in foreign subsidiaries and the extent to which they resemble MNC home country and/or local host country practices, considerably less attention has been directed at the question of how these practices come to exist. Accordingly, this thesis aims to shed light on the processes that shape HRM practices and capabilities in MNC subsidiaries. The main contribution of the thesis is the focus on how; how HRM practices are integrated in MNC subsidiaries, and how subsidiary HRM capabilities are developed through involvement in social networks. Furthermore, this thesis includes a time aspect which, despite not being purely longitudinal, provides an indication of the ongoing changes in HRM in MNC subsidiaries in China. Data for this study were collected in 2005-2006 through structured face to face interviews with 153 general managers and HR managers in 87 subsidiaries of European MNCs located in China. Five of the six thesis papers build on this questionnaire data and one paper builds on qualitative data collected at the same time. Two papers build on dual data sets, meaning that they in addition to the abovementioned data include quantitative questionnaire data from 1996 and 1999 respectively. The thesis focuses on the following four sub-questions i) To what extent do subsidiary HRM practices resemble parent MNC and host country practices? How has this changed over time and why? ii) How are HRM practices integrated into MNC subsidiaries and why are certain integration mechanisms used? iii) How does involvement in internal and external social networks influence subsidiary HRM capabilities? iv) What factors influence the strategic role of the subsidiary HR department? Regarding the first sub-question the findings indicate that the HRM practices of MNC subsidiaries in China are converging with both local company practices and parent MNC practices. This is interesting in the sense that it suggests that the isomorphic pressures the subsidiary faces from the MNC and from its local host environment are not always in conflict with each other. Concerning the question of how HRM practices are integrated into MNC subsidiaries and why certain integration mechanisms are used, the thesis provides a fine-grained examination of four mechanisms that MNCs use to integrate HRM practices in subsidiaries. The findings suggest that MNCs use a variety of different integration mechanisms as complements rather than as substitutes for each other. Furthermore, it is apparent that different contextual factors in the subsidiary and the subsidiary-headquarters relationship influence why certain mechanisms are or are not used. The most interesting contribution of the thesis in regard to the third question is that it highlights the importance of network involvement for learning about HRM practices in the Chinese context. Networks with other MNCs in China clearly emerged as particularly important contributors to enhanced HRM capabilities. Finally, concerning the fourth sub-question the findings indicate that the role of the HR department in MNC subsidiaries in China had become more strategic between 1999 and 2006.

Integrating strong and weak discontinuities without integration subcells and example applications in an XFEM/GFEM framework

Partition of unity methods, such as the extended finite element method, allows discontinuities to be simulated independently of the mesh (Int. J. Numer. Meth. Engng. 1999; 45:601-620). This eliminates the need for the mesh to be aligned with the discontinuity or cumbersome re-meshing, as the discontinuity evolves. However, to compute the stiffness matrix of the elements intersected by the discontinuity, a subdivision of the elements into quadrature subcells aligned with the discontinuity is commonly adopted. In this paper, we use a simple integration technique, proposed for polygonal domains (Int. J. Nuttier Meth. Engng 2009; 80(1):103-134. DOI: 10.1002/nme.2589) to suppress the need for element subdivision. Numerical results presented for a few benchmark problems in the context of linear elastic fracture mechanics and a multi-material problem show that the proposed method yields accurate results. Owing to its simplicity, the proposed integration technique can be easily integrated in any existing code. Copyright (C) 2010 John Wiley & Sons, Ltd.

Adaptive dendron: A bile acid oligomer behaving as both normal and inverse micellar mimic

The normal and inverse micellar property of a bile-acid-based dendritic structure was established through dye solubilization studies in both polar and nonpolar media.

Composite signal decomposition by digital inverse filtering

Inverse filters are conventionally used for resolving overlapping signals of identical waveshape. However, the inverse filtering approach is shown to be useful for resolving overlapping signals, identical or otherwise, of unknown waveshapes. Digital inverse filter design based on autocorrelation formulation of linear prediction is known to perform optimum spectral flattening of the input signal for which the filter is designed. This property of the inverse filter is used to accomplish composite signal decomposition. The theory has been presented assuming constituent signals to be responses of all-pole filters. However, the approach may be used for a general situation.

An integer arithmetic method to compute generalized matrix inverse and solve linear equations exactly

An algorithm that uses integer arithmetic is suggested. It transforms anm ×n matrix to a diagonal form (of the structure of Smith Normal Form). Then it computes a reflexive generalized inverse of the matrix exactly and hence solves a system of linear equations error-free.