Holistic rail network operation by integration of train automation and traffic management

Nowadays, railways play an increasingly important role in our daily lives. Many experts and engineers are making their own efforts to optimise railways whether it involves increasing capacity, saving energy and reducing costs. However, the experts from different fields have their own intention, method and evaluation on optimisation. This thesis aims to analyse these differences systematically in order to build a more holistic optimisation method, with special focus on two specific areas: traffic management and train operation.It has been proved that traffic management and train operation work well separately, but not collaboratively. Traffic management’s strength lies in traffic conflict prevention and resolution, but it lacks sufficient on-board computing power and real-time transmitted train data, which will reduce the accuracy of traffic plan execution. On the contrary, train operation has sufficient on-board computing power and real-time train data transmission, but it has no knowledge of other trains’ status to prevent or resolve conflicts. Therefore, the optimisation strategies of traffic management and train operation are complementary.The thesis endeavours to integrate the two fields by proposing an integrated optimisation model, which highlights the importance of the bidirectional communication between traffic management and train operation. The former provides the strategy of conflict resolution for the latter, while the latter offers real-time feedback of train characteristics to the former. Moreover, the thesis introduces a decision-making structure into the integrated optimisation model by using the Analytical Hierarchy Process (AHP) method. Therefore, it can adapt to different optimisation circumstances and achieve a balance in multidimensional, at times contradicted optimisation goals. Furthermore, the thesis develops a lab-demonstrator to prove the feasibility of the integrated optimisation model.In addition, the thesis contributes to the railway capacity study. It proposes a new classification of capacity definitions, which distinguishes the dynamic capacity influenced by different optimisation methods from the theoretical capacity influenced by different infrastructure conditions. This classification can reduce the impact of confusion of capacity definitions in the discussion of capacity, especially when it involves experts from different backgrounds. Moreover, the thesis proposes a new 4-quadrant capacity model, which provides a new method to evaluate the trade-off between dynamic capacity and quality in traffic planning and operations. Furthermore, the thesis proves the feasibility of the new 4-quadrant capacity model in a practical case study.To sum up, the integrated optimisation model and the proposed 4-quadrant capacity model both indicate that the tendency of railway optimisation is not to maximise the capacity at the expense of quality, but to increase the capacity and improve the quality at the same time

A new rail optimisation model by integration of traffic management and train automation

This paper reviews and classifies the traffic optimisation schemes of current mainline railway into two groups. One is to improve the efficiency of traffic management by providing resolutions for traffic conflicts, while the other is to improve trains’ driving behaviour by providing driver assistance or introducing train automation. Based on a comparison of these two groups, this paper proposes to combine the functions of traffic management and train automation into an integrated optimisation model. This model includes the following contributions. First, in the function of traffic management, this paper explores the flexibility in generating different train running trajectories to prevent potential traffic conflicts. The trajectory can improve traffic flow by avoiding unplanned train stops. This is regarded as a supplementary conflict resolution to train reordering or rerouting or retiming. Second, this paper defines a series of train control commands to determine different intensities of the train’s tractive force and braking force. These commands are seen as the key to train automation. Moreover, a decision-making procedure is introduced to select the most attractive train running trajectory or train control command according to different optimisation objectives. Lastly, this paper proves the importance of bidirectional communication between traffic management and train automation based on a case study

Application of metagenomic next-generation sequencing in the clinical diagnosis of infectious diseases after allo-HSCT: a single-center analysis

Abstract Background We investigated the value of metagenomic next-generation sequencing (mNGS) in diagnosing infectious diseases in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods Fifty-four patients who had fever following allo-HSCT from October 2019 to February 2022 were enrolled. Conventional microbiological tests (CMTs) and mNGS, along with imaging and clinical manifestations, were used to diagnose infection following allo-HSCT. The clinical diagnostic value of mNGS was evaluated. Results A total of 61 mNGS tests were performed, resulting in the diagnosis of 46 cases of infectious diseases. Among these cases, there were 22 cases of viral infection, 13 cases of fungal infection, and 11 cases of bacterial infection. Moreover, 27 cases (58.7%) were classified as bloodstream infections, 15 (32.6%) as respiratory infections, 2 (4.3%) as digestive system infections, and 2 (4.3%) as central nervous system infections. Additionally, there were 8 cases with non-infectious diseases (8/54, 14.81%), including 2 cases of interstitial pneumonia, 2 cases of bronchiolitis obliterans, 2 cases of engraftment syndrome, and 2 cases of acute graft-versus-host disease. The positive detection rates of mNGS and CMT were 88.9% and 33.3%, respectively, with significant differences (P < 0.001). The sensitivity of mNGS was 97.82%, the specificity was 25%, the positive predictive value was 93.75%, and the negative predictive value was 50%. Following treatment, 51 patients showed improvement, and 3 cases succumbed to multidrug-resistant bacterial infections. Conclusions mNGS plays an important role in the early clinical diagnosis of infectious diseases after allo-HSCT, which is not affected by immunosuppression status, empiric antibiotic therapy, and multi-microbial mixed infection

Design, synthesis, and biological evaluation of multiple targeting antimalarials

International audienceMalaria still threatens global health seriously today. While the current discoveries of antimalarials are almost totally focused on single mode-of-action inhibitors, multi-targeting inhibitors are highly desired to overcome the increasingly serious drug resistance. Here, we performed a structure-based drug design on mitochondrial respiratory chain of Plasmodium falciparum and identified an extremely potent molecule, RYL-581, which binds to multiple protein binding sites of P. falciparum simultaneousl

Target Elucidation by Cocrystal Structures of NADH-Ubiquinone Oxidoreductase of <i>Plasmodium falciparum</i> (<i>Pf</i>NDH2) with Small Molecule To Eliminate Drug-Resistant Malaria

Drug-resistant malarial strains have been continuously emerging recently, which posts a great challenge for the global health. Therefore, new antimalarial drugs with novel targeting mechanisms are urgently needed for fighting drug-resistant malaria. NADH-ubiquinone oxidoreductase of <i>Plasmodium falciparum</i> (<i>Pf</i>NDH2) represents a viable target for antimalarial drug development. However, the absence of structural information on <i>Pf</i>NDH2 limited rational drug design and further development. Herein, we report high resolution crystal structures of the <i>Pf</i>NDH2 protein for the first time in Apo-, NADH-, and RYL-552 (a new inhibitor)-bound states. The <i>Pf</i>NDH2 inhibitor exhibits excellent potency against both drug-resistant strains in vitro and parasite-infected mice in vivo via a potential allosteric mechanism. Furthermore, it was found that the inhibitor can be used in combination with dihydroartemisinin (DHA) synergistically. These findings not only are important for malarial <i>Pf</i>NDH2 protein-based drug development but could also have broad implications for other NDH2-containing pathogenic microorganisms such as <i>Mycobacterium tuberculosis</i>