Expression of miR-200c corresponds with increased reactive oxygen species and hypoxia markers after transient focal ischemia in mice

Embolic stroke results in a necrotic core of cells destined to die, but also a peri-ischemic, watershed penumbral region of potentially salvageable brain tissue. Approaches to effectively differentiate between the ischemic and peri-ischemic zones is critical for novel therapeutic discovery to improve outcomes in survivors of stroke. MicroRNAs are a class of small non-coding RNAs regulating gene translation that have region- and cell-specific expression and responses to ischemia. We have previously reported that global inhibition of cerebral microRNA200c after experimental stroke in mice is protective, however delineating the post-stroke sub-regional and celltype specific patterns of post-stroke miR-200c expression are necessary to minimize off-target effects and advance translational application. Here, we detail a novel protocol to visualize regional miR-200c expression after experimental stroke, complexed with visualization of regional ischemia and markers of oxidative stress in an experimental stroke model in mice. In the present study we demonstrate that the fluorescent hypoxia indicator pimonidazole hydrochloride, the reactive-oxygen-species marker 8-hydroxy-deoxyguanosine, neuronal marker MAP2 and NeuN, and the reactive astrocyte marker GFAP can be effectively complexed to determine regional differences in ischemic injury as early as 30 min post-reperfusion after experimental stroke, and can be effectively used to distinguish ischemic core from surrounding penumbral and unaffected regions for targeted therapy. This multi-dimensional post-stroke immunofluorescent imaging protocol enables a greater degree of subregional mechanistic investigation, with the ultimate goal of developing more effective post-stroke pharmaceutical therapy.Peer reviewe

Measurements, Models, Systems and Design

531 s.

Into the intangible: an exploration of gravity dream motifs among psychotherapists

This study explores seven therapists’ phenomenological experiences of the gravity dream motif, as well as their lived experiences at the times they had these dreams and the impact the dream sequences had on their lives and practices. The ‘Phenomenology of Practice,’ as described by Van Manen was used to guide the methodology. Three final thematic aspects were established through the interviews. The first was essential to the experience of the gravity dream: The necessary dream, the changing motif and the journey of the developing self. This theme highlighted the fact that the dream served a purpose in some way. The motif changed alongside the developing self, particularly through the search for a sense of authenticity and identity. Two further themes were essential to the interview process, the first of which was: An emergence of a new hermeneutic meaning of the dream’s significance. All the participants derived new understandings of their dreams through the use of metaphor, life parallels and their felt sense of their dreams. The final theme: The therapy space - reduction, retrieval, revival and reconnection with our dream self, materialised through the interview process. The invitation to talk about an intangible subject, the reflective distance from the dream space and then the phenomenological interview itself, all enabled the participants to reconnect with their dream selves. They were also able to retrieve new awarenesses and revive their interest in working with dreams. In addition, the study also discovered that the seven participants were employing a reductive way of working with dreams and it calls for an enhancement of dream training, with more attention paid to the value of working with dreams in therapy. Finally, it suggests greater attention should be paid to the significance of a dream motif

“Playable” Nationalism: Nusantara Online and the “Gamic” Reconstructions of National History

Abstract: Nusantara Online is an Indonesian-made massively multiplayer online role-playing game that imaginatively reconstructs the history of the archipelago. As an “allegorithm” for the Indonesian nation, the game suggests a distinct model of digital nationalism, here dubbed “playable” nationalism. This concept captures the formulation of “Nusantara” as the idealized yet playful version of the Indonesian archipelago, a version emphasizing the principles of digital collaboration. The promotion of this model of “digital nationalism” as an egalitarian model of Indonesian popular nationalism has certain limitations

Artificial ontogenesis: a connectionist model of development

This thesis suggests that ontogenetic adaptive processes are important for generating intelligent beha- viour. It is thus proposed that such processes, as they occur in nature, need to be modelled and that such a model could be used for generating artificial intelligence, and specifically robotic intelligence. Hence, this thesis focuses on how mechanisms of intelligence are specified.A major problem in robotics is the need to predefine the behaviour to be followed by the robot. This makes design intractable for all but the simplest tasks and results in controllers that are specific to that particular task and are brittle when faced with unforeseen circumstances. These problems can be resolved by providing the robot with the ability to adapt the rules it follows and to autonomously create new rules for controlling behaviour. This solution thus depends on the predefinition of how rules to control behaviour are to be learnt rather than the predefinition of rules for behaviour themselves.Learning new rules for behaviour occurs during the developmental process in biology. Changes in the structure of the cerebral 'cortex underly behavioural and cognitive development throughout infancy and beyond. The uniformity of the neocortex suggests that there is significant computational uniformity across the cortex resulting from uniform mechanisms of development, and holds out the possibility of a general model of development. Development is an interactive process between genetic predefinition and environmental influences. This interactive process is constructive: qualitatively new behaviours are learnt by using simple abilities as a basis for learning more complex ones. The progressive increase in competence, provided by development, may be essential to make tractable the process of acquiring higher -level abilities.While simple behaviours can be triggered by direct sensory cues, more complex behaviours require the use of more abstract representations. There is thus a need to find representations at the correct level of abstraction appropriate to controlling each ability. In addition, finding the correct level of abstrac- tion makes tractable the task of associating sensory representations with motor actions. Hence, finding appropriate representations is important both for learning behaviours and for controlling behaviours. Representations can be found by recording regularities in the world or by discovering re- occurring pat- terns through repeated sensory -motor interactions. By recording regularities within the representations thus formed, more abstract representations can be found. Simple, non -abstract, representations thus provide the basis for learning more complex, abstract, representations.A modular neural network architecture is presented as a basis for a model of development. The pat- tern of activity of the neurons in an individual network constitutes a representation of the input to that network. This representation is formed through a novel, unsupervised, learning algorithm which adjusts the synaptic weights to improve the representation of the input data. Representations are formed by neurons learning to respond to correlated sets of inputs. Neurons thus became feature detectors or pat- tern recognisers. Because the nodes respond to patterns of inputs they encode more abstract features of the input than are explicitly encoded in the input data itself. In this way simple representations provide the basis for learning more complex representations. The algorithm allows both more abstract represent- ations to be formed by associating correlated, coincident, features together, and invariant representations to be formed by associating correlated, sequential, features together.The algorithm robustly learns accurate and stable representations, in a format most appropriate to the structure of the input data received: it can represent both single and multiple input features in both the discrete and continuous domains, using either topologically or non -topologically organised nodes. The output of one neural network is used to provide inputs for other networks. The robustness of the algorithm enables each neural network to be implemented using an identical algorithm. This allows a modular `assembly' of neural networks to be used for learning more complex abilities: the output activations of a network can be used as the input to other networks which can then find representations of more abstract information within the same input data; and, by defining the output activations of neurons in certain networks to have behavioural consequences it is possible to learn sensory -motor associations, to enable sensory representations to be used to control behaviour

Sight, sound, the chicken and the egg: Audio-visual co-dependency in music

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Amongst the modern day abundance of audio-visual media, where sounds represent everything from the swooping of virtual cameras through 3D spaces to the pressing of buttons and receiving of emails, and conversely where VJs routinely accompany live musical performance with an increasingly sophisticated language of abstract computer animation, the notion of music as a necessarily exclusively aural medium seems somewhat out of place. Psychological theories relating to the cognition of sound, in particular physical schema, accounting for the ubiquity of vertical plane pitch metaphors in most musical cultures, provide evidence of a deep-rooted spatially informed understanding of sound thus providing a common ground for both sound and vision in music. Furthermore, Western Classical composition is rife with examples of visually conceived forms from Bach’s Crab Canon (1747) to Xenakis’ architecturally inspired Metastasis (1954). However, in practice the gap between the listener’s auditory experience and the composer’s visual concept is often insurmountable. Rising to Schaeffer’s call for “Primacy to the ear!” (Schaeffer, 1967, pp. 28-30), acousmatic composers have sought to derive music exclusively from experientially verifiable criteria. However, in its pervasiveness of other musical genres, no doubt aided by technologically and commercially driven domination of the pre-recorded over the live listening experience in the latter half of the twentieth century, such an approach has lead to the neglect of visual aspects in the live performance of much art-music. This research aims to begin to redress this balance through the composition of, largely computer realised, audio-visual works whose conception arises not from a superimposition of one medium upon another, but through the very relations between the media themselves. Utilising modern computers’ ability to synchronise physical and virtual visual events with synthesised sound in real time not only affords composers an invaluable tool for enhancing listener’s perception of formal structures but also implies causal relationships between the sonic and the visual which can provide a base of intuitive understanding on which more complex formal ideas can be built.Sponsored by the Brunel University Isambard Scholarship