Biological and environmental factors contribute collectively to the development of human cancers. The primary focus of this research project was to investigate the impact of germline gene mutations, as a significant biological factor, on 29 major primary human cancers. For this I obtained data from multiple databases, including the Genetic Association Database (GAD), Sanger database (COSMIC), HGMD database, OMIM data and PubMed literature. Using the Extraction Transform and Load (ETL) process, 424 genes were obtained with 8,879 cancer mutation records. By integrating these gene mutation records a Human Cancer Map (HCM) was constructed, from which several sub-maps were derived based on particular mutation classes. Furthermore, a Protein-Protein Interaction Map (PPIM) was constructed based on the encoded proteins of the 424 gene set. Several key questions were addressed using the HCM and its sub-maps including the following: (i) Are individual groups of primary cancers associated with specific subset of genes (within the 424 full set)? (ii) Are groups of primary cancers associated with particular mutation classes? (iii) If both questions prove to be true, are groups of cancers associated with particular mutation class of target genes? This project also explored whether a corresponding Protein-Protein Interaction Map, derived from the Missense/Non-sense Mutation portion of the HCM gene set, would provide further information on gene associations between primary cancers in terms of the consequent identical amino acid changes involved. Results showed that: (1) closely-connected human cancers in the HCM exhibited a strong association with a particular mutation class; (2) Missense /Nonsense and Regulatory mutations played a central role in connecting cancers (i.e. via primary nodes) and so significantly influenced the construction of the HCM; (3) Genes with Missense/Nonsense and Regulatory mutations tended to be involved in cancer-associated pathways; (4) Using the kappa test to measure the extent of agreement between two connected primary cancers in the sub-HCMs, BRCA1, BRCA2, PALB2, MSH2, MSH6, MLH1, CDKN2A, and TP53 showed highest agreement for 5 of 10 mutation classes; (5) From the PIPM, it was evident that BRCA1, MSH6, BARD1, TP53, MSH2 and CHEK2 proteins best connected Breast, Ovarian, Prostate and Bowel primary cancers, and so the latter could represent 'driver proteins' for these cancers. In summary, this project has approached the analysis of gene involvement in human primary cancers from the starting position of the mutation class that harbours the specific gene mutation. Together with their downstream resultant alterations in the associated proteins, this analysis can provide insights into the relatedness of primary human cancers and their potential gene hierarchies. These data may therefore help us to understand more fully the etiology, diagnosis and potentially personalized treatments for cancer.

Includes bibliographical references (leaves 136-156) Two novel in vitro preparations were developed from which recordings were made from colonic afferents in the rat and mouse.

The goal of this thesis was to investigate the role of colour in visual selective attention. Previous experiments exploring this topic in tasks where location varied led to mixed results. Some studies only found evidence of colour as a guide to a specific location where selection then takes place (e.g., Nissen, 1985). Others reported an effect, but could not decide clearly if the benefit was due to direct selection of colour in perception (e.g., Humphreys, 1981). One major contributor to the inconsistencies of findings seems to be the confounding of colour and location in these tasks. For that reason the initial paradigm used here was a rapid serial visual presentation (RSVP) task. Previous studies using similar paradigms have found no evidence for direct selection by colour (Poder, 2001; Shih & Sperling, 1996), but in these studies advance colour information was of limited usefulness because it only reduced the set of candidate stimuli by half. To assess an effect of colour in selection similar to the one associated with location, in all experiments reported here valid colour information led to only one item, as is typical in location cuing tasks. The first RSVP experiment explored whether colour certainty improved performance over a colour uncertainty condition. Colour was the defining feature of the target participants had to discriminate. In one condition the target colour was certain; in the other it could be one of two colours. Performance was improved when participants could focus on one colour. Further experiments used colour not as a defining feature of the target but as additional information presented in the form of cues, similar to the typical use of location cues. The participants� task was to discriminate whether a target letter within the RSVP sequence appeared in its upper or lower case version, and an advance cue indicated the colour in which the target letter was most likely to occur. An accuracy benefit of valid colour information was found, supporting the hypothesis that colour cuing allows the direct selection of objects for further perceptual processing. In addition, an effect of invalid colour cues was also observed. Subsequent experiments investigated possible factors influencing the colour cuing effect. Together, task requirements and properties of the stimulus set were shown to have an influence on the effect size, whereas an increase in perceptual load had no impact. Furthermore, the colour cuing effect seems to be due partially to both automatic and strategic processes. In all these experimental variations, benefits of colour cuing remained, indicating that the effect is very robust. Colour cuing effects were also found in a design where location could vary, extending the previous findings from selection in the time domain to selection in space. The two last experiments investigated whether advance colour knowledge would also lead to a performance benefit in single item tasks. No effect of colour cuing was found, indicating that colour information is only helpful in multiple item displays when a selection of one target stimulus among distractor items is necessary.

Graduation date: 1996

Thesis (M.S.)--University of Delaware, 2007. / Principal faculty advisor: Gonzalo Arce, Dept. of Electrical and Computer Engineering. Includes bibliographical references.

Thesis (Ph.D.)--Virginia Commonwealth University, 2009. / Prepared for: Dept. of Radiology. Title from title-page of electronic thesis. Bibliography: leaves 117-124.

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The detection of specific temporal patterns in communication signals may be of vital importance for certain organisms. In crickets, for instance, a female will move towards a singing male only if she can recognize the appropriate pulse rate characteristic to its own species' song. Additionally, in order to evade predatory insectivorous bats, flying crickets must be able to track the predator's ultrasonic echolocation signals, which are emitted at a variety of pulse rates. In this thesis, the temporal processing, or the integration of stimulus through time, in the peripheral1 auditory system of the cricket will be investigated. / The ON1 interneuron temporal processing was first examined and compared at high (bat-like) and low carrier (cricket-like) frequencies in three different experimental paradigms. First, integration time, which corresponds to the time it takes for a neuron to reach threshold when stimulated at the minimum effective intensity, was found to be significantly shorter at high carrier frequency than at low carrier frequency. Second, phase locking to sinusoidally amplitude modulated (SAM) signals was more efficient at high frequency, especially at high modulation rates and low modulation depths. Finally, we examined the efficiency with which ON1 detects gaps in a constant tone. As reflected by the decrease in firing rate in the vicinity of the gap, ON1 is better at detecting gaps at low carrier frequency. Following a gap, firing rate increases beyond the pre-gap level. This "rebound" phenomenon is similar for low and high carrier frequencies. / To determine the source of this differential temporal processing, the sensory afferents making synapses with ON1 were investigated. Low frequency (MT-type) and ultrasound auditory receptors were compared on the basis of latency, maximum firing rate, adaptation, information transmission, bursting and feature detection. Ultrasound receptors (HFs) were found to have a shorter latency, a higher maximum firing rate and stronger adaptation than low-frequency receptors (LFs). Individual HFs transmitted more linear (lower-bound) information than LFs. However, HFs' responses were more correlated than LFs' (i.e. they had larger mutual information), so that when superposing the spike trains of LFs, information transmission in the lowest amplitude modulation rates was greatly improved, and, in some cases, reached the level of HFs. Feature detection by spike in HFs was better than in LFs. Feature detection by bursts was better than for spikes, but equivalent in both types of receptors. The level of bursting in HFs, however, was much higher than in LFs, making them better feature detectors in general. / 1Because it lies in the prothoracic ganglion, ON1 is technically part of the central nervous system. For the purpose of this thesis, however, because ON1 receives direct input from the receptors, it will be considered to be part of the peripheral auditory systems.

No description available.

We used the auditory system of crickets as a model system to examine the importance of temporal coding in sensory processing. The bilaterally paired Ascending Neurons 1 and 2 (AN1 and AN2) of crickets receive inputs from the auditory receptors on one side and carry the information to the brain. We used stimuli with either conspecific-like or predator-like (i.e. bats) carrier frequency to quantify the accuracy with which the interneurons code the information contained within the amplitude modulation (AM) envelope of the stimulus. AN1, which is tuned to the dominant carrier frequency of cricket songs, selectively codes the limited range of amplitude-modulation frequencies that occur in these signals. AN2, which is most sensitive to ultrasound, serves as a "bat-detector" and codes a broader range of AM frequencies, as occur in bat calls. / A striking characteristic in AN2's responses to ultrasound is the presence of bursts of high-frequency spiking separated by relatively sparse spikes. We examined the relative importance of isolated spikes and bursts in the processing of ultrasound. We showed that bursts reliably signal the occurrence of salient amplitude increases. Furthermore, we showed that burst, but not isolated spikes, reliably predict behavioural responses. We suggest AN2 encodes behaviourally important information with bursts. / The Omega Neuron 1 (ON1) responds to conspecific signals and to the ultrasonic echolocation sounds. ON1's temporal coding properties vary with carrier frequency, allowing it to encode both of these behaviourally important signals. Furthermore, the temporal coding properties of ON1 in response to cricket-like sound and bat-like sound match those of AN1 and AN2 respectively. / ON1 is a source of contralateral inhibition to AN1 and AN2, enhancing binaural contrast and facilitating sound localization. We used dichotic stimulation to examine the importance of the temporal structure of contralateral inhibition for enhancing binaural contrast. Contralateral inhibition degrades the accuracy with which amplitude modulation is encoded by AN 1 and AN2, but only if the temporal pattern of inhibitory input matches that of excitation. Our results show that the CF-specific coding properties of ON1 allow this single neuron to enhance localization cues most effectively for both cricket-like and bat-like acoustic signals.