Circulating microRNAs as potential new biomarkers for prostate cancer

Since they were first described in the 1990s, circulating microRNAs (miRNAs) have provided an active and rapidly evolving area of current research that has the potential to transform cancer diagnostics and therapeutics. In particular, miRNAs could provide potential new biomarkers for prostate cancer, the most common cause of cancer in UK men. Current diagnostic tests for prostate cancer have low specificity and poor sensitivity. Further, although many prostate cancers are so slow growing as not to pose a major risk to health, there is currently no test to distinguish between these and cancers that will become aggressive and life threatening. Circulating miRNAs are highly stable and are both detectable and quantifiable in a range of accessible bio fluids, thus have the potential to be useful diagnostic, prognostic and predictive biomarkers. This review aims to summarise the current understanding of circulating miRNAs in prostate cancer patients and their potential role as biomarkers

Implementing Groundness Analysis with Definite Boolean Functions

The domain of definite Boolean functions, Def, can be used to express the groundness of, and trace grounding dependencies between, program variables in (constraint) logic programs. In this paper, previously unexploited computational properties of Def are utilised to develop an efficient and succinct groundness analyser that can be coded in Prolog. In particular, entailment checking is used to prevent unnecessary least upper bound calculations. It is also demonstrated that join can be defined in terms of other operations, thereby eliminating code and removing the need for preprocessing formulae to a normal form. This saves space and time. Furthermore, the join can be adapted to straightforwardly implement the downward closure operator that arises in set sharing analyses. Experimental results indicate that the new Def implementation gives favourable results in comparison with BDD-based groundness analyses

Academic achievement : the role of praise in motivating students

The motivation of students is an important issue in higher education, particularly in the context of the increasing diversity of student populations. A social-cognitive perspective assumes motivation to be dynamic, context-sensitive and changeable, thereby rendering it to be a much more differentiated construct than previously understood. This complexity may be perplexing to tutors who are keen to develop applications to improve academic achievement. One application that is within the control of the tutor, at least to some extent, is the use of praise. Using psychological literature the article argues that in motivating students, the tutor is not well served by relying on simplistic and common sense understandings of the construct of praise and that effective applications of praise are mediated by students' goal orientations, which of themselves may be either additive or interactive composites of different objectives and different contexts

An assertion language for constraint logic programs

In an advanced program development environment, such as that discussed in the introduction of this book, several tools may coexist which handle both the program and information on the program in different ways. Also, these tools may interact among themselves and with the user. Thus, the different tools and the user need some way to communicate. It is our design principie that such communication be performed in terms of assertions. Assertions are syntactic objects which allow expressing properties of programs. Several assertion languages have been used in the past in different contexts, mainly related to program debugging. In this chapter we propose a general language of assertions which is used in different tools for validation and debugging of constraint logic programs in the context of the DiSCiPl project. The assertion language proposed is parametric w.r.t. the particular constraint domain and properties of interest being used in each different tool. The language proposed is quite general in that it poses few restrictions on the kind of properties which may be expressed. We believe the assertion language we propose is of practical relevance and appropriate for the different uses required in the tools considered

Haemodynamical stress in mouse aortic arch with atherosclerotic plaques: Preliminary study of plaque progression

Atherosclerotic plaques develop at particular sites in the arterial tree, and this regional localisation depends largely on haemodynamic parameters (such as wall shear stress; WSS) as described in the literature. Plaque rupture can result in heart attack or stroke and hence understanding the development and vulnerability of atherosclerotic plaques is critically important. The purpose of this study is to characterise the haemodynamics of blood flow in the mouse aortic arch using numerical modelling. The geometries are digitalised from synchrotron imaging and realistic pulsatile blood flow is considered under rigid wall assumptions. Two cases are considered; arteries with and without plaque. Mice that are fed under fat diet present plaques in the aortic arch whose size is dependent on the number of weeks under the diet. The plaque distribution in the region is however relatively constant through the different samples. This result underlines the influence of the geometry and consequently of the wall shear stresses for plaque formation with plaques growing in region of relative low shear stresses. A discussion of the flow field in real geometry in the presence and absence of plaques is conducted. The presence of plaques was shown to alter the blood flow and hence WSS distribution, with regions of localised high WSS, mainly on the wall of the brachiocephalic artery where luminal narrowing is most pronounced. In addition, arch plaques are shown to induce recirculation in the blood flow, a phenomenon with potential influence on the progression of the plaques. The oscillatory shear index and the relative residence time have been calculated on the geometry with plaques to show the presence of this recirculation in the arch, an approach that may be useful for future studies on plaque progression

Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B

Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells. Application of PKA inhibitors, KT5720 or H89, caused a significant inhibition of Kv currents. Tonic PKA-mediated activation of Kv appears maximal as application of isoprenaline (a β-adrenoceptor agonist) or dibutyryl-cAMP failed to enhance Kv currents. We also show that this modulation of Kv by PKA can be reversed by protein phosphatase 2B/calcineurin (PP2B). PKA-dependent inhibition of Kv by KT5720 can be abrogated by pre-treatment with the PP2B inhibitor cyclosporin A, or inclusion of a PP2B auto-inhibitory peptide in the pipette solution. Finally, we demonstrate that tonic PKA-mediated modulation of Kv requires intact caveolae. Pre-treatment of the cells with methyl-β-cyclodextrin to deplete cellular cholesterol, or adding caveolin-scaffolding domain peptide to the pipette solution to disrupt caveolae-dependent signalling each attenuated PKA-mediated modulation of the Kv current. These findings highlight a novel, caveolae-dependent, tonic modulatory role of PKA on Kv channels providing new insight into mechanisms and the potential for pharmacological manipulation of vascular tone

Sports review: A content analysis of the International Review for the Sociology of Sport, the Journal of Sport and Social Issues and the Sociology of Sport Journal across 25 years

The International Review for the Sociology of Sport, the Journal of Sport and Social Issues and Sociology of Sport Journal have individually and collectively been subject to a systematic content analysis. By focusing on substantive research papers published in these three journals over a 25-year time period it is possible to identify the topics that have featured within the sociology of sport. The purpose of the study was to identify the dominant themes, sports, countries, methodological frameworks and theoretical perspectives that have appeared in the research papers published in these three journals. Using the terms, identified by the author(s), that appear in the paper’s title, abstract and/or listed as a key word, subject term or geographical term, a baseline is established to reflect on the development of the sub-discipline as represented by the content of these three journals. It is suggested that the findings illustrate what many of the more experienced practitioners in the field may have felt subjectively. On the basis of this systematic, empirical study it is now possible to identify those areas have received extensive coverage and those which are under-researched within the sociology of sport. The findings are used to inform a discussion of the role of academic journals and the recent contributions made by Michael Silk, David Andrews, Michael Atkinson and Dominic Malcolm on the past, present and future of the ‘sociology of sport’