Kallikrein-related peptidases in prostate cancer: From molecular function to clinical application

Prostate cancer is a leading contributor to male cancer-related deaths worldwide. Kallikrein-related peptidases (KLKs) are serine proteases that exhibit deregulated expression in prostate cancer, with KLK3, or prostate specific antigen (PSA), being the widely-employed clinical biomarker for prostate cancer. Other KLKs, such as KLK2, show promise as prostate cancer biomarkers and, additionally, their altered expression has been utilised for the design of KLK-targeted therapies. There is also a large body of in vitro and in vivo evidence supporting their role in cancer-related processes. Here, we review the literature on studies to date investigating the potential of other KLKs, in addition to PSA, as biomarkers and in therapeutic options, as well as their current known functional roles in cancer progression. Increased knowledge of these KLK-mediated functions, including degradation of the extracellular matrix, local invasion, cancer cell proliferation, interactions with fibroblasts, angiogenesis, migration, bone metastasis and tumour growth in vivo, may help define new roles as prognostic biomarkers and novel therapeutic targets for this cancer.

4th International Workshop on Theory and Application of Visualizations and Human-centric Aspects in Processes

This is the fourth TAProViz workshop being run at the 13th International Conference on Business Process Management (BPM). The intention this year is to consolidate on the results of the previous successful workshops by further developing this important topic, identifying the key research topics of interest to the BPM visualization community. Towards this goal, the workshop topics were extended to human computer interaction and related domains. Submitted papers were evaluated by at least three program committee members, in a double blind manner, on the basis of significance, originality, technical quality and exposition. Three full and one position papers were accepted for presentation at the workshop. In addition, we invited a keynote speaker, Jakob Pinggera, a postdoctoral researcher at the Business Process Management Research Cluster at the University of Innsbruck, Austria.

Impact of cool roof application on commercial buildings: A contribution to sustainable design in Australia

This study investigated the cool roof technology effects on annual energy saving of a large one-storey commercial building in Queensland, Australia. A computer model of the case study was developed using commercial software by using the appropriate geometrical and thermal building specifications. Field study data were used to validate the model. The model was then used to extend the investigation to other cities in various Australian climate zones. The results of this research show that significant energy savings can be obtained using cool roof technology, particularly in warm, sunny climates, and the thesis can contribute to provide a guideline for application of cool roof technology to single-storey commercial building throughout Australia.

Multi-Hypotheses Tracking using the Dempster–Shafer Theory, application to ambiguous road context

This paper presents a Multi-Hypotheses Tracking (MHT) approach that allows solving ambiguities that arise with previous methods of associating targets and tracks within a highly volatile vehicular environment. The previous approach based on the Dempster–Shafer Theory assumes that associations between tracks and targets are unique; this was shown to allow the formation of ghost tracks when there was too much ambiguity or conflict for the system to take a meaningful decision. The MHT algorithm described in this paper removes this uniqueness condition, allowing the system to include ambiguity and even to prevent making any decision if available data are poor. We provide a general introduction to the Dempster–Shafer Theory and present the previously used approach. Then, we explain our MHT mechanism and provide evidence of its increased performance in reducing the amount of ghost tracks and false positive processed by the tracking system.

Resolution of Cryptic Species Complexes of Tephritid Pests to Enhance SIT Application and Facilitate International Trade

Tephritid fruit flies (Diptera: Tephritidae) are considered by far the most important group of horticultural pests worldwide. Female fruit flies lay eggs directly into ripening fruit, where the maggots feed causing fruit loss. Each and every continent is plagued by a number of fruit fly pests, both indigenous as well as invasive ones, causing tremendous economic losses. In addition to the direct losses through damage, they can negatively impact commodity trade through restrictions to market access. The quarantine and regulatory controls put in place to manage them are expensive, while the on-farm control costs and loss of crop affect the general well-being of growers. These constraints can have huge implications on loss in revenues and limitations to developing fruit and vegetable-based agroindustries in developing, emergent and developed nations. Because fruit flies are a global problem, the study of their biology and management requires significant international attention to overcome the hurdles they pose. The Joint Food and Agriculture Organisation / International Atomic Energy Agency (FAO/IAEA) Programme on Nuclear Techniques in Food and Agriculture has been on the foreground in assisting Member States in developing and validating environment-friendly fruit fly suppression systems to support viable fresh fruit and vegetable production and export industries. Such international attention has resulted in the successful development and validation of a Sterile Insect Technique (SIT) package for the Mediterranean fruit fly. Although demands for R&D support with respect to Mediterranean fruit fly are diminishing due to successful integration of this package into sustainable control programmes against this pest in many countries, there were increasing demands from Member States in Africa, Asia and Latin America, to address other major fruit fly pests and a related, but sometimes neglected issue of tephritid species complexes of economic importance. Any research, whether it is basic or applied, requires a taxonomic framework that provides reliable and universally recognized entities and names. Among the currently recognized major fruit fly pests, there are groups of species whose morphology is very similar or identical, but biologically they are distinct species. As such, some insect populations that are grouped taxonomically within the same pest species, display different biological and genetic traits and show reproductive isolation which suggest that they are different species. On the other hand, different species may have been taxonomically described, but there may be doubt as to whether they actually represent distinct biological species or merely geographical variants of the same species. This uncertain taxonomic status has practical implications on the effective development and use of the SIT against such complexes, particularly at the time of determining which species to mass-rear, and significantly affects international movement of fruit and vegetables through the establishment of trade barriers to important agricultural commodities which are hosts to these pest tephritid species...

Constellations: A participatory, online application for research collaboration in higher education interdisciplinary courses

The research establishes a model for online learning centering on the needs of integrative knowledge practices. Through the metaphor of Constellations, the practice-based research explores the complexities of working within interdisciplinary learning contexts and the potential of tools such as the Folksonomy learning platform for providing necessary conceptual support.

Spectral analysis of pair-correlation bandwidth: Application to cell biology images

Images from cell biology experiments often indicate the presence of cell clustering, which can provide insight into the mechanisms driving the collective cell behaviour. Pair-correlation functions provide quantitative information about the presence, or absence, of clustering in a spatial distribution of cells. This is because the pair-correlation function describes the ratio of the abundance of pairs of cells, separated by a particular distance, relative to a randomly distributed reference population. Pair-correlation functions are often presented as a kernel density estimate where the frequency of pairs of objects are grouped using a particular bandwidth (or bin width), Δ>0. The choice of bandwidth has a dramatic impact: choosing Δ too large produces a pair-correlation function that contains insufficient information, whereas choosing Δ too small produces a pair-correlation signal dominated by fluctuations. Presently, there is little guidance available regarding how to make an objective choice of Δ. We present a new technique to choose Δ by analysing the power spectrum of the discrete Fourier transform of the pair-correlation function. Using synthetic simulation data, we confirm that our approach allows us to objectively choose Δ such that the appropriately binned pair-correlation function captures known features in uniform and clustered synthetic images. We also apply our technique to images from two different cell biology assays. The first assay corresponds to an approximately uniform distribution of cells, while the second assay involves a time series of images of a cell population which forms aggregates over time. The appropriately binned pair-correlation function allows us to make quantitative inferences about the average aggregate size, as well as quantifying how the average aggregate size changes with time.

Application of inverse filtering technique in power system studies

This paper demonstrates the application of inverse filtering technique for power systems. In order to implement this method, the control objective should be based on a system variable that needs to be set on a specific value for each sampling time. A control input is calculated to generate the desired output of the plant and the relationship between the two is used design an auto-regressive model. The auto-regressive model is converted to a moving average model to calculate the control input based on the future values of the desired output. Therefore, required future values to construct the output are predicted to generate the appropriate control input for the next sampling time.

The importance of modelling heterogeneity in complex disease: application to NIMH Schizophrenia Genetics Initiative data

As for other complex diseases, linkage analyses of schizophrenia (SZ) have produced evidence for numerous chromosomal regions, with inconsistent results reported across studies. The presence of locus heterogeneity appears likely and may reduce the power of linkage analyses if homogeneity is assumed. In addition, when multiple heterogeneous datasets are pooled, inter-sample variation in the proportion of linked families (alpha) may diminish the power of the pooled sample to detect susceptibility loci, in spite of the larger sample size obtained. We compare the significance of linkage findings obtained using allele-sharing LOD scores (LOD(exp))-which assume homogeneity-and heterogeneity LOD scores (HLOD) in European American and African American NIMH SZ families. We also pool these two samples and evaluate the relative power of the LOD(exp) and two different heterogeneity statistics. One of these (HLOD-P) estimates the heterogeneity parameter alpha only in aggregate data, while the second (HLOD-S) determines alpha separately for each sample. In separate and combined data, we show consistently improved performance of HLOD scores over LOD(exp). Notably, genome-wide significant evidence for linkage is obtained at chromosome 10p in the European American sample using a recessive HLOD score. When the two samples are combined, linkage at the 10p locus also achieves genome-wide significance under HLOD-S, but not HLOD-P. Using HLOD-S, improved evidence for linkage was also obtained for a previously reported region on chromosome 15q. In linkage analyses of complex disease, power may be maximised by routinely modelling locus heterogeneity within individual datasets, even when multiple datasets are combined to form larger samples.

The impact of a streamlined funding application process on application time: Two cross-sectional surveys of Australian researchers

Objective: To examine if streamlining a medical research funding application process saved time for applicants. Design: Cross-sectional surveys before and after the streamlining. Setting: The National Health and Medical Research Council (NHMRC) of Australia. Participants: Researchers who submitted one or more NHMRC Project Grant applications in 2012 or 2014. Main outcome measures: Average researcher time spent preparing an application and the total time for all applications in working days. Results: The average time per application increased from 34 working days before streamlining (95% CI 33 to 35) to 38 working days after streamlining (95% CI 37 to 39; mean difference 4 days, bootstrap p value <0.001). The estimated total time spent by all researchers on applications after streamlining was 614 working years, a 67-year increase from before streamlining. Conclusions: Streamlined applications were shorter but took longer to prepare on average. Researchers may be allocating a fixed amount of time to preparing funding applications based on their expected return, or may be increasing their time in response to increased competition. Many potentially productive years of researcher time are still being lost to preparing failed applications.

Influences on novice drivers' speed selection - a systematic review: Application and limitations of theory and methodology

Background Excessive speed is a primary contributing factor to young novice road trauma, including intentional and unintentional speeds above posted limits or too fast for conditions. The objective of this research was to conduct a systematic review of recent investigations into novice drivers’ speed selection, with particular attention to applications and limitations of theory and methodology. Method Systematic searches of peer-reviewed and grey literature were conducted during September 2014. Abstract reviews identified 71 references potentially meeting selection criteria of investigations since the year 2000 into factors that influence (directly or indirectly) actual speed (i.e., behaviour or performance) of young (age <25 years) and/or novice (recently-licensed) drivers. Results Full paper reviews resulted in 30 final references: 15 focused on intentional speeding and 15 on broader speed selection investigations. Both sets identified a range of individual (e.g., beliefs, personality) and social (e.g., peer, adult) influences, were predominantly theory-driven and applied cross-sectional designs. Intentional speed investigations largely utilised self-reports while other investigations more often included actual driving (simulated or ‘real world’). The latter also identified cognitive workload and external environment influences, as well as targeted interventions. Discussion and implications Applications of theory have shifted the novice speed-related literature beyond a simplistic focus on intentional speeding as human error. The potential to develop a ‘grand theory’ of intentional speeding emerged and to fill gaps to understand broader speed selection influences. This includes need for future investigations of vehicle-related and physical environment-related influences and methodologies that move beyond cross-sectional designs and rely less on self-reports.

Chronic disease risks and use of a smartphone application during a physical activity and dietary intervention in Australian truck drivers

- Objective This study examined chronic disease risks and the use of a smartphone activity tracking application during an intervention in Australian truck drivers (April-October 2014). - Methods Forty-four men (mean age=47.5 [SD 9.8] years) completed baseline health measures, and were subsequently offered access to a free wrist-worn activity tracker and smartphone application (Jawbone UP) to monitor step counts and dietary choices during a 20-week intervention. Chronic disease risks were evaluated against guidelines; weekly step count and dietary logs registered by drivers in the application were analysed to evaluate use of the Jawbone UP. - Results Chronic disease risks were high (e.g. 97% high waist circumference [≥94 cm]). Eighteen drivers (41%) did not start the intervention; smartphone technical barriers were the main reason for drop out. Across 20-weeks, drivers who used the Jawbone UP logged step counts for an average of 6 [SD 1] days/week; mean step counts remained consistent across the intervention (weeks 1–4=8,743[SD 2,867] steps/day; weeks 17–20=8,994[SD 3,478] steps/day). The median number of dietary logs significantly decreased from start (17 [IQR 38] logs/weeks) to end of the intervention (0 [IQR 23] logs/week; p<0.01); the median proportion of healthy diet choices relative to total diet choices logged increased across the intervention (weeks 1–4=38[IQR 21]%; weeks 17–20=58[IQR 18]%). - Conclusions Step counts were more successfully monitored than dietary choices in those drivers who used the Jawbone UP. - Implications Smartphone technology facilitated active living and healthy dietary choices, but also prohibited intervention engagement in a number of these high-risk Australian truck drivers.

Analysing the Impact of Learning Inputs - Application to Terrain Traversability Estimation

Data-driven approaches such as Gaussian Process (GP) regression have been used extensively in recent robotics literature to achieve estimation by learning from experience. To ensure satisfactory performance, in most cases, multiple learning inputs are required. Intuitively, adding new inputs can often contribute to better estimation accuracy, however, it may come at the cost of a new sensor, larger training dataset and/or more complex learning, some- times for limited benefits. Therefore, it is crucial to have a systematic procedure to determine the actual impact each input has on the estimation performance. To address this issue, in this paper we propose to analyse the impact of each input on the estimate using a variance-based sensitivity analysis method. We propose an approach built on Analysis of Variance (ANOVA) decomposition, which can characterise how the prediction changes as one or more of the input changes, and also quantify the prediction uncertainty as attributed from each of the inputs in the framework of dependent inputs. We apply the proposed approach to a terrain-traversability estimation method we proposed in prior work, which is based on multi-task GP regression, and we validate this implementation experimentally using a rover on a Mars-analogue terrain.

Location and scale mixtures of Gaussians with flexible tail behaviour: Properties, inference and application to multivariate clustering

The family of location and scale mixtures of Gaussians has the ability to generate a number of flexible distributional forms. The family nests as particular cases several important asymmetric distributions like the Generalized Hyperbolic distribution. The Generalized Hyperbolic distribution in turn nests many other well known distributions such as the Normal Inverse Gaussian. In a multivariate setting, an extension of the standard location and scale mixture concept is proposed into a so called multiple scaled framework which has the advantage of allowing different tail and skewness behaviours in each dimension with arbitrary correlation between dimensions. Estimation of the parameters is provided via an EM algorithm and extended to cover the case of mixtures of such multiple scaled distributions for application to clustering. Assessments on simulated and real data confirm the gain in degrees of freedom and flexibility in modelling data of varying tail behaviour and directional shape.

A new family of multivariate heavy-tailed distributions with variable marginal amounts of tailweight: Application to robust clustering

We propose a family of multivariate heavy-tailed distributions that allow variable marginal amounts of tailweight. The originality comes from introducing multidimensional instead of univariate scale variables for the mixture of scaled Gaussian family of distributions. In contrast to most existing approaches, the derived distributions can account for a variety of shapes and have a simple tractable form with a closed-form probability density function whatever the dimension. We examine a number of properties of these distributions and illustrate them in the particular case of Pearson type VII and t tails. For these latter cases, we provide maximum likelihood estimation of the parameters and illustrate their modelling flexibility on simulated and real data clustering examples.