Hebbian analysis of the transformation of medial entorhinal grid-cell inputs to hippocampal place fields.

The discovery of grid cells in the medial entorhinal cortex (MEC) permits the characterization of hippocampal computation in much greater detail than previously possible. The present study addresses how an integrate-and-fire unit driven by grid-cell spike trains may transform the multipeaked, spatial firing pattern of grid cells into the single-peaked activity that is typical of hippocampal place cells. Previous studies have shown that in the absence of network interactions, this transformation can succeed only if the place cell receives inputs from grids with overlapping vertices at the location of the place cell's firing field. In our simulations, the selection of these inputs was accomplished by fast Hebbian plasticity alone. The resulting nonlinear process was acutely sensitive to small input variations. Simulations differing only in the exact spike timing of grid cells produced different field locations for the same place cells. Place fields became concentrated in areas that correlated with the initial trajectory of the animal; the introduction of feedback inhibitory cells reduced this bias. These results suggest distinct roles for plasticity of the perforant path synapses and for competition via feedback inhibition in the formation of place fields in a novel environment. Furthermore, they imply that variability in MEC spiking patterns or in the rat's trajectory is sufficient for generating a distinct population code in a novel environment and suggest that recalling this code in a familiar environment involves additional inputs and/or a different mode of operation of the network.

Race and discourse analysis: Building a dialogue in health service research and health care settings

Using a framework for discourse analysis developed by Van Dijk, the investigator will pinpoint the pathological forms of discourse on race, defined as 'race talk' in three professional domains: health services research, public health provider organizations, and literature on multiculturalism. Attention will then turn to developing an analytical strategy for building more meaningful dialogue on race. The retrieval of potential resources for dialogue will be drawn from the third domain. Analysis will focus on enhancing the prospects of converting 'race talk' into dialogue. This will be accomplished by characterizing the normative preconditions as formal procedural requirements for dialogue and then supplementing these conditions with others related specifically to race. From here, the practical implications of combining procedural requirements and resources in each of the domains will be considered. Finally, the author will attempt to determine how these selected resources might be employed to transform 'race talk' in practice and lay the groundwork for a dialogue of understanding. ^

Genetic analysis of tumor progression susceptibility in the mouse skin model

In the field of chemical carcinogenesis the use of animal models has proved to be a useful tool in dissecting the multistage process of tumor formation. In this regard the outbred SENCAR mouse has been the strain of choice in the analysis of skin carcinogenesis given its high sensitivity to the chemically induced acquisition of premalignant lesions, papillomas, and the later progression of these lesions into squamous cell carcinomas (SCC).^ The derivation of an inbred strain from the SENCAR stock called SSIN, that in spite of a high sensitivity to the development of papillomas lack the ability to transform these premalignant lesions into SCC, suggested that tumor promotion and progression were under the genetic control of different sets of genes.^ In the present study the nature of susceptibility to tumor progression was investigated. Analysis of F1 hybrids between the outbred SENCAR and SSIN mice suggested that there is at least one dominant gene responsible for susceptibility to tumor progression.^ Later development of another inbred strain from the outbred SENCAR stock, that had sensitivity to both tumor promotion and progression, allowed the formulation of a more accurate genetic model. Using this newly derived line, SENCAR B/Pt. and SSIN it was determined that there is one dominant tumor progression susceptibility gene. Linkage analysis showed that this gene maps to mouse chromosome 14 and it was possible to narrow the region to a 16 cM interval.^ In order to better characterize the nature of the progression susceptibility differences between these two strains, their proliferative pattern was investigated. It was found that SENCAR B/Pt, have an enlarged proliferative compartment with overexpression of cyclin D1, p16 and p21. Further studies showed an aberrant overexpression of TGF-$\beta$ in the susceptible strain, an increase in apoptosis, p53 protein accumulation and early loss of connexin 26. These results taken together suggest that papillomas in the SENCAR B/Pt. mice have higher proliferation and may have an increase in genomic instability, these two factors would contribute to a higher sensitivity to tumor progression. ^

A LAPLACE TRANSFORM PAIR MODEL TO DETERMINE BREMSSTRAHLUNG SPECTRA FROM ATTENUATION DATA (RADIATION, X-RAY, SPECTRAL MODELING)

Every x-ray attenuation curve inherently contains all the information necessary to extract the complete energy spectrum of a beam. To date, attempts to obtain accurate spectral information from attenuation data have been inadequate.^ This investigation presents a mathematical pair model, grounded in physical reality by the Laplace Transformation, to describe the attenuation of a photon beam and the corresponding bremsstrahlung spectral distribution. In addition the Laplace model has been mathematically extended to include characteristic radiation in a physically meaningful way. A method to determine the fraction of characteristic radiation in any diagnostic x-ray beam was introduced for use with the extended model.^ This work has examined the reconstructive capability of the Laplace pair model for a photon beam range of from 50 kVp to 25 MV, using both theoretical and experimental methods.^ In the diagnostic region, excellent agreement between a wide variety of experimental spectra and those reconstructed with the Laplace model was obtained when the atomic composition of the attenuators was accurately known. The model successfully reproduced a 2 MV spectrum but demonstrated difficulty in accurately reconstructing orthovoltage and 6 MV spectra. The 25 MV spectrum was successfully reconstructed although poor agreement with the spectrum obtained by Levy was found.^ The analysis of errors, performed with diagnostic energy data, demonstrated the relative insensitivity of the model to typical experimental errors and confirmed that the model can be successfully used to theoretically derive accurate spectral information from experimental attenuation data. ^

An exploratory analysis of variance and volatility in epileptic electroencephalograms

The electroencephalogram (EEG) is a physiological time series that measures electrical activity at different locations in the brain, and plays an important role in epilepsy research. Exploring the variance and/or volatility may yield insights for seizure prediction, seizure detection and seizure propagation/dynamics.^ Maximal Overlap Discrete Wavelet Transforms (MODWTs) and ARMA-GARCH models were used to determine variance and volatility characteristics of 66 channels for different states of an epileptic EEG – sleep, awake, sleep-to-awake and seizure. The wavelet variances, changes in wavelet variances and volatility half-lives for the four states were compared for possible differences between seizure and non-seizure channels.^ The half-lives of two of the three seizure channels were found to be shorter than all of the non-seizure channels, based on 95% CIs for the pre-seizure and awake signals. No discernible patterns were found the wavelet variances of the change points for the different signals. ^