789 research outputs found

    Virtual reality learning resources in building pathology

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    Building surveying students must be capable of analysing the condition of buildings and their components and, where this falls below an agreed standard, make recommendations for their repair. Hence university courses must provide opportunities for students to learn about the main causes of deterioration. Fieldwork exercises are essential but there are often problems locating appropriate buildings, programming visits to satisfy course timetables and complying with health and safety requirements. Whilst virtual surveys of existing buildings are not considered to be a substitute for real-life educational visits, this paper critically examines the development of a novel building pathology educational resource. Alternative technologies for creating digital panoramas are examined, prior to the development of an interactive case study, which enables students to conduct an on-line survey of a Grade 1 listed 16th Century hunting lodge. 360 degree panoramic scenes are linked with hot spots to create an interactive virtual tour of the building. The paper considers how virtual resources can be embedded within the curriculum, gauges tutor reaction to case study materials and identifies opportunities for the development of a suite of building pathology educational media-rich learning materials

    B. How a Major Creditor Views the New Proposals

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    SUMMARY The articles by Jolyon Larkman, Sir Kit McMahon and Sir Jeremy Morse all evaluate critically the Brady Proposals. RESUME Les articles de Jolyon Larkman, Sir Kit McMahon et Sir Jeremy Morse font tous une évaluation critique des propositions Brady. RESUMEN Los artículos de Jolyon Larkman, Sir Kit McMahon y Sir Jeremy Morse constituyen una evaluación crítica de la propuesta Brady

    The electrophysiology of adult rat facial motoneurones in a novel In Vitro brainstem slice: ionic mechanism and pharmacological characterisation of serotonin (5-hydroxytryptamine)-evoked depolarization

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    This study describes intracellular recordings from adult rat cranial motoneurones constituting the Facial Motor Nucleus of the brainstem, using a novel in vitro slice. Facial motoneurones (FMn's) were identified histologically using retrograde labelling with HRP and by antidromic invasion. Antidromically evoked action potentials were overshooting, with initial segment and somato-dendritic components and were often followed by depolarizing potentials. Directly-evoked overshooting action potentials were followed by a fast after hyperpolarization, a brief delayed depolarization and a longer lasting apamin sensitive ahp which was annulled near the predicted equilibrium potential for K⁺ ions. Intracellular Cs+ led to a widening of the spike and a reduction in the amplitude of the ahp. Depolarizing current pulses of longer duration showed a depolarizing prepotential to precede spike generation. Passive membrane properties were investigated using longer duration current pulses and showed the response to be ohmic over a narrow voltage range around rest. The time constant for membrane charging (r) ranged from 1.5 to 4msec. Larger hyperpolarizing current pulses evoked voltage responses with a time dependent sag characteristic of inward "anomalous" rectification which reached steady state within the pulse. A rebound depolarizing potential occurred subsequent to the current pulse. Voltage clamp studies showed this sag to be the result of a slowly developing inward current.Intracellular recordings in vitro from a variety of central neuronal types have shown both inhibition and excitation to be modulatory consequences of serotonin receptor activation. Iontophoretic application of 5-HT in vivo on rat facial motoneurones has been shown to evoke a depolarization associated with increased input resistance (Rm). This study has confirmed and further investigated the mechanism and pharmacology of this action in vitro. Superfusion of 5-HT evokes a slow depolarization associated with increased Rm, and a lengthening of r through a direct action on the post-synaptic membrane. Manual clamping of the membrane potential at the peak of the 5-HT response back to control levels shows a component of the increase in Rm to be due to voltage dependent rectification. Estimated reversal potentials from peak currentvoltage plots under these conditions were more negative than the predicted K⁺ equilibrium potential. Increasing the extracellular K⁺ concentration, [K⁺]ₒ, shifted the reversal potential to more positive values in a manner predicted by the Nernst equation for a K⁺ conductance. Nor-adrenaline (NA) evoked a similar depolarization associated with increased Rm. However, lower NA concentrations were needed for equivalent size depolarizations and the change in input resistance was usually greater. The estimated reversal potential for the NA effect was more positive than for 5-HT and when manually clamped agreed well with the predicted value. Increasing [K⁺]ₒ changed the reversal potential to a more positive level. Voltage clamp studies show both 5-HT and NA to evoke a slow inward current associated with a decrease in conductance which was greater for NA. 8-OH-DPAT and dipropyl-5-CT, 5-HT₁ₐ selective agonists and 2-CH₃-5-HT a 5-HT₃ agonist were unable to mimic or antagonise 5-HT evoked responses. Methysergide selectively antagonized the 5-HT response leaving the NA response unaffected. LY-53857 also antagonised the 5-HT response while ketanserin was unable to fully abolish 5-HT depolarization even after prolonged expposure. Spiperone, methiothepin and ICS 205-930 were all ineffective antagonists

    Differential sensitivity of TREK-1, TREK-2 and TRAAK background potassium channels to the polycationic dye ruthenium red

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    BACKGROUND AND PURPOSE: Pharmacological separation of the background potassium currents of closely related K2P channels is a challenging problem. We previously demonstrated that ruthenium red (RR) inhibits TASK-3 (K2 P 9.1), but not TASK-1 (K2 P 3.1) channels. RR has been extensively used to distinguish between TASK currents in native cells. In the present study, we systematically investigate the RR sensitivity of a more comprehensive set of K2 P channels. EXPERIMENTAL APPROACH: K+ currents were measured by two-electrode voltage clamp in Xenopus oocytes and by whole-cell patch clamp in mouse dorsal root ganglion (DRG) neurons. KEY RESULTS: RR differentiates between two closely related members of the TREK subfamily. TREK-2 (K2 P 10.1) proved to be highly sensitive to RR (IC50 = 0.2 muM), whereas TREK-1 (K2 P 2.1) was not affected by the compound. We identified aspartate 135 (D135) as the target of the inhibitor in mouse TREK-2c. D135 lines the wall of the extracellular ion pathway (EIP), a tunnel structure through the extracellular cap characteristic for K2 P channels. TREK-1 contains isoleucine in the corresponding position. The mutation of this isoleucine (I110D) rendered TREK-1 sensitive to RR. The third member of the TREK subfamily, TRAAK (K2 P 4.1) was more potently inhibited by ruthenium violet, a contaminant in some RR preparations, than by RR. DRG neurons predominantly express TREK-2 and RR-resistant TREK-1 and TRESK (K2 P 18.1) background K+ channels. We detected the RR-sensitive leak K+ current component in DRG neurons. CONCLUSIONS AND IMPLICATIONS: We propose that RR may be useful for distinguishing TREK-2 (K2P 10.1) from TREK-1 (K2P 2.1) and other RR-resistant K2 P channels in native cells

    Dyrk1A Influences Neuronal Morphogenesis Through Regulation of Cytoskeletal Dynamics in Mammalian Cortical Neurons

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    Down syndrome (DS) is the most frequent genetic cause of mental retardation. Cognitive dysfunction in these patients is correlated with reduced dendritic branching and complexity, along with fewer spines of abnormal shape that characterize the cortical neuronal profile of DS. DS phenotypes are caused by the disruptive effect of specific trisomic genes. Here, we report that overexpression of dual-specificity tyrosine phosphorylation-regulated kinase 1A, DYRK1A, is sufficient to produce the dendritic alterations observed in DS patients. Engineered changes in Dyrk1A gene dosage in vivo strongly alter the postnatal dendritic arborization processes with a similar progression than in humans. In cultured mammalian cortical neurons, we determined a reduction of neurite outgrowth and synaptogenesis. The mechanism underlying neurite dysgenesia involves changes in the dynamic reorganization of the cytoskeleton

    To what extent does object knowledge bias the perception of goal-directed actions?

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    Predictive processing accounts of action understanding suggest that inferred goals generate top-down predictions that bias perception towards expected goals. These predictions are thought to be derived, in part, from the affordances of available objects. This thesis had three aims: (1) to test whether high-level action goals based on object knowledge can bias action perception, (2) to investigate the degree to which this perceptual bias can be influenced by high-level person knowledge, or by expertise in particular objects, (3) to explore the low-level mechanisms underlying the anticipatory representation of action goals associated with objects. Experiments used a modified representational momentum paradigm, as well as RT-based measures. In Chapter 2, we found that the presentation of a prime object led to a predictive bias in the perception of a subsequent action towards a functionally related target object. This bias was present for reaching actions, but not withdrawing actions (Experiment 1a) and persisted even when the functionally related target was simultaneously presented with an unrelated distractor (Experiment 1b). Crucially, this effect was specific to intentional actions, but was eliminated when the hand was replaced by a non-biological object following the same trajectory. This finding supports predictive processing views that action perception is guided by goal predictions, based on prior knowledge about the context in which the action occurs. We found no evidence that this perceptual bias could be influenced by prior knowledge about the gender of the actor (Chapter 3) or by participants' expertise in particular objects (Chapter 4). Chapter 5 tested for motor biases resulting from object-based goal predictions. Originally designed as a TMS study (Experiment 4a), this was tested online using RT measures as an index for motor preparation. We found no evidence that object affordances can be reliably measured using online RTs. Taken together these findings highlight the important role of object knowledge in action perception, while showing the limits to which this might be modulated by person knowledge and expertise. The final chapter highlights the challenges of developing robust behavioural measures for online testing of object affordances

    Towards three-dimensional non-invasive recording of incised rock art

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    Ancient art cut into rock is difficult to research and manage off-site without precise three-dimensional records. Experiments with photographic modelling by the authors led to a relatively accessible and economical way of making them

    Observed network dynamics from altering the balance between excitatory and inhibitory neurons in cultured networks

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    Complexity in the temporal organization of neural systems may be a reflection of the diversity of its neural constituents. These constituents, excitatory and inhibitory neurons, comprise an invariant ratio in vivo and form the substrate for rhythmic oscillatory activity. To begin to elucidate the dynamical mechanisms that underlie this balance, we construct novel neural circuits not ordinarily found in nature. We culture several networks of neurons composed of excitatory and inhibitory cells and use a multi-electrode array to study their temporal dynamics as the balance is modulated. We use the electrode burst as the temporal imprimatur to signify the presence of network activity. Burst durations, inter-burst intervals, and the number of spikes participating within a burst are used to illustrate the vivid dynamical differences between the various cultured networks. When the network consists largely of excitatory neurons, no network temporal structure is apparent. However, the addition of inhibitory neurons evokes a temporal order. Calculation of the temporal autocorrelation shows that when the number of inhibitory neurons is a major fraction of the network, a striking network pattern materializes when none was previously present
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