Rail Track Maintenance Planning: An Assessment Model

In Australia, railway track maintenance costs comprise between 25-35 percent of total freight train operating costs. Track maintenance planning models have been shown to reduce maintenance costs by 5 to 10 percent though improved planning. This paper describes a model which has been developed to deal with the track maintenance planning function at the medium to long-term levels. This model simulates the impacts of degrading railway track conditions and related maintenance work, in contrast to tradition models that mainly use expert systems. The model simulates the degrading track condition using an existing track degradation model. Track condition data from that model is used to determine if safety related speed restrictions are needed and what immediate maintenance work may be required for safe train operations. The model outputs the net present value of the benefits of undertaking a given maintenance strategy, when compared with a base-case scenario. The model approach has advantages over current models in investigating what if scenarios. The track engineer can assess the possible benefits in reduced operating costs from upgrading track infrastructure or from the use of improved maintenance equipment. After describing the model inputs and the assumptions used, the paper deals with the simulation of track maintenance and of train operating costs over time. The results of applying the model to a test track section using a number of different maintenance strategies are also given

Perturbation Detection Through Modeling of Gene Expression on a Latent Biological Pathway Network: A Bayesian hierarchical approach

Cellular response to a perturbation is the result of a dynamic system of biological variables linked in a complex network. A major challenge in drug and disease studies is identifying the key factors of a biological network that are essential in determining the cell's fate. Here our goal is the identification of perturbed pathways from high-throughput gene expression data. We develop a three-level hierarchical model, where (i) the first level captures the relationship between gene expression and biological pathways using confirmatory factor analysis, (ii) the second level models the behavior within an underlying network of pathways induced by an unknown perturbation using a conditional autoregressive model, and (iii) the third level is a spike-and-slab prior on the perturbations. We then identify perturbations through posterior-based variable selection. We illustrate our approach using gene transcription drug perturbation profiles from the DREAM7 drug sensitivity predication challenge data set. Our proposed method identified regulatory pathways that are known to play a causative role and that were not readily resolved using gene set enrichment analysis or exploratory factor models. Simulation results are presented assessing the performance of this model relative to a network-free variant and its robustness to inaccuracies in biological databases

Algebraic and combinatorial aspects of sandpile monoids on directed graphs

The sandpile group of a graph is a well-studied object that combines ideas from algebraic graph theory, group theory, dynamical systems, and statistical physics. A graph's sandpile group is part of a larger algebraic structure on the graph, known as its sandpile monoid. Most of the work on sandpiles so far has focused on the sandpile group rather than the sandpile monoid of a graph, and has also assumed the underlying graph to be undirected. A notable exception is the recent work of Babai and Toumpakari, which builds up the theory of sandpile monoids on directed graphs from scratch and provides many connections between the combinatorics of a graph and the algebraic aspects of its sandpile monoid. In this paper we primarily consider sandpile monoids on directed graphs, and we extend the existing theory in four main ways. First, we give a combinatorial classification of the maximal subgroups of a sandpile monoid on a directed graph in terms of the sandpile groups of certain easily-identifiable subgraphs. Second, we point out certain sandpile results for undirected graphs that are really results for sandpile monoids on directed graphs that contain exactly two idempotents. Third, we give a new algebraic constraint that sandpile monoids must satisfy and exhibit two infinite families of monoids that cannot be realized as sandpile monoids on any graph. Finally, we give an explicit combinatorial description of the sandpile group identity for every graph in a family of directed graphs which generalizes the family of (undirected) distance-regular graphs. This family includes many other graphs of interest, including iterated wheels, regular trees, and regular tournaments.Comment: v2: Cleaner presentation, new results in final section. Accepted for publication in J. Combin. Theory Ser. A. 21 pages, 5 figure

Ventricular Tachycardia in the Absence of Structural Heart Disease

In up to 10% of patients who present with ventricular tachycardia (VT), obvious structural heart disease is not identified. In such patients, causes of ventricular arrhythmia include right ventricular outflow tract (RVOT) VT, extrasystoles, idiopathic left ventricular tachycardia (ILVT), idiopathic propranolol-sensitive VT (IPVT), catecholaminergic polymorphic VT (CPVT), Brugada syndrome, and long QT syndrome (LQTS). RVOT VT, ILVT, and IPVT are referred to as idiopathic VT and generally do not have a familial basis. RVOT VT and ILVT are monomorphic, whereas IPVT may be monomorphic or polymorphic. The idiopathic VTs are classified by the ventricle of origin, the response to pharmacologic agents, catecholamine dependence, and the specific morphologic features of the arrhythmia. CPVT, Brugada syndrome, and LQTS are inherited ion channelopathies. CPVT may present as bidirectional VT, polymorphic VT, or catecholaminergic ventricular fibrillation. Syncope and sudden death in Brugada syndrome are usually due to polymorphic VT. The characteristic arrhythmia of LQTS is torsades de pointes. Overall, patients with idiopathic VT have a better prognosis than do patients with ventricular arrhythmias and structural heart disease. Initial treatment approach is pharmacologic and radiofrequency ablation is curative in most patients. However, radiofrequency ablation is not useful in the management of inherited ion channelopathies. Prognosis for patients with VT secondary to ion channelopathies is variable. High-risk patients (recurrent syncope and sudden cardiac death survivors) with inherited ion channelopathies benefit from implantable cardioverter-defibrillator placement. This paper reviews the mechanism, clinical presentation, and management of VT in the absence of structural heart disease

Computational modeling of TC0583 as a putative component of the Chlamydia muridarum V-type ATP synthase complex and assessment of its protective capabilities as a vaccine antigen.

Numerous Chlamydia trachomatis proteins have been identified as potential subunit vaccines, of which the major outer-membrane protein (MOMP) has, so far, proven the most efficacious. Recently, subunit A of the V-type ATP synthase (ATPase; TC0582) complex was shown to elicit partial protection against infection. Computational modeling of a neighboring gene revealed a novel subunit of the V-type ATPase (TC0583). To determine if this newly identified subunit could induce protection and/or enhance the partial protection provided by subunit A alone, challenge studies were performed using a combination of these recombinant proteins. The TC0583 subunit alone and concurrently with TC0582, was used to vaccinate BALB/c mice utilizing CpG-1826 and Montanide ISA 720 VG as adjuvants. Vaccinated animals were challenged intranasally with Chlamydia muridarum and the course of the infection was followed. Mice immunized with individual antigens showed minimal alleviation of body weight reduction; however, mice immunized with TC0583 and TC0582 in combination, displayed weight loss levels close to those observed with MOMP. Importantly, immunization with a combination of recombinant subunit proteins reduced chlamydial inclusion forming units by approximately a log-fold. These protection levels support that, these highly conserved Chlamydia proteins, in combination with other antigens, may serve as potential vaccine candidates

A European research agenda for lifelong learning

It is a generally accepted truth that without a proper educational system no country will prosper, nor will its inhabitants. With the arrival of the post-industrial society, in Europe and elsewhere, it has become increasingly clear that people should continue learning over their entire life-spans lest they or their society suffer the dire consequences. But what does this future lifelong learning society exactly look like? And how then should education prepare for it? What should people learn and how should they do so? How can we afford to pay for all this, what are the socio-economic constraints of the move towards a lifelong-learning society? And, of course, what role can and should the educational establishment of schools and universities play? This are questions that demand serious research efforts, which is what this paper argues for