155 research outputs found

    Network measures in civil air transport: A case study of Lufthansa

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    Network analysis has already a long history in operations research and quantitative social science research. In the past, much attention has been paid to shortest-route algorithms (for example, the travelling salesman problem), where the spatial configuration of networks was put in the centre of empirical investigation. Integer programming, linear and nonlinear programming turned out to offer a proper analytical toolbox. In recent years, we have seen several new trends, in particular, the rise of hub-and-spoke systems in liberalized networks, the emergence of dynamic adjustments to new competitive conditions and the increase in complexity in international networks. Furthermore, it appears that in the past decades many social, spatial and economic systems show an organized pattern characterized by network features, such as transportation, telecommunication, information or energy systems. As a consequence, much attention has recently been paid to the study of network properties emerging in many social, spatial and economic fields, as witnessed by the vast amount of literature published in the past years. Air transport is a prominent example of modern network constellations and will be addressed in this paper from a connectivity perspective. Air transport shows indeed clear network features, which impact on the way single airline carriers operate. The abundant scientific literature on airline networks has addressed this topic in terms of theoretical modelling and empirical measurements on different typologies of airline network configurations. This strand of recent research aimed to measure the network structure in relation to the effects of: (a) the market deregulation in United States in 1978 and in the European Union in the 1990s, (b) new trends in recent airline business strategies denoted as \u2018low cost\u2019 principles. Low cost carriers developed rather fast after the deregulation policy, by acquiring a competitive network advantage on traditional airlines, which consequently seemed to reorganise rapidly their airline network to respond to the new market dynamics. In this context, interesting research has emerged that mainly addressed the issue of describing and classifying networks by means of geographical concentration indices of traffic or flight frequency. These measures, such as the Gini concentration index or the Theil index, provide a proper measure of frequency or traffic concentration of the main airports in a simple, well-organized network. However, if a real-world network structure is complex, including multi-hub or mixed point-to-point and hub-spokes connections, the concentration indices may record high values for all types of structure, but fail to clearly discriminate between different network shapes. There is a need for a more appropriate measurement of connectivity structures in complex networks. Starting from the above considerations and research challenges, the present paper aims to investigate the scientific potential and applicability of a series of network connectivity/concentration indices, in order to properly typify and map out complex airline network configurations. Specifically, these various network indicators will be adopted and tested to describe the main properties \u2013 in terms of the network connectivity and configuration \u2013 of Lufthansa\u2019s airline system

    Assessment of New Hub-and-spoke and Point-to-point Airline Network Configurations

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    This paper aims to provide new measures of airline network configuration with a view to analyse effectively the complexity of modern carriers' network design. It studies network configurations in the airline sector by taking into account both spatial and temporal dimensions. The spatial dimension is measured by using both the Gini index and the Freeman index, which originate from social science research. The temporal dimension is measured by the connectivity ratio, i.e. the share of indirect connections over the total number of connections. According to these indicators, the configuration of the largest full-service carriers and the largest low-cost carriers in Europe is investigated. The results show that the temporal dimension provides a clear distinction between full-service carriers and low-cost carriers; while the spatial dimension appears useful when identifying the peculiarities within groups

    Protective Effects of Pyridoxamine Supplementation in the Early Stages of Diet-Induced Kidney Dysfunction

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    Pyridoxamine, a structural analog of vitamin B6 that exerts antiglycative effects, has been proposed as supplementary approach in patients with initial diabetic nephropathy. However, the molecular mechanism(s) underlying its protective role has been so far slightly examined. C57Bl/6J mice were fed with a standard diet (SD) or a diet enriched in fat and fructose (HD) for 12 weeks. After 3 weeks, two subgroups of SD and HD mice started pyridoxamine supplementation (150 mg/kg/day) in the drinking water. HD fed mice showed increased body weight and impaired glucose tolerance, whereas pyridoxamine administration significantly improved insulin sensitivity, but not body weight, and reduced diet-induced increase in serum creatinine and urine albumin. Kidney morphology of HD fed mice showed strong vacuolar degeneration and loss of tubule brush border, associated with a drastic increase in both advanced glycation end products (AGEs) and AGEs receptor (RAGE). These effects were significantly counteracted by pyridoxamine, with consequent reduction of the diet-induced overactivation of NF-kB and Rho/ROCK pathways. Overall, the present study demonstrates for the first time that the administration of the antiglycative compound pyridoxamine can reduce the early stages of diet-dependent kidney injury and dysfunction by interfering at many levels with the profibrotic signaling and inflammatory cascades

    Deletion of RAGE fails to prevent hepatosteatosis in obese mice due to impairment of other AGEs receptors and detoxifying systems

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    Abstract Advanced glycation endproducts (AGEs) are involved in several diseases, including NAFLD and NASH. RAGE is the main receptor mediating the pro-inflammatory signalling induced by AGEs. Therefore, targeting of RAGE has been proposed for prevention of chronic inflammatory diseases. However, the role of RAGE in the development of NAFLD and NASH remains poorly understood. We thus aimed to analyse the effect of obesity on AGEs accumulation, AGE-receptors and AGE-detoxification, and whether the absence of RAGE might improve hepatosteatosis and inflammation, by comparing the liver of lean control, obese (LeptrDb−/−) and obese RAGE-deficient (RAGE−/− LeptrDb−/−) mice. Obesity induced AGEs accumulation and RAGE expression with hepatosteatosis and inflammation in LeptrDb−/−, compared to lean controls. Despite the genetic deletion of RAGE in the LeptrDb−/− mice, high levels of intrahepatic AGEs were maintained accompanied by decreased expression of the protective AGE-receptor-1, impaired AGE-detoxifying system glyoxalase-1, and increased expression of the alternative AGE-receptor galectin-3. We also found sustained hepatosteatosis and inflammation as determined by persistent activation of the lipogenic SREBP1c and proinflammatory NLRP3 signalling pathways. Thus, RAGE targeting is not effective in the prevention of NAFLD in conditions of obesity, likely due to the direct liver specific crosstalk of RAGE with other AGE-receptors and AGE-detoxifying systems

    Investigation of the Impacts of Effective Fuel Cost Increase on the US Air Transportation Network and Fleet

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    The cost of aviation fuel increased 244% between July 2004 and July 2008, becoming the largest operating cost item for airlines. Given the potential for future increases in crude oil prices, as well as environmental costs (i.e. from cap and trade schemes or taxes), the effective cost of aviation fuel may continue to increase, further impacting airlines’ financial performance and the provision of air service nationwide. We evaluate how fuel price increase and volatility affected continental US air transportation networks and fleets in the short- and medium-term using the increase in the 2007-08 and 2004-08 periods as a natural experiment. It was found that non-hub airports serving small communities lost 12% of connections, compared to an average loss of 2.8%, July 2004-08. It is believed that reduced access to the national air transportation system had social and economic impacts for small communities. Complementary analyses of aircraft fuel efficiency, airline economics, and airfares provided a basis for understanding some airline decisions. Increased effective fuel costs will provide incentives for airlines to improve fleet fuel efficiency, reducing the environmental effects of aviation, but may cause an uneven distribution of social and economic impacts as airline networks adapt. Government action may be required to determine acceptable levels of access to service as the air transportation system transitions to higher fuel costs.The authors would like to thank the MIT Partnership on AiR Transportation Noise & Emissions Reduction (PARTNER) for access to the Piano-X software package and Brian Yutko for his assistance in its use. This work was supported by the MIT/Masdar Institute of Science and Technology under grant number Mubadala Development Co. Agreement 12/1/06

    Deletion of RAGE fails to prevent hepatosteatosis in obese mice due to impairment of other AGEs receptors and detoxifying systems

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    Advanced glycation endproducts (AGEs) are involved in several diseases, including NAFLD and NASH. RAGE is the main receptor mediating the pro-inflammatory signalling induced by AGEs. Therefore, targeting of RAGE has been proposed for prevention of chronic inflammatory diseases. However, the role of RAGE in the development of NAFLD and NASH remains poorly understood. We thus aimed to analyse the effect of obesity on AGEs accumulation, AGE-receptors and AGE-detoxification, and whether the absence of RAGE might improve hepatosteatosis and inflammation, by comparing the liver of lean control, obese (LeptrDb−/−) and obese RAGE-deficient (RAGE−/− LeptrDb−/−) mice. Obesity induced AGEs accumulation and RAGE expression with hepatosteatosis and inflammation in LeptrDb−/−, compared to lean controls. Despite the genetic deletion of RAGE in the LeptrDb−/− mice, high levels of intrahepatic AGEs were maintained accompanied by decreased expression of the protective AGE-receptor-1, impaired AGE-detoxifying system glyoxalase-1, and increased expression of the alternative AGE-receptor galectin-3. We also found sustained hepatosteatosis and inflammation as determined by persistent activation of the lipogenic SREBP1c and proinflammatory NLRP3 signalling pathways. Thus, RAGE targeting is not effective in the prevention of NAFLD in conditions of obesity, likely due to the direct liver specific crosstalk of RAGE with other AGE-receptors and AGE-detoxifying systems

    Effects of exogenous dietary advanced glycation end products on the cross-talk mechanisms linking microbiota to metabolic inflammation

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    Heat-processed diets contain high amounts of advanced glycation end products (AGEs). Here we explore the impact of an AGE-enriched diet on markers of metabolic and inflammatory disorders as well as on gut microbiota composition and plasma proteins glycosylation pattern. C57BL/6 mice were allocated into control diet (CD, n = 15) and AGE-enriched diet (AGE-D, n = 15) for 22 weeks. AGE-D was prepared replacing casein by methylglyoxal hydroimidazolone-modified casein. AGE-D evoked increased insulin and a significant reduction of GIP/GLP-1 incretins and ghrelin plasma levels, altered glucose tolerance, and impaired insulin signaling transduction in the skeletal muscle. Moreover, AGE-D modified the systemic glycosylation profile, as analyzed by lectin microarray, and increased N\u3b5-carboxymethyllysine immunoreactivity and AGEs receptor levels in ileum and submandibular glands. These effects were associated to increased systemic levels of cytokines and impaired gut microbial composition and homeostasis. Significant correlations were recorded between changes in bacterial population and in incretins and inflammatory markers levels. Overall, our data indicates that chronic exposure to dietary AGEs lead to a significant unbalance in incretins axis, markers of metabolic inflammation, and a reshape of both the intestinal microbiota and plasma protein glycosylation profile, suggesting intriguing pathological mechanisms underlying AGEs-induced metabolic derangements

    Temporal trend of drug-resistance and APOBEC editing in PBMC genotypic resistance tests from HIV-1 infected virologically suppressed individuals

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    Background: We aimed at evaluating the temporal trend of drug-resistance and APOBEC editing from HIV-DNA genotypic resistance tests (GRT) in virologically suppressed individuals.Material and methods: Major resistance mutations (MRM), genotypic susceptibility score (GSS) for the current regimen and APOBEC-related mutations (APO-M) were evaluated. Potential changes in trends of MRM and APO-M over-time were assessed and predictors of MRM detection or sub-optimal GSS (GSS<2) at HIV-DNA-GRT were estimated through logistic regression analyses.Results: Among the 1126 individuals included, 396 (35.2%) harboured at least one MRM (23.4% to NRTI, 18.8% to NNRTI, 7.7% to PI and 1.4% to INSTI [N=724]); 132 (12.3%) individuals showed a GSS <2. APO-M and stop codons were found in 229 (20.3%) and 105 (9.3%) individuals, respectively. APO-DRMs were found in 16.8% of individuals and were more likely observed in those individuals with stop codons (40.0%) compared to those without (14.4%, P<0.001). From 2010 to 2021 no significant changes of resistance or APO-M were found. Positive predictors of MRM detection at HIV-DNA GRT were drug abuse, subtype B infection, and a prolonged and complex treatment history. Perinatal infection and having at least 2 stop codons were associated with a current suboptimal regimen.Conclusions: In virologically suppressed individuals, resistance in HIV-DNA and the extent of APOBEC editing were generally stable in the last decade. A careful evaluation of APOBEC editing might be helpful to improve the reliability of HIV-DNA GRT. Further investigations are required to understand how to apply the estimation of APOBEC editing in refining genotypic evaluation
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