The hippocampus and spatial constraints on mental imagery

We review a model of imagery and memory retrieval based on allocentric spatial representation by place cells and boundary vector cells (BVCs) in the medial temporal lobe, and their translation into egocentric images in retrosplenial and parietal areas. In this model, the activity of place cells constrain the contents of imagery and retrieval to be coherent and consistent with the subject occupying a single location, while the activity of head-direction cells along Papez's circuit determine the viewpoint direction for which the egocentric image is generated. An extension of this model is discussed in which a role for grid cells in dynamic updating of representations (mental navigation) is included. We also discuss the extension of this model to implement a version of the dual representation theory of post-traumatic stress disorder (PTSD) in which PTSD arises from an imbalance between weak allocentric hippocampal-mediated contextual representations and strong affective/sensory representations. The implications of these models for behavioral, neuropsychological, and neuroimaging data in humans are explored

Structural response of cross-laminated timber compression elements exposed to fire

A set of novel structural fire tests on axially loaded cross-laminated timber (CLT) compression elements (walls), locally exposed to thermal radiation sufficient to cause sustained flaming combustion, are presented and discussed. Test specimens were subjected to a sustained compressive load, equivalent to 10% or 20% of their nominal ambient axial compressive capacity. The walls were then locally exposeFI to a nominal constant incident heat flux of 50 kW/m(2) over their mid height area until failure occurred. The axial and lateral deformations of the walls were measured and compared against predictions calculated using a finite Bernoulli beam element analysis, to shed light on the fundamental mechanics and needs for rational structural design of CLT compression elements in fire. For the walls tested herein, failure at both ambient and elevated temperature was due to global buckling. At high temperature failure results from excessive lateral deflections and second order flexural effects due to reductions the walls' effective cross-section and flexural rigidity, as well as a shift of the effective neutral axis in bending during fire. Measured' average one-dimensional charring rates ranged between 0.82 and 1.0 mm/min in these tests. As expected, the lamellae configuration greatly influenced the walls' deformation responses and times to failure; with 3-ply walls failing earlier than those with 5-plies. The walls' deformation response during heating suggests that, if a conventional reduced cross section method (RCSM), zero strength layer analysis were undertaken, the required zero strength layer depths would range between 15.2 mm and 21.8 mm. Deflection paths further suggest that the concept of a zero strength layer is inadequate for properly capturing the mechanical response of fire-exposed CLT compression elements. (C) 2017 Elsevier Ltd. All rights reserved

Innovative learning at The University of Edinburgh

The activities available to civil engineering students during the University of Edinburgh's innovative learning week in 2012 were examined. The academic staff proposed a wide range of possible activities and student participation was optional. Popular activities were those with a ‘hands-on’ element: making or doing something. The practical activities offered included designing and building trebuchets, relaying railway permanent way on a heritage railway, practical workshops on engineering in international development and learning to juggle. These activities suggested that heuristic learning by trial and error was likely to enhance the visualisation skills that contribute to good engineering design. Further, the linking of achievement to purposeful practice rather than innate talent could inform teaching methods in the future. They also showed that in some cases safety culture messages were still not fully assimilated by students

Time-resolved nanosecond fluorescence lifetime imaging and picosecond infrared spectroscopy of combretastatin A-4 in solution and in cellular systems

Fluorescence lifetime images of intrinsic fluorescence obtained with two-photon excitation at 630 nm are shown following uptake of a series of E-combretastatins into live cells, including human umbilical vein endothelial cells (HUVECs) that are the target for the anticancer activity of combretastatins. Images show distribution of the compounds within the cell cytoplasm and in structures identified as lipid droplets by comparison with images obtained following Nile red staining of the same cells. The intracellular fluorescent lifetimes are generally longer than in fluid solution as a consequence of the high viscosity of the cellular environment. Following incubation the intracellular concentrations of a fluorinated derivative of E combretastatin A4 in HUVECs are up to between 2 and 3 orders of magnitude higher than the concentration in the surrounding medium. Evidence is presented to indicate that at moderate laser powers (up to 6 mW) it is possible to isomerize up to 25% of the combretastatin within the femtolitre focal volume of the femtosecond laser beam. This suggests that it may be possible to activate the E-combretastatin (with low cellular toxicity) to the Z-isomer with high anticancer drug activity using two-photon irradiation. The isomerization of Z- and E-combretastatins by 266 nm irradiation has been probed by ultrafast time-resolved infrared spectroscopy. Results for the E-isomer show a rapid loss of excess vibrational energy in the excited state with a lifetime of 7 ps, followed by a slower process with a lifetime of 500 ps corresponding to the return to the ground state as also determined from the fluorescence lifetime. In contrast the Z-isomer, whilst also appearing to undergo a rapid cooling of the initial excited state, has a much shorter overall excited state lifetime of 14 ps

Anticancer phototherapy using activation of E-combretastatins by two-photon–induced isomerization

The photoisomerization of relatively nontoxic E-combretastatins to clinically active Z-isomers is shown to occur in solution through both one- and two-photon excitations at 340 and 625 nm, respectively. The photoisomerization is also demonstrated to induce mammalian cell death by a two-photon absorption process at 625 nm. Unlike conventional photodynamic therapy (PDT), the mechanism of photoisomerization is oxygen- independent and active in hypoxic environments such as in tumors. The use of red or near-infrared (NIR) light for two-photon excitation allows greater tissue penetration than conventional UV one-photon excitation. The results provide a baseline for the development of a novel phototherapy that overcomes nondiscriminative systemic toxicity of Z-combretastatins and the limitations of PDT drugs that require the presence of oxygen to promote their activity, with the added benefits of two-photon red or NIR excitation for deeper tissue penetration