Environmental exposure effects on composite materials for commercial aircraft

The effects of environmental exposure on composite materials are studied. The environments considered are representative of those experienced by commercial jet aircraft. Initial results have been compiled for the following material systems: T300/5208, T300/5209 and T300/934. Specimens were exposed on the exterior and interior of Boeing 737 airplanes of three airlines, and to continuous ground level exposure at four locations. In addition specimens were exposed in the laboratory to conditions such as: simulated ground-air-ground, weatherometer, and moisture. Residual strength results are presented for specimens exposed for up to two years at three ground level exposure locations and on airplanes from two airlines. Test results are also given for specimens exposed to the laboratory simulated environments. Test results indicate that short beam shear strength is sensitive to environmental exposure and dependent on the level of absorbed moisture

Damage tolerant composite wing panels for transport aircraft

Commercial aircraft advanced composite wing surface panels were tested for durability and damage tolerance. The wing of a fuel-efficient, 200-passenger airplane for 1990 delivery was sized using grahite-epoxy materials. The damage tolerance program was structured to allow a systematic progression from material evaluations to the optimized large panel verification tests. The program included coupon testing to evaluate toughened material systems, static and fatigue tests of compression coupons with varying amounts of impact damage, element tests of three-stiffener panels to evaluate upper wing panel design concepts, and the wing structure damage environment was studied. A series of technology demonstration tests of large compression panels is performed. A repair investigation is included in the final large panel test

Gap junctions and connexin hemichannels in the regulation of haemostasis and thrombosis

Platelets are involved in the maintenance of haemostasis but their inappropriate activation leads to thrombosis, a principal trigger for heart attack and ischemic stroke. Although platelets circulate in isolation, upon activation they accumulate or aggregate together to form a thrombus, where they function in a coordinated manner to prevent loss of blood and control wound repair. Recent reports indicate that the stability and functions of a thrombus are maintained through sustained, contact dependent signalling between platelets. Given the role of gap junctions in the coordination of tissue responses, it was hypothesized that gap junctions may be present within a thrombus and mediate intercellular communication between platelets. Therefore studies were performed to explore the presence and functions of connexins in platelets. In this brief review, the roles of hemichannels and gap junctions in the control of thrombosis and haemostasis and the future directions for this research will be discussed

The platelet-surface thiol isomerase enzyme ERp57 modulates platelet function

Background: Thiol isomerases are a family of endoplasmic reticulum enzymes which orchestrate redox-based modifications of protein disulphide bonds. Previous studies have identified important roles for the thiol isomerases PDI and ERp5 in the regulation of normal platelet function. Objectives: Recently, we demonstrated the presence of a further five thiol isomerases at the platelet surface. In this report we aim to report the role of one of these enzymes - ERp57 in the regulation of platelet function. Methods/Results: Using enzyme activity function blocking antibodies, we demonstrate a role for ERp57 in platelet aggregation, dense granule secretion, fibrinogen binding, calcium mobilisation and thrombus formation under arterial conditions. In addition to the effects of ERp57 on isolated platelets, we observe the presence of ERp57 in the developing thrombus in vivo. Furthermore the inhibition of ERp57 function was found to reduce laser-injury induced arterial thrombus formation in a murine model of thrombosis. Conclusions: These data suggest that ERp57 is important for normal platelet function and opens up the possibility that the regulation of platelet function by a range of cell surface thiol isomerases may represent a broad paradigm for the regulation of haemostasis and thrombosis

PPARγ agonists negatively regulate αIIbβ3 integrin outside-in signalling and platelet function through upregulation of protein kinase A activity

BACKGROUND: Agonists for the peroxisome proliferator activated receptor PPARγ, have been shown to have inhibitory effects on platelet activity following stimulation by GPVI and GPCR agonists. OBJECTIVES: Profound effects on thrombus formation led us to suspect a role for PPARγ agonists in the regulation of integrin αIIbβ3 mediated signalling. Both GPVI and GPCR signalling pathways lead to αIIbβ3 activation, and signalling through αIIbβ3 plays a critical role in platelet function and normal haemostasis. METHODS: The effects of PPARγ agonists on the regulation of αIIbβ3 outside-in signalling was determined by monitoring the ability of platelets to adhere and spread on fibrinogen and undergo clot retraction. Effects on signalling components downstream of αIIbβ3 activation were also determined following adhesion to fibrinogen by western blotting. RESULTS: Treatment of platelets with PPARγ agonists inhibited platelet adhesion and spreading on fibrinogen and diminished clot retraction. A reduction in phosphorylation of several components of αIIbβ3 signalling, including the integrin β3 subunit, Syk, PLCγ2, FAK and Akt was also observed as a result of reduced interaction of the integrin β3 subunit with Gα13. Studies of VASP phosphorylation revealed that this was a due to an increase in PKA activity following treatment with PPARγ receptor agonists. CONCLUSIONS: This study provides further evidence for anti-platelet actions of PPARγ agonists, identifies a negative regulatory role for PPARγ agonists in the control of integrin αIIbβ3 outside-in signalling, and provides a molecular basis by which the PPARγ agonists negatively regulate platelet activation and thrombus formation

Platelet endothelial cell adhesion molecule-1 regulates collagen-stimulated platelet function by modulating the association of phosphatidylinositol 3-kinase with Grb-2-associated binding protein-1 and linker for activation of T cells

Background: Platelet activation by collagen depends on signals transduced by the glycoprotein (GP)VI–Fc receptor (FcR)-chain collagen receptor complex, which involves recruitment of phosphatidylinositol 3-kinase (PI3K) to phosphorylated tyrosines in the linker for activation of T cells (LAT). An interaction between the p85 regulatory subunit of PI3K and the scaffolding molecule Grb-2-associated binding protein-1 (Gab1), which is regulated by binding of the Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2) to Gab1, has been shown in other cell types to sustain PI3K activity to elicit cellular responses. Platelet endothelial cell adhesion molecule-1 (PECAM-1) functions as a negative regulator of platelet reactivity and thrombosis, at least in part by inhibiting GPVI–FcR-chain signaling via recruitment of SHP-2 to phosphorylated immunoreceptor tyrosine-based inhibitory motifs in PECAM-1. Objective: To investigate the possibility that PECAM-1 regulates the formation of the Gab1–p85 signaling complexes, and the potential effect of such interactions on GPVI-mediated platelet activation in platelets. Methods: The ability of PECAM-1 signaling to modulate the LAT signalosome was investigated with immunoblotting assays on human platelets and knockout mouse platelets. Results: PECAM-1-associated SHP-2 in collagen-stimulated platelets binds to p85, which results in diminished levels of association with both Gab1 and LAT and reduced collagen-stimulated PI3K signaling. We therefore propose that PECAM-1-mediated inhibition of GPVI-dependent platelet responses result, at least in part, from recruitment of SHP-2–p85 complexes to tyrosine-phosphorylated PECAM-1, which diminishes the association of PI3K with activatory signaling molecules, such as Gab1 and LAT

A humanized monoclonal antibody that inhibits platelet-surface ERp72 reveals a role for ERp72 in thrombosis

Background: Within the endoplasmic reticulum, thiol isomerase enzymes modulate the formation and rearrangement of disulphide bonds in newly folded proteins entering the secretory pathway to ensure correct protein folding. In addition to their intracellular importance, thiol isomerases have been recently identified to be present on the surface of a number of cell types where they are important for cell function. Several thiol isomerases are known to be present on the resting platelet surface including PDI, ERp5 and ERp57 and levels are increased following platelet activation. Inhibition of the catalytic activity of these enzymes results in diminished platelet function and thrombosis. Aim: We previously determined that ERp72 is present at the resting platelet surface and levels increase upon platelet activation, however its functional role on the cell surface was unclear. We aimed to investigate the role of ERp72 in platelet function and its role in thrombosis. Methods: Using HuCAL technology, fully humanised Fc-null anti-ERp72 antibodies were generated. Eleven antibodies were screened for their ability to inhibit ERp72 activity and the most potent inhibitory antibody (anti-ERp72) selected for further testing in platelet functional assays. Results and conclusions: Anti-ERp72 inhibited platelet aggregation, granule secretion, calcium mobilisation and integrin activation revealing an important role for extracellular ERp72 in the regulation of platelet activation. Consistent with this, infusion of anti-ERp72 into mice protected against thrombosis

RXR ligands negatively regulate thrombosis and hemostasis

OBJECTIVE: Platelets have been found to express intracellular nuclear receptors including the Retinoid X receptors (RXRα and RXRβ). Treatment of platelets with ligands of RXR has been shown to inhibit platelet responses to ADP and thromboxane A2, however the effects on responses to other platelet agonists as well as the underlying mechanism has not been fully characterised. APPROACH AND RESULTS: The effect of 9-cis-retinoic acid (9-cis-RA), docosahexaenoic acid and synthetic ligand for RXR, methoprene acid on collagen receptor (GPVI) agonists and Thrombin stimulated platelet function; including aggregation, granule secretion, integrin activation, calcium mobilisation, integrin αIIbβ3 outside-in signalling and thrombus formation in vitro and in vivo were determined. Treatment of platelets with RXR ligands resulted in attenuation of platelet functional responses following stimulation by GPVI agonists and thrombin and inhibition of integrin αIIbβ3 outside-in signalling. Treatment with 9-cis-RA caused inhibition of thrombus formation in vitro and an impairment of thrombosis and haemostasis in vivo. Both RXR ligands stimulated protein kinase A activation, measured by VASP S157 phosphorylation, that was found to be dependent on both cAMP and NFκB activity. CONCLUSIONS: This study identifies a widespread, negative regulatory role for RXR in the regulation of platelet functional responses and thrombus formation and describes novel events that lead to the upregulation of PKA, a known negative regulator of many aspects of platelet function. This mechanism may offer a possible explanation for the cardioprotective effects described in vivo following treatment with RXR ligands

Variability in stream discharge and temperature: a preliminary assessment of the implications for juvenile and spawning Atlantic salmon

This study focuses on understanding the temporal variability in hydrological and thermal conditions in a small mountain stream and its potential implication for two life stages of Atlantic salmon (<I>Salmo salar</I>) &ndash; stream resident juveniles and returning adult spawners. Stream discharge and temperature in the Girnock Burn, NE Scotland, were characterised over ten hydrological years (1994/1995&ndash;2003/2004). Attention was focussed on assessing variations during particular ecologically 'sensitive' time periods when selected life-stages of salmon behaviour may be especially influenced by hydrological and thermal conditions. <P style='line-height: 20px;'> Empirical discharge data were used to derive hydraulic parameters to predict the Critical Displacement Velocity (CDV) of juvenile salmon. This is the velocity above which fish may no longer be able to hold station in the water column and thus can be used as an index of time periods where feeding behaviour might be constrained. In the Girnock Burn, strong inter- and intra-annual variability in hydrological and thermal conditions may have important implications for feeding opportunities for juvenile fish; both during important growth periods in late winter and early spring, and the emergence of fry in the late spring. Time periods when foraging behaviour of juvenile salmon may be constrained by hydraulic conditions were assessed as the percentage time when CDV for 0+ and 1+ fish were exceeded by mean daily stream velocities. Clear seasonal patterns of CDV were apparent, with higher summer values driven by higher stream temperatures and fish length. Inter-annual variability in the time when mean stream velocity exceeded CDV for 0+ fish ranged between 29.3% (1997/1998) and 44.7% (2000/2001). For 1+ fish mean stream velocity exceeded CDV between 14.5% (1997/1998) and 30.7% (2000/2001) of the time. <P style='line-height: 20px;'> The movement of adult spawners into the Girnock Burn in preparation for autumn spawning (late October to mid-November) exhibited a complex relationship with hydrological variability with marked inter-annual contrasts. In years when discharge in the period prior to spawning was low, fish movement was increasingly triggered by suboptimal flow increases as spawning time approached. In contrast, wet years with numerous events allowed a much more even distribution of fish entry. Elucidating links between discharge/temperature variability and foraging opportunities and upriver migration of adult Atlantic salmon have the potential to contribute to the improvement of conservation strategies in both regulated and unregulated rivers

Corporate governance compliance and disclosure in the banking sector: using data from Japan

Using regression model this study investigates which characteristics of a bank is associated with the extent of corporate governance disclosure in Japan. The findings suggest that on average 8 banks out of a sample of 46 disclose optimal corporate governance information. The regression model results reveal in general that non-executive directors, cross-ownership, capital adequacy ratio and type of auditors are associated with the extent of corporate governance disclosure. Of these four variables, non-executive directors have a more significant impact on the extent of disclosure contrary to total assets and audit firms of banks in the context of Japan. The findings of this paper are relevant for corporate regulators, professional associations and developers of corporate governance code when designing or updating corporate governance code