Metaphor, indeterminacy, and intention

David Cooper has argued that it is a constraint on any acceptable theory of metaphor that it account for the 'indeterminacy' of metaphorical content, that is, the sense that many metaphors admit of more than one acceptable interpretation, none of which can be uniquely demonstrated to be correct. He further argues that the 'speaker's meaning' model of metaphorical content proposed by Searle and others cannot meet this constraint, and thus must be disregarded as a prospective account of such content. In this paper I argue firstly that Cooper's characterisation of the proposed constraint is misguided, and that we should be careful to distinguish the role that intention plays in determining metaphorical content from the question of whether we can have satisfying interpretations of metaphors that do not take speaker intention into account. I then give my own characterisation of the problem, relating it to a more general tension between the intuition that first person ascriptions of intentions carry a certain authority, and the fact that it seems to misrepresent the phenomenology of metaphor production to ascribe to the speaker a pre-existing and precise cognitive content which his metaphorical utterance is intended to convey. I go on to argue that we can resolve this tension by following Crispin Wright in viewing self ascriptions of intention as essentially response dependent; with our best judgements constituting rather than tracking the facts about what we intend. I conclude that while such an account must be refined in order to distinguish intentions related to specifically metaphorical content from the literal case, the general shape of the account is sufficient to remove the intuitions that Cooper's objection trades on

Moral facts and suitably informed subjects

The nature of moral facts, and their relationship to rationality, imagination and sentiment, have been central and pressing issues in recent moral philosophy. In this paper, I discuss and criticise a meta-ethical theory put forward by Alison Denham, which views moral facts as being constituted by the responses of ideal, empathetic agents. I argue that Denham's account is radically unstable, in that she has given us an account of the nature of such agents which is inconsistent with an independently plausible principle relating to concept acquisition. I go on to discuss one line of defence that Denham might employ, but argue that taking such a line entails abandoning what she takes to be an important advantage of her account over rival ideal-observer theories such as Michael Smith's

Space station pressurized laboratory safety guidelines

Before technical safety guidelines and requirements are established, a common understanding of their origin and importance must be shared between Space Station Program Management, the User Community, and the Safety organizations involved. Safety guidelines and requirements are driven by the nature of the experiments, and the degree of crew interaction. Hazard identification; development of technical safety requirements; operating procedures and constraints; provision of training and education; conduct of reviews and evaluations; and emergency preplanning are briefly discussed

Mentoring, teaching and professional transformation

No abstract available

Anti-GD1a antibody targeted disruption of the node of Ranvier in a mouse model of acute motor axonal neuropathy

Guillain-Barré syndrome (GBS) is a peripheral neuropathy characterised by acute flaccid paralysis. The axonal variant is associated with anti-GD1a ganglioside antibody-dependent, complement-mediated injury to the peripheral axon with conduction block. The blood-nerve barrier (BNB) relatively protects axons from factors in the extra-neural environment; however, it does not extend over the neuromuscular junction, leaving this terminal portion of the axon unprotected. It is here that susceptibility to antibody attack in a mouse model of GBS has previously been demonstrated. It was the aim of this thesis to determine to what extent more proximal portions of the distal axon are at risk from circulating antibody and what exogenous protection can be provided therapeutically. GD1a is expressed at the nodes of Ranvier (NoR) of intramuscular axons. To investigate the injury caused by anti-GD1a antibodies in relation to BNB permeability, anti-GD1a antibodies were applied to mice genetically engineered both to over-express GD1a and to express cyan fluorescent protein (CFP) in the cytoplasm of axons. Endogenous fluorescence allowed identification of intramuscular nerve bundles and their terminal branches, which were categorized depending on bundle size. Within these categories, IgG and the final product of the complement pathway (membrane attack complex, MAC) deposition were quantified after an acute injury, alongside the deleterious effects on NoR protein’s. Nerve conduction studies were also performed to better elucidate the pathological pathway. IgG and MAC were localized in a gradient-dependent manner, with significantly more deposition at NoR as the bundles progressively branch to a single terminating fibre. Furthermore, MAC deposition was associated with the loss or disruption to immunostaining for nodal protein’s including voltage gated sodium channel and ankyrin G. This is indicative of targeted injury to this region of the distal axon in an acute model. The loss of nodal protein staining is associated with the activation of complement and the Ca2+-dependent protease calpain as determined by the protection of staining by the complement inhibitor Eculizumab and the calpain inhibitor AK295. A similar disruption to nodal protein staining is also shown at the proximal NoR of the desheathed phrenic nerve. Extracellular nerve recordings demonstrate a detrimental effect on function as there is a decrease in the peak of the compound nerve action potential over time, which can be associated with Nav channel staining loss. This study is suggestive of a resilient proximal barrier that becomes more permeable towards the nerve terminal. Therefore, it is not only the axon at the terminal that can be a target of injury, but also the distal axons at their nodes of Ranvier, resulting in disruption at this site. Prevention of staining loss by Eculizumab and AK295 exemplify the route of injury and identify a potential point of therapeutic intervention in human disease

Identification and functional characterization of modulators of pro-apoptotic proteins Caspase 3 and Bax

Oxidative-stress-induced neuronal apoptosis has been implicated in the development of neurodegenerative diseases such as ischemic stroke. Pro-apoptotic proteins including Caspase 3 and Bax are critical components of the apoptotic pathway. In this study we aimed to identify specific inhibitors of Caspase 3 and Bax. We isolated two single domain antibodies (sdAbs) against Caspase 3; one (VhhCasp3 1) capable of blocking Caspase 3 function in vitro and in vivo, and the other (VhhCasp32) acting oppositely. The genes and antibodies coded by them can be used as a platform for therapeutic development for neuroprotective or anti-cancer agents. We also screened a pharmacaphore library of small molecular weight compounds capable of binding to Bax and blocking function in the same manner as a specific anti-Bax sdAb inhibitor previously found by our group. We found compound 22, which was capable of competitive binding to Bax and blocked Bax function in vitro and in vivo

Reality is Broken: Why Games Make US Better and How They Can Change The World

This book is designed to do just that. It will build up your ability to enjoy life more, to solve tougher problems, and to lead others in world-changing efforts. In part 1 : Why Games Make Us Happy , you’ll go inside the minds of top game designers and game researchers. You’ll find out exactly which emotions that most succesful games are carefully engineered to provoke-and how these feelings can spil over, in positive and surprising ways, into our real lives and relationships. In part 2 : Reinventing Reality , you’ll discover the world of alternate reality games. It’s the rapidly growing field of news software, services, and experiences meant to make us happy and successful in our real lives as we are when we’re playing our favorite video games. In part 3 : How Very Big Games Can Change the World, you’ll get a glimpse of the future. You’ll discover ten games designed to help ordinary people achieve the world’s most urgent goals : curing cancer, stopping climate change, spreading peace, ending poverty

Integration of pneumatic fracturing and in situ vitrification in coarse grained soils

This thesis investigates conceptual integration of the Pneumatic Fracturing (PF) process with In Situ Vitrification (ISV) for remediation of contaminated soil. Integration will permit ISV melts to be initiated below the ground surface and extend the depth of the ISV process. Bench scale experiments were conducted in 4.9 ft3 (0.14 m3) Plexiglas tanks filled with a test soil that was specifically blended to simulate the Hanford Formation in Richland, WA. Discrete pneumatic fractures were successfully created and filled with the ISV starter path material. Conductivity measurements made across two graphite electrodes exhibited a pre-fracture soil resistance of 427 ohms, which was reduced to an average of 0.80 ohms after fracture injection. A model was developed to predict transport distance of the ISV starter path media in pneumatically induced fractures. The model estimates fracture propagation distance using a finitedifference approach, as well as the critical fluid velocity necessary to keep the starter path media suspended, Model calculations show the effective radius of the integrated process should range up to several meters in the Hanford Formation. The thesis concludes with operational recommendations for full scale application