The emerging field of personalized medicine and the prediction of side effects experienced due to pharmaceutical drugs is being studied intensively in the post genomic era. The molecular basis of inheritance and disease susceptibility is being unravelled, especially through the use of rapidly evolving new technologies. This in turn facilitates analyses of individual variations in the whole genome of both single subjects and large groups of subjects. Genetic variation is a common occurrence and although most genetic variations do not have any apparent effect on the gene product some do exhibit effects, such as an altered ability to detoxify xenobiotics. The human body has a highly effective detoxification system that detoxifies and excretes endogenous as well as exogenous toxins. Numerous studies have proved that specific genetic variations have an influence on the efficacy of the metabolism of pharmaceutical drugs and consequently the dosage administered. The primary aim of this project was the local implementation and assessment of two different genotyping approaches namely: the Applied Biosystems SNaPshot technique and Affymetrix DMET microarray. A secondary aim was to investigate if links could be found between the genetic data and the biochemical detoxification profile of participants. I investigated the approaches and gained insight into which method would be better for specific local applications, taking into consideration the robustness and ease of implementation as well as cost effectiveness in terms of data generated. The final study cohort comprised of 18 participants whose detoxification profiles were known. Genotyping was performed using the DMET microarray and SNaPshot techniques. The SNaPshot technique was used to genotype 11 SNPs relating to DNA repair and detoxification and was performed locally. Each DMET microarray delivers significantly more data in that it genotypes 1931 genetic markers relating to drug metabolism and transport. Due to the absence of a local service supplier, the DMET - microarrays were outsourced to DNALink in South Korea. DNALink generated raw data which was analysed locally. I experienced many problems with the implementation of the SNaPshot technique. Numerous avenues of troubleshooting were explored with varying degrees of success. I concluded that SNaPshot technology is not the best suited approach for genotyping. Data obtained from the DMET microarray was fed into the DMET console software to obtain genotypes and subsequently analysed with the help of the NWU statistical consultation services. Two approaches were followed: firstly, clustering the data and, secondly, a targeted gene approach. Neither of the two methods was able to establish a relationship between the DMET genotyping data and the detoxification profiling. For future studies to successfully correlate SNPs or SNP groups and a specific detoxification profile, two key issues should be addressed: i) The procedure for determining the detoxification profile following substrate loading should be further refined by more frequent sampling after substrate loading. ii) The number of participants should be increased to provide statistical power that will enable a true representation of the particular genetic markers in the specific population. The statistical analyses, such as latent class analyses to cluster the participants will also be of much more use for data analyses and interpretation if the study is not underpowered. / Thesis (M.Sc. (Biochemistry))--North-West University, Potchefstroom Campus, 2011.

Many studies have reported individual differences in resting metabolic rate (RMR), the energetic cost of self-maintenance. Differences among individuals in the energetic cost of self-maintenance may influence life-history decisions and hence, fitness. In this study, we examined potential causes of intra-specific variation in RMR in zebrafish, Danio rerio. First, the repeatability of RMR was determined to check whether a single measure was reflective of future physiological performance. As predicted, RMR was repeatable over a period of three weeks. However, none of stress-coping style, baseline cortisol levels, metabolically-active organ (gill, heart, intestine and liver) mass, aggression or activity levels were correlated with RMR, i.e. none of these factors were significant contributors to individual variation in RMR. These results imply that other factors must be sought to explain the inter-individual variation in RMR observed in zebrafish.

This study investigates variable positioning of adverbs in compound verb tenses in vernacular Quebec French using the sociolinguistic framework of Variation Theory (Weinreich et al. 1968; Labov 1969). While variable adverb placement is addressed in both the prescriptive and linguistic literature, whether their explanations for it hold in practice remains to be determined; quantitative research of this phenomenon in usage-based corpora is limited, and rare in French. The research objectives are therefore to determine the productivity of variable adverb placement in French in these verbal contexts, to uncover the linguistic and/or social factors which constrain it, and to evaluate the extent to which current treatments of this variable in the literature accurately reflect what occurs in speech. Data is thus extracted from a corpus of spontaneous discourse, is coded for several linguistic and social factors, and is quantitatively analysed using standard variationist methodology (Poplack & Tagliamonte 2001). Overall rates of variant use suggest that variable adverb placement is robust, with adverbs occurring just slightly more frequently after the past participle than between the auxiliary and the participle; placement at the beginning of the sentence is rare. The results of the distributional and multivariate analyses largely confirm the purported conditioning effects of the tested linguistic factors, suggesting that prescriptive and theoretical linguistic approaches are generally correct in their accounts of this phenomenon. However, closer investigation reveals these effects to be sensitive to the lexical identity of the adverb, namely, their particular placement preferences; once these positioning predilections are taken into consideration, the conditioning effects of the linguistic factors essentially disappear. Sociodemographic factors are also found to be mildly implicated in variable adverb placement, and these too are sensitive to the influence of the lexical identity of the adverb. Ultimately, it is argued that this variable is primarily lexically-constrained, a finding which can be only minimally and indirectly inferred from the relevant literature. Taken together, the results of this study provide new and vital insight into the mechanisms underlying variable adverb placement in French, and also highlight the importance of quantitatively investigating such variable language phenomena in corpora of vernacular speech.

The emerging field of personalized medicine and the prediction of side effects experienced due to pharmaceutical drugs is being studied intensively in the post genomic era. The molecular basis of inheritance and disease susceptibility is being unravelled, especially through the use of rapidly evolving new technologies. This in turn facilitates analyses of individual variations in the whole genome of both single subjects and large groups of subjects. Genetic variation is a common occurrence and although most genetic variations do not have any apparent effect on the gene product some do exhibit effects, such as an altered ability to detoxify xenobiotics. The human body has a highly effective detoxification system that detoxifies and excretes endogenous as well as exogenous toxins. Numerous studies have proved that specific genetic variations have an influence on the efficacy of the metabolism of pharmaceutical drugs and consequently the dosage administered. The primary aim of this project was the local implementation and assessment of two different genotyping approaches namely: the Applied Biosystems SNaPshot technique and Affymetrix DMET microarray. A secondary aim was to investigate if links could be found between the genetic data and the biochemical detoxification profile of participants. I investigated the approaches and gained insight into which method would be better for specific local applications, taking into consideration the robustness and ease of implementation as well as cost effectiveness in terms of data generated. The final study cohort comprised of 18 participants whose detoxification profiles were known. Genotyping was performed using the DMET microarray and SNaPshot techniques. The SNaPshot technique was used to genotype 11 SNPs relating to DNA repair and detoxification and was performed locally. Each DMET microarray delivers significantly more data in that it genotypes 1931 genetic markers relating to drug metabolism and transport. Due to the absence of a local service supplier, the DMET - microarrays were outsourced to DNALink in South Korea. DNALink generated raw data which was analysed locally. I experienced many problems with the implementation of the SNaPshot technique. Numerous avenues of troubleshooting were explored with varying degrees of success. I concluded that SNaPshot technology is not the best suited approach for genotyping. Data obtained from the DMET microarray was fed into the DMET console software to obtain genotypes and subsequently analysed with the help of the NWU statistical consultation services. Two approaches were followed: firstly, clustering the data and, secondly, a targeted gene approach. Neither of the two methods was able to establish a relationship between the DMET genotyping data and the detoxification profiling. For future studies to successfully correlate SNPs or SNP groups and a specific detoxification profile, two key issues should be addressed: i) The procedure for determining the detoxification profile following substrate loading should be further refined by more frequent sampling after substrate loading. ii) The number of participants should be increased to provide statistical power that will enable a true representation of the particular genetic markers in the specific population. The statistical analyses, such as latent class analyses to cluster the participants will also be of much more use for data analyses and interpretation if the study is not underpowered. / Thesis (M.Sc. (Biochemistry))--North-West University, Potchefstroom Campus, 2011.

This dissertation examined the participation of eight lower-achieving readers in two intermediate-level elementary classrooms (one fourth- and one fifth-grade) during group discussions about literary texts. The purpose of the investigation was to determine the extent to which lower-achieving readers (defined as students who had persistent struggles to attain minimum scores on state, district, and classroom assessments in reading) displayed discourse features that indicated the students' high-level thinking during heterogeneous and homogeneous (by reading level) discussions about literary texts. Several characteristics of discourse indicate high-level thinking, including but not limited to: generalizations, analyses, speculations, affective responses, inter-textual connections, and elaborated explanations. A secondary purpose was to describe what happened when lower-achieving readers, their peers, and teachers engaged in group discussions about text. / A multiple case study design was used in this investigation. Data were collected between October 2005 and May 2006. Data sources included: field notes collected from participant observation, transcripts and indices of student and teacher interviews, transcripts and indices of audiotaped and videotaped discussions and reading lessons, and students' writing assignments and other artifacts. Multiple strategies were used to analyze the data, including analytic induction and descriptive statistical techniques. A discourse analysis coding scheme was used to determine the extent to which lower-achieving readers likely used high-level thinking about literary texts during group discussions. / The findings revealed focal students used the discourse of discussion as a tool to comprehend text in two ways. The students used the discourse about texts as intellectual scaffolds for their own thinking and transformation in understanding of the texts. In addition, the discussions created authentic opportunities for students to explore reading comprehension strategies (e.g., meanings of new words, visualizing the story). This means students drew on their knowledge of comprehension strategies and incorporated them into their discussions to reason about the texts without explicit instruction from the teacher. Focal students both evoked and heard others refer to and talk about the comprehension strategies during discussions. Moreover, an important contextual foundation of the discussions that seemed to relate to the focal students' thoughtful responses, or those that suggested the students went beyond recalling the literal details of the stories, was the use of the discourse to problem-solve about the meaning of the texts. Finally, in respect to the students' writing assignments that often followed the discussions about the texts, lower-achieving readers made use of the ideas of the discussions in their writing. / Regarding high-level thinking during discussions, the lower-achieving readers' discourse suggested that they thought in high-level ways about texts during discussions, and that they thought in high-level ways to the same extent or nearly the same extent as their peers did in the same discussions about texts. The one major difference in their talk about texts related to the instances of elaborated explanations or instances when students stated a position and explained their thoughts about the position with more than one reason or with evidence from the text. Higher-achieving readers produced significantly more 'elaborated explanations' during discussions than the lower-achieving readers in this study. / From a theoretical perspective, this investigation extends our understanding of lower-achieving readers' use of discursive practices that influence thinking and reasoning about text. From pedagogical perspectives, the findings suggest teachers might need to understand ways to encourage a kind of discourse that elicits genuine problem-solving about the meanings of text. Likewise, teachers might need to understand the discourse features that indicate high-level thinking to model and discuss the features in their work with lower-achieving readers during discussions about literary texts.

Epithelial ovarian cancer is the leading cause of death by gynaecological malignancy. Elucidation of the driver genes of ovarian cancer will lead to treatment targets and tailored therapy for this disease. The Affymetrix Genome-Wide SNP Array 6.0 was used to study 100 serous ovarian samples and 10 normal ovarian samples to identify loci and driver genes. The ovarian cancer genome was found to have high overall genomic instability across all chromosomes and key known genes in this disease were identified in the dataset. Aberrant regions of copy number gain were located in “blocks” of constant copy number at 1p, 1q, 8q, 12p, 19q and 20q. The range in copy number for gains was 4.2 to 5.1. The “blocks” of genes were located at 8p and 5p for copy number losses. The range for copy number loss was 0.6 to 0.9.

Epithelial ovarian cancer is the leading cause of death by gynaecological malignancy. Elucidation of the driver genes of ovarian cancer will lead to treatment targets and tailored therapy for this disease. The Affymetrix Genome-Wide SNP Array 6.0 was used to study 100 serous ovarian samples and 10 normal ovarian samples to identify loci and driver genes. The ovarian cancer genome was found to have high overall genomic instability across all chromosomes and key known genes in this disease were identified in the dataset. Aberrant regions of copy number gain were located in “blocks” of constant copy number at 1p, 1q, 8q, 12p, 19q and 20q. The range in copy number for gains was 4.2 to 5.1. The “blocks” of genes were located at 8p and 5p for copy number losses. The range for copy number loss was 0.6 to 0.9.

Resting metabolic rate (RMR) is the minimum energy expenditure necessary for survival. RMR varies widely both among and within species and a central question in evolutionary physiology concerns the functional basis for this variation. Juvenile North American red squirrels were used to investigate fitness consequences of variation in RMR by considering how expenditure relates to differences in food availability and to overwinter survival. Additionally, this thesis examines whether red squirrels exhibit phenotypic plasticity in RMR in response to varying levels of food availability. Results indicate that heavier juveniles with relatively low RMRs were more likely to survive overwinter. Moreover, these juveniles were capable of allocating more energy towards mechanical work and possessed larger food stores. Food supplemented yearlings exhibited higher RMRs than unsupplemented controls at the onset of the breeding season, while no difference in RMR was detected following termination of supplementation. / Wildlife Ecology

A long term study of fish populations on the Bonaparte Plateau, B.C., has revealed the possibility of 2-year cyclic recruitment variation in the pygmy pikeminnow (Ptychocheilus oregonensis). This thesis reviews possible causes of the cycle, and evaluates an inexpensive and non-destructive visual survey method to estimate juvenile population numbers over short summer periods while pikeminnow juveniles are recruiting to the lakes and dying rapidly, for use in future studies of the cyclic pattern. To provide an index of the abundance of juvenile pikeminnow, strip-transect surveys were conducted from shore. Each strip transect area was a full circumference of each of three study lakes, and extended from shore to a distance of up to 3 meters offshore. The visual surveys were shown to be accurate and repeatable when estimating the number of fish and the lengths of the fish in a shoal. The strip transects provide an index of abundance for juvenile northern pikeminnow and this index of abundance can be used to calculate daily summer and interannual mortality rates, providing estimates close to those predicted from the Lorenzen model for size-dependent mortality rates of fish in general. Stationary point surveys were also conducted to investigate juvenile pikeminnow behaviour, and these point surveys reveal a link between sunlight intensity and pikeminnow activity, and provide evidence of direct agonistic interactions between age 0 and age 1 juveniles, which could result in higher mortality rates of age 0 fish when age 1 fish are abundant. Analysis of survey data collected to date over five years from three lakes supports the possibility of a recruitment cycle with lakes out of phase with each other, suggesting that ecological interactions drive the cycles. These interactions are worthy of further investigation.

This thesis reports on a design and modeling of a micro-machined gyroscope. The proposed sensor is a dual mass type, electro-statically driven to primary mode oscillation and senses, capacitively, the output signal. Full decoupling between drive and sense modes minimizes the mechanical crosstalk and based on this a novel gyroscope is designed and modeled which has separate sensing and driving masses. The dual mass gyroscope is designed such that driving and sensing resonant frequency is 23101 Hz with 0% mismatch (in simulation)with quality factor of 31.6227 and bandwidth of 730.51Hz. The gyroscope when actuated in simulation with 25V ac and 10V dc showed sensing capacitance variation of 126aF for 1 rad/s with base capacitance of 244.16fF. To the design of the gyroscope a new semi automatic tool was formulated for the noise analysis and noise based optimization of the resonant MEMS structures. Design of a sensitive gyroscope needs to take into account the noise shaping induced by damping phenomena at micro scale and is critical for optimization. The analysis was further extended to the design of the gyroscope and estimation shows that there is a trade of between the S/N ratio and the sensitivity and the design could be made much better in-terms of S/N by tuning its resonant frequency to 10⁶Hz.