Not too late to learn from the Sydney Olympics experience: Opportunities offered by multimodality in current transport policy

Sydney is the Australian city that attracts the most global attention with its beautiful harbour, its iconic attractions of the harbour bridge and opera house. Tourists may leave Sydney with a complimentary view of Sydney’s public transport but the Sydneysider’s assessments of Sydney’s public transport system is often much harsher, especially if the journey requires travel beyond the immediate centre of the city. In Sydney, the reference point of what constitutes a functioning transport system is informed by the success of the transport system in meeting the needs of the participants and observers at the Olympics in 2000. Changes to the transport system to provide more multimodal travel were supported by Sydneysiders and visitors and this paper analyses why this success has not been translated into everyday public transport. The analysis of the paper allows the opportunities which still exist for Sydney to benefit from the success of the Olympics to be highlighted. These opportunities involve strengthening the opportunities for, and acceptance of, multimodal trips by the travelling public

Inhibition of MAPK-Erk pathway in vivo attenuates aortic valve disease processes in Emilin1-deficient mouse model

Aortic valve disease (AVD) is a common condition with a progressive natural history, and presently, there are no pharmacologic treatment strategies. Elastic fiber fragmentation (EFF) is a hallmark of AVD, and increasing evidence implicates developmental elastic fiber assembly defects. Emilin1 is a glycoprotein necessary for elastic fiber assembly that is present in both developing and mature human and mouse aortic valves. The Emilin1‐deficient mouse (Emilin1 (−/−)) is a model of latent AVD, characterized by activated TGFβ/MEK/p‐Erk signaling and upregulated elastase activity. Emilin1 (−/−) aortic valves demonstrate early EFF and aberrant angiogenesis followed by late neovascularization and fibrosis. The objective of this study was to test the effectiveness of three different targeted therapies. Aged (12–14 months) Emilin1 (−/−) mice were treated with refametinib (RDEA‐119, MEK1/2 inhibitor), doxycycline (elastase inhibitor), or G6‐31 (anti‐VEGF‐A mouse antibody) for 4 weeks. Refametinib‐ and doxycycline‐treated Emilin1 (−/−) mice markedly reduced MEK/p‐Erk activation in valve tissue. Furthermore, both refametinib and doxycycline attenuated elastolytic cathepsin K, L, MMP‐2, and MMP‐9 activation, and abrogated macrophage and neutrophil infiltration in Emilin1 (−/−) aortic valves. RNAseq analysis was performed in aortic valve tissue from adult (4 months) and aged (14 months) Emilin1 (−/−) and age‐matched wild‐type control mice, and demonstrated upregulation of genes associated with MAPK/MEK/p‐Erk signaling and elastases at the adult stage and inflammatory pathways at the aged stage controlling for age. These results suggest that Erk1/2 signaling is an important modulator of early elastase activation, and pharmacological inhibition using refametinib may be a promising treatment to halt AVD progressio

Metastable Pores at the Onset of Constant-Current Electroporation

Single metastable nanopores, appearing before the actual electroporation under constant-current conditions, are used to characterize the onset of electroporation. Unlike the long-lived electropores typical of the current controlled methods, these pores survive for milliseconds and observing them is possible due to slow development of electroporation, provided by the gradual accumulation of charges on a planar membrane. Analysis of the metastable pore appearance frequency and lifetime shows the first introductory stage of electroporation. During this stage two species of metastable pores open, the majority of very low conductance that seem not fully developed as hydrophilic electropores. The experiments reveal that voltage value defines the electroporation onset while the current value affects the rate of electroporation. Membrane capacitance has a great impact on the membrane susceptibility to the pore appearance, related to its thickness and integrity. Pores of nonperfect membranes appear more easily, but they do not live any longer than others

Creating a model of diseased artery damage and failure from healthy porcine aorta

Large quantities of diseased tissue are required in the research and development of new generations of medical devices, for example for use in physical testing. However, these are difficult to obtain. In contrast, porcine arteries are readily available as they are regarded as waste. Therefore, reliable means of creating from porcine tissue physical models of diseased human tissue that emulate well the associated mechanical changes would be valuable. To this end, we studied the effect on mechanical response of treating porcine thoracic aorta with collagenase, elastase and glutaraldehyde. The alterations in mechanical and failure properties were assessed via uniaxial tension testing. A constitutive model composed of the Gasser-Ogden-Holzapfel model, for elastic response, and a continuum damage model, for the failure, was also employed to provide a further basis for comparison (Calvo and Pena, 2006 and Gasser et al., 2006). For the concentrations used here it was found that: collagenase treated samples showed decreased fracture stress in the axial direction only; elastase treated samples showed increased fracture stress in the circumferential direction only; and glutaraldehyde samples showed no change in either direction. With respect to the proposed constitutive model, both collagenase and elastase had a strong effect on the fibre-related terms. The model more closely captured the tissue response in the circumferential direction, due to the smoother and sharper transition from damage initiation to complete failure in this direction. Finally, comparison of the results with those of tensile tests on diseased tissues suggests that these treatments indeed provide a basis for creation of physical models of diseased arteries

Growing the Urban Ecosystem in Detroit, Michigan

Many views of the future are seen as bleak and devoid of the life where once stood beauty and abundance. However, the Living Cities Design Competition challenges these views and calls for a vision of the future that inspires hope, biodiversity, and a healthy interaction between human and natural systems. We chose to redesign the city of Detroit, Michigan to be a living city by the year 2035. As the earth scientist on an interdisciplinary team, I acted as an ecological consultant. By developing the urban ecosystem of Detroit, a number of social, economical, and environmental problems can be solved. Green infrastructure such as urban forests and ecological corridors should be implemented to lessen our impact on the environment. Urban agriculture should be developed in order to provide the community with healthy, sustainable, and local food as well as reviving the local economy. Protopia aims to provide a sustainable vision of the future in which the city replicates a natural ecosystem