Long terminal repeats act as androgen-responsive enhancers for the PSA-Kallikrein locus

The androgen receptor (AR) signaling pathway is a common therapeutic target for prostate cancer, because it is critical for the survival of both hormone-responsive and castrate-resistant tumor cells. Most of the detailed understanding that we have of AR transcriptional activation has been gained by studying classical target genes. For more than two decades, Kallikrein 3 (KLK3) (prostate-specific antigen) has been used as a prototypical AR target gene, because it is highly androgen responsive in prostate cancer cells. Three regions upstream of the KLK3 gene, including the distal enhancer, are known to contain consensus androgen-responsive elements required for AR-mediated transcriptional activation. Here, we show that KLK3 is one of a specific cluster of androgen-regulated genes at the centromeric end of the kallikrein locus with enhancers that evolved from the long terminal repeat (LTR) (LTR40a) of an endogenous retrovirus. Ligand-dependent recruitment of the AR to individual LTR-derived enhancers results in concurrent up-regulation of endogenous KLK2, KLK3, and KLKP1 expression in LNCaP prostate cancer cells. At the molecular level, a kallikrein-specific duplication within the LTR is required for maximal androgen responsiveness. Therefore, KLK3 represents a subset of target genes regulated by repetitive elements but is not typical of the whole spectrum of androgen-responsive transcripts. These data provide a novel and more detailed understanding of AR transcriptional activation and emphasize the importance of repetitive elements as functional regulatory units

Genetic polymorphisms in the human tissue kallikrein (KLK) locus and their implication in various malignant and non-malignant diseases

The Kallikrein (KLK) gene locus encodes a family of serine proteases and is the largest contiguous cluster of protease-encoding genes attributed an evolutionary age of 330 million years. The KLK locus has been implicated as a high susceptibility risk loci in numerous cancer studies through the last decade. The KLK3 gene already has established clinical relevance as a biomarker in prostate cancer prognosis through its encoded protein, prostate-specific antigen. Data mined through genome-wide association studies (GWAS) and next-generation sequencing point to many important candidate single nucleotide polymorphisms (SNPs) in KLK3 and other KLK genes. SNPs in the KLK locus have been found to be associated with several diseases including cancer, hypertension, cardiovascular disease and atopic dermatitis. Moreover, introducing a model incorporating SNPs to improve the efficiency of prostate-specific antigen in detecting malignant states of prostate cancer has been recently suggested. Establishing the functional relevance of these newly-discovered SNPs, and their interactions with each other, through in silico investigations followed by experimental validation, can accelerate the discovery of diagnostic and prognostic biomarkers. In this review, we discuss the various genetic association studies on the KLK loci identified either through candidate gene association studies or at the GWAS and post-GWAS front to aid researchers in streamlining their search for the most significant, relevant and therapeutically promising candidate KLK gene and/or SNP for future investigations.

Fine-mapping identifies multiple prostate cancer risk loci on 5p15 some associating with TERT expression

Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease.

A dynamic mapping of the UK's creative industries

This paper argues that, despite its strengths, the UK Department of Culture, Media and Sport (DCMS) classification of the creative industries contains inconsistencies which need to be addressed to make it fully fit for purpose. It presents an improved methodology which retains the strengths of the DCMS's approach while addressing its deficiencies. We focus on creative intensity: the proportion of total employment within an industry that is engaged in creative occupations.

Towards persistent indoor appearance-based localization, mapping and navigation using CAT-Graph

The challenge of persistent appearance-based navigation and mapping is to develop an autonomous robotic vision system that can simultaneously localize, map and navigate over the lifetime of the robot. However, the computation time and memory requirements of current appearance-based methods typically scale not only with the size of the environment but also with the operation time of the platform; also, repeated revisits to locations will develop multiple competing representations which reduce recall performance. In this paper we present a solution to the persistent localization, mapping and global path planning problem in the context of a delivery robot in an office environment over a one-week period. Using a graphical appearance-based SLAM algorithm, CAT-Graph, we demonstrate constant time and memory loop closure detection with minimal degradation during repeated revisits to locations, along with topological path planning that improves over time without using a global metric representation. We compare the localization performance of CAT-Graph to openFABMAP, an appearance-only SLAM algorithm, and the path planning performance to occupancy-grid based metric SLAM. We discuss the limitations of the algorithm with regard to environment change over time and illustrate how the topological graph representation can be coupled with local movement behaviors for persistent autonomous robot navigation.

Trait anxiety and coping strategies among ballet dancers

This study examined relationships between competitive trait anxiety and coping strategies among ballet dancers. Participants were 104 classical dancers (81 females and 23 males) ranging in age from 15 to 35 years (mean 19.4 years; SD 3.8 years) from three professional ballet companies, two private dance schools, and two university dance courses in Australia. Participants completed the Modified COPE scale and the Sport Anxiety Scale. Trait anxiety scores, in particular for somatic anxiety and worry, were significant predictors of 7 of the 12 coping strategies (wishful thinking, r2 = 42.3%; selfblame, r2 = 35.7%; suppression of competing activities, r2 = 27.1%; venting of emotions, r2 = 23.2%; denial, r2 = 17.7%; effort, r2 = 16.6%; active coping, r2 = 14.3%). Approximately 96% of dancers could be classified correctly as high or low trait-anxious from their reported coping style. No significant effects of gender or status (professional versus students) were found. Findings showed that high trait-anxious athletes tend to use more maladaptive, emotion-focused coping strategies compared with low trait-anxious athletes; a tendency that has been proposed to lead to negative performance effects. Dancers who are by nature anxious about performance may need special attention to help them to learn to cope with performance-related stress. Med Probl Perform Art 18:59–64, 2003.

Genetic association of the KLK4 locus with risk of prostate cancer

The Kallikrein-related peptidase, KLK4, has been shown to be significantly overexpressed in prostate tumours in numerous studies and is suggested to be a potential biomarker for prostate cancer. KLK4 may also play a role in prostate cancer progression through its involvement in epithelial-mesenchymal transition, a more aggressive phenotype, and metastases to bone. It is well known that genetic variation has the potential to affect gene expression and/or various protein characteristics and hence we sought to investigate the possible role of single nucleotide polymorphisms (SNPs) in the KLK4 gene in prostate cancer. Assessment of 61 SNPs in the KLK4 locus (±10 kb) in approximately 1300 prostate cancer cases and 1300 male controls for associations with prostate cancer risk and/or prostate tumour aggressiveness (Gleason score <7 versus ≥7) revealed 7 SNPs to be associated with a decreased risk of prostate cancer at the Ptrend<0.05 significance level. Three of these SNPs, rs268923, rs56112930 and the HapMap tagSNP rs7248321, are located several kb upstream of KLK4; rs1654551 encodes a non-synonymous serine to alanine substitution at position 22 of the long isoform of the KLK4 protein, and the remaining 3 risk-associated SNPs, rs1701927, rs1090649 and rs806019, are located downstream of KLK4 and are in high linkage disequilibrium with each other (r2≥0.98). Our findings provide suggestive evidence of a role for genetic variation in the KLK4 locus in prostate cancer predisposition.

A snapshot of radiation therapy techniques and technology in Queensland : an aid to mapping undergraduate curriculum

Introduction: Undergraduate students studying the Bachelor of Radiation Therapy at Queensland University of Technology (QUT) attend clinical placements in a number of department sites across Queensland. To ensure that the curriculum prepares students for the most common treatments and current techniques in use in these departments, a curriculum matching exercise was performed. Methods: A cross-sectional census was performed on a pre-determined “Snapshot” date in 2012. This was undertaken by the clinical education staff in each department who used a standardized proforma to count the number of patients as well as prescription, equipment, and technique data for a list of tumour site categories. This information was combined into aggregate anonymized data. Results: All 12 Queensland radiation therapy clinical sites participated in the Snapshot data collection exercise to produce a comprehensive overview of clinical practice on the chosen day. A total of 59 different tumour sites were treated on the chosen day and as expected the most common treatment sites were prostate and breast, comprising 46% of patients treated. Data analysis also indicated that intensity-modulated radiotherapy (IMRT) use is relatively high with 19.6% of patients receiving IMRT treatment on the chosen day. Both IMRT and image-guided radiotherapy (IGRT) indications matched recommendations from the evidence. Conclusion: The Snapshot method proved to be a feasible and efficient method of gathering useful

What relationships exist between general self efficacy, locus of control and the nursing practice environment and caring efficacy and job satisfaction?

Research Question: What relationships exist between general self efficacy, locus of control and the nursing practice environment and caring efficacy and job satisfaction? Background: Important characteristics of current nursing practice include nurses having the ability to develop and continue therapeutic relationships with patients, nurses having autonomy and control over the practice environment and nurses having more involvement in decision making. In addition, employee satisfaction is enhanced when organisations offer access to authority. Despite this, nurses continue to complain of feeling powerless in their ability to make decisions. Sample: The study population and criteria for selection included Registered Nurses in Australia who were at the time members of an Australian professional and industrial organisation. Methods: A cross-sectional survey was undertaken. Data analysis was conducted using descriptive and bivariate statistics, and structural equation modeling. Results: The model fit the data well (χ² = 2.3594, χ²/df = 2.3594 and CFI = 0.9987). Twenty four percent of variation in caring efficacy (CE) can be accounted for by general self-efficacy (GSE); work locus of control (WLC) and practice environment (PE) and 62% of the variation in job satisfaction (JS) can be accounted for by GSE, WLC and PE. All pathways were found to be significant except PE to CE. GSE positively explained CE (β = 0.38). WLC was negatively related to CE i.e., as CE scores increased WLC scores decreased (β = -0.23). Further testing of the model found CE was positively related to GSE (βZ = 0.38, p < 0.001) and negatively related to WLC (βZ = - 0.23, p = 0.001). PE was not significantly associated with CE (βZ = - 0.01, p = 0.85). JS was explained by PE, which was positively related (βZ = 0.69, p = < 0.001); GSE which was negatively related (βZ - 0 .09, p < 0.001) and WLC, which was also negatively related (βZ = - 0.20, p < 0.001). Implications for Practice Nursing and organisational leaders should ensure the development of strategies for professional development and orientation programmes which may enhance nurses’ ability to develop caring relationships and express caring behaviours to their patients and as a result improve organisational and patient outcomes. Nursing shortages and turnover rates are associated with job satisfaction and the nursing practice environment. Improving the nursing environment can produce benefits to the health system such as better job satisfaction, improved workforce retention and better patient outcomes.

From movie screens to moving screens : mapping qualities of new urban interactions

Next generation screens of diverse dimensions such as the Pebble e-paper watch, Google’s Project Glass, Microsoft’s Kinect and IllumiRoom, and large-scale multi-touch screen surface areas, increasingly saturate and diversify the urban mediascape. This paper seeks to contribute to media architecture and interaction design theory by starting to critically examine how these different screen formats are creating a ubiquitous screen mediascape across the city. We introduce next generation personal, domestic, and public screens. The paper critically challenges conventional dichotomies such as local / global, online / offline, private / public, large / small, mobile / static, that have been created in the past to describe some of the qualities and characteristics of interfaces and their usage. More and more scholars recognise that the black and white nature of these dichotomies does not adequately represent the fluid and agile capabilities of many new screen interfaces. With this paper, we hope to illustrate the more nuanced ‘trans-scalar’ qualities of these new urban interactions, that is, ways in which they provide a range functionality, without being locked into either end of a scale.

Novel keratins identified by quantitative proteomic analysis as the major cytoskeletal proteins of equine (Equus caballus) hoof lamellar tissue

The dermo-epidermal interface that connects the equine distal phalanx to the cornified hoof wall withstands great biomechanical demands, but is also a region where structural failure often ensues as a result of laminitis. The cytoskeleton in this region maintains cell structure and facilitates intercellular adhesion, making it likely to be involved in laminitis pathogenesis, although it is poorly characterized in the equine hoof lamellae. The objective of the present study was to identify and quantify the cytoskeletal proteins present in the epidermal and dermal lamellae of the equine hoof by proteomic techniques. Protein was extracted from the mid-dorsal epidermal and dermal lamellae from the front feet of 5 Standardbred geldings and 1 Thoroughbred stallion. Mass spectrometry-based spectral counting techniques, PAGE, and immunoblotting were used to identify and quantify cytoskeletal proteins, and indirect immunofluorescence was used for cellular localization of K14 and K124 (where K refers to keratin). Proteins identified by spectral counting analysis included 3 actin microfilament proteins; 30 keratin proteins along with vimentin, desmin, peripherin, internexin, and 2 lamin intermediate filament proteins; and 6 tubulin microtubule proteins. Two novel keratins, K42 and K124, were identified as the most abundant cytoskeletal proteins (22.0 ± 3.2% and 23.3 ± 4.2% of cytoskeletal proteins, respectively) in equine hoof lamellae. Immunoreactivity to K14 was localized to the basal cell layer, and that to K124 was localized to basal and suprabasal cells in the secondary epidermal lamellae. Abundant proteins K124, K42, K14, K5, and α1-actin were identified on 1- and 2-dimensional polyacrylamide gels and aligned with the results of previous studies. Results of the present study provide the first comprehensive analysis of cytoskeletal proteins present in the equine lamellae by using mass spectrometry-based techniques for protein quantification and identification.

3D thermal mapping of building interiors using an RGB-D and thermal camera

The building sector is the dominant consumer of energy and therefore a major contributor to anthropomorphic climate change. The rapid generation of photorealistic, 3D environment models with incorporated surface temperature data has the potential to improve thermographic monitoring of building energy efficiency. In pursuit of this goal, we propose a system which combines a range sensor with a thermal-infrared camera. Our proposed system can generate dense 3D models of environments with both appearance and temperature information, and is the first such system to be developed using a low-cost RGB-D camera. The proposed pipeline processes depth maps successively, forming an ongoing pose estimate of the depth camera and optimizing a voxel occupancy map. Voxels are assigned 4 channels representing estimates of their true RGB and thermal-infrared intensity values. Poses corresponding to each RGB and thermal-infrared image are estimated through a combination of timestamp-based interpolation and a pre-determined knowledge of the extrinsic calibration of the system. Raycasting is then used to color the voxels to represent both visual appearance using RGB, and an estimate of the surface temperature. The output of the system is a dense 3D model which can simultaneously represent both RGB and thermal-infrared data using one of two alternative representation schemes. Experimental results demonstrate that the system is capable of accurately mapping difficult environments, even in complete darkness.

Mapping Multiple Literacies: An Introduction to Deleuzian Literacy Studies

Mapping Multiple Literacies brings together the latest theory and research in the fields of literacy study and European philosophy, Multiple Literacies Theory (MLT) and the philosophical work of Gilles Deleuze. It frames the process of becoming literate as a fluid process involving multiple modes of presentation, and explains these processes in terms of making maps of our social lives and ways of doing things together. For Deleuze, language acquisition is a social activity of which we are a part, but only one part amongst many others. Masny and Cole draw on Deleuze's thinking to expand the repertoires of literacy research and understanding. They outline how we can understand literacy as a social activity and map the ways in which becoming literate may take hold and transform communities. The chapters in this book weave together theory, data and practice to open up a creative new area of literacy studies and to provoke vigorous debate about the sociology of literacy.