Gene expression profiling of human hibernating myocardium: Increased expression of B-type natriuretic peptide and proenkephalin in hypocontractile vs normally-contracting regions of the heart

A greater understanding of the molecular basis of hibernating myocardium may assist in identifying those patients who would most benefit from revascularization. Paired heart biopsies were taken from hypocontractile and normally-contracting myocardium (identified by cardiovascular magnetic resonance) from 6 patients with chronic stable angina scheduled for bypass grafting. Gene expression profiles of hypocontractile and normally-contracting samples were compared using Affymetrix microarrays. The data for patients with confirmed hibernating myocardium were analysed separately and a different, though overlapping, set (up to 380) of genes was identified which may constitute a molecular fingerprint for hibernating myocardium. The expression of B-type natriuretic peptide (BNP) was increased in hypocontractile relative to normally-contracting myocardium. The expression of BNP correlated most closely with the expression of proenkephalin and follistatin 3, which may constitute additional heart failure markers. Our data illustrate differential gene expression in hypocontractile and/hibernating myocardium relative to normally-contracting myocardium within individual human hearts. Changes in expression of these genes, including increased relative expression of natriuretic and other factors, may constitute a molecular signature for hypocontractile and/or hibernating myocardium.

Communities of practice in UK large contracting firms: contrasting application and non-utilized merits

The idea of a community of practice (CoP) has been offered as the engine to unlock the potential of organizational resources, mainly knowledge and people, to achieve the strategic goal of sustained competitiveness. The relevance and application of CoPs in large UK contracting companies was investigated using two case studies. Contrasting variations in the understanding of the concept between the two contracting companies were observed. While a CoP was applied in one company with strategic intent, the concept was not fully understood in the other. In one company, only a third of CoP members surveyed agreed that CoPs were a vehicle for driving best practice and innovation throughout the business; this compared with more than 60% in agreement in the other contracting firm. The higher agreement and satisfaction of CoP members in the latter case study was the result of the management's understanding and commitment. CoPs require time and organizational support to mature. The strategic inception and management support of CoP application is vital for their maturation and progress. Although the construction industry change discourses portray CoPs as fostering an environment of trust, and hence serving as innovation and competiveness enablers, their potential contribution to contracting firms does not provide a compelling case and hence merits further research studies.

Performance-based contracting in the construction sector

Construction procurement is complex and there is a very wide range of options available to procurers. Inappropriate choices about how to procure may limit practical opportunities for innovation. In particular, traditional approaches to construction procurement set up many obstacles for technology suppliers to provide innovative solutions. This is because they are often employed as sub-contractors simply to provide and install equipment to specifications developed before the point at which they become involved in a project. A research team at the University of Reading has developed a procurement framework that comprehensively defines the various options open to procurers in a more fine-grained way than has been known in the past. This enables informed decisions that can establish tailor-made procurement approaches that take into account the needs of specific clients. It enables risk and reward structures to be aligned so that contracts and payment mechanisms are aligned precisely with what a client seeks to achieve. This is not a “one-size-fits-all” approach. Rather, it is an approach that enables informed decisions about how to organize individual procurements that are appropriate to particular circumstances, acknowledging that they differ for each client and for each procurement exercise. Within this context, performance-based contracting (PBC) is explored in terms of the different ways in which technology suppliers within constructed facilities might be encouraged and rewarded for the kinds of innovation sought by the ultimate clients. Examples from various industry sectors are presented, from public sector and from private sector, with a commentary about what they sought to achieve and the extent to which they were successful. The lessons from these examples are presented in terms of feasibility in relation to financial issues, governance, economics, strategic issues, contractual issues and cash flow issues for clients and for contractors. Further background documents and more detailed readings are provided in an appendix for those who wish to find out more.

Nexus between contracting and construction professional service businesses: empirical evidence from international market

he construction market around the world has witnessed the growing eminence of construction professional services (CPSs), such as urban planning, architecture, engineering, and consultancy, while the traditional contracting sector remains strong. Nowadays, it is not uncommon to see a design firm taking over the work of a traditional main contractor, or vice versa, of overseeing the delivery of a project. Although the two sectors of contracting and CPS share the same purpose of materializing the built environment, they are as different as they are interrelated. Much has been mentioned about the nexus between the two but little has been done to articulate it using empirical evidence. This study examined the nexus between contracting and CPS businesses by offering and testing lead-lag effects between the two sectors in the international market. A longitudinal panel data composed of 23 top international contractors and CPS firms was adopted. Surprisingly, results of the panel data analyses show that CPS business does not have a significant positive causal effect on contracting as a downstream business, and vice versa. CPS and contracting subsidiaries, although within the same company, do not necessarily form a consortium to undertake the same project; rather, they often collaborate with other CPS or contracting counterparts to undertake projects. This paper provides valuable insights into the sophisticated nexus between contracting and CPS in the international construction market. It will support business executives’ rational decision making for selecting proper contracting or CPS allies, or a proper mergers and acquisitions strategy in the international market. The paper also provides a fresh perspective through which researchers can better investigate the diversification strategies adopted by international contracting and CPS firms.

Ion flows and heating at a contracting polar-cap boundary: GISMOS observations indicating viscous-like interaction on the flanks of the magnetotail

This paper complements that in this issue by Clauer et al. concerning the international GISMOS campaign of 3–5 June 1987. From a detailed study of the EISCAT data, the polar-cap boundary, as defined by an almost shear east-west convection reversal, is found to contract across the EISCAT field of view between 04 and 07 MLT. An annulus of enhanced ion temperature and non-thermal plasma is observed immediately equatorward of the contracting boundary due to the lag in the response of the neutral-wind pattern to the change in ion flows. The ion flow inside the polar cap and at the boundary is shown to be relatively smooth, compared with that in the auroral oval, at 15-second resolution. The flow at the boundary is directed poleward, with velocities which exceed that of the boundary itself. The effect of velocity shears on the beamswinging technique used to derive the ion flows has been analysed in detail and it is found that spurious flows across a moving boundary can be generated. However, these are much smaller than the observed flows into the polar cap and cannot explain the 7 kV potential difference across the observed segment of the cap boundary between 04:30–06:30 UT. The ion temperature enhancements at the two observing azimuths is used to define the boundary orientation. The results are consistent with recent observations of slow anti-sunward flow of closed field lines on the flanks of the geomagnetic tail, which appears to be generated by some form of “viscous” coupling to the magnetosheath plasma.

Ion flows and heating at a contracting polar-cap boundary

Data recorded by the POLAR experiment run on the EISCAT radar during the international GISMOS campaign of 3–5 June 1987 are studied in detail. The polar-cap boundary, as denned by an almost shear East-West convection reversal, was observed to jump southward across the EISCAT field of view in two steps at 02:00 and 03:00 Magnetic Local Time and subsequently to contract back between 04:00 and 07:00 M.L.T. An annulus of enhanced ion temperature and non-thermal plasma was observed immediately equatorward of the contracting boundary due to the lag in the response of the neutral-wind pattern to the change in ion flows. The ion flow at the boundary is shown to be relatively smooth at 15 s resolution and directed northward, with velocities which exceed that of the boundary itself. The effect of velocity shears on the beamswinging technique used to derive the ion flows is analyzed in detail and it is shown that, for certain orientations of the cap boundary, spurious flows into the cap can be generated. However, these are much smaller than the observed flows into the polar cap and cannot explain the potential difference across the observed segment of the cap boundary (extending over 2 h of M.L.T.) which is roughly 7 kV. Similarly, an observed slowing of the zonal flow near the boundary cannot be explained as an error introduced by the use of the beamswinging technique. The results could be interpreted as being due to reconnection occurring on the dawn flank of the magnetopause (mapping to the polar cap at 04:30 06:30 M.L.T.). However, they are more consistent with recent observations of slow anti-sunward flow of closed field lines on the flanks of the geomagnetic tail, which appears to be generated by some form of “viscous” coupling to the magnetosheath plasma.

Regulation of glycolysis and expression of glucose metabolism-related genes by reactive oxygen species in contracting skeletal muscle cells

Contractile activity induces a marked increase in glycolytic activity and gene expression of enzymes and transporters involved in glucose metabolism in skeletal muscle. Muscle contraction also increases the production of reactive oxygen species (ROS). In this study, the effects of treatment with N-acetylcysteine (NAC), a potent antioxidant compound, on contraction-stimulated glycolysis were investigated in electrically stimulated primary rat skeletal muscle cells. The following parameters were measured: 2-[(3)H]deoxyglucose (2-DG) uptake; activities of hexokinase, phosphofructokinase (PFK), and glucose-6-phosphate dehydrogenase (G6PDH); lactate production; and expression of the glucose transporter 4 (GLUT4), hexokinase II (HKII), and PFK genes after one bout of electrical stimulation in primary rat myotubes. NAC treatment decreased ROS signal by 49% in resting muscle cells and abolished the muscle contraction-induced increase in ROS levels. In resting cells, NAC decreased mRNA and protein contents of GLUT4, mRNA content and activity of PFK, and lactate production. NAC treatment suppressed the contraction-mediated increase in 2-DG uptake; lactate production; hexokinase, PFK, and G6PDH activities; and gene expression of GLUT4. HKII, and PFK. Similar to muscle contraction, exogenous H(2)O(2) (500 nM) administration increased 2-DG uptake; lactate production; hexokinase, PFK, and G6PDH activities; and gene expression of GLUT4. HKII, and PFK. These findings support the proposition that ROS endogenously produced play an important role in the changes in glycolytic activity and gene expression of GLUT4, HKII, and PFK induced by contraction in skeletal muscle cells. (C) 2010 Elsevier Inc. All rights reserved.

Electronic contracting in aircraft aftercare: A case study

Distributed systems comprised of autonomous self-interested entities require some sort of control mechanism to ensure the predictability of the interactions that drive them. This is certainly true in the aerospace domain, where manufacturers, suppliers and operators must coordinate their activities to maximise safety and profit, for example. To address this need, the notion of norms has been proposed which, when incorporated into formal electronic documents, allow for the specification and deployment of contract-driven systems. In this context, we describe the CONTRACT framework and architecture for exactly this purpose, and describe a concrete instantiation of this architecture as a prototype system applied to an aerospace aftercare scenario.

Towards a Formalisation of Electronic Contracting Environments

The IST-CONTRACT project is in the process of creating an electronic contracting language. One of the goals of this language is that it has formal underpinnings, and formalizations at a number of levels have been created. One of the lowest levels, upon which the other levels are built is the normative level. At this level, we identify how contract clauses (modeled as norms) may evolve over time. In this paper, we describe this formalization, and show how we may associate various states with a norm throughout its lifecycle. We also show how more complex evaluations may be carried out over a norm, and conclude with an example showing the application of the framework over a contract and its associated norms.

Contracting with repeated moral hazard and private evaluations

A repeated moral hazard setting in which the Principal privately observes the Agent’s output is studied. It is shown that there is no loss from restricting the analysis to contracts in which the Agent is supposed to exert effort every period, receives a constant efficiency wage and no feedback until he is fired. The optimal contract for a finite horizon is characterized, and shown to require burning of resources. These are only burnt after the worst possible realization sequence and the amount is independent of both the length of the horizon and the discount factor (δ). For the infinite horizon case a family of fixed interval review contracts is characterized and shown to achieve first best as δ → 1. The optimal contract when δ << 1 is partially characterized. Incentives are optimally provided with a combination of efficiency wages and the threat of termination, which will exhibit memory over the whole history of realizations. Finally, Tournaments are shown to provide an alternative solution to the problem.