The Price of Robustness in Timetable Information

In timetable information in public transport the goal is to search for a good passenger\u27s path between an origin and a destination. Usually, the travel time and the number of transfers shall be minimized. In this paper, we consider robust timetable information, i.e. we want to identify a path which will bring the passenger to the planned destination even in the case of delays. The classic notion of strict robustness leads to the problem of identifying those changing activities which will never break in any of the expected delay scenarios. We show that this is in general a strongly NP-hard problem. Therefore, we propose a conservative heuristic which identifies a large subset of these robust changing activities in polynomial time by dynamic programming and so allows us to find strictly robust paths efficiently. We also transfer the notion of light robustness, originally introduced for timetabling, to timetable information. In computational experiments we then study the price of strict and light robustness: How much longer is the travel time of a robust path than of a shortest one according to the published schedule? Based on the schedule of high-speed trains within Germany of 2011, we quantitatively explore the trade-off between the level of guaranteed robustness and the increase in travel time. Strict robustness turns out to be too conservative, while light robustness is promising: a modest level of guarantees is achievable at a reasonable price for the majority of passengers

Genome wide analysis of gene dosage in 24,092 individuals estimates that 10,000 genes modulate cognitive ability

International audienceGenomic copy number variants (CNVs) are routinely identified and reported back to patients with neuropsychiatric disorders, but their quantitative effects on essential traits such as cognitive ability are poorly documented. We have recently shown that the effect size of deletions on cognitive ability can be statistically predicted using measures of intolerance to haploinsufficiency. However, the effect sizes of duplications remain unknown. It is also unknown if the effect of multigenic CNVs are driven by a few genes intolerant to haploinsufficiency or distributed across tolerant genes as well. Here, we identified all CNVs > 50 kilobases in 24,092 individuals from unselected and autism cohorts with assessments of general intelligence. Statistical models used measures of intolerance to haploinsufficiency of genes included in CNVs to predict their effect size on intelligence. Intolerant genes decrease general intelligence by 0.8 and 2.6 points of intelligence quotient when duplicated or deleted, respectively. Effect sizes showed no heterogeneity across cohorts. Validation analyses demonstrated that models could predict CNV effect sizes with 78% accuracy. Data on the inheritance of 27,766 CNVs showed that deletions and duplications with the same effect size on intelligence occur de novo at the same frequency. We estimated that around 10,000 intolerant and tolerant genes negatively affect intelligence when deleted, and less than 2% have large effect sizes. Genes encompassed in CNVs were not enriched in any GOterms but gene regulation and brain expression were GOterms overrepresented in the intolerant subgroup. Such pervasive effects on cognition may be related to emergent properties of the genome not restricted to a limited number of biological pathways

The role of the complement system in traumatic brain injury: a review

Traumatic brain injury (TBI) is an important cause of disability and mortality in the western world. While the initial injury sustained results in damage, it is the subsequent secondary cascade that is thought to be the significant determinant of subsequent outcomes. The changes associated with the secondary injury do not become irreversible until some time after the start of the cascade. This may present a window of opportunity for therapeutic interventions aiming to improve outcomes subsequent to TBI. A prominent contributor to the secondary injury is a multifaceted inflammatory reaction. The complement system plays a notable role in this inflammatory reaction; however, it has often been overlooked in the context of TBI secondary injury. The complement system has homeostatic functions in the uninjured central nervous system (CNS), playing a part in neurodevelopment as well as having protective functions in the fully developed CNS, including protection from infection and inflammation. In the context of CNS injury, it can have a number of deleterious effects, evidence for which primarily comes not only from animal models but also, to a lesser extent, from human post-mortem studies. In stark contrast to this, complement may also promote neurogenesis and plasticity subsequent to CNS injury. This review aims to explore the role of the complement system in TBI secondary injury, by examining evidence from both clinical and animal studies. We examine whether specific complement activation pathways play more prominent roles in TBI than others. We also explore the potential role of complement in post-TBI neuroprotection and CNS repair/regeneration. Finally, we highlight the therapeutic potential of targeting the complement system in the context of TBI and point out certain areas on which future research is needed

Concentrations of organic contaminants in industrial and municipal bioresources recycled in agriculture in the UK

Many types of bioresource materials are recycled in agriculture for soil improvement and as bedding materials for livestock and have potential for transfer into plant and animal foods. Representative types of industrial and municipal bioresources were selected to assess the extent of organic chemical contamination, including: (i) land applied materials: treated sewage sludge biosolids), meat and bone meal ash (MBMA), poultry litter ash (PLA), paper sludge ash (PSA) and compost-like-output (CLO), and (ii) bedding materials: recycled waste wood (RWW), dried paper sludge (DPS), paper sludge ash (PSA) and shredded cardboard. The materials generally contained lower concentrations of polychlorinated dibenzo-pdioxins/dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (PCBs) relative to earlier reports, indicating the decline in environmental emissions of these established contaminants. However, concentrations of polycyclic aromatic hydrocarbons (PAHs) remain elevated in biosolids samples from urban catchments. Polybrominated dibenzo-p-dioxins/dibenzofurans (PBDD/Fs) were present in larger amounts in biosolids and CLO compared to their chlorinated counterparts and hence are of potentially greater significance in contemporary materials. The presence of non-ortho-polychlorinated biphenyls (PCBs) in DPS was probably due to non-legacy sources of PCBs in paper production. Emerging flame retardant compounds, including: decabromodiphenylethane (DBDPE)and organophosphate flame retardants (OPFRs), were detected in several of the materials. The profile of perfluoroalkyl substances (PFAS) depended on the type of waste category; perfluoroundecanoic acid (PFUnDA) was the most significant PFAS for DPS, whereas perfluorooctane sulfonate (PFOS) was dominant in biosolids and CLO. The concentrations of polychlorinated alkanes (PCAs) and di-2-ethylhexyl phthalate (DEHP) were generally much larger than the other contaminants measured, indicating that there are major anthropogenic sources of these potentially hazardous chemicals entering the environment. The study results suggest that continued vigilance is required to control emissions and sources of these contaminants to support the beneficial use of secondary bioresource materials

The price of robustness in timetable information

In timetable information in public transport the goal is to search for a good passenger's path between an origin and a destination. Usually, the travel time and the number of transfers shall be minimized. In this paper, we consider robust timetable information, i.e. we want to identify a path which will bring the passenger to the planned destination even in the case of delays. The classic notion of strict robustness leads to the problem of identifying those changing activities which will never break in any of the expected delay scenarios. We show that this is in general a strongly NP-hard problem. Therefore, we propose a conservative heuristic which identifies a large subset of these robust changing activities in polynomial time by dynamic programming and so allows us to find strictly robust paths efficiently. We also transfer the notion of light robustness, originally introduced for timetabling, to timetable information. In computational experiments we then study the price of strict and light robustness: How much longer is the travel time of a robust path than of a shortest one according to the published schedule? Based on the schedule of high-speed trains within Germany of 2011, we quantitatively explore the trade-off between the level of guaranteed robustness and the increase in travel time. Strict robustness turns out to be too conservative, while light robustness is promising: a modest level of guarantees is achievable at a reasonable price for the majority of passengers

The price of strict and light robustness in timetable information

In timetable information in public transport the goal is to search for a good path between an origin and a destination. Usually, the travel time and the number of transfers will be minimized. In this paper, we consider robust timetable information; i.e., we want to identify a path that will bring the passenger to the planned destination even in the case of delays. The classic notion of strict robustness leads to the problem of identifying those transfer activities that will never break in any of the expected delay scenarios. We show that this is, in general, a strongly NP-hard problem. Therefore, we propose a conservative heuristic which identifies a large subset of these strictly robust transfer activities in polynomial time by dynamic programming and so allows us to efficiently find strictly robust paths. We also transfer the notion of light robustness, originally introduced for timetabling, to timetable information. In computational experiments we then study the price of strict and light robustness: how much longer is the travel time of a robust path than of a shortest one, according to the published schedule? Based on the 2011 train schedule within Germany, we quantitatively explore the trade-off between the level of guaranteed robustness and the increase in travel time. Strict robustness turns out to be too conservative, whereas light robustness is promising: a modest level of guarantees is achievable at a reasonable price for the majority of passengers

Modellierung troposphärischer Mehrphasenprozesse: Werkzeuge und chemische Mechanismen, Akronym: MODMEP : Abschlussbericht zum AFO2000-Verbundprojekt ; ein Beitrag zum Bereich A von AFO 2000 "Forschung zur Verbesserung des Systemverständnisses der Atmosphäre ; zum Forschungsschwerpunkt "Mehrphasenprozesse in der Troposphäre und Stratosphäre"

[no abstract available