A review of key planning and scheduling in the rail industry in Europe and UK

Planning and scheduling activities within the rail industry have benefited from developments in computer-based simulation and modelling techniques over the last 25 years. Increasingly, the use of computational intelligence in such tasks is featuring more heavily in research publications. This paper examines a number of common rail-based planning and scheduling activities and how they benefit from five broad technology approaches. Summary tables of papers are provided relating to rail planning and scheduling activities and to the use of expert and decision systems in the rail industry.EPSR

Ventral Tegmental Area Regulation Of Stress-Induced Reinstatement Of Cocaine-Seeking Behavior

No FDA approved medications currently exist for the prevention of drug craving, drug seeking, and relapse to cocaine use. Stress is a major factor in causing relapse in cocaine dependent individuals. Cocaine use is positively correlated with stress-induced craving and relapse outcomes. Corticotropin-releasing factor (CRF) is a 41-amino acid neuropeptide that plays an important role in the stress response and in the reinstatement rodent model of stress-induced relapse. CRF is released during stress in brain regions associated with the effects of drugs of abuse, notably the ventral tegmental area (VTA). This dissertation addresses key unknown mechanisms behind drug-induced neuroplasticity and how that neuroplasticity gates the ability of stress to cause relapse. Chapter two reports that stress and intra-VTA CRF administration produces robust reinstatement in animals allowed extended long-access (LgA) but not short-access (ShA) cocaine self-administration. Moreover, LgA cocaine use increases susceptibility to stressor-induced relapse in part by augmenting CRF receptor 1 (CRF-R1) dependent regulation of VTA neurocircuitry. Chapter three characterizes VTA dopamine neuron activation under conditions where stress reinstates cocaine seeking. Dopamine neuron activation was significantly increased in ShA but not LgA rats. However, when examined across groups only in rats that display relapse in response to stress is a significant increase in dopamine neuron activation observed. This suggests that stress-induced reinstatement is associated with increased activation of VTA dopamine neurons. Lastly, chapter 4 addresses the necessity of VTA glutamate and GABA receptors in footshock and intra-VTA CRF dependent reinstatement of cocaine seeking. Intra-VTA administration of NMDA, AMPA, and GABAA receptor antagonists fail to block reinstatement. In contrast, GABAB receptor antagonism blocked reinstatement by both footshock and intra-VTA CRF suggesting GABAB activation is necessary for CRF actions in the VTA. The findings from this dissertation provide much needed insight into the neuroadaptations that occur in the VTA to regulate later stressor induced relapse in cocaine addicts. The hope is that these findings will help with the understanding and eventual long-term management of stressor-induced relapse in abstinent cocaine addicts

A software architecture for autonomous maintenance scheduling: Scenarios for UK and European Rail

A new era of automation in rail has begun offering developments in the operation and maintenance of industry standard systems. This article documents the development of an architecture and range of scenarios for an autonomous system for rail maintenance planning and scheduling. The Unified Modelling Language (UML) has been utilized to visualize and validate the design of the prototype. A model for information exchange between prototype components and related maintenance planning systems is proposed in this article. Putting forward an architecture and set of usage mode scenarios for the proposed system, this article outlines and validates a viable platform for autonomous planning and scheduling in rail

An intelligent framework and prototype for autonomous maintenance planning in the rail industry

This paper details the development of the AUTONOM project, a project that aims to provide an enterprise system tailored to the planning needs of the rail industry. AUTONOM extends research in novel sensing, scheduling, and decision-making strategies customised for the automated planning of maintenance activities within the rail industry. This paper sets out a framework and software prototype and details the current progress of the project. In the continuation of the AUTONOM project it is anticipated that the combination of techniques brought together in this work will be capable of addressing a wider range of problem types, offered by Network rail and organisations in different industries

Augmented Cocaine Seeking in Response to Stress or CRF Delivered into the Ventral Tegmental Area Following Long-Access Self-Administration Is Mediated by CRF Receptor Type 1 But Not CRF Receptor Type 2

Stressful events are determinants of relapse in recovering cocaine addicts. Excessive cocaine use may increase susceptibility to stressor-induced relapse through alterations in brain corticotropin-releasing factor (CRF) regulation of neurocircuitry involved in drug seeking. We previously reported that the reinstatement of cocaine seeking by a stressor (footshock) is CRF dependent and is augmented in rats that self-administered cocaine under long-access (LgA; 6 h daily) conditions for 14 d when compared with rats provided shorter daily cocaine access [short access (ShA) rats; 2 h daily]. Further, we have demonstrated that reinstatement in response to intracerebroventricular CRF administration is heightened in LgA rats. This study examined the role of altered ventral tegmental area (VTA) responsiveness to CRF in intake-dependent increases in CRF- and stress-induced cocaine seeking. Bilateral intra-VTA administration of CRF (250 or 500 ng/side) produced reinstatement in LgA but not ShA rats. In LgA rats, intra-VTA CRF-induced reinstatement was blocked by administration of the CRF-receptor type 1 (CRF-R1) antagonist antalarmin (500 ng/side) or CP-376395 (500 ng/side), but not the CRF-R2 antagonist astressin-2B (500 ng or 1 μg/side) or antisauvagine-30(ASV-30; 500 ng/side) into the VTA. Likewise, intra-VTA antalarmin, but not astressin-2B, blocked footshock-induced reinstatement in LgA rats. By contrast, neither intra-VTA antalarmin nor CP-376395 altered food-reinforced lever pressing. Intra-VTA injection of the CRF-R1-selective agonist cortagine (100 ng/side) but not the CRF-R2-selective agonist rat urocortin II (rUCN II; 250 ng/side) produced reinstatement. These findings reveal that excessive cocaine use increases susceptibility to stressor-induced relapse in part by augmenting CRF-R1-dependent regulation of addiction-related neurocircuitry in the VTA

Antagonism of GABA-B but not GABA-A receptors in the VTA prevents stress- and intra-VTA CRF-induced reinstatement of extinguished cocaine seeking in rats

Stress-induced reinstatement of cocaine seeking requires corticotropin releasing factor (CRF) actions in the ventral tegmental area (VTA). However the mechanisms through which CRF regulates VTA function to promote cocaine use are not fully understood. Here we examined the role of GABAergic neurotransmission in the VTA mediated by GABA-A or GABA-B receptors in the reinstatement of extinguished cocaine seeking by a stressor, uncontrollable intermittent footshock, or bilateral intra-VTA administration of CRF. Rats underwent repeated daily cocaine self-administration (1.0 mg/kg/ing; 14 × 6 h/day) and extinction and were tested for reinstatement in response to footshock (0.5 mA, 0.5” duration, average every 40 s; range 10–70 s) or intra-VTA CRF delivery (500 ng/side) following intra-VTA pretreatment with the GABA-A antagonist, bicuculline, the GABA-B antagonist, 2-hydroxysaclofen or vehicle. Intra-VTA bicuculline (1, 10 or 20 ng/side) failed to block footshock- or CRF-induced cocaine seeking at either dose tested. By contrast, 2-hydroxysaclofen (0.2 or 2 μg/side) prevented reinstatement by both footshock and intra-VTA CRF at a concentration that failed to attenuate food-reinforced lever pressing (45 mg sucrose-sweetened pellets; FR4 schedule) in a separate group of rats. These data suggest that GABA-B receptor-dependent CRF actions in the VTA mediate stress-induced cocaine seeking and that GABA-B receptor antagonists may have utility for the management of stress-induced relapse in cocaine addicts

Casting a Wide Net: Role of Perineuronal Nets in Neural Plasticity.

Perineuronal nets (PNNs) are unique extracellular matrix structures that wrap around certain neurons in the CNS during development and control plasticity in the adult CNS. They appear to contribute to a wide range of diseases/disorders of the brain, are involved in recovery from spinal cord injury, and are altered during aging, learning and memory, and after exposure to drugs of abuse. Here the focus is on how a major component of PNNs, chondroitin sulfate proteoglycans, control plasticity, and on the role of PNNs in memory in normal aging, in a tauopathy model of Alzheimer's disease, and in drug addiction. Also discussed is how altered extracellular matrix/PNN formation during development may produce synaptic pathology associated with schizophrenia, bipolar disorder, major depression, and autism spectrum disorders. Understanding the molecular underpinnings of how PNNs are altered in normal physiology and disease will offer insights into new treatment approaches for these diseases

Neurobiological Mechanisms That Contribute to Stress-related Cocaine Use

The ability of stressful life events to trigger drug use is particularly problematic for the management of cocaine addiction due to the unpredictable and often uncontrollable nature of stress. For this reason, understanding the neurobiological processes that contribute to stress-related drug use is important for the development of new and more effective treatment strategies aimed at minimizing the role of stress in the addiction cycle. In this review we discuss the neurocircuitry that has been implicated in stress-induced drug use with an emphasis on corticotropin releasing factor actions in the ventral tegmental area (VTA) and an important pathway from the bed nucleus of the stria terminalis to the VTA that is regulated by norepinephrine via actions at beta adrenergic receptors. In addition to the neurobiological mechanisms that underlie stress-induced cocaine seeking, we review findings suggesting that the ability of stressful stimuli to trigger cocaine use emerges and intensifies in an intake-dependent manner with repeated cocaine self-administration. Further, we discuss evidence that the drug-induced neuroadaptations that are necessary for heightened susceptibility to stress-induced drug use are reliant on elevated levels of glucocorticoid hormones at the time of cocaine use. Finally, the potential ability of stress to function as a “stage setter” for drug use – increasing sensitivity to cocaine and drug-associated cues – under conditions where it does not directly trigger cocaine seeking is discussed. As our understanding of the mechanisms through which stress promotes drug use advances, the hope is that so too will the available tools for effectively managing addiction, particularly in cocaine addicts whose drug use is stress-driven

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse