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.

Monocyte chemoattractant protein-1 and nitric oxide promote adipogenesis in a model that mimics obesity

Objective: An increasing body of evidence is emerging linking adipogenesis and inflammation. Obesity, alone or as a part of the metabolic syndrome, is characterized by a state of chronic low-level inflammation as revealed by raised plasma levels of inflammatory cytokines and acute-phase proteins. If inflammation can, in turn, increase adipose tissue growth, this may be the basis for a positive feedback loop in obesity. We have developed a tissue engineering model for growing adipose tissue in the mouse that allows quantification of increases in adipogenesis. In this study, we evaluated the adipogenic potential of the inflammogens monocyte chemoattractant protein (MCP)-I and zymosan-A (Zy) in a murine tissue engineering model. Research Methods and Procedures: MCP-I and Zy were added to chambers filled with Matrigel and fibroblastgrowth factor 2. To analyze the role of inducible nitric oxide synthase (iNOS), the iNOS inhibitor aminoguanidine was added to the chamber. Results: Our results show that MCP-I generated proportionally large quantities of new adipose tissue. This neoadipogenesis was accompanied by an ingrowth of macrophages and could be mimicked by Zy. Aminoguanidine significantly inhibited the formation of adipose tissue. Discussion: Our findings demonstrate that low-grade inflammation and iNOS expression are important factors in adipogenesis, Because fat neoformation in obesity and the metabolic syndrome is believed to be mediated by macrophage-derived proinflammatory cytokines, this adipose tissue engineering system provides a model that could potentially be used to further unravel the pathogenesis of these two metabolic disorders.

Influence of jet inclination on structural loading in an experimentally simulated microburst

Steady and pulsed flow stationary impinging jets have been employed to simulate the wind field produced by a thunderstorm microburst. The effect on the low level wind field due to jet inclination with respect to the impingement surface has been studied. A single point velocity time history has been compared to the full-scale Andrews AFB microburst for model validation. It was found that for steady flow, jet inclination increased the radial extent of high winds but did not increase the magnitude of these winds when compared to the perpendicular impingement case. It was found that for inclined pulsed flow the design wind conditions could increase compared to perpendicular impingement. It was found that the location of peak winds was affected by varying the outlet conditions.

The role of intellectual resources, product innovation capability, reputational resources and marketing capability combinations in SME growth

This article examines the extent to which combinations of intellectual resources and product innovation capability, and reputational resources and marketing capability, influence the ability of small and medium-sized enterprises (SME) to meet or exceed performance goals. Empirical results drawn from 171 SMEs suggest that when the combination of intellectual resources and product innovation capability in addition to the combination of reputational resources and marketing capability are high, SME growth is enhanced. However, a high level of intellectual resources combined with a low level of product innovation capability as well as a combination of a high level of reputational resources with a low level of marketing capability (and vice versa) are not significantly related to growth. These results imply that a high level of resources cannot compensate for a low level of capabilities (and vice versa).

Scene signatures : localised and point-less features for localisation

This paper is about localising across extreme lighting and weather conditions. We depart from the traditional point-feature-based approach as matching under dramatic appearance changes is a brittle and hard thing. Point feature detectors are fixed and rigid procedures which pass over an image examining small, low-level structure such as corners or blobs. They apply the same criteria applied all images of all places. This paper takes a contrary view and asks what is possible if instead we learn a bespoke detector for every place. Our localisation task then turns into curating a large bank of spatially indexed detectors and we show that this yields vastly superior performance in terms of robustness in exchange for a reduced but tolerable metric precision. We present an unsupervised system that produces broad-region detectors for distinctive visual elements, called scene signatures, which can be associated across almost all appearance changes. We show, using 21km of data collected over a period of 3 months, that our system is capable of producing metric localisation estimates from night-to-day or summer-to-winter conditions.

Multiliteracies pedagogy : creating claymations with adolescent, post-beginner English language learners

In addressing literacy in high school education, it is important to foreground the particular issues faced by growing numbers of English Language Learners (ELLs). In our increasingly culturally and linguistically diverse classrooms, this is a matter for all literacy teachers, as well as ELL specialists. In Australia, teachers of ELLs are experimenting with Multiliteracies pedagogy which provides rich opportunities to explore language learning experiences and outcomes that stretch beyond exercises in reproduction in written and oral modes only. This paper documents the practice of a high school teacher who uses a claymation project, producing a movie by stop-motion filming of clay figures, with a class of low-level English literacy learners. Drawing on observations of three particular students, the paper outlines a number of possibilities of this approach for English language learners. These include increased individual agency; enhanced engagement through collaboration; and the opportunity to explore various elements of multimodal text design.

Occupational Health and Safety, Courts and Crime: the legal construction of occupational health and safety offences in Victoria

This book reports on an empirically-based study of the manner in which the Magistrates' Courts in Victoria, construct occupational health and safety (OHS) issues when hearing prosecutions for offences under the Victorian OHS legislation. Prosecution has always been a controversial element in the enforcement armoury of OHS regulators, but at the same time it has long been argued that the low level of fines imposed by courts has had an important chilling effect on the OHS inspectorate's enforcement approaches, and on the impact of OHS legislation. Using a range of empirical research methods, including three samples of OHS prosecutions carried out in the Victorian Magistrates' Courts, Professor Johnstone shows how courts, inspectors, prosecutors and defence counsel are involved in filtering or reshaping OHS issues during the prosecution process, both pre-trial and in court. He argues that OHS offences are constructed by focusing on "events", in most cases incidents resulting in injury or death. This "event-focus" ensures that the attention of the parties is drawn to the details of the incident, and away from the broader context of the event. During the court-based sentencing process defence counsel is able to adopt a range of techniques which isolate the incident from its micro and macro contexts, thereby individualising and decontextualising the incident.

An examination of Saudi high school teachers' ICT knowledge and implementation

This study investigated Saudi high school teachers' implementation of ICT in schools. The study also explored the relationship between the teachers' level of TPACK and their implementation of ICT. In the first phase of the study, more than 250 Saudi teachers from Al-Madinah administrative area filled in a four-part self reported questionnaire while in the second, 12 teachers completed semi-structured interviews. Findings from both phases of the study revealed that Saudi high school teachers demonstrated low level of effectiveness of ICT implementation. Among a number of barriers, Teachers' TPACK knowledge was found as the best predictor of the effectiveness of ICT implementation.

Impact of simulated hyperopia on academic-related performance in children

Purpose: To investigate the impact of simulated hyperopia and sustained near work on children’s ability to perform a range of academic-related tasks. Methods: Fifteen visually normal children (mean age: 10.9 ± 0.8 years; 10 males and 5 females) were recruited. Performance on a range of standardised academic-related outcome measures was assessed with and without 2.50 D of simulated bilateral hyperopia (administered in a randomised order), before and after 20 minutes of sustained near work, at two separate testing sessions. Academic-related measures included a standardised reading test (the Neale Analysis of Reading Ability), visual information processing tests (Coding and Symbol Search subtests from the Wechsler Intelligence Scale for Children) and a reading-related eye movement test (the Developmental Eye Movement test). Results: Simulated bilateral hyperopia and sustained near work each independently impaired reading, visual information processing and reading-related eye movement performance (p<0.001). A significant interaction was also demonstrated between these factors (p<0.001), with the greatest decrement in performance observed when simulated hyperopia was combined with sustained near work. This combination resulted in performance reductions of between 5% and 24% across the range of academic-related measures. A significant moderate correlation was also found between the change in horizontal near heterophoria and the change in several of the academic-related outcome measures, following the addition of simulated hyperopia. Conclusions: A relatively low level of simulated bilateral hyperopia impaired children’s performance on a range of academic–related outcome measures, with sustained near work further exacerbating this effect. Further investigations are required to determine the impact of correcting low levels of hyperopia on academic performance in children.

Coding livecoding

Livecoding is an artistic programming practice in which an artist's low-level interaction can be observed with sufficiently high fidelity to allow for transcription and analysis. This paper presents the first reported" coding" of livecoding videos. From an identified corpus of videos available on the web, we coded performances of two different livecoding artists, recording both the (textual) programming edit events and the musical effect of these edits.

Towards universal search design

For people with cognitive disabilities, technology is more often thought of as a support mechanism, rather than a source of division that may require intervention to equalize access across the cognitive spectrum. This paper presents a first attempt at formalizing the digital gap created by the generalization of search engines. This was achieved through the development of a mapping of cognitive abilities required by users to execute low- level tasks during a standard Web search task. The mapping demonstrates how critical these abilities are to successfully use search engines with an adequate level of independence. It will lead to a set of design guidelines for search engine interfaces that will allow for the engagement of users of all abilities, and also, more importantly, in search algorithms such as query suggestion and measure of relevance (i.e. ranking).

Relevance feature discovery for text mining

It is a big challenge to guarantee the quality of discovered relevance features in text documents for describing user preferences because of large scale terms and data patterns. Most existing popular text mining and classification methods have adopted term-based approaches. However, they have all suffered from the problems of polysemy and synonymy. Over the years, there has been often held the hypothesis that pattern-based methods should perform better than term-based ones in describing user preferences; yet, how to effectively use large scale patterns remains a hard problem in text mining. To make a breakthrough in this challenging issue, this paper presents an innovative model for relevance feature discovery. It discovers both positive and negative patterns in text documents as higher level features and deploys them over low-level features (terms). It also classifies terms into categories and updates term weights based on their specificity and their distributions in patterns. Substantial experiments using this model on RCV1, TREC topics and Reuters-21578 show that the proposed model significantly outperforms both the state-of-the-art term-based methods and the pattern based methods.

Shape up or ship out : can we enhance productivity in coastal aquaculture to compete with other uses?

Coastal resources are coming under increasing pressure from competition between recreational, commercial and conservation uses. This is particularly so in coastal areas adjacent to major population centres. Given high recreational and conservation values in such areas, economic activities need to be highly efficient in order to persist. Management of these industries must therefore also encourage efficient production and full utilisation of the areas available. In order to achieve this, managers must first understand the level and drivers of productivity, and how these can be influenced. In this study, by way of illustration, the focus was on the Sydney rock oyster industry within Queensland's Moreton Bay, a multiple use marine park with high recreational and conservation value adjacent to Australia's third largest city. Productivity of the oyster industry in Moreton Bay is currently low compared to historic levels, and management has an objective of reversing this trend. It is unclear whether this difference is due to oyster farmers' business choices and personal characteristics or whether varying environmental conditions in the Moreton Bay limit the capacity of the oyster industry. These require different management responses in order to enhance productivity. The study examined different productivity measures of the oyster industry using data envelopment analysis (DEA) to determine where productivity gains can be made and by how much. The findings suggest that the industry is operating at a high level of capacity utilisation, but a low level of efficiency. The results also suggest that both demographic and environmental conditions affect technical efficiency in the Bay, with water characteristics improvements and appropriate training potentially providing the greatest benefits to the industry. Methods used in this study are transferable to other industries and provide a means by which coastal aquaculture may be managed to ensure it remains competitive with other uses of coastal resources.

Risk factors for delayed healing in venous leg ulcers : a review of the literature

Background Chronic leg ulcers, remaining unhealed after 4–6 weeks, affect 1-3% of the population, with treatment costly and health service resource intensive. Venous disease contributes to approximately 70% of all chronic leg ulcers and these ulcers are often associated with pain, reduced mobility and a decreased quality of life. Despite evidence-based care, 30% of these ulcers are unlikely to heal within a 24-week period and therefore the recognition and identification of risk factors for delayed healing of venous leg ulcers would be beneficial. Aim To review the available evidence on risk factors for delayed healing of venous leg ulcers. Methods: A review of the literature in regard to risk factors for delayed healing in venous leg ulcers was conducted from January 2000 to December 2013. Evidence was sourced through searches of relevant databases and websites for resources addressing risk factors for delayed healing in venous leg ulcers specifically. Results Twenty-seven studies, of mostly low-level evidence (Level III and IV), identified risk factors associated with delayed healing. Risk factors that were consistently identified included: larger ulcer area, longer ulcer duration, a previous history of ulceration, venous abnormalities and lack of high compression. Additional potential predictors with inconsistent or varying evidence to support their influence on delayed healing of venous leg ulcers included decreased mobility and/or ankle range of movement, poor nutrition and increased age. Discussion Findings from this review indicate that a number of physiological risk factors are asso- ciated with delayed healing in venous leg ulcers and that social and/or psychological risk factors should also be considered and examined further. Conclusion The findings from this review can assist health professionals to identify prognostic indicators or risk factors significantly associated with delayed healing in venous leg ulcers. This will facilitate realistic outcome planning and inform implementation of appropriate early strategies to promote healing.

Curiosity driven reinforcement learning for motion planning on humanoids

Most previous work on artificial curiosity (AC) and intrinsic motivation focuses on basic concepts and theory. Experimental results are generally limited to toy scenarios, such as navigation in a simulated maze, or control of a simple mechanical system with one or two degrees of freedom. To study AC in a more realistic setting, we embody a curious agent in the complex iCub humanoid robot. Our novel reinforcement learning (RL) framework consists of a state-of-the-art, low-level, reactive control layer, which controls the iCub while respecting constraints, and a high-level curious agent, which explores the iCub's state-action space through information gain maximization, learning a world model from experience, controlling the actual iCub hardware in real-time. To the best of our knowledge, this is the first ever embodied, curious agent for real-time motion planning on a humanoid. We demonstrate that it can learn compact Markov models to represent large regions of the iCub's configuration space, and that the iCub explores intelligently, showing interest in its physical constraints as well as in objects it finds in its environment.