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The ideas and findings in this report should not be construed as an official DoD position. It is published in the interest of scientific and technical information exchange. Use of any trademarks in this report is not intended in any way to infringe on the rights of the trademark holder. Internal use. Permission to reproduce this document and to prepare(More)
A visually reinforced infant speech discrimination (VRISD) paradigm is described and evaluated. Infants at two ages were tested with the new paradigm on the following speech contrasts: [sa] vs [va], [sa] vs [fa], [sa] VS [za], [as] vs [a:s], vs [a:z], [at] vs [a:d], [a:t] vs [a:d], [at] vs [a:t], [fa] vs [thetaa]and [fi] vs [thetai]. The data reported are(More)
G-protein-coupled inwardly rectifying potassium channels (GIRKs) are important for regulation of synaptic transmission and neuronal firing rates. Because of their key role in brain function, we asked if these potassium channels are targets of alcohol action. Ethanol enhanced function of cerebellar granule cell GIRKs coupled to GABAB receptors. Enhancement(More)
A new in vitro model has been developed for investigating extravascular diffusion of therapeutic agents in tumour tissue. V79-171b or EMT6/Ak cells are grown on porous Teflon support membranes and submerged in a large reservoir of medium, to give diffusion-limited 'multicellular membranes' (MMs) c. 200 microm in thickness. MMs are histologically similar to(More)
Prodrug activation gene therapy is a developing approach to cancer treatment, whereby prodrug-activating enzymes are expressed in tumour cells. After administration of a non-toxic prodrug, its conversion to cytotoxic metabolites directly kills tumour cells expressing the activating enzyme, whereas the local spread of activated metabolites can kill nearby(More)
Activation of prodrugs in tumors (e.g., by bioreduction in hypoxic zones) has the potential to generate active metabolites that can diffuse within the tumor microenvironment. Such "bystander effects" may offset spatial heterogeneity in prodrug activation but the relative importance of this effect is not understood. Here, we quantify the contribution of(More)
The paper highlights the dif®culties in adopting investment strategies designed to exploit book-to-market and size effects on the New Zealand share market, which is small and illiquid by world standards. The small number of suitable companies listed on the market, and the high return volatility of individual equities make it dif®cult to reliably achieve(More)
An important feature of gene-directed enzyme-prodrug therapy is that prodrug activation can provide diffusible cytotoxic metabolites capable of generating a local bystander effect in tumours. Activation of the aziridinyl dinitrobenzamide CB 1954 by E. coli nitroreductase (NTR) provides a bystander effect assumed to be due to the potently cytotoxic(More)
English- and Spanish-learning infants were tested for perception of 2 synthetic speech contrasts differing in voice onset time. The 2 pairs were chosen so that they were native to either Spanish or English. Using the Visually Reinforced Infant Speech Discrimination (VRISD) paradigm, 6--8-month-old infants were taught to respond to a change in auditory(More)