8 resultados para Ifn-alpha-beta

em Aston University Research Archive


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The perception of an object as a single entity within a visual scene requires that its features are bound together and segregated from the background and/or other objects. Here, we used magnetoencephalography (MEG) to assess the hypothesis that coherent percepts may arise from the synchronized high frequency (gamma) activity between neurons that code features of the same object. We also assessed the role of low frequency (alpha, beta) activity in object processing. The target stimulus (i.e. object) was a small patch of a concentric grating of 3c/°, viewed eccentrically. The background stimulus was either a blank field or a concentric grating of 3c/° periodicity, viewed centrally. With patterned backgrounds, the target stimulus emerged--through rotation about its own centre--as a circular subsection of the background. Data were acquired using a 275-channel whole-head MEG system and analyzed using Synthetic Aperture Magnetometry (SAM), which allows one to generate images of task-related cortical oscillatory power changes within specific frequency bands. Significant oscillatory activity across a broad range of frequencies was evident at the V1/V2 border, and subsequent analyses were based on a virtual electrode at this location. When the target was presented in isolation, we observed that: (i) contralateral stimulation yielded a sustained power increase in gamma activity; and (ii) both contra- and ipsilateral stimulation yielded near identical transient power changes in alpha (and beta) activity. When the target was presented against a patterned background, we observed that: (i) contralateral stimulation yielded an increase in high-gamma (>55 Hz) power together with a decrease in low-gamma (40-55 Hz) power; and (ii) both contra- and ipsilateral stimulation yielded a transient decrease in alpha (and beta) activity, though the reduction tended to be greatest for contralateral stimulation. The opposing power changes across different regions of the gamma spectrum with 'figure/ground' stimulation suggest a possible dual role for gamma rhythms in visual object coding, and provide general support of the binding-by-synchronization hypothesis. As the power changes in alpha and beta activity were largely independent of the spatial location of the target, however, we conclude that their role in object processing may relate principally to changes in visual attention.

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The recognition of faces and of facial expressions in an important evolutionary skill, and an integral part of social communication. It has been argued that the processing of faces is distinct from the processing of non-face stimuli and functional neuroimaging investigations have even found evidence of a distinction between the perception of faces and of emotional expressions. Structural and temporal correlates of face perception and facial affect have only been separately identified. Investigation neural dynamics of face perception per se as well as facial affect would allow the mapping of these in space, time and frequency specific domains. Participants were asked to perform face categorisation and emotional discrimination tasks and Magnetoencephalography (MEG) was used to measure the neurophysiology of face and facial emotion processing. SAM analysis techniques enable the investigation of spectral changes within specific time-windows and frequency bands, thus allowing the identification of stimulus specific regions of cortical power changes. Furthermore, MEG’s excellent temporal resolution allows for the detection of subtle changes associated with the processing of face and non-face stimuli and different emotional expressions. The data presented reveal that face perception is associated with spectral power changes within a distributed cortical network comprising occipito-temporal as well as parietal and frontal areas. For the perception of facial affect, spectral power changes were also observed within frontal and limbic areas including the parahippocampal gyrus and the amygdala. Analyses of temporal correlates also reveal a distinction between the processing of faces and facial affect. Face perception per se occurred at earlier latencies whereas the discrimination of facial expression occurred within a longer time-window. In addition, the processing of faces and facial affect was differentially associated with changes in cortical oscillatory power for alpha, beta and gamma frequencies. The perception of faces and facial affect is associated with distinct changes in cortical oscillatory activity that can be mapped to specific neural structures, specific time-windows and latencies as well as specific frequency bands. Therefore, the work presented in this thesis provides further insight into the sequential processing of faces and facial affect.

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Classification of metamorphic rocks is normally carried out using a poorly defined, subjective classification scheme making this an area in which many undergraduate geologists experience difficulties. An expert system to assist in such classification is presented which is capable of classifying rocks and also giving further details about a particular rock type. A mixed knowledge representation is used with frame, semantic and production rule systems available. Classification in the domain requires that different facets of a rock be classified. To implement this, rocks are represented by 'context' frames with slots representing each facet. Slots are satisfied by calling a pre-defined ruleset to carry out the necessary inference. The inference is handled by an interpreter which uses a dependency graph representation for the propagation of evidence. Uncertainty is handled by the system using a combination of the MYCIN certainty factor system and the Dempster-Shafer range mechanism. This allows for positive and negative reasoning, with rules capable of representing necessity and sufficiency of evidence, whilst also allowing the implementation of an alpha-beta pruning algorithm to guide question selection during inference. The system also utilizes a semantic net type structure to allow the expert to encode simple relationships between terms enabling rules to be written with a sensible level of abstraction. Using frames to represent rock types where subclassification is possible allows the knowledge base to be built in a modular fashion with subclassification frames only defined once the higher level of classification is functioning. Rulesets can similarly be added in modular fashion with the individual rules being essentially declarative allowing for simple updating and maintenance. The knowledge base so far developed for metamorphic classification serves to demonstrate the performance of the interpreter design whilst also moving some way towards providing a useful assistant to the non-expert metamorphic petrologist. The system demonstrates the possibilities for a fully developed knowledge base to handle the classification of igneous, sedimentary and metamorphic rocks. The current knowledge base and interpreter have been evaluated by potential users and experts. The results of the evaluation show that the system performs to an acceptable level and should be of use as a tool for both undergraduates and researchers from outside the metamorphic petrography field. .

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Linear Elastic Fracture Mechanics has been used to study the microstructural factors controlling the strength and toughness of two alpha-beta, titanium alloys. Fracture toughness was found to be independent of orientation for alloy Ti/6A1/4-V, but orientation dependent for IMI 700, bend and tension specimens giving similar toughness values. Increasing the solution temperature led to the usual inverse relationship between strength and toughness, with toughness becoming a minimum as the beta transus was approached. The production of a double heat treated microstructure led to a 100% increase in toughness in the high strength alloy and a 20% increase in alloy Ti/6A1/4V, with little decrease in strength. The double heat treated microstruoture was produced by cooling from the beta field into the alpha beta field, followed. by conventional solution treatment and ageing. Forging above the beta transus led to an increase in toughness over alpha beta forging in the high strength alloy, but had little effect on the toughness of Ti/6A1/4V. Light and electron microscopy showed that the increased toughness resulted from the alpha phase being changed from mainly continuous to a discontinuous platelet form in a transformed beta matrix. Void formation occurred at the alpha-beta interface and crack propagation was via the interface or across the platelet depending on which process required the least energy. Varying the solution treatment temperature produced a varying interplatelet spacing and platelet thickness. The finest interplatelet spacing was associated with the highest toughness, since a higher applied stress was required to give the necessary stress concentration to initiate void formation. The thickest alpha platelet size gave the highest toughness which could be interpreted in terms of Krafftt's "process zone size" and the critical crack tip displacement criterion by Hahn and Rosenfield from an analysis by Goodier and Field.

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The initiation and early propagation of short fatigue cracks has been studied in detail in two alpha / beta titanium alloys as a function of microstructure. Detailed metallography is presented relating short crack growth rates to the microstructural features present. The work shows the significant differences in short crack propagation rates which can be achieved by microstructural changes within a single alloy.

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Both tumor necrosis factor-alpha (TNF-alpha)/interferon-gamma (IFN-gamma) and angiotensin II (ANG II) induced an increase in total protein degradation in murine myotubes, which was completely attenuated by treatment with beta-hydroxy-beta-methylbutyrate (HMB; 50 microM). There was an increase in formation of reactive oxygen species (ROS) within 30 min, as well as an increase in the activity of both caspase-3 and -8, and both effects were attenuated by HMB. Moreover, inhibitors of caspase-3 and -8 completely attenuated both ROS formation and total protein degradation induced by TNF-alpha/IFN-gamma and ANG II. There was an increased autophosphorylation of double-stranded RNA-dependent protein kinase (PKR), which was attenuated by the specific caspase-3 and -8 inhibitors. Neither ROS formation or protein degradation occurred in myotubes expressing a catalytically inactive PKR variant, PKRDelta6, in response to TNF-alpha/IFN-gamma, compared with myotubes expressing wild-type PKR, although there was still activation of caspase-3 and -8. HMB also attenuated activation of PKR, suggesting that it was important in protein degradation. Formation of ROS was attenuated by rotenone, an inhibitor of the mitochondrial electron transport chain, nitro-l-arginine methyl ester, an inhibitor of nitric oxide synthase, and SB 203580, a specific inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), which also attenuated total protein degradation. Activation of p38 MAPK by PKR provides the link to ROS formation. These results suggest that TNF-alpha/IFN-gamma and ANG II induce muscle protein degradation by a common signaling pathway, which is attenuated by HMB, and that this involves the initial activation of caspase-3 and -8, followed by autophosphorylation and activation of PKR, which then leads to increased ROS formation via activation of p38 MAPK. Increased ROS formation is known to induce protein degradation through the ubiquitin-proteasome pathway.

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beta-Hydroxy-beta-methylbutyrate (HMB; 50 microM) has been shown to attenuate the depression in protein synthesis in murine myotubes in response to lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha) with or without interferon-gamma (IFN-gamma), and angiotensin II (ANG II). The mechanism for the depression of protein synthesis by all three agents was the same and was attributed to activation of double-stranded RNA-dependent protein kinase (PKR) with the subsequent phosphorylation of eukaryotic initiation factor 2 (eIF2) on the alpha-subunit as well as increased phosphorylation of the elongation factor (eEF2). Myotubes expressing a catalytically inactive PKR variant, PKRDelta6, showed no depression of protein synthesis in response to either LPS or TNF-alpha, confirming the importance of PKR in this process. There was no effect of any of the agents on phosphorylation of mammalian target of rapamycin (mTOR) or initiation factor 4E-binding protein (4E-BP1), and thus no change in the amount of eIF4E bound to 4E-BP1 or the concentration of the active eIF4E.eIF4G complex. HMB attenuated phosphorylation of eEF2, possibly by increasing phosphorylation of mTOR, and also attenuated phosphorylation of eIF2alpha by preventing activation of PKR. These results suggest that HMB may be effective in attenuating muscle atrophy in a range of catabolic conditions.