71 research outputs found

    Verfahren zum Einfügen der zusätzlichen non-zyklischen Pfade in die bestehenden zyklischen Fahrpläne

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    With the development of high-speed railway (HSR), cyclic timetable shows many advantages. However, the pure cyclic timetable is not suitable in China's HSR. Consequently, a hybrid timetable concept named "cyclic + non-cyclic" timetable is proposed, with a cyclic core timetable in which some trains are inserted as non-cyclic trains. Nowadays, the cyclic timetables have been well developed but the technique of inserting additional train paths is still a significant demand for research. The Adding Train Paths (ATP) problem firstly is an integration of timetable scheduling and rescheduling problem. Therefore it is considered involving many general constraints, such as flexible running time, dwell time and headways. Based on an event-activity graph, a general mixed integer program model for the ATP problem is formulated. In addition, several real-world constraints that concerning the acceleration and deceleration time, priority for overtaking, station capacity, allowed adjustments, periodic structure and frequency of services are incorporated into the general model. In order to get a new timetable that with low deviations to the initial services and high quality of the performance to the additional trains, objective functions of minimizing travel time, minimizing total adjustments, minimizing the makespan and maximizing the robustness of the new timetable are discussed in this thesis. More importantly, many additional trains may not be inserted because of a shortage of train-sets. So how to cover the entire trains with minimum train-sets must be also taken into account in this problem. The train-set circulation in the ATP problem is decomposed to two sub-problems. (i) For initial trains, the initial train-set route is assumed to be fixed; it is solved as a rescheduling problem of a tight constraint to keep the current circulation. (ii) For additional trains, it is a train-set planning problem to cover all the additional trains with minimal number of train-sets. In order to solve the problem in a reasonable time, we start from fixed train-set route, and then apply flexible train-set route that provides possible alternative turning activities to decrease the waiting time of a train-set in an overnight turn-around. Case studies based on Shanghai-Hangzhou HSR line in China investigate the proposed framework and associated techniques. Meanwhile, the performances of various settings are compared to analyse the affecting factors to this specific problem.Zusammen mit der Entwicklung von Hochgeschwindigkeitsverkehr (HGV) hat der zyklische Fahrplan als sehr vorteilhaft bewiesen. Allerdings ist der zyklische Fahrplan für HGV in China nicht geeignet. Demzufolge wird ein Hybrid-Fahrplan Konzept mit „zyklisch + non-zyklisch“ vorgeschlagen. Mit dem zyklischen Fahrplan als Basis werden neue non-zyklischen Pfade eingefügt. Der zyklische Fahrplan wird bereits intensiv geforscht. Beim Einfügen von zusätzlicher non-zyklischen Pfade besteht jedoch großer Forschungsbedarf. Dieses Problem umfasst sowohl den Bereich der Planung als auch der Umplanung von Fahrplan. Mehrere Restriktionen werden berücksichtigt, z.B.: flexibel Fahrzeit, Haltezeit und Zugfolgezeit. Basiert auf Event-Activity-Graph, ein generisches gemischtes integrales Modell wird entwickelt. Zusätzlich werden die praxisrelevanten Restriktionen wie Beschleunigungszeit, Bremszeit, Priorität der Züge, Anzahl der Bahnhofsgleise, zulässige Verschiebung der Abfahrtszeit, periodische Struktur und Taktfrequenz mitbetrachtet. Um ein neuer Fahrplan mit einer geringen Verschiebung der Abfahrtszeit und zugleich eine hohe Qualität der zusätzlichen Züge zu ermöglichen, wird in dieser Arbeit die folgenden Kriterien als Zielfunktionen untersucht: Reisezeit, Summe der gesamten Zeitverschiebung, Spannbreite der Zeitverschiebung und Robustheit der Fahrplan. Die Anzahl der zusätzlichen non-zyklischen Pfade hängt wesentlich von der Anzahl der Züge ab, welche noch verfügbar sind. Daher ist ein optimaler Fahrzeugumlaufplan für die zusätzlichen Zugfahrten ein wichtiges Zielkriterium. Umlauf der bestehenden Zugfahrten und der zusätzlichen Zugfahrten werden separat betrachtet. (i) Bei der bestehenden Zugfahrten wird keine Änderung an Fahrzeugumlauf vorgenommen, auch nach Verschiebung der Abfahrtszeit bleibt der Umlauf unverändert. (ii) Für die zusätzlichen Zugfahrten wird die Anzahl der benötigen Züge minimiert. Um die Aufgabe in einer annehmbaren Rechenzeit zu lösen, werden anfangs die zusätzlichen Zugfahrten, deren Laufweg mit den zyklischen Zugfahrten identisch ist, untersucht. Anschließend werden weitere Zugfahrten mit flexiblen Laufweg eingefügt, welche durch Wenden im Unterwegsbahnhof die Wartezeit bzw. Aufenthaltszeit über Nacht am Endbahnhof möglichst reduzieren kann. Als Fallstudie wird HGV Shanghai-Hangzhou in China untersucht. Die Rechenzeiten von der unterschiedlichen Parametereinstellungen werden während der Untersuchung getestet, analysiert und verglichen

    Cyclic Timetable Scheduling Problem on High-speed Railway Line

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    Due to several obvious advantages both in transport marketing and train operation planning, the cyclic timetable has already applied in many high-speed railway (HSR) countries. In order to adopt the cyclic timetable in China's HSR system, a Mixed Integer Programmer (MIP) model is proposed in this paper involving many general constraints, such as running time, dwell time, headway, and connection constraints. In addition, the real-world overtaking rule that concerning a train with higher priority will not be overtaken by a slower one is incorporated into the cyclic timetable optimization model. An approach based on fixed departure is proposed to get a cyclic timetable with minimum total journey time within a reasonable time. From numerical investigations using data from Guangzhou-Zhuhai HSR line in China, the proposed model and associated approach are tested and shown to be effective

    Inserting Extra Train Services on High-Speed Railway

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    With the aim of supporting future traffic needs, an account of how to reconstruct an existing cyclic timetable by inserting additional train services will be given in this paper. The Timetable-based Extra Train Services Inserting (TETSI) problem is regarded as an integration of railway scheduling and rescheduling problem. The TETSI problem therefore is considered involving many constraints, such as flexible running times, dwell times, headway and time windows. Characterized based on an event-activity graph, a general Mixed Integer Program model for this problem is formulated. In addition, several extensions to the general model are further proposed. The real-world constraints that concerning the acceleration and deceleration times, priority for overtaking, allowed adjustments, periodic structure and frequency of services are incorporated into the general model. From numerical investigations using data from Shanghai-Hangzhou High-Speed Railway in China, the proposed framework and associated techniques are tested and shown to be effective

    Hemiballism-hemichorea induced by ketotic hyperglycemia: case report with PET study and review of the literature

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    Hemiballism-hemichorea (HB-HC) is commonly used to describe the basal ganglion dysfunction in non-ketotic hyperglycemic elderly patients. Here we report two elderly female patients with acute onset of involuntary movements induced by hyperglycemia with positive urine ketones. We described the computed tomography and magnetic resonance imaging findings in these two patients, which is similar to that of non-ketotic hyperglycemic HB-HC patients. FDG-PET was performed and the glucose metabolism in the corresponding lesion in these two patients was contradictory with each other. We tried to clarify the underlying mechanisms of HB-HC and explain the contradictory neuroradiological findings in FDG-PET as being performed at different clinical stages

    A Novel Splicing Mutation in the CSF1R Gene in a Family With Hereditary Diffuse Leukoencephalopathy With Axonal Spheroids

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    Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a rare autosomal dominant disorder that typically presents with early-onset cognitive decline or personality change. The disease is associated with heterozygous mutations in the colony stimulating factor-1 receptor (CSF1R) gene. CSF1R activation regulates microglial survival, proliferation, and differentiation. The different gene mutations may be related to the various clinical phenotypes. Here, we described comprehensive clinical, neuroimaging, neuropathological, and genetic analyses of a family with HDLS. A novel splicing mutation in intron 13 (c.1858+1G>T) of CSF1R was found in this family. It is located at the splice site of intron 13, resulting in a splice donor site leading to exon 13 skipping from the CSF1R mRNA. The mother and two elderly siblings of the proband had the same CSF1R mutation as the proband but showed very mild neuroimaging abnormalities and mild memory loss, which did not affect daily life, indicating very uneven penetrance and distinctly different disease progression among family members. This report provides diverse neuroimaging and clinical characteristics of a novel CSF1R mutation with different disease penetrance. The large clinical heterogeneity in the same family who all had the same mutation indicates that modifying genes and environmental factors may play a role in the pathogenesis of HDLS

    DJ-1 can inhibit microtubule associated protein 1 B formed aggregates

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    <p>Abstract</p> <p>Background</p> <p>Abnormal accumulation and aggregation of microtubule associated proteins (MAPs) plays an important role in the pathogenesis of neurodegenerative diseases. Loss-of-function mutation of DJ-1/Park7 can cause early onset of PD. DJ-1, a molecular chaperone, can inhibit α-synuclein aggregation. Currently, little is known whether or not loss of function of DJ-1 contributes to abnormal MAPs aggregation in neurodegenerative disorders such as PD.</p> <p>Results</p> <p>We presented evidence that DJ-1 could bind to microtubule associated protein1b Light Chain (MAP1b-LC). Overexpression of DJ-1 prevented MAP1b-LC aggregation in HEK293t and SH-SY5Y cells while DJ-1 knocking down (KD) enhanced MAP1b-LC aggregation in SH-SY5Y cells. The increase in insoluble MAP1b-LC was also observed in the DJ-1 null mice brain. Moreover, in the DJ-1 KD SH-SY5Y cells, overexpression of MAP1B-LC led to endoplasmic reticulum (ER) stress-induced apoptosis.</p> <p>Conclusion</p> <p>Our results suggest that DJ-1 acts as a molecular chaperone to inhibit MAP1B aggregation thus leading to neuronal apoptosis. Our study provides a novel insight into the mechanisms that underly the pathogenesis of Parkinson's disease (PD).</p

    Lack of Association Between DJ-1 Gene Promoter Polymorphism and the Risk of Parkinson’s Disease

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    Low DJ-1 protein level caused by DJ-1 gene mutation leads to autosomal recessive Parkinson’s disease (PD) due to impaired antioxidative activity. In sporadic PD patients, although mutations were rarely found, lower DJ-1 protein level was also reported. Dysregulation of DJ-1 gene expression might contribute to low DJ-1 protein level. Since the promoter is the most important element to initiate gene expression, whether polymorphisms in the DJ-1 promoter result in the dysregulation of gene expression, thus leading to low protein level and causing PD, is worth exploring. The DJ-1 promoter region was sequenced in a Chinese cohort to evaluate possible links between DJ-1 promoter polymorphisms, PD risk and clinical phenotypes. Dual-luciferase reporter assay was conducted to evaluate the influence of promoter polymorphisms on DJ-1 transcriptional activity. Related information in an existing genome-wide association studies (GWAS) database were looked up, meta-analysis of the present study and other previous reports was conducted, and expression quantitative trait loci (eQTL) analysis was performed to further explore the association. Three single nucleotide polymorphisms (SNPs) (rs17523802, rs226249, and rs35675666) and one 18 bp deletion (rs200968609) were observed in our cohort. However, there was no significant association between the four detected genetic variations and the risk of PD either in allelic or genotype model, in single-point analysis or haplotype analysis. This was supported by the meta-analysis of this study and previous reports as well as that of GWAS database PDGene. Dual luciferase reporter assay suggested these promoter polymorphisms had no influence on DJ-1 transcriptive activity, which is consistent with the eQTL analysis results using the data from GTEx database. Thus, DJ-1 promoter polymorphisms may play little role in the dysregulation of DJ-1 expression and PD susceptibility in sporadic PD
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