Signalling layout for fixed-block railway lines with real-coded genetic algorithms.

Signalling layout design is one of the keys to railway operations with fixed-block signalling system and it also carries direct effect on overall train efficiency and safety. Based on an analysis to system objectives, this paper presents an optimization model with two objectives in order to devise an efficient signalling layout scheme. Taking into account the present railway line design practices in China, the paper describes steps of the computer-based signalling layout optimisation with real-coded genetic algorithms. A computer-aided system, based on train movement simulator, has also been employed to assist the optimisation process. A case study on a practical railway line has been conducted to make comparisons between the proposed GA-based approach and the current practices. The results illustrate the improved performance of the proposed approach in reducing signal block joints and shortening minimum train service headway.

New drugs for the treatment of coronary artery syndromes

Background: Acute coronary syndromes are a major cause of mortality and morbidity. Objectives/Methods: The objective of this evaluation is to review the clinical trials of two new drugs being developed for the treatment of acute coronary syndromes. The first drug is the anti-coagulant otamixaban, and the trial compared otamixaban with unfractionated heparin and eptifibatide in acute coronary syndromes. The second drug is the anti-platelet ticagrelor, and the trial compared ticagrelor with clopidogrel in acute coronary syndromes. Results: In the SEPIA-ACS1 TIMI 42 trial, the primary efficacy endpoint occurred in 6.2% of subjects treated with unfractionated heparin and eptifibatide, and to a significantly lesser extent with otamixaban. In the PLATO trial, the primary efficacy endpoint had occurred less in the ticagrelor group (9.8%) than in the clopidogrel group (11.7%) at 12 months. Conclusions: Two new drugs for acute coronary syndromes, otamixaban and ticagrelor, have recently been shown to have benefits in subjects undergoing percutaneous interventions compared to the present standard regimens for this condition.

The hedgehog pathway inhibitor GDC-0449 shows potential in skin and other cancers

Background: The hedgehog signaling pathway is vital in early development, but then becomes dormant, except in some cancer tumours. Hedgehog inhibitors are being developed for potential use in cancer. Objectives/Methods: The objective of this evaluation is to review the initial clinical studies of the hedgehog inhibitor, GDC-0449, in subjects with cancer. Results: Phase I trials have shown that GDC-0449 has benefits in subjects with metastatic or locally advanced basal-cell carcinoma and in one subjects with medulloblastoma. GDC-0449 was well tolerated. Conclusions: Long term efficacy and safety studies of GDC-0449 in these conditions and other solid cancers are now underway. These clinical trials with GDC-0449, and trials with other hedgehog inhibitors, will reveal whether it is beneficial and safe to inhibit the hedgehog pathway, in a wide range of solid tumours or not.

Good results for early treatment of clinically isolated syndrome prior to multiple sclerosis with interferon beta-1b and glatiramer

Background: The first sign of developing multiple sclerosis is a clinically isolated syndrome that resembles a multiple sclerosis relapse. Objective/methods: The objective was to review the clinical trials of two medicines in clinically isolated syndromes (interferon β and glatiramer acetate) to determine whether they prevent progression to definite multiple sclerosis. Results: In the BENEFIT trial, after 2 years, 45% of subjects in the placebo group developed clinically definite multiple sclerosis, and the rate was lower in the interferon β-1b group. Then all subjects were offered interferon β-1b, and the original interferon β-1b group became the early treatment group, and the placebo group became the delayed treatment group. After 5 years, the number of subjects with clinical definite multiple sclerosis remained lower in the early treatment than late treatment group. In the PreCISe trial, after 2 years, the time for 25% of the subjects to convert to definite multiple sclerosis was prolonged in the glatiramer group. Conclusions: Interferon β-1b and glatiramer acetate slow the progression of clinically isolated syndromes to definite multiple sclerosis. However, it is not known whether this early treatment slows the progression to the physical disabilities experienced in multiple sclerosis.

Oral fingolimod for relapsing-remitting multiple sclerosis

Background: Most people with multiple sclerosis have the relapsing-remitting type. Objective/methods: The objective was to evaluate two clinical trials of fingolimod in relapsing multiple sclerosis. Results: FREEDOMS (FTY720 Research Evaluation Effects of Daily Oral therapy in Multiple Sclerosis), a Phase III placebo-controlled trial, showed that fingolimod (0.5 or 1.25 mg) reduced the relapse rate and disability in multiple sclerosis, compared to placebo. Fingolimod (0.5 or 1.25 mg) has been compared to interferon β-1a in a Phase III clinical trial (TRANSFORMS; Trial Assessing Injectable Interferon versus FTY720 Oral in Relapsing-Remitting Multiple Sclerosis) and shown to be more efficacious than interferon β-1a in reducing relapse rates. However, fingolimod did increase the risk of infections and skin cancers. Conclusions: Only the lower dose of fingolimod (0.5 mg), which possibly has less toxicity, should be considered for prevention of relapses in relapsing-remitting multiple sclerosis.

Does the p38 MAP kinase inhibitor pamapimod have potential for the treatment of rheumatoid arthritis?

Background: Methotrexate alone or in combination with other agents is the standard treatment for moderate-to-severe rheumatoid arthritis. As the biological agents are expensive, they are not usually used until methotrexate has failed to give a good response. Thus, there is scope for the development of cheaper drugs that can be used instead of methotrexate or in addition to methotrexate. Objectives/methods: Pamapimod is a p38α inhibitor being developed for use in the treatment of rheumatoid arthritis. The objective was to evaluate the recent clinical trials of pamapimod in subjects with rheumatoid arthritis. Results: There is no clear cut evidence that pamapimod alone or in the presence of methotrexate is efficacious in subjects with rheumatoid arthritis, but it does cause adverse effects. Conclusion: It is unlikely that pamapimod will be useful in the treatment of rheumatoid arthritis.

Resolvin inflammation with pain

Background: Inflammation and pain coexist in conditions such as arthritis, inflammatory bowel disease, and lower back pain. The drugs currently used to treat the combination of inflammation and pain all have disadvantages. Thus, new drugs and new approaches are needed to treat inflammation with pain. The resolvins are considered to be part of the natural resolving mechanism for inflammation, and have been shown to prevent inflammation in animal models. Objectives/methods: To evaluate a paper suggesting that the resolvins RvE1 and RvD1 attenuate inflammatory pain in animal models. Results: RvE1 has been shown to attenuate inflammation and, to a lesser extent, pain in animal models. Limited results are presented of the effectiveness of RvD1 against inflammatory pain. Conclusion: Drugs that mimic or potentiate the effects of the resolvins may be useful for the treatment of some inflammation with pain.

Application of reinforcement learning in an open railway access market price negotiation

In an open railway access market price negotiation, it is feasible to achieve higher cost recovery by applying the principles of price discrimination. The price negotiation can be modeled as an optimization problem of revenue intake. In this paper, we present the pricing negotiation based on reinforcement learning model. A negotiated-price setting technique based on agent learning is introduced, and the feasible applications of the proposed method for open railway access market simulation are discussed.

The conflict resolution in connected railway junctions

Purpose of study: Traffic conflicts occur when trains on different routes approach a converging junction in a railway network at the same time. To prevent collisions, a right-of-way assignment is needed to control the order in which the trains should pass the junction. Such control action inevitably requires the braking and/or stopping of trains, which lengthens their travelling times and leads to delays. Train delays cause a loss of punctuality and hence directly affect the quality of service. It is therefore important to minimise the delays by devising a suitable right-of-way assignment. One of the major difficulties in attaining the optimal right-of-way assignment is that the number of feasible assignments increases dramatically with the number of trains. Connected-junctions further complicate the problem. Exhaustive search for the optimal solution is time-consuming and infeasible for area control (multi-junction). Even with the more intelligent deterministic optimisation method revealed in [1], the computation demand is still considerable, which hinders real-time control. In practice, as suggested in [2], the optimality may be traded off by shorter computation time, and heuristic searches provide alternatives for this optimisation problem.

Coast control of train movement with genetic algorithms

Railway service is now the major transportation means in most of the countries around the world. With the increasing population and expanding commercial and industrial activities, a high quality of railway service is the most desirable. We present an application of genetic algorithms (GA) to search for the appropriate coasting point(s) and investigate the possible improvement on fitness of genes. Single and multiple coasting point control with simple GA are developed to attain the solutions and their corresponding train movement is examined. The multiple coasting point control with hierarchical genetic algorithm (HGA) is then proposed to integrate the determination of the number of coasting points.

Coasting control of train operation by genetic algorithm

Balancing between the provision of high quality of service and running within a tight budget is one of the biggest challenges for most metro railway operators around the world. Conventionally, one possible approach for the operator to adjust the time schedule is to alter the stop time at stations, if other system constraints, such as traction equipment characteristic, are not taken into account. Yet it is not an effective, flexible and economical method because the run-time of a train simply cannot be extended without limitation, and a balance between run-time and energy consumption has to be maintained. Modification or installation of a new signalling system not only increases the capital cost, but also affects the normal train service. Therefore, in order to procure a more effective, flexible and economical means to improve the quality of service, optimisation of train performance by coasting point identification has become more attractive and popular. However, identifying the necessary starting points for coasting under the constraints of current service conditions is no simple task because train movement is attributed by a large number of factors, most of which are non-linear and inter-dependent. This paper presents an application of genetic algorithms (GA) to search for the appropriate coasting points and investigates the possible improvement on computation time and fitness of genes.

Generation evolution in GA application on railway traffic control

This paper presents a Genetic Algorithms (GA) approach to resolve traffic conflicts at a railway junction. The formulation of the problem for the suitable application of GA will be discussed and three neighborhoods have been proposed for generation evolution. The performance of the GA is evaluated by computer simulation. This study paves the way for more applications of artificial intelligence techniques on a rather conservative industry.

Railway junction conflict resolution by local search method

This study investigates the application of local search methods on the railway junction traffic conflict-resolution problem, with the objective of attaining a quick and reasonable solution. A procedure based on local search relies on finding a better solution than the current one by a search in the neighbourhood of the current one. The structure of neighbourhood is therefore very important to an efficient local search procedure. In this paper, the formulation of the structure of the solution, which is the right-of-way sequence assignment, is first described. Two new neighbourhood definitions are then proposed and the performance of the corresponding local search procedures is evaluated by simulation. It has been shown that they provide similar results but they can be used to handle different traffic conditions and system requirements.

Patterns, heuristics for architectural design support: making use of evolutionary modelling in design

Software used by architectural and industrial designers – has moved from becoming a tool for drafting, towards use in verification, simulation, project management and project sharing remotely. In more advanced models, parameters for the designed object can be adjusted so a family of variations can be produced rapidly. With advances in computer aided design technology, numerous design options can now be generated and analyzed in real time. However the use of digital tools to support design as an activity is still at an early stage and has largely been limited in functionality with regard to the design process. To date, major CAD vendors have not developed an integrated tool that is able to both leverage specialized design knowledge from various discipline domains (known as expert knowledge systems) and support the creation of design alternatives that satisfy different forms of constraints. We propose that evolutionary computing and machine learning be linked with parametric design techniques to record and respond to a designer’s own way of working and design history. It is expected that this will lead to results that impact on future work on design support systems-(ergonomics and interface) as well as implicit constraint and problem definition for problems that are difficult to quantify.

A Heuristic algorithm for fixed train runtime

This paper proposes a train movement model with fixed runtime that can be employed to find feasible control strategies for a single train along an inter-city railway line. The objective of the model is to minimize arrival delays at each station along railway lines. However, train movement is a typical nonlinear problem for complex running environments and different requirements. A heuristic algorithm is developed to solve the problem in this paper and the simulation results show that the train could overcome the disturbance from train delay and coordinates the operation strategies to sure punctual arrival of trains at the destination. The developed algorithm can also be used to evaluate the running reliability of trains in scheduled timetables.