P2 purinergic receptor mRNA in rat and human sinoatrial node and other heart regions.

It is known that adenosine 5'-triphosphate (ATP) is a cotransmitter in the heart. Additionally, ATP is released from ischemic and hypoxic myocytes. Therefore, cardiac-derived sources of ATP have the potential to modify cardiac function. ATP activates P2X(1-7) and P2Y(1-14) receptors; however, the presence of P2X and P2Y receptor subtypes in strategic cardiac locations such as the sinoatrial node has not been determined. An understanding of P2X and P2Y receptor localization would facilitate investigation of purine receptor function in the heart. Therefore, we used quantitative PCR and in situ hybridization to measure the expression of mRNA of all known purine receptors in rat left ventricle, right atrium and sinoatrial node (SAN), and human right atrium and SAN. Expression of mRNA for all the cloned P2 receptors was observed in the ventricles, atria, and SAN of the rat. However, their abundance varied in different regions of the heart. P2X(5) was the most abundant of the P2X receptors in all three regions of the rat heart. In rat left ventricle, P2Y(1), P2Y(2), and P2Y(14) mRNA levels were highest for P2Y receptors, while in right atrium and SAN, P2Y(2) and P2Y(14) levels were highest, respectively. We extended these studies to investigate P2X(4) receptor mRNA in heart from rats with coronary artery ligation-induced heart failure. P2X(4) receptor mRNA was upregulated by 93% in SAN (P < 0.05), while a trend towards an increase was also observed in the right atrium and left ventricle (not significant). Thus, P2X(4)-mediated effects might be modulated in heart failure. mRNA for P2X(4-7) and P2Y(1,2,4,6,12-14), but not P2X(2,3) and P2Y(11), was detected in human right atrium and SAN. In addition, mRNA for P2X(1) was detected in human SAN but not human right atrium. In human right atrium and SAN, P2X(4) and P2X(7) mRNA was the highest for P2X receptors. P2Y(1) and P2Y(2) mRNA were the most abundant for P2Y receptors in the right atrium, while P2Y(1), P2Y(2), and P2Y(14) were the most abundant P2Y receptor subtypes in human SAN. This study shows a widespread distribution of P2 receptor mRNA in rat heart tissues but a more restricted presence and distribution of P2 receptor mRNA in human atrium and SAN. This study provides further direction for the elucidation of P2 receptor modulation of heart rate and contractility.

Molecular architecture of the human sinus node: insights into the function of the cardiac pacemaker.

BACKGROUND: Although we know much about the molecular makeup of the sinus node (SN) in small mammals, little is known about it in humans. The aims of the present study were to investigate the expression of ion channels in the human SN and to use the data to predict electrical activity. METHODS AND RESULTS: Quantitative polymerase chain reaction, in situ hybridization, and immunofluorescence were used to analyze 6 human tissue samples. Messenger RNA (mRNA) for 120 ion channels (and some related proteins) was measured in the SN, a novel paranodal area, and the right atrium (RA). The results showed, for example, that in the SN compared with the RA, there was a lower expression of Na(v)1.5, K(v)4.3, K(v)1.5, ERG, K(ir)2.1, K(ir)6.2, RyR2, SERCA2a, Cx40, and Cx43 mRNAs but a higher expression of Ca(v)1.3, Ca(v)3.1, HCN1, and HCN4 mRNAs. The expression pattern of many ion channels in the paranodal area was intermediate between that of the SN and RA; however, compared with the SN and RA, the paranodal area showed greater expression of K(v)4.2, K(ir)6.1, TASK1, SK2, and MiRP2. Expression of ion channel proteins was in agreement with expression of the corresponding mRNAs. The levels of mRNA in the SN, as a percentage of those in the RA, were used to estimate conductances of key ionic currents as a percentage of those in a mathematical model of human atrial action potential. The resulting SN model successfully produced pacemaking. CONCLUSIONS: Ion channels show a complex and heterogeneous pattern of expression in the SN, paranodal area, and RA in humans, and the expression pattern is appropriate to explain pacemaking.

(-)-CGP12177 increases contractile force through beta1l-adrenoceptors but not through beta3-adrenoceptors in human right atrial myocardium

(-)-CGP12177 is a non-conventional partial agonist that causes modest and transient increases of contractile force in human atrial trabeculae (Kaumann and Molenaar, 2008). These effects are markedly increased and maintained by inhibition of phosphodiesterase PDE3. As verified with recombinant receptors, the cardiostimulant effect of (-)-CGP12177 is mediated through a site at the beta1-adrenoceptor with lower affinity (beta1LAR) compared to the site through which (-)-CGP12177 antagonizes the effects of catecholamines (beta1HAR). However, in a recent report it was proposed that the positive inotropic effects of CGP12177 are mediated through beta3-adrenoceptors (Skeberdis et al 2008). We therefore investigated whether the effects of (-)-CGP12177 on human atrial trabeculae are antagonized by the beta3-adrenoceptor-selective antagonist L-748,337 (1 microM). (-)-CGP12177 (200 nM) caused a stable increase in force which was significantly reduced by the addition of (-)-bupranolol (1 microM), P = 0.002, (basal 4.45 ± 0.78 mN, IBMX (PDE inhibitor) 5.47 ± 1.01 mN, (-)-CGP12177 9.34 ± 1.33 mN, (-)-bupranolol 5.79 ± 1.08 mN, n = 6) but not affected by the addition of L-748,337 (1 microM), P = 0.12, (basal 4.48 ± 1.32 mN, IBMX 7.15 ± 2.28 mN, (-)-CGP12177 12.51 ± 3.71 mN, L-748,337 10.90 ± 3.49 mN, n = 6). Cumulative concentration-effect curves for (-)-CGP12177 were not shifted to the right by L-748,337 (1 microM). The –logEC50M values of (-)-CGP12177 in the absence and presence of L-748,337 were 7.21±0.09 and 7.41±0.13, respectively (data from 25 trabeculae from 8 patients, P=0.2) The positive inotropic effects of (-)-CGP12177 (IBMX present) were not antagonized by L-748,337 but were blunted by (-)-bupranolol (1 microM). The results rule out an involvement of beta3-adrenoceptors in the positive inotropic effects (-)-CGP12177 in human right atrial myocardium and are consistent with mediation through beta1LAR. Kaumann A and Molenaar P (2008) Pharmacol Ther 118, 303-336 Skeberdis VA et al (2008) J Clin Invest, 118, 3219-3227

Mathematical models for describing the shape of the in vitro unstretched human crystalline lens

We developed orthogonal least-squares techniques for fitting crystalline lens shapes, and used the bootstrap method to determine uncertainties associated with the estimated vertex radii of curvature and asphericities of five different models. Three existing models were investigated including one that uses two separate conics for the anterior and posterior surfaces, and two whole lens models based on a modulated hyperbolic cosine function and on a generalized conic function. Two new models were proposed including one that uses two interdependent conics and a polynomial based whole lens model. The models were used to describe the in vitro shape for a data set of twenty human lenses with ages 7–82 years. The two-conic-surface model (7 mm zone diameter) and the interdependent surfaces model had significantly lower merit functions than the other three models for the data set, indicating that most likely they can describe human lens shape over a wide age range better than the other models (although with the two-conic-surfaces model being unable to describe the lens equatorial region). Considerable differences were found between some models regarding estimates of radii of curvature and surface asphericities. The hyperbolic cosine model and the new polynomial based whole lens model had the best precision in determining the radii of curvature and surface asphericities across the five considered models. Most models found significant increase in anterior, but not posterior, radius of curvature with age. Most models found a wide scatter of asphericities, but with the asphericities usually being positive and not significantly related to age. As the interdependent surfaces model had lower merit function than three whole lens models, there is further scope to develop an accurate model of the complete shape of human lenses of all ages. The results highlight the continued difficulty in selecting an appropriate model for the crystalline lens shape.

How current pedagogy methods in games teaching in the UK, Australia and the US have been shaped by historical, socio cultural, environmental and political constraints

Crucial to enhancing the status and quality of games teaching in schools is a developed understanding of the teaching strategies adopted by practitioners. In this paper, we will demonstrate that contemporary games‟ teaching is a product of individual, task and environmental constraints (Newell, 1986). More specifically, we will show that current pedagogy in the U.K., Australia and the United States is strongly influenced by historical, socio-cultural environmental and political constraints. In summary, we will aim to answer the question „why do teachers teach games the way they do.‟ In answering this question, we conclude that teacher educators, who are trying to influence pedagogical practice, must understand these potential constraints and provide appropriate pre-service experiences to give future physical education teachers the knowledge, confidence and ability to adopt a range of teaching styles when they become fully fledged teachers. Essential to this process is the need to enable future practitioners to base their pedagogical practice on a sound understanding of contemporary learning theories of skill acquisition.

“I smile when I’m angry!” an examination of emotional dissonance among police officers

With the growth of service industry occupations, managing emotions at work has increased as a topic of interest among scholars and practitioners in organisational behaviour and human resource management(Grandey, 2000). Emotional dissonance occurs when there is discrepancy between organisational sanctioned emotions and actual emotions of employees(Zapf, Vogt, Seifert, Mertini, & Isic, 1999). This discrepancy can be associated with significant levels of psychological ill-health (Zapf, Seifert, Schmutte, Mertini, & Holz, 2001). Policing is consistently ranked among the top five stressful/high-risk occupations (e.g. Coman, Evans, Stanley, & Burrows, 1991). Police officers act as the front-line contact when dealing directly with community members; they are expected to be social workers, teachers, role models, and counsellors. Operational police officers are often required to suppress their actual emotions during their work, in order to perform their job to formally designated procedures and standards.

Conceptualisation and facilitation of SOA governance

As organisations strive to improve their capabilities in the areas of Service Management and Service-oriented Architectures (SOA), SOA Governance is becoming an increasingly important success factor. However, the concept of SOA Governance is complex and not well-understood, and the adoption of an adequate SOA Governance approach in an organisation can be difficult. Tools that support SOA Governance mostly have a technical bias and rarely address organisational aspects. In this paper, we contribute to the field by specifying a conceptual meta model for SOA Governance that integrates the structure of major IT and SOA Governance frameworks into one consolidated view. By presenting this conceptualisation and a corresponding prototypical implementation of a tool that supports SOA Governance maturity assessment, reference framework exploration and company-specific tailoring of SOA Governance, we provide insights into the first step of a Design Science research project, i.e. the development of an important IT artefact.

Empirical evaluation of a service analysis and design methodology

Service-orientation has gained widespread acceptance and is increasingly being employed as a paradigm for structuring both business and IT architectures. An earlier study of extant service analysis and design methodologies discovered a need for holistic approaches that equally account for both business and software services, which motivated the design of a new, consolidated service analysis and design methodology. A challenge in design-oriented research is to evaluate the utility of the newly created artefacts (here: the methodology), as they are often intended to become part of complex socio-technical systems. Therefore, after presenting a brief overview of the consolidated methodology, the paper discusses possible approaches for the “evaluate” phase of this design-science research process and presents the results of an empirical evaluation conducted in an Action Research study at one of Australia’s largest financial services providers.

Creating an asset registry for railway electrical traction equipment with open standards

An asset registry arguably forms the core system that needs to be in place before other systems can operate or interoperate. Most systems have rudimentary asset registry functionality that store assets, relationships, or characteristics, and this leads to different asset management systems storing similar sets of data in multiple locations in an organisation. As organisations have been slowly moving their information architecture toward a service-oriented architecture, they have also been consolidating their multiple data stores, to form a “single point of truth”. As part of a strategy to integrate several asset management systems in an Australian railway organisation, a case study for developing a consolidated asset registry was conducted. A decision was made to use the MIMOSA OSA-EAI CRIS data model as well as the OSA-EAI Reference Data in building the platform due to the standard’s relative maturity and completeness. A pilot study of electrical traction equipment was selected, and the data sources feeding into the asset registry were primarily diagrammatic based. This paper presents the pitfalls encountered, approaches taken, and lessons learned during the development of the asset registry.

A Theoretical and Analytical Synthesis of Autopoiesis and Sociolinguistics for the Study of Organisational Communication

The purpose of this paper is threefold. First, we propose a systemic view of communication based in autopoiesis, the theory of living systems formulated by Maturana & Varela (1980, 1987). Second, we show the links between the underpinning assumptions of autopoiesis and the sociolinguistic approaches of Halliday (1978), Fairclough (1989, 1992, 1995) and Lemke (1995, 1994). Third, we propose a theoretical and analytical synthesis of autopoiesis and sociolinguistics for the study of organisational communication. In proposing a systemic theory for organisational communication, we argue that traditional approaches to communication, information, and the role of language in human organisations have, to date, been placed in teleological constraints because of an inverted focus on organisational purpose-the generally perceived role of an organisation within society-that obscure, rather than clarify, the role of language within human organisations. We argue that human social systems are, according to the criteria defined by Maturana and Varela, third-order, non-organismic living systems constituted in language. We further propose that sociolinguistics provides an appropriate analytical tool which is both compatible and penetrating in synthesis with the systemic framework provided by an autopoietic understanding of social organisation.

Towards a service portfolio management framework

Services in the form of business services or IT-enabled (Web) Services have become a corporate asset of high interest in striving towards the agile organisation. However, while the design and management of a single service is widely studied and well understood, little is known about how a set of services can be managed. This gap motivated this paper, in which we explore the concept of Service Portfolio Management. In particular, we propose a Service Portfolio Management Framework that explicates service portfolio goals, tasks, governance issues, methods and enablers. The Service Portfolio Management Framework is based upon a thorough analysis and consolidation of existing, well-established portfolio management approaches. From an academic point of view, the Service Portfolio Management Framework can be positioned as an extension of portfolio management conceptualisations in the area of service management. Based on the framework, possible directions for future research are provided. From a practical point of view, the Service Portfolio Management Framework provides an organisation with a novel approach to managing its emerging service portfolios.

Service aggregators in business networks

This position paper examines the development of a dedicated service aggregator role in business networks. We predict that these intermediaries will soon emerge in service ecosystems and add value through the application of dedicated domain knowledge in the process of creating new, innovative services or service bundles based on the aggregation, composition, integration or orchestration of existing services procured from different service providers in the service ecosystem. We discuss general foundations of service aggregators and present Fourth-Party Logistics Providers as a real-world example of emerging business service aggregators. We also point out a demand for future research, e.g. into governance models, risk management tools, service portfolio management approaches and service bundling techniques, to be able to better understand core determinants of competitiveness and success of service aggregators.

It's time to be more serious about activating youngsters : lessons for childhood obesity

The epidemic of obesity is impacting an increasing proportion of children, adolescents and adults with a common feature being low levels of physical activity (PA). Despite having more knowledge than ever before about the benefits of PA for health and the growth and development of youngsters, we are only paying lip-service to the development of motor skills in children. Fun, enjoyment and basic skills are the essential underpinnings of meaningful participation in PA. A concurrent problem is the reported increase in sitting time with the most common sedentary behaviors being TV viewing and other screen-based games. Limitations of time have contributed to a displacement of active behaviors with inactive pursuits, which has contributed to reductions in activity energy expenditure. To redress the energy imbalance in overweight and obese children, we urgently need out-of-the-box multisectoral solutions. There is little to be gained from a shame and blame mentality where individuals, their parents, teachers and other groups are singled out as causes of the problem. Such an approach does little more than shift attention from the main game of prevention and management of the condition, which requires a concerted, whole-of-government approach (in each country). The failure to support and encourage all young people to participate in regular PA will increase the chance that our children will live shorter and less healthy lives than their parents. In short, we need novel environmental approaches to foster a systematic increase in PA. This paper provides examples of opportunities and challenges for PA strategies to prevent obesity with a particular emphasis on the school and home settings.

L'étendue internationale des nouvelles firmes de hautes technologies: le rôle du capital humain et de l'intention stratégique des fondateurs

De récentes recherches ont mis l’accent sur l’importance pour les nouvelles entreprises internationales de l’existence de ressources et de compétences spécifiques. La présente recherche, qui s’inscrit dans ce courant, montre en particulier l’importance du capital humain acquis par les entrepreneurs sur base de leur expérience internationale passée. Mais nous montrons en même temps que ces organisations sont soutenues par une intention délibérée d’internationalisation dès l’origine. Notre recherche empirique est basée sur l’analyse d’un échantillon de 466 nouvelles entreprises de hautes technologies anglaises et allemandes. Nous montrons que ce capital humain est un actif qui facilite la pénétration rapide des marchés étrangers, et plus encore quand l’entreprise nouvelle est accompagnée d’une intention stratégique délibérée d’internationalisation. Des conclusions similaires peuvent être étendues au niveau des ressources que l’entrepreneur consacre à la start-up : plus ces ressources sont importantes, plus le processus d’internationalisation tend à se faire à grande échelle ; et là aussi, l’influence de ces ressources est augmenté par l’intention stratégique d’internationalisation. Dans le cadre des études empiriques sur les born-globals (entreprises qui démarrent sur un marché globalisé), cette recherche fournit une des premières études empiriques reliant l’influence des conditions initiales de création aux probabilités de croissance internationale rapide.