117 resultados para Esclerose lateral amiotrófica


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This paper presents a numerical study on the response of axially loaded slender square concrete filled steel tube (CFST) columns under low velocity lateral impact loading. A finite element analysis (FEA) model was developed using the explicit dynamic nonlinear finite element code LS -DYNA in which the strain rate effects of both steel and concrete, contact between steel tube and concrete and confinement effect provided by the steel tube for the concrete were considered. The model also benefited from a relatively recent feature of LS-DYNA for applying a pre-loading in the explicit solver. The developed numerical model was verified for its accuracy and adequacy by comparing the results with experimental results available in the literature. The verified model was then employed to conduct a parametric study to investigate the influence of axial load level, impact location, support conditions, and slenderness ratio on the response of the CFST columns. A good agreement between the numerical and experimental results was achieved. The model could reasonably predict the impact load-deflection history and deformed shape of the column at the end of the impact event. The results of the parametric study showed that whilst impact location, axial load level and slenderness ratio can have a significant effect on the peak impact force, residual lateral deflection and maximum lateral deflection, the influence of support fixity is minimal. With an increase of axial load to up to a certain level, the peak force increases; however, a further increase in the axial load causes a decrease in the peak force. Both residual lateral deflection and maximum lateral deflection increase as axial load level increases. Shifting the impact location towards the supports increases the peak force and reduces both residual and maximum lateral deflections. A rise in slenderness ratio decreases the peak force and increases the residual and maximum lateral deflections.

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Individual variability in the acquisition, consolidation and extinction of conditioned fear potentially contributes to the development of fear pathology including posttraumatic stress disorder (PTSD). Pavlovian fear conditioning is a key tool for the study of fundamental aspects of fear learning. Here, we used a selected mouse line of High and Low Pavlovian conditioned fear created from an advanced intercrossed line (AIL) in order to begin to identify the cellular basis of phenotypic divergence in Pavlovian fear conditioning. We investigated whether phosphorylated MAPK (p44/42 ERK/MAPK), a protein kinase required in the amygdala for the acquisition and consolidation of Pavlovian fear memory, is differentially expressed following Pavlovian fear learning in the High and Low fear lines. We found that following Pavlovian auditory fear conditioning, High and Low line mice differ in the number of pMAPK-expressing neurons in the dorsal sub nucleus of the lateral amygdala (LAd). In contrast, this difference was not detected in the ventral medial (LAvm) or ventral lateral (LAvl) amygdala sub nuclei or in control animals. We propose that this apparent increase in plasticity at a known locus of fear memory acquisition and consolidation relates to intrinsic differences between the two fear phenotypes. These data provide important insights into the micronetwork mechanisms encoding phenotypic differences in fear. Understanding the circuit level cellular and molecular mechanisms that underlie individual variability in fear learning is critical for the development of effective treatment of fear-related illnesses such as PTSD.

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A key question in neuroscience is how memory is selectively allocated to neural networks in the brain. This question remains a significant research challenge, in both rodent models and humans alike, because of the inherent difficulty in tracking and deciphering large, highly dimensional neuronal ensembles that support memory (i.e., the engram). In a previous study we showed that consolidation of a new fear memory is allocated to a common topography of amygdala neurons. When a consolidated memory is retrieved, it may enter a labile state, requiring reconsolidation for it to persist. What is not known is whether the original spatial allocation of a consolidated memory changes during reconsolidation. Knowledge about the spatial allocation of a memory, during consolidation and reconsolidation, provides fundamental insight into its core physical structure (i.e., the engram). Using design-based stereology, we operationally define reconsolidation by showing a nearly identical quantity of neurons in the dorsolateral amygdala (LAd) that expressed a plasticity-related protein, phosphorylated mitogen-activated protein kinase, following both memory acquisition and retrieval. Next, we confirm that Pavlovian fear conditioning recruits a stable, topographically organized population of activated neurons in the LAd. When the stored fear memory was briefly reactivated in the presence of the relevant conditioned stimulus, a similar topography of activated neurons was uncovered. In addition, we found evidence for activated neurons allocated to new regions of the LAd. These findings provide the first insight into the spatial allocation of a fear engram in the LAd, during its consolidation and reconsolidation phase.

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Understanding the physical encoding of a memory (the engram) is a fundamental question in neuroscience. Although it has been established that the lateral amygdala is a key site for encoding associative fear memory, it is currently unclear whether the spatial distribution of neurons encoding a given memory is random or stable. Here we used spatial principal components analysis to quantify the topography of activated neurons, in a select region of the lateral amygdala, from rat brains encoding a Pavlovian conditioned fear memory. Our results demonstrate a stable, spatially patterned organization of amygdala neurons are activated during the formation of a Pavlovian conditioned fear memory. We suggest that this stable neuronal assembly constitutes a spatial dimension of the engram. © 2011 This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.

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Pavlovian auditory fear conditioning involves the integration of information about an acoustic conditioned stimulus (CS) and an aversive unconditioned stimulus in the lateral nucleus of the amygdala (LA). The auditory CS reaches the LA subcortically via a direct connection from the auditory thalamus and also from the auditory association cortex itself. How neural modulators, especially those activated during stress, such as norepinephrine (NE), regulate synaptic transmission and plasticity in this network is poorly understood. Here we show that NE inhibits synaptic transmission in both the subcortical and cortical input pathway but that sensory processing is biased toward the subcortical pathway. In addition binding of NE to β-adrenergic receptors further dissociates sensory processing in the LA. These findings suggest a network mechanism that shifts sensory balance toward the faster but more primitive subcortical input

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The galvanic replacement of isolated nanostructures of copper and silver on conducting supports as well as continuous films of copper with gold is reported. The surface morphology was characterized by scanning electron microscopy and the replacement with gold was confirmed by EDX analysis. It was found that lateral charge propagation during the replacement reaction had a significant effect in all cases. For the isolated nanostructures the deposition of gold was observed not only at the sacrificial template but also at the surrounding unmodified areas of the conducting substrate. In the case of copper films the role of lateral charge propagation was also confirmed by connecting it to an ITO electrode through an external circuit upon which gold deposition was also observed to occur. Interestingly, by inhibiting the rate of charge propagation, through the introduction of a series resistor, the morphology of gold on the copper substrate could be changed from discrete surface decoration with cube like nanoparticles to a more porous rough surface.

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The galvanic replacement of isolated electrodeposited semiconducting CuTCNQ microstructures on a glassy carbon (GC) substrate with gold is investigated. It is found that anisotropic metal nanoparticles are formed which are not solely confined to the redox active sites on the semiconducting materials but are also observed on the GC substrate which occurs via a lateral charge propagation mechanism. We also demonstrate that this galvanic replacement approach can be used for the formation of isolated AgTCNQ/Au microwire composites which occurs via an analogous mechanism. The resultant MTCNQ/Au (M = Cu, Ag) composite materials are characterized by Raman, spectroscopy, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and investigated for their catalytic properties for the reduction of ferricyanide ions with thiosulphate ions in aqueous solution. Significantly it is demonstrated that gold loading, nanoparticle shape and in particular the MTCNQ–Au interface are important factors that influence the reaction rate. It is shown that there is a synergistic effect at the CuTCNQ/Au composite when compared to AgTCNQ/Au at similar gold loadings.

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Detailed procedure for second-order analysis has been coded in the newest Eurocode 3 and the Hong Kong steel code (2005). The effective length method has been noted to be inapplicable to analysis of shallow domes of imperfect members exhibiting snap-through buckling, to portals with leaning columns and others. On the other hand, the advanced analysis is not limited to buckling design of these structures. This paper demonstrates its application to the design of a simple plane sway portal and a three diminsional non-sway steel building. The results by the advanced analysis and the first-order linear analysis are compared and the technique for practical second-order analysis steel structures is described. It is observed that the use of a straight element by itself cannot model the buckling resistance of columns governed by different buckling curves for hot-rolled and cold-formed sections of various shapes like I, H, hollow etc. Also the curvature of the conventional cubic Hermite element is not varied by the external axial force and thus it cannot simulate the response of a buckling column. Thus its use for second-order analysis is basically unacceptable. A technique for additional checking of beams undergoing lateral-torsional buckling is also suggested making the advanced analysis a complete design tool for conventional steel frames.

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This research is carried out by using finite element modelling of building prototypes with three different layouts (rectangular, octagonal and L-shaped) for three different heights (98.0 m, 147.0 m and 199.5 m) for the optimization of lateral load-resisting systems in composite high-rise buildings. Variations of lateral bracings (different number and varied placement along model height of belt-truss and outrigger floors) with RCC (reinforced cement concrete) core wall are used in composite high-rise building models. Prototypes of composite buildings are analysed for dynamic wind and seismic loads. The effects on serviceability (deflection and frequency) of models are studied and conclusions are deduced.

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Synaptic changes at sensory inputs to the dorsal nucleus of the lateral amygdala (LAd) play a key role in the acquisition and storage of associative fear memory. However, neither the temporal nor spatial architecture of the LAd network response to sensory signals is understood. We developed a method for the elucidation of network behavior. Using this approach, temporally patterned polysynaptic recurrent network responses were found in LAd (intra-LA), both in vitro and in vivo, in response to activation of thalamic sensory afferents. Potentiation of thalamic afferents resulted in a depression of intra-LA synaptic activity, indicating a homeostatic response to changes in synaptic strength within the LAd network. Additionally, the latencies of thalamic afferent triggered recurrent network activity within the LAd overlap with known later occurring cortical afferent latencies. Thus, this recurrent network may facilitate temporal coincidence of sensory afferents within LAd during associative learning.

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Changes in dendritic spine number and shape are believed to reflect structural plasticity consequent to learning. Previous studies have strongly suggested that the dorsal subnucleus of the lateral amygdala is an important site of physiological plasticity in Pavlovian fear conditioning. In the present study, we examined the effect of auditory fear conditioning on dendritic spine numbers in the dorsal subnucleus of the lateral amygdala using an immunolabelling procedure to visualize the spine-associated protein spinophilin. Associatively conditioned rats that received paired tone and shock presentations had 35% more total spinophilin-immunoreactive spines than animals that had unpaired stimulation, consistent with the idea that changes in the number of dendritic spines occur during learning and account in part for memory.

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Glucocorticoids, released in high concentrations from the adrenal cortex during stressful experiences, bind to glucocorticoid receptors in nuclear and peri-nuclear sites in neuronal somata. Their classically known mode of action is to induce gene promoter receptors to alter gene transcription. Nuclear glucocorticoid receptors are particularly dense in brain regions crucial for memory, including memory of stressful experiences, such as the hippocampus and amygdala. While it has been proposed that glucocorticoids may also act via membrane bound receptors, the existence of the latter remains controversial. Using electron microscopy, we found glucocorticoid receptors localized to non-genomic sites in rat lateral amygdala, glia processes, presynaptic terminals, neuronal dendrites, and dendritic spines including spine organelles and postsynaptic membrane densities. The lateral nucleus of the amygdala is a region specifically implicated in the formation of memories for stressful experiences. These newly observed glucocorticoid receptor immunoreactive sites were in addition to glucocorticoid receptor immunoreactive signals observed using electron and confocal microscopy in lateral amygdala principal neuron and GABA neuron soma and nuclei, cellular domains traditionally associated with glucocorticoid immunoreactivity. In lateral amygdala, glucocorticoid receptors are thus also localized to non-nuclear-membrane translocation sites, particularly dendritic spines, where they show an affinity for postsynaptic membrane densities, and may have a specialized role in modulating synaptic transmission plasticity related to fear and emotional memory.