Transit network timetabling and vehicle assignment for regulating authorities

In the literature on transit planning, network timetabling and vehicle scheduling are usually treated as separate problems. In this paper, we focus on combining important features of these two steps and propose a simultaneous solution approach to redefine timetables with the objective of bringing improvements to both quality of service and vehicle costs incurred. This includes the objectives of quantity and quality of the transfers proposed, evenness of the line headways, fleet size and length of the deadheads. The model proposed for this simultaneous approach is adapted to the problem faced by regulating authorities, encouraging intermodality and taking into account a variety of practical features. We introduce an optimization procedure based on Iterated Local Search and present computational experiments carried out on data from a large existing transit network, showing substantial improvements in both quality of service and level of resources compared to the current practice

Travailler nos propres représentations et notre professionnalisme sur l'adoption d'enfants à besoins spécifiques

Médecins du Monde, association humanitaire médicale, est la seule en France à avoir intégré l’adoption dans ses statuts fondateurs et créé une mission chargée de l’adoption internationale. L’association a ainsi accompagné l’adoption de plus de trois mille sept cents enfants entre 1990 et 2010. Pour mener à bien ses objectifs, la mission Adoption s’appuie sur l’engagement de deux cent quinze personnes, dont 98 % de bénévoles, réparties entre le siège et quinze antennes régionales. Nous avons demandé à cinq d’entre elles comment les adoptions complexes faisaient évoluer leurs pratiques et leurs objectifs

An optimization model for line planning and timetabling in automated urban metro subway networks

In this paper we present a Mixed Integer Nonlinear Programming model that we developed as part of a pilot study requested by the R&D company Metrolab in order to design tools for finding solutions for line planning and timetable situations in automated urban metro subway networks. Our model incorporates important factors in public transportation systems from both, a cost-oriented and a passenger-oriented perspective, as time-dependent demands, interchange stations, short-turns and technical features of the trains in use. The incoming flows of passengers are modeled by means of piecewise linear demand functions which are parameterized in terms of arrival rates and bulk arrivals. Decisions about frequencies, train capacities, short-turning and timetables for a given planning horizon are jointly integrated to be optimized in our model. Finally, a novel Math-Heuristic approach is proposed to solve the problem. The results of extensive computational experiments are reported to show its applicability and effectiveness to handle real-world subway networksComment: 30 pages, 6 figures, 9 table

Sex Differences in Immunology: More Severe Development of Experimental Pulmonary Hypertension in Male Rats Exposed to Vascular Endothelial Growth Factor Receptor Blockade

Background. The epidemiology of pulmonary hypertension (PH) is characterized by a female preponderance, whereas males share higher severity of the disease. Objective. To compare the severity of experimental PH between male and female athymic rats. Methods. PH was induced in 11 male and 11 female athymic rats (resp., SU_M and SU_F groups) using an inhibitor of VEGF-receptors I and II, semaxanib (40 mg/kg). After 28 days, right ventricular (RV) remodeling, systolic function, and hemodynamics were measured using echocardiography and a pressure-volume admittance catheter. Morphometric analyses of lung vasculature and RV myocardium were performed. Results. Four weeks after semaxanib injection, RV end-systolic pressure was higher in SU_M than in SU_F. Males developed marked RV enlargement and systolic dysfunction compared to females. Impairment of RV-PA coupling efficiency was observed only in SU_M. The smooth muscle cells of the pulmonary arteries switched from a contractile state to a dedifferentiated state only in males. Conclusions. Female athymic rats were protected against the development of severe PH. RV-PA coupling was preserved in females through limitation of pulmonary artery muscularization. Control of smooth muscle cells plasticity may be a promising therapeutic approach to reverse established vascular remodeling in PH patients

Decreased expression of miR-29 family associated with autoimmune myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) is a rare autoimmune disease mainly mediated by autoantibodies against the acetylcholine receptor (AChR) at the neuromuscular junction. The thymus is the effector organ, and its removal alleviates the symptoms of the disease. In the early-onset form of MG, the thymus displays functional and morphological abnormalities such as B cell infiltration leading to follicular hyperplasia, and the production of AChR antibodies. Type-I interferon (IFN-I), especially IFN-β, is the orchestrator of thymic changes observed in MG. As Dicer and miR-29 subtypes play a role in modulating the IFN-I signalization in mouse thymus, we investigated their expression in MG thymus. METHODS: The expression of DICER and miR-29 subtypes were thoroughly investigated by RT-PCR in human control and MG thymuses, and in thymic epithelial cells (TECs). Using miR-29a/b-1-deficient mice, with lower miR-29a/b-1 expression, we investigated their susceptibility to experimental autoimmune MG (EAMG) as compared to wild-type mice. RESULTS: DICER mRNA and all miR-29 subtypes were down-regulated in the thymus of MG patients and DICER expression was correlated with the lower expression of miR-29a-3p. A decreased expression of miR-29 subtypes was similarly observed in MG TECs; a decrease also induced in TECs upon IFN-β treatment. We demonstrated that miR-29a/b-1-deficient mice were more susceptible to EAMG without higher levels of anti-AChR IgG subtypes. In the thymus, if no B cell infiltration was observed, an increased expression of Ifn-β associated with Baff expression and the differentiation of Th17 cells associated with increased expression of Il-6, Il-17a and Il-21 and decreased Tgf-β1 mRNA were demonstrated in miR-29a/b-1-deficient EAMG mice. CONCLUSIONS: It is not clear if the decreased expression of miR-29 subtypes in human MG is a consequence or a causative factor of thymic inflammation. However, our results from the EAMG mouse model indicated that a reduction in miR-29a/b1 may contribute to the pathophysiological process involved in MG by favoring the increased expression of IFN-β and the emergence of pro-inflammatory Th17 cells

ICAM-1 PROMOTES THE ABNORMAL ENDOTHELIAL CELLPHENOTYPE IN CHRONIC THROMBOEMBOLIC PULMONARYHYPERTENSION

International audienceBACKGROUND - Pulmonary endothelial cells play a key role in the pathogenesis of ChronicThromboembolic Pulmonary Hypertension (CTEPH). Increased synthesis and/or release ofIntercellular Adhesion Molecule 1 (ICAM-1) by pulmonary endothelial cells of patients withCTEPH has been recently reported, suggesting a potential role for ICAM-1 in CTEPH.METHODS - We studied pulmonary endarterectomy specimens from 172 patients with CTEPHand pulmonary artery specimens from 97 controls undergoing lobectomy for low-stage cancerwithout metastasis.RESULTS - ICAM-1 was overexpressed in vitro in isolated and cultured endothelial cells fromendarterectomy specimens. Endothelial cell (EC) growth and apoptosis resistance weresignificantly higher in CTEPH specimens than in controls (P<0.001). Both abnormalities wereabolished by pharmacological inhibition of ICAM-1 synthesis or activity. Overexpression ofICAM-1 contributed to the acquisition and maintenance of abnormal EC growth and apoptosisresistance via phosphorylation of SRC, p38 and ERK1/2 and overproduction of Survivin.Regarding the ICAM-1 E469K polymorphism, the KE heterozygote genotype was significantlymore frequent in CTEPH than in controls, but was not associated with disease severity amongpatients with CTEPH.CONCLUSIONS - ICAM-1 contributes to maintaining the abnormal endothelial cell phenotypein CTEPH

Transport analytics in action: a cloud-based decision support system for efficient city bus transportation

Optimising city bus transport operations helps conserve fuel by providing the urban transport service as efficiently as possible. This study develops a Cloud-based Decision Support System (C-DSS) for transport analytics. The C-DSS is based on an intelligent model on location of depots for opening new depots and/or closing a few existing depots and allocation of city-buses to depots. The C-DSS is built on the Cloud Computing architecture with three layers and includes an efficient and simple greedy heuristic algorithm. Using modern information and communications technology tools, the proposed C-DSS minimizes the cost of city bus transport operations and in turn to reduce fuel consumption and CO2 emissions in urban passenger transport. The proposed C-DSS is demonstrated for its workability and evaluated for its performance on 25 large scale pseudo data generated based on the observation from Bangalore Metropolitan Transport Corporation (BMTC) in India

Causes and Consequences of miR-150-5p Dysregulation in Myasthenia Gravis

Autoimmune Myasthenia gravis (MG) is a chronic neuromuscular disease mainly due to antibodies against the acetylcholine receptor (AChR) at the neuromuscular junction that induce invalidating muscle weaknesses. In early-onset MG, the thymus is the effector organ and is often characterized by B-cell infiltrations leading to ectopic germinal center (GC) development. The microRNA miR-150-5p has been previously characterized as a biomarker in MG due to its increase in the serum of patients and its decrease after thymectomy, correlated with an improvement of symptoms. Here, we investigated the causes and consequences of the miR-150 increase in the serum of early-onset MG patients. We observed that miR-150 expression was upregulated in MG thymuses in correlation with the presence of thymic B cells and showed by in situ hybridization experiments, that miR-150 was mainly expressed by cells of the mantle zone of GCs. However, we did not observe any correlation between the degree of thymic hyperplasia and the serum levels in MG patients. In parallel, we also investigated the expression of miR-150 in peripheral blood mononuclear cells (PBMCs) from MG patients. We observed that miR-150 was down-regulated, especially in CD4+ T cells compared to controls. These results suggest that the increased serum levels of miR-150 could result from a release from activated peripheral CD4+ T cells. Next, we demonstrated that the in vitro treatment of PBMCs with miR-150 or antimiR-150 oligonucleotides, respectively, decreased or increased the expression of one of its major target gene: the proto-oncogene MYB, a well-known actor of hematopoiesis. These results revealed that increased serum levels of miR-150 in MG patients could have a functional effect on PBMCs. We also showed that antimiR-150 caused increased cellular death of CD4+ and CD8+ T cells, along with the overexpression of pro-apoptotic genes targeted by miR-150 suggesting that miR-150 controlled the survival of these cells. Altogether, these results showed that miR-150 could play a role in MG both at the thymic level and in periphery by modulating the expression of target genes and peripheral cell survival