Planning for cycling in the West Midlands

The issues involved in planning for pedal cyclists are examined with reference to the West Midlands County. Working with a local cycling campaign group, the researcher uses action research methods to investigate and influence the campaign. Development of cycle planning is traced through the literature, focusing on bicycle ownership, bicycle use and cycling policy. UK practice is contrasted with the integrated approach of other countries. An extensive bibliography is provided. Local authority cycle planning through the TPP process is systematically assessed over three years. This provides a context for the information regarding cycling in the West Midlands. Existing data is presented from the 1981 Census and local police road accident and bicycle theft records. The developing relationship between the local authority and the cycle campaign group is narrated in detail, explaining the problems that can beset efforts to improve conditions for cyclists. The researcher was closely involved in this interaction, particularly with policy and a major public inquiry. A survey of the Cycle Campaign Network indicates that the local group was not atypical. To provide information relevant to the local campaign and for effective local planning, a survey of 3,500 West Midlands residents was conducted using a novel combination of questionnaires and interviews. It shows that 1) Bicycle ownership and use is considerably higher than indicated by the 1978/9 National Travel Survey 2) Cycling is most import to certain disadvantaged sections of the community, particularly the young, those without access to a car and in the lower SEGs. The broader issues of transport policy are discussed, concluding that cycling is regarded as a marginal activity and that changes in general transport policy, land use planning and fiscal arrangements are necessary conditions for cycle planning to succeed. An integrated package of cycling measures involving engineering, education, enforcement and encouragement is also required. Recommendations are made concerning central government, local authorities and cycle campaign groups. Subjects for further research are identified.

Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to the development of pulmonary arterial hypertension

Aims: Pulmonary arterial hypertension [1] is a proliferative disorder associated with enhanced proliferation and suppressed apoptosis of pulmonary artery smooth muscle cells (PASMCs). Reactive oxygen species (ROS) is implicated in the development of PAH and regulates the vascular tone and functions. However, which cellular signaling mechanisms are triggered by ROS in PAH is still unknown. Hence, here we wished to characterize the signaling mechanisms triggered by ROS. Methods and Results: By Western blots, we showed that increased intracellular ROS caused inhibition of the glycolytic pyruvate kinase M2 (PKM2) activity through promoting the phosphorylation of PKM2. Monocrotaline (MCT)-induced rats developed severe PAH and right ventricular hypertrophy, with a significant increase in the P-PKM2 and decrease in pyruvate kinase activity which could be attenuated with the treatments of PKM2 activators, FBP and l-serine. The antioxidant NAC, apocynin and MnTBAP had the similar protective effects in the development of PAH. In vitro assays confirmed that inhibition of PKM2 activity could modulate the flux of glycolytic intermediates in support of cell proliferation through the increased pentose phosphate pathway (PPP). Increased ROS and decreased PKM2 activity also promoted the Cav1.2 expression and intracellular calcium. Conclusion: Our data provide new evidence that PKM2 makes a critical regulatory contribution to the PAHs for the first time. Decreased pyruvate kinase M2 activity confers additional advantages to rat PASMCs by allowing them to sustain anti-oxidant responses and thereby support cell survival in PAH. It may become a novel treatment strategy in PAH by using of PKM2 activators.

Effect of cancer cachexia on triacylglycerol/fatty acid substrate cycling in white adipose tissue

The effect of cancer cachexia on the TAG/FA substrate cycle in white adipose tissue was determined in vivo using the MAC16 murine model of cachexia. When compared with non-tumor-bearing animals, the rate of TAG-glycerol production was found to be increased almost threefold in animals bearing the MAC13 tumor, which does not induce cachexia, but was not further elevated in animals bearing the MAC16 tumor. In both cases TAG-glycerol production and de novo synthesis of TAG-FA were also increased above non-tumor-bearing animals. In animals bearing the MAC16 tumor, the TAG-FA rates were significantly higher than in animals bearing the MAC13 tumor. This suggests that the presence of the tumor alone is sufficient to cause an increase in cycling rate, and in the absence of an elevated energy intake (MAC16) this may contribute to the depletion of adipose tissue.

Multiobjective design optimization of IGBT power modules considering power cycling and thermal cycling

Insulated-gate bipolar transistor (IGBT) power modules find widespread use in numerous power conversion applications where their reliability is of significant concern. Standard IGBT modules are fabricated for general-purpose applications while little has been designed for bespoke applications. However, conventional design of IGBTs can be improved by the multiobjective optimization technique. This paper proposes a novel design method to consider die-attachment solder failures induced by short power cycling and baseplate solder fatigue induced by the thermal cycling which are among major failure mechanisms of IGBTs. Thermal resistance is calculated analytically and the plastic work design is obtained with a high-fidelity finite-element model, which has been validated experimentally. The objective of minimizing the plastic work and constrain functions is formulated by the surrogate model. The nondominated sorting genetic algorithm-II is used to search for the Pareto-optimal solutions and the best design. The result of this combination generates an effective approach to optimize the physical structure of power electronic modules, taking account of historical environmental and operational conditions in the field.