The mechanical rigidity of the extracellular matrix regulates the structure, motility, and proliferation of glioma cells

Glioblastoma multiforme (GBM) is a malignant astrocytoma of the central nervous system associated with a median survival time of 15 months, even with aggressive therapy. This rapid progression is due in part to diffuse infiltration of single tumor cells into the brain parenchyma, which is thought to involve aberrant interactions between tumor cells and the extracellular matrix (ECM). Here, we test the hypothesis that mechanical cues from the ECM contribute to key tumor cell properties relevant to invasion. We cultured a series of glioma cell lines (U373-MG, U87-MG, U251-MG, SNB19, C6) on fibronectin-coated polymeric ECM substrates of defined mechanical rigidity and investigated the role of ECM rigidity in regulating tumor cell structure, migration, and proliferation. On highly rigid ECMs, tumor cells spread extensively, form prominent stress fibers and mature focal adhesions, and migrate rapidly. As ECM rigidity is lowered to values comparable with normal brain tissue, tumor cells appear rounded and fail to productively migrate. Remarkably, cell proliferation is also strongly regulated by ECM rigidity, with cells dividing much more rapidly on rigid than on compliant ECMs. Pharmacologic inhibition of nonmuscle myosin II–based contractility blunts this rigidity-sensitivity and rescues cell motility on highly compliant substrates. Collectively, our results provide support for a novel model in which ECM rigidity provides a transformative, microenvironmental cue that acts through actomyosin contractility to regulate the invasive properties of GBM tumor cells.

Random Gabor based templates for facial expression recognition in images with facial occlusion

Robust facial expression recognition (FER) under occluded face conditions is challenging. It requires robust algorithms of feature extraction and investigations into the effects of different types of occlusion on the recognition performance to gain insight. Previous FER studies in this area have been limited. They have spanned recovery strategies for loss of local texture information and testing limited to only a few types of occlusion and predominantly a matched train-test strategy. This paper proposes a robust approach that employs a Monte Carlo algorithm to extract a set of Gabor based part-face templates from gallery images and converts these templates into template match distance features. The resulting feature vectors are robust to occlusion because occluded parts are covered by some but not all of the random templates. The method is evaluated using facial images with occluded regions around the eyes and the mouth, randomly placed occlusion patches of different sizes, and near-realistic occlusion of eyes with clear and solid glasses. Both matched and mis-matched train and test strategies are adopted to analyze the effects of such occlusion. Overall recognition performance and the performance for each facial expression are investigated. Experimental results on the Cohn-Kanade and JAFFE databases demonstrate the high robustness and fast processing speed of our approach, and provide useful insight into the effects of occlusion on FER. The results on the parameter sensitivity demonstrate a certain level of robustness of the approach to changes in the orientation and scale of Gabor filters, the size of templates, and occlusions ratios. Performance comparisons with previous approaches show that the proposed method is more robust to occlusion with lower reductions in accuracy from occlusion of eyes or mouth.

Management of multiple heterogeneous UAVs using capability and autonomy visualisation: theory, experiment and result

The interest in utilising multiple heterogeneous Unmanned Aerial Vehicles (UAVs) in close proximity is growing rapidly. As such, many challenges are presented in the effective coordination and management of these UAVs; converting the current n-to-1 paradigm (n operators operating a single UAV) to the 1-to-n paradigm (one operator managing n UAVs). This paper introduces an Information Abstraction methodology used to produce the functional capability framework initially proposed by Chen et al. and its Level Of Detail (LOD) indexing scale. This framework was validated through comparing the operator workload and Situation Awareness (SA) of three experiment scenarios involving multiple autonomously heterogeneous UAVs. The first scenario was set in a high LOD configuration with highly abstracted UAV functional information; the second scenario was set in a mixed LOD configuration; and the final scenario was set in a low LOD configuration with maximal UAV functional information. Results show that there is a significant statistical decrease in operator workload when a UAV’s functional information is displayed at its physical form (low LOD - maximal information) when comparing to the mixed LOD configuration.

Theory based production and project management

This paper gives an overview of an ongoing project endeavouring to advance theory-based production and project management, and the rationale for this approach is briefly justified. The status of the theoretical foundation of production management, project management and allied disciplines is discussed, with emphasis on metaphysical grounding of theories, as well as the nature of the heuristic solution method commonly used in these disciplines. Then, on-going work related to different aspects of production and project management is reviewed from both theoretical and practical orientation. Next, information systems agile project management is explored with a view to its re-use in generic project management. In production management, the consequences and implementation of a new, wider theoretical basis are analyzed. The theoretical implications and negative symptoms of the peculiarities of the construction industry for supply chains and supply chain management in construction are observed. Theoretical paths for improvements of inter-organisational relationships in construction which are fundamental for improvement of construction supply chains are described. To conclude, the observations made in this paper vis-à-vis production, project and supply chain management are related again to the theoretical basis of this paper, and finally directions for theory development and future research are given and discussed.

Out of their minds: legal theory in neural networks

This paper examines the use of connectionism (neural networks) in modelling legal reasoning. I discuss how the implementations of neural networks have failed to account for legal theoretical perspectives on adjudication. I criticise the use of neural networks in law, not because connectionism is inherently unsuitable in law, but rather because it has been done so poorly to date. The paper reviews a number of legal theories which provide a grounding for the use of neural networks in law. It then examines some implementations undertaken in law and criticises their legal theoretical naïvete. It then presents a lessons from the implementations which researchers must bear in mind if they wish to build neural networks which are justified by legal theories.

Matrix metalloproteinase-9 of tubular and macrophage origin contributes to the pathogenesis of renal fibrosis via macrophage recruitment through osteopontin cleavage

A pro-fibrotic role of matrix metalloproteinase-9 (MMP-9) in tubular cell epithelial-mesenchymal transition (EMT) is well established in renal fibrosis; however studies from our group and others have demonstrated some previously unrecognized complexity of MMP-9 that has been overlooked in renal fibrosis. Therefore, the aim of this study was to determine the expression pattern, origin and the exact mechanism underlying the contribution of MMP-9 to unilateral ureteral obstruction (UUO), a well-established model of renal fibrosis via MMP-9 inhibition. Renal MMP-9 expression in BALB/c mice with UUO was examined on day 1, 3, 5, 7, 9, 11 and 14. To inhibit MMP-9 activity, MMP-2/9 inhibitor or MMP-9-neutralizing antibody was administered daily for 4 consecutive days from day 0-3, 6-9 or 10-13 and tissues harvested at day 14. In UUO, there was a bi-phasic early- and late-stage upregulation of MMP-9 activity. Interestingly, tubular epithelial cells (TECs) were the predominant source of MMP-9 during early stage, whereas TECs, macrophages and myofibroblasts produced MMP-9 during late-stage UUO. Early- and late-stage inhibition of MMP-9 in UUO mice significantly reduced tubular cell EMT and renal fibrosis. Moreover, MMP-9 inhibition caused a significant reduction in MMP-9-cleaved osteopontin and macrophage infiltration in UUO kidney. Our in vitro study showed MMP-9-cleaved osteopontin enhanced macrophage transwell migration and MMP-9 of both primary TEC and macrophage induced tubular cell EMT. In summary, our result suggests that MMP-9 of both TEC and macrophage origin may directly or indirectly contribute to the pathogenesis of renal fibrosis via osteopontin cleavage, which, in turn further recruit macrophage and induce tubular cell EMT. Our study also highlights the time dependency of its expression and the potential of stage-specific inhibition strategy against renal fibrosis.

Using communicative ecology theory to scope the emerging role of social media in the evolution of urban food systems

Urban agriculture plays an increasingly vital role in supplying food to urban populations. Changes in Information and Communications Technology (ICT) are already driving widespread change in diverse food-related industries such as retail, hospitality and marketing. It is reasonable to suspect that the fields of ubiquitous technology, urban informatics and social media equally have a lot to offer the evolution of core urban food systems. We use communicative ecology theory to describe emerging innovations in urban food systems according to their technical, discursive and social components. We conclude that social media in particular accentuate fundamental social interconnections normally effaced by conventional industrialised approaches to food production and consumption.

Knowledge ecosystems of early career academics : a grounded theory of experiencing information use for learning in developmental networks

This study explored early career academics' experiences in using information to learn while building their networks for professional development. A 'knowledge ecosystem' model was developed consisting of informal learning interactions such as relating to information to create knowledge and engaging in mutually supportive relationships. Findings from this study present an alternative interpretation of information use for learning that is focused on processes manifesting as human interactions with informing entities revolving around the contexts of reciprocal human relationships.

Port-Hamiltonian theory of motion control for marine craft

Port-Hamiltonian Systems (PHS) have a particular form that incorporates explicitly a function of the total energy in the system (energy function) and also other functions that describe structure of the system in terms of energy distribution. For PHS, the product of the input and output variables gives the rate of energy change. This type of systems have the property that under certain conditions on the energy function, the system is passive; and thus, stable. Therefore, if one can design a controller such that the closed-loop system retains - or takes - a PHS form, such closed-loop system will inherit the properties of passivity and stability. In this paper, the classical model of marine craft is put into a PHS form. It is shown that models used for positioning control do not have a PHS form due to a kinematic transformation, but a control design can be done such that the closed-loop system takes a PHS form. It is further shown how integral action can be added and how the PHS-form can be exploited to provide a procedure for control design that ensures passivity and thus stability.

Roles of the matrix metalloproteinases in mammary gland development and cancer

Tissue remodeling is a key process involved in normal development, wound healing, bone remodeling, and embryonic implantation, as well as pathological conditions such as tumor invasion and metastasis, and angiogenesis. The degradation of the extracellular matrix that is associated with those processes is mediated by a number of families of extracellular proteinases. These families include the serine proteinases, such as the plasminogen-urokinase plasminogen activator system and leukocyte elastases, the cysteine proteinases, like cathepsin D and L, and the zinc-dependent matrix metalloproteinases (MMPs). Accumulating evidence has highlighted the central role of MMP-driven extracellular matrix remodeling in mammary gland development and breast cancer.

Service encounter needs theory : a dyadic, psychosocial approach to understanding service encounters

Interactions between customers and service providers are ubiquitous. Some of these encounters are routine, but many are characterized by conflict and intense emotions. This chapter introduces a new theory, service encounter needs theory (SENT) that aims to elucidate the mechanisms through which service encounter behaviors affect outcomes for customers and employees. Evidence is presented for the preeminence within these encounters of eight psychosocial needs, and propositions are advanced regarding likely antecedents to fulfillment and violation of these needs. Emotional experiences and displays are viewed as important consequences of need fulfillment and violation, as are numerous cognitive, behavioral, and health-related outcomes.

SPARC/osteonectin induces matrix metalloproteinase 2 activation in human breast cancer cell lines

Activation of the matrix metalloproteinase 2 (MMP-2) has been shown to play a major role in the proteolysis of extracellular matrix (ECM) associated with tumor invasion. Although the precise mechanism of this activation remains elusive, levels of the membrane type 1-MMP (MT1-MMP) at the cell surface and of the tissue inhibitor of MMP-2 (TIMP-2) appear to be two important determinants. Induction of MMP-2 activation in cells cultivated on collagen type I gels indicated that the ECM is important in the regulation of this process. In this study, we show that SPARC/osteonectin, a small ECM- associated matricellular glycoprotein, can induce MMP-2 activation in two invasive breast cancer cell lines (MDA-MB-231 and BT549) but not in a noninvasive counterpart (MCF7), which lacks MT1-MMP. Using a set of peptides from different regions of SPARC, we found that peptide 1.1 (corresponding to the NH2-terminal region of the protein) contained the activity that induced NIMP-2 activation. Despite the requirement for MT1-MMP, seen in MCF-7 cells transfected with MT1-MMP, the activation of MMP-2 by SPARC peptide 1.1 was not associated with increased steady-state levels of MT1-MMP mRNA or protein in either MT1-MMP-transfected MCF-7 cells or constitutively expressing MDA- MB-231 and BT549 cells. We did, however, detect decreased levels of TIMP-2 protein in the media of cells incubated with peptide 1.1 or recombinant SPARC; thus, the induction of MMP-2 activation by SPARC might be due in part to a diminution of TIMP-2 protein. We conclude that SPARC, and specifically its NH2-terminal domain, regulates the activation of MMP-2 at the cell surface and is therefore likely to contribute to the proteolytic pathways associated with tumor invasion.

Activation of matrix metalloproteinase-2 (MMP-2) by membrane type 1 matrix metalloproteinase through an artificial receptor for ProMMP-2 generates active MMP-2

The suggested model for pro-matrix metalloproteinase-2 (proMMP-2) activation by membrane type 1 MMP (MT1-MMP) implicates the complex between MT1-MMP and tissue inhibitor of MMP-2 (TIMP-2) as a receptor for proMMP-2. To dissect this model and assess the pathologic significance of MMP-2 activation, an artificial receptor for proMMP-2 was created by replacing the signal sequence of TIMP-2 with cytoplasmic/transmembrane domain of type II transmembrane mosaic serine protease (MSP-T2). Unlike TIMP-2, MSP-T2 served as a receptor for proMMP-2 without inhibiting MT1-MMP, and generated TIMP-2-free active MMP-2 even at a low level of MT1-MMP. Thus, MSP-T2 did not affect direct cleavage of the substrate testican-1 by MT1-MMP, whereas TIMP-2 inhibited it even at the level that stimulates proMMP-2 processing. Expression of MSP-T2 in HT1080 cells enhanced MMP-2 activation by endogenous MT1-MMP and caused intensive hydrolysis of collagen gel. Expression of MSP-T2 in U87 glioma cells, which express a trace level of endogenous MT1-MMP, induced MMP-2 activation and enhanced cell-associated protease activity, activation of extracellular signal-regulated kinase, and metastatic ability into chick embryonic liver and lung. MT1-MMP can exert both maximum MMP-2 activation and direct cleavage of substrates with MSP-T2, which cannot be achieved with TIMP-2. These results suggest that MMP-2 activation by MT1-MMP potentially amplifies protease activity, and combination with direct cleavage of substrate causes effective tissue degradation and enhances tumor invasion and metastasis, which highlights the complex role of TIMP-2. MSP-T2 is a unique tool to analyze physiologic and pathologic roles of MMP-2 and MT1-MMP in comparison with TIMP-2.