The evolution of the coastal dunes in the western Belgian coastal plain

Two main dune systems exist in the area west of Nieuwpoort: the Younger Dunes along the present coastline, and the Older Dunes isolated within the coastal plain near the French border and also running parallel to the coast. Both systems have recently been subjected to geological and palynological investigations. The Older dune system is believed to be older than 4300 B. P. The Younger Dune-area appears to have a complex history. A stretch of older dunesediments (however not as old as these of the Older dunesystem) was found underneath the Younger Dunes, also near the French border. The age of these sediments is ranging from 2800 B. P. to 900 B. P. Furthermore two subphases of Younger Dune-formation are distinguished. Prior to the 14th century A. D. the dune area consisted of a relatively level plain. The completion of this plain marked the end of an active eolian phase. This phase started in the 11th century A. D., probably as the result of an increased incidence of storm-floods at that time (the Dunkerque-3 transgression). From the end of the 14th century on, large parabolic dunes partially buried the former landsurface. Some of them are still moving nowadays. Here the evolution of the Younger Dunearea near De Panneis described in more detail including aspects of the vegetational history of the dune area and adjacent coastal plain. Some attention is also drawn on the position of former coastlines

Parmodulins Inhibit Thrombus Formation Without Inducing Endothelial Injury Caused by Vorapaxar

Protease-activated receptor-1 (PAR1) couples the coagulation cascade to platelet activation during myocardial infarction and to endothelial inflammation during sepsis. This receptor demonstrates marked signaling bias. Its activation by thrombin stimulates prothrombotic and proinflammatory signaling, whereas its activation by activated protein C (APC) stimulates cytoprotective and antiinflammatory signaling. A challenge in developing PAR1-targeted therapies is to inhibit detrimental signaling while sparing beneficial pathways. We now characterize a novel class of structurally unrelated small-molecule PAR1 antagonists, termed parmodulins, and compare the activity of these compounds to previously characterized compounds that act at the PAR1 ligand–binding site. We find that parmodulins target the cytoplasmic face of PAR1 without modifying the ligand-binding site, blocking signaling through Gαq but not Gα13 in vitro and thrombus formation in vivo. In endothelium, parmodulins inhibit prothrombotic and proinflammatory signaling without blocking APC-mediated pathways or inducing endothelial injury. In contrast, orthosteric PAR1 antagonists such as vorapaxar inhibit all signaling downstream of PAR1. Furthermore, exposure of endothelial cells to nanomolar concentrations of vorapaxar induces endothelial cell barrier dysfunction and apoptosis. These studies demonstrate how functionally selective antagonism can be achieved by targeting the cytoplasmic face of a G-protein–coupled receptor to selectively block pathologic signaling while preserving cytoprotective pathways

Cyclists in shared bus lanes: could there be unrecognised impacts on bus journey times?

This paper contributes to debates around improving the modelling of cycles, through an exploratory case study of bus–cycle interactions in London. This case study examines undocumented delays to buses caused by high volumes of cyclists in bus lanes. It has generally been assumed that cyclists do not noticeably delay buses in shared lanes. However, in many contexts where cyclists routinely share bus lanes, cyclist numbers have historically been low. In some such places, bus lanes are now seeing very high volumes of cyclists, far above those previously studied. This may have implications for bus – and cycle – journey times, but traditionally traffic modelling has not represented the effects of such interactions well. With some manipulation of parameters taken from models of other cities, the model described here demonstrates that cycles can cause significant delays to buses in shared lanes, at high cycling volumes. These delays are likely to become substantially larger if London's cycling demographic becomes more diverse, because cyclist speeds will decline. Hence bus journey time benefits may derive from separating cycles from buses, where cycle flows are high. The project also suggests that microsimulation modelling software, as typically used, remains problematic for representing cyclists

Identification of safety effects of infrastructure related measures, Deliverable 5.2 of the H2020 project SafetyCube

Identification of safety effects of infrastructure related measures, Deliverable 5.2 of the H2020 project SafetyCub

Inventory of assessed infrastructure risk factors and measures, Deliverable 5.4 of the H2020 project SafetyCube

Inventory of assessed infrastructure risk factors and measures, Deliverable 5.4 of the H2020 project SafetyCub

Primary Human Lung Alveolus-on-a-chip Model of Intravascular Thrombosis for Assessment of Therapeutics

Pulmonary thrombosis is a significant cause of patient mortality; however, there are no effective in vitro models of thrombi formation in human lung microvessels that could also assess therapeutics and toxicology of antithrombotic drugs. Here, we show that a microfluidic lung alveolus-on-a-chip lined by human primary alveolar epithelium interfaced with endothelium and cultured under flowing whole blood can be used to perform quantitative analysis of organ-level contributions to inflammation-induced thrombosis. This microfluidic chip recapitulates in vivo responses, including platelet-endothelial dynamics and revealed that lipopolysaccharide (LPS) endotoxin indirectly stimulates intravascular thrombosis by activating the alveolar epithelium, rather than acting directly on endothelium. This model is also used to analyze inhibition of endothelial activation and thrombosis due to a protease activated receptor-1 (PAR-1) antagonist, demonstrating its ability to dissect complex responses and identify antithrombotic therapeutics. Thus, this methodology offers a new approach to study human pathophysiology of pulmonary thrombosis and advance drug development