Tetraspanins as regulators of the tumour microenvironment : implications for metastasis and therapeutic strategies

One of the hallmarks of cancer is the ability to activate invasion and metastasis (Hanahan et al., 2011). Cancer morbidity and mortality are largely related to the spread of the primary, localised tumour to adjacent and distant sites (Pantel et al., 2004). Appropriate management and treatment decisions of predicting metastatic disease at the time of diagnosis is thus crucial, which supports better understanding of the metastatic process. There are common events that occur during metastasis: dissociation from the primary tumour mass, reorganisation/remodelling of extracellular matrix, cell migration, recognition and transversal of endothelial cells and the vascular circulation and lodgement and proliferation within ectopic stroma (Wells, 2006). One of the key and initial events is the increased capability of cancer cells to move, escaping the regulation of normal physiological control. The cellular cytoskeleton plays an important role in cancer cell motility and active cytoskeletal rearrangement can result in metastatic disease. This active change in cytoskeletal dynamics results in manipulation of plasma membrane and cellular balance between cellular adhesion and motility which in turn determines cancer cell movement. Members of the tetraspanins play important roles in regulation of cancer migration and cancer-endothelial cell interactions, which are critical for cancer invasion and metastasis. Their involvements in active cytoskeletal dynamics, cancer metastasis and potential clinical application will be discussed in this review. In particular, tetraspanin member, CD151, is highlighted for its major role in cancer invasion and metastasis

A comparative study of the proliferation and osteogenic differentiation of human periodontal ligament cells cultured on β-TCP ceramics and demineralized bone matrix with or without osteogenic inducers in vitro

The repair of bone defects that result from periodontal diseases remains a clinical challenge for periodontal therapy. β-tricalcium phosphate (β-TCP) ceramics are biodegradable inorganic bone substitutes with inorganic components that are similar to those of bone. Demineralized bone matrix (DBM) is an acid-extracted organic matrix derived from bone sources that consists of the collagen and matrix proteins of bone. A few studies have documented the effects of DBM on the proliferation and osteogenic differentiation of human periodontal ligament cells (hPDLCs). The aim of the present study was to investigate the effects of inorganic and organic elements of bone on the proliferation and osteogenic differentiation of hPDLCs using three-dimensional porous β-TCP ceramics and DBM with or without osteogenic inducers. Primary hPDLCs were isolated from human periodontal ligaments. The proliferation of the hPDLCs on the scaffolds in the growth culture medium was examined using a Cell‑Counting kit‑8 (CCK-8) and scanning electron microscopy (SEM). Alkaline phosphatase (ALP) activity and the osteogenic differentiation of the hPDLCs cultured on the β-TCP ceramics and DBM were examined in both the growth culture medium and osteogenic culture medium. Specific osteogenic differentiation markers were examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). SEM images revealed that the cells on the β-TCP were spindle-shaped and much more spread out compared with the cells on the DBM surfaces. There were no significant differences observed in cell proliferation between the β-TCP ceramics and the DBM scaffolds. Compared with the cells that were cultured on β-TCP ceramics, the ALP activity, as well as the Runx2 and osteocalcin (OCN) mRNA levels in the hPDLCs cultured on DBM were significantly enhanced both in the growth culture medium and the osteogenic culture medium. The organic elements of bone may exhibit greater osteogenic differentiation effects on hPDLCs than the inorganic elements.

Transplantation of human amnion epithelial cells reduces hepatic fibrosis in immunocompetent CCl4-treated mice

Chronic liver injury and inflammation lead to hepatic fibrosis, cirrhosis, and liver failure. Embryonic and mesenchymal stem cells have been shown to reduce experimental liver fibrosis but have potential limitations, including the formation of dysplastic precursors, tumors, and profibrogenic cells. Other stem-like cells may reduce hepatic inflammation and fibrosis without tumor and profibrogenic cell formation. To test this hypothesis we transplanted human amnion epithelial cells (hAEC), isolated from term delivered placenta, into immunocompetent C57/BL6 mice at week 2 of a 4-week regimen of carbon tetrachloride (CCl4) exposure to induce liver fibrosis. Two weeks following hAEC infusion, intact cells expressing the human-specific markers inner mitochondrial membrane protein and human leukocyte antigen-G were found in mouse liver without evidence of host rejection of the transplanted cells. Human albumin, known to be produced by hAEC, was detected in sera of hAEC-treated mice. Human DNA was detected in mouse liver and also spleen, lungs, and heart of some animals. Following hAEC transplantation, CCl4-treated animals showed decreased serum ALT levels and reduced hepatocyte apoptosis, compared to controls. hAEC-treated mouse liver had lower TNF-α and IL-6 protein levels and higher IL-10 compared to animals given CCl4 alone. Compared to CCl4 controls, hAEC-treated mice showed fewer activated collagen-producing hepatic stellate cells and less fibrosis area and collagen content. Reduced hepatic TGF-β levels in conjunction with a twofold increase in the active form of the collagen-degrading enzyme matrix metalloproteinase-2 in hAEC-treated mice compared to CCl4 controls may account for the reduction in fibrosis. hAEC transplantation into immunocompetent mice leads to cell engraftment, reduced hepatocyte apoptosis, and decreased hepatic inflammation and fibrosis.

Ruptures in the heterosexual matrix through teenage flows and multiplicities

Feminist research on girlhood has drawn extensively on Butler's conceptual work in order to theorise the normative forces of heterosexuality in the everyday construction of gender. This chapter explores girlhood by drawing on memories and artwork generated in a collective biography workshop held in Australian on the topic of girlhood and sexuality. We are interested in thinking through Butler's notion of the heterosexual matrix. Following Renold and Ringrose (2008) we do so with the help of Deleuze and Guattari, who invite us to think about difference as differenciation or continuous becoming, where difference is an evolutionary multiplicity.

Trait resilience fosters adaptive coping when control opportunities are high : implications for the motivating potential of active work

Purpose: We examine the interaction between trait resilience and control in predicting coping and performance. Drawing on a person–environment fit perspective, we hypothesized resilient individuals would cope and perform better in demanding work situations when control was high. In contrast, those low in resilience would cope and perform better when control was low. Recognizing the relationship between trait resilience and performance also could be indirect, adaptive coping was examined as a mediating mechanism through which high control enables resilient individuals to demonstrate better performance. Methodology: In Study 1 (N = 78) and Study 2 (N = 94), participants completed a demanding inbox task in which trait resilience was measured and high and low control was manipulated. Study 3 involved surveying 368 employees on their trait resilience, control, and demand at work (at Time 1), and coping and performance 1 month later at Time 2. Findings: For more resilient individuals, high control facilitated problem-focused coping (Study 1, 2, and 3), which was indirectly associated with higher subjective performance (Study 1), mastery (Study 2), adaptive, and proficient performance (Study 3). For more resilient individuals, high control also facilitated positive reappraisal (Study 2 and 3), which was indirectly associated with higher adaptive and proficient performance (Study 3). Implications: Individuals higher in resilience benefit from high control because it enables adaptive coping. Originality/value: This research makes two contributions: (1) an experimental investigation into the interaction of trait resilience and control, and (2) investigation of coping as the mechanism explaining better performance.

Modelling and performance of an active heave compensator for offshore operations

The development of offshore oil and gas fields require the placement of different equipment on the sea floor. This is done by deploying the equipment from vessels operating in dynamic positioning on the surface. The deployment operation has different phases, and in higher sea states, it may require wave-load synchronization, when the load is going through the splash zone, and heave compensation when the load is close to the sea floor. In this paper, we analyse the performance of a particular type of hardware operating in a heave compensation mode. We derive a comprehensive model, analyse limits of performance and evaluate a control strategy.

Applying the Haddon Matrix in the context of work-related road safety

The Haddon Matrix was developed in the 1960s road safety arena, and has since been used in many public health settings. The literature and two specific case studies are reviewed to describe the background to the Haddon Matrix, identify how it has been critiqued and developed over time and practical applications in the work-related road safety context. Haddon’s original focus on the road, vehicle and driver has been extended and applied to include organisational safety culture, journey management and wider issues in society that affect occupational drivers and the communities in which they work. The paper shows that the Haddon Matrix has been applied in many projects and contexts. Practical work-related road safety applications include providing a comprehensive systems-based safety management framework to inform strategy. It has also been used to structure the review or gap analysis of current programs and processes, identify and develop prevention measures and as a tool for effective post-event investigations.

Fourier active appearance models

Gaining invariance to camera and illumination variations has been a well investigated topic in Active Appearance Model (AAM) fitting literature. The major problem lies in the inability of the appearance parameters of the AAM to generalize to unseen conditions. An attractive approach for gaining invariance is to fit an AAM to a multiple filter response (e.g. Gabor) representation of the input image. Naively applying this concept with a traditional AAM is computationally prohibitive, especially as the number of filter responses increase. In this paper, we present a computationally efficient AAM fitting algorithm based on the Lucas-Kanade (LK) algorithm posed in the Fourier domain that affords invariance to both expression and illumination. We refer to this as a Fourier AAM (FAAM), and show that this method gives substantial improvement in person specific AAM fitting performance over traditional AAM fitting methods.

Factors influencing robustness and effectiveness of conditional random fields in active learning frameworks

Active learning approaches reduce the annotation cost required by traditional supervised approaches to reach the same effectiveness by actively selecting informative instances during the learning phase. However, effectiveness and robustness of the learnt models are influenced by a number of factors. In this paper we investigate the factors that affect the effectiveness, more specifically in terms of stability and robustness, of active learning models built using conditional random fields (CRFs) for information extraction applications. Stability, defined as a small variation of performance when small variation of the training data or a small variation of the parameters occur, is a major issue for machine learning models, but even more so in the active learning framework which aims to minimise the amount of training data required. The factors we investigate are a) the choice of incremental vs. standard active learning, b) the feature set used as a representation of the text (i.e., morphological features, syntactic features, or semantic features) and c) Gaussian prior variance as one of the important CRFs parameters. Our empirical findings show that incremental learning and the Gaussian prior variance lead to more stable and robust models across iterations. Our study also demonstrates that orthographical, morphological and contextual features as a group of basic features play an important role in learning effective models across all iterations.

An SECM study on the influence of cationic, membrane-active peptides on a gold-supported self-assembled monolayer

The influence of the membrane active peptides, Tat44–57 (activator in HIV-1) and melittin (active content of bee venom), on self-assembled monolayers of 6-mercaptohexanoic acid (MHA) on gold electrodes has been studied with scanning electrochemical microscopy (SECM). It was found that MHA, when deprotonated at physiological pH, significantly affected the relative rates of electron transfer between the [Fe(CN)6]4− solution based mediator and the underlying gold electrode, predominantly by the electrostatic interaction between the mediator and MHA. Upon the introduction of Tat44–57 ormelittin to the electrolyte, the relative rate of electron transfer through the MHA layer could be increased or decreased depending on the mediator used. However, in all cases it was found that these peptides have the ability to be incorporated into synthetic SAMs, which has implications for future electrochemical studies carried out using cell mimicking membranes immobilised on such layers.

Large scale multiuser digital mind mapping tool : a study in usability

Project work can involve multiple people from varying disciplines coming together to solve problems as a group. Large scale interactive displays are presenting new opportunities to support such interactions with interactive and semantically enabled cooperative work tools such as intelligent mind maps. In this paper, we present a novel digital, touch-enabled mind-mapping tool as a first step towards achieving such a vision. This first prototype allows an evaluation of the benefits of a digital environment for a task that would otherwise be performed on paper or flat interactive surfaces. Observations and surveys of 12 participants in 3 groups allowed the formulation of several recommendations for further research into: new methods for capturing text input on touch screens; inclusion of complex structures; multi-user environments and how users make the shift from single- user applications; and how best to navigate large screen real estate in a touch-enabled, co-present multi-user setting.

Prevalence of active foot disease and foot disease risk factors in a subacute inpatient rehabilitation facility: a cross-sectional prevalence study

Background Australian subacute inpatient rehabilitation facilities face significant challenges from the ageing population and the increasing burden of chronic disease. Foot disease complications are a negative consequence of many chronic diseases. With the rapid expansion of subacute rehabilitation inpatient services, it seems imperative to investigate the prevalence of foot disease and foot disease risk factors in this population. The primary aim of this cross-sectional study was to determine the prevalence of active foot disease and foot disease risk factors in a subacute inpatient rehabilitation facility. Methods Eligible participants were all adults admitted at least overnight into a large Australian subacute inpatient rehabilitation facility over two different four week periods. Consenting participants underwent a short non-invasive foot examination by a podiatrist utilising the validated Queensland Health High Risk Foot Form to collect data on age, sex, medical co-morbidity history, foot disease risk factor history and clinically diagnosed foot disease complications and foot disease risk factors. Descriptive statistics were used to determine the prevalence of clinically diagnosed foot disease complications, foot disease risk factors and groups of foot disease risk factors. Logistic regression analyses were used to investigate any associations between defined explanatory variables and appropriate foot disease outcome variables. Results Overall, 85 (88%) of 97 people admitted to the facility during the study periods consented; mean age 80 (±9) years and 71% were female. The prevalence (95% confidence interval) of participants with active foot disease was 11.8% (6.3 – 20.5), 32.9% (23.9 – 43.5) had multiple foot disease risk factors, and overall, 56.5% (45.9 – 66.5) had at least one foot disease risk factor. A self-reported history of peripheral neuropathy diagnosis was independently associated with having multiple foot disease risk factors (OR 13.504, p = 0.001). Conclusion This study highlights the potential significance of the burden of foot disease in subacute inpatient rehabilitation facilities. One in eight subacute inpatients were admitted with active foot disease and one in two with at least one foot disease risk factor in this study. It is recommended that further multi-site studies and management guidelines are required to address the foot disease burden in subacute inpatient rehabilitation facilities. Keywords: Subacute; Inpatient; Foot; Complication; Prevalence

Modeling and control of a CLC resonant dual active bridge

This paper proposes a linear large signal state-space model for a phase controlled CLC (Capacitor Inductor Capacitor) Resonant Dual Active Bridge (RDAB). The proposed model is useful for fast simulation and for the estimation of state variables under large signal variation. The model is also useful for control design because the slow changing dynamics of the dq variables are relatively easy to control. Simulation results of the proposed model are presented and compared to the simulated circuit model to demonstrate the proposed model's accuracy. This proposed model was used for the design of a Proportional-Integral (PI) controller and it has been implemented in the circuit simulation to show the proposed models usefulness in control design.