Systemic risk approach to mitigate delay cascading in railway networks

In public railway systems, minor disruptions can trigger cascading events that lead to delays in the entire system. Typically, delays originate and propagate because the equipment is blocking ways, operational units are unavailable, or at the wrong place at the needed time. The specific understanding of the origins and processes involved in delay-spreading is still a challenge, even though large-scale simulations of national railway systems are becoming available on a highly detailed scale. Without this understanding, efficient management of delay propagation, a growing concern in some Western countries, will remain impossible. Here, we present a systemic risk-based approach to manage daily delay cascading on national scales. We compute the {\em systemic impact} of every train as the maximum of all delays it could possibly cause due to its interactions with other trains, infrastructure, and operational units. To compute it, we design an effective impact network where nodes are train services and links represent interactions that could cause delays. Our results are not only consistent with highly detailed and computationally intensive agent-based railway simulations but also allow us to pinpoint and identify the causes of delay cascades in detail. The systemic approach reveals structural weaknesses in railway systems whenever shared resources are involved. We use the systemic impact to optimally allocate additional shared resources to the system to reduce delays with minimal costs and effort. The method offers a practical and intuitive solution for delay management by optimizing the effective impact network through the introduction of new cheap local train services.Comment: 27 pages, 14 figure

Overexpression of activated protein C hampers bacterial dissemination during pneumococcal pneumonia

During pneumonia, inflammation and coagulation are activated as part of anti-bacterial host defense. Activated protein C (APC) has anticoagulant and anti-inflammatory properties and until recently was a registered drug for the treatment of severe sepsis. Streptococcus (S.) pneumoniae is the most common causative pathogen in community-acquired pneumonia. We aimed to investigate the effect of high APC levels during experimental pneumococcal pneumonia. Wild type (WT) and APC overexpressing (APC(high))-mice were intranasally infected with S. pneumoniae and sacrificed after 6, 24 or 48 hours, or followed in a survival study. In comparison to WT mice, APC(high)-mice showed decreased bacterial dissemination to liver and spleen, while no differences in bacterial loads were detected at the primary site of infection. Although no differences in the extent of lung histopathology were seen, APC(high)-mice showed a significantly decreased recruitment of neutrophils into lung tissue and bronchoalveolar lavage fluid. Activation of coagulation was not altered in APC(high)-mice. No differences in survival were observed between WT and APC(high)-mice (P =0.06). APC overexpression improves host defense during experimental pneumococcal pneumonia. This knowledge may add to a better understanding of the regulation of the inflammatory and procoagulant responses during severe Gram-positive pneumoni