The relationship between Bayesian motor unit number estimation and histological measurements of motor neurons in wild-type and SOD1 G93A mice

Objective: To assess the relationship between Bayesian MUNE and histological motor neuron counts in wild-type mice and in an animal model of ALS. Methods: We performed Bayesian MUNE paired with histological counts of motor neurons in the lumbar spinal cord of wild-type mice and transgenic SOD1 G93A mice that show progressive weakness over time. We evaluated the number of acetylcholine endplates that were innervated by a presynaptic nerve. Results: In wild-type mice, the motor unit number in the gastrocnemius muscle estimated by Bayesian MUNE was approximately half the number of motor neurons in the region of the spinal cord that contains the cell bodies of the motor neurons supplying the hindlimb crural flexor muscles. In SOD1 G93A mice, motor neuron numbers declined over time. This was associated with motor endplate denervation at the end-stage of disease. Conclusion: The number of motor neurons in the spinal cord of wild-type mice is proportional to the number of motor units estimated by Bayesian MUNE. In SOD1 G93A mice, there is a lower number of estimated motor units compared to the number of spinal cord motor neurons at the end-stage of disease, and this is associated with disruption of the neuromuscular junction. Significance: Our finding that the Bayesian MUNE method gives estimates of motor unit numbers that are proportional to the numbers of motor neurons in the spinal cord supports the clinical use of Bayesian MUNE in monitoring motor unit loss in ALS patients. © 2012 International Federation of Clinical Neurophysiology.

Up the junction? Exploiting knowledge-based development through supply chain and SME cluster interactions

Maximisation of Knowledge-Based Development (KBD) benefits requires effective dissemination and utilisation mechanisms to accompany the initial knowledge creation process. This work highlights the potential for interactions between Supply Chains (SCs) and Small and Medium sized Enterprise Clusters (SMECs), (including via ‘junction’ firms which are members of both networks), to facilitate such effective dissemination and utilisation of knowledge. In both these network types there are firms that readily utilise their relationships and ties for ongoing business success through innovation. The following chapter highlights the potential for such beneficial interactions between SCs and SMECs in key elements of KBD, particularly knowledge management, innovation and technology transfer. Because there has been little focus on the interactions between SCs and SMECs, particularly when firms simultaneously belong to both, this chapter examines the conduits through which information and knowledge can be transferred and utilised. It shows that each network type has its own distinct advantages in the types of information searched for and transferred amongst network member firms. Comparing and contrasting these advantages shows opportunities for both networks to leverage the knowledge sharing strengths of each other, through these ‘junctions’ to address their own weaknesses, allowing implications to be drawn concerning new ways of utilising relationships for mutual network gains.

Coordinated road-junction traffic control by dynamic programming

This paper presents a novel approach to road-traffic control for interconnected junctions. With a local fuzzy-logic controller (FLC) installed at each junction, a dynamic-programming (DP) technique is proposed to derive the green time for each phase in a traffic-light cycle. Coordination parameters from the adjacent junctions are also taken into consideration so that organized control is extended beyond a single junction. Instead of pursuing the absolute optimization of traffic delay, this study examines a practical approach to enable the simple implementation of coordination among junctions, while attempting to reduce delays, if possible. The simulation results show that the delay per vehicle can be substantially reduced, particularly when the traffic demand reaches the junction capacity. The implementation of this controller does not require complicated or demanding hardware, and such simplicity makes it a useful tool for offline studies or realtime control purposes.

Railway junction traffic control by heuristic methods

Traffic conflicts at railway junctions are very conmon, particularly on congested rail lines. While safe passage through the junction is well maintained by the signalling and interlocking systems, minimising the delays imposed on the trains by assigning the right-of-way sequence sensibly is a bonus to the quality of service. A deterministic method has been adopted to resolve the conflict, with the objective of minimising the total weighted delay. However, the computational demand remains significant. The applications of different heuristic methods to tackle this problem are reviewed and explored, elaborating their feasibility in various aspects and comparing their relative merits for further studies. As most heuristic methods do not guarantee a global optimum, this study focuses on the trade-off between computation time and optimality of the resolution.

Fuzzy logic traffic control at a road junction with time-varying flow rates

Fuzzy logic has been applied to control traffic at road junctions. A simple controller with one fixed rule-set is inadequate to minimise delays when traffic flow rate is time-varying and likely to span a wide range. To achieve better control, fuzzy rules adapted to the current traffic conditions are used.

Railway junction conflict resolution by genetic algorithm

In general, simple and traditional methods are applied to resolve traffic conflicts at railway junctions. They are, however, either inefficient or computationally demanding. A simple genetic algorithm is presented to enable a search for a near optimal resolution to be carried out while meeting the constraints on generation evolution and minimising the search time.

Hierarchical fuzzy logic traffic control at a road junction

Traffic control at road junctions is one of the major concerns in most metropolitan cities. Controllers of various approaches are available and the required control action is the effective green-time assigned to each traffic stream within a traffic-light cycle. The application of fuzzy logic provides the controller with the capability to handle uncertain natures of the system, such as drivers’ behaviour and random arrivals of vehicles. When turning traffic is allowed at the junction, the number of phases in the traffic-light cycle increases. The additional input variables inevitably complicate the controller and hence slow down the decision-making process, which is critical in this real-time control problem. In this paper, a hierarchical fuzzy logic controller is proposed to tackle this traffic control problem at a 2-way road junction with turning traffic. The two levels of fuzzy logic controllers devise the minimum effective green-time and fine-tune it respectively at each phase of a traffic-light cycle. The complexity of the controller at each level is reduced with smaller rule-set. The performance of this hierarchical controller is examined by comparison with a fixed-time controller under various traffic conditions. Substantial delay reduction has been achieved as a result and the performance and limitation of the controller will be discussed.

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.

Hierarchical fuzzy logic traffic control at a road junction using genetic algorithms

Traffic control at a road junction by a complex fuzzy logic controller is investigated. The increase in the complexity of junction means more number of input variables must be taken into account, which will increase the number of fuzzy rules in the system. A hierarchical fuzzy logic controller is introduced to reduce the number of rules. Besides, the increase in the complexity of the controller makes formulation of the fuzzy rules difficult. A genetic algorithm based off-line leaning algorithm is employed to generate the fuzzy rules. The learning algorithm uses constant flow-rates as training sets. The system is tested by both constant and time-varying flow-rates. Simulation results show that the proposed controller produces lower average delay than a fixed-time controller does under various traffic conditions.

Substrate recognition and catalysis by the Holliday junction resolving enzyme Hje

Two archaeal Holliday junction resolving enzymes, Holliday junction cleavage (Hjc) and Holliday junction endonuclease (Hje), have been characterized. Both are members of a nuclease superfamily that includes the type II restriction enzymes, although their DNA cleaving activity is highly specific for four-way junction structure and not nucleic acid sequence. Despite 28% sequence identity, Hje and Hjc cleave junctions with distinct cutting patterns—they cut different strands of a four-way junction, at different distances from the junction centre. We report the high-resolution crystal structure of Hje from Sulfolobus solfataricus. The structure provides a basis to explain the differences in substrate specificity of Hje and Hjc, which result from changes in dimer organization, and suggests a viral origin for the Hje gene. Structural and biochemical data support the modelling of an Hje:DNA junction complex, highlighting a flexible loop that interacts intimately with the junction centre. A highly conserved serine residue on this loop is shown to be essential for the enzyme's activity, suggesting a novel variation of the nuclease active site. The loop may act as a conformational switch, ensuring that the active site is completed only on binding a four-way junction, thus explaining the exquisite specificity of these enzymes.

Neuromuscular imbalances in the track sprinter

Athletic coaching can involve observation of a motor control task and then proposing guidance to an athlete about how the task performance can be developed. Coaches can identify the technique elements that seem to hinder performance and then provide instruction. Recently, a variety of training methods were proposed to enhance sprint performance, however a number of authors have identified these methods as characterised by low scientific evaluation or support (Brown & Vescovi, 2012; Jones, Bezodis, & Thompson, 2009). This article will outline a scientifically robust neuromuscular theory underlying poor movement techniques that may be visible when coaches observe sprint performance. The goal of this article is to inform the sprint coach of a method to identify and correct suboptimal biomechanics to enhance athletic performance.

A spatiotemporal analysis of gait freezing and the impact of pedunculopontine nucleus stimulation

Gait freezing is an episodic arrest of locomotion due to an inability to take normal steps. Pedunculopontine nucleus stimulation is an emerging therapy proposed to improve gait freezing, even where refractory to medication. However, the efficacy and precise effects of pedunculopontine nucleus stimulation on Parkinsonian gait disturbance are not established. The clinical application of this new therapy is controversial and it is unknown if bilateral stimulation is more effective than unilateral. Here, in a double-blinded study using objective spatiotemporal gait analysis, we assessed the impact of unilateral and bilateral pedunculopontine nucleus stimulation on triggered episodes of gait freezing and on background deficits of unconstrained gait in Parkinson’s disease. Under experimental conditions, while OFF medication, Parkinsonian patients with severe gait freezing implanted with pedunculopontine nucleus stimulators below the pontomesencephalic junction were assessed during three conditions; off stimulation, unilateral stimulation and bilateral stimulation. Results were compared to Parkinsonian patients without gait freezing matched for disease severity and healthy controls. Pedunculopontine nucleus stimulation improved objective measures of gait freezing, with bilateral stimulation more effective than unilateral. During unconstrained walking, Parkinsonian patients who experience gait freezing had reduced step length and increased step length variability compared to patients without gait freezing; however, these deficits were unchanged by pedunculopontine nucleus stimulation. Chronic pedunculopontine nucleus stimulation improved Freezing of Gait Questionnaire scores, reflecting a reduction of the freezing encountered in patients’ usual environments and medication states. This study provides objective, double-blinded evidence that in a specific subgroup of Parkinsonian patients, stimulation of a caudal pedunculopontine nucleus region selectively improves gait freezing but not background deficits in step length. Bilateral stimulation was more effective than unilateral.

The role of neuromuscular inhibition in hamstring strain injury recurrence

Hamstring strain injuries are amongst the most common and problematic injuries in a wide range of sports that involve high speed running. The comparatively high rate of hamstring injury recurrence is arguably the most concerning aspect of these injuries. A number of modifiable and nonmodifiable risk factors are proposed to predispose athletes to hamstring strains. Potentially, the persistence of risk factors and the development of maladaptations following injury may explain injury recurrence. Here, the role of neuromuscular inhibition following injury is discussed as a potential mechanism for several maladaptations associated with hamstring re-injury. These maladaptations include eccentric hamstring weakness, selective hamstring atrophy and shifts in the knee flexor torque-joint angle relationship. Current evidence indicates that athletes return to competition after hamstring injury having developed maladaptations that predispose them to further injury. When rehabilitating athletes to return to competition following hamstring strain injury, the role of neuromuscular inhibition in re-injury should be considered.