In the present study clinical performance of new highly cardiospecific biochemical markers of myocardial injury was investigated and these markers were compared with conventional enzymes. The multimarker risk assessment score index, including biochemical markers of myocardial injury, inflammation and haemostasis, was developed for the prognosis of patients after ACS. The prognostic value of BNP concentration changes in predicting LV remodeling and dysfunction after MI was evaluated along with other biochemical markers of myocardial injury.

The objective of this thesis was to investigate the genomic changes that have occurred due to the effects of long-term artificial selection applied by soybean breeders. A total of 42 cultivars from six different breeding programs, comprising the multi-generational pedigree of OAC Bayfield were genotyped with molecular markers and chromosomal inheritance was tracked throughout the pedigree. The graphical genotype profile of the 20 chromosomes revealed substantial allelic structure that has been built up in certain chromosomes, in the form of specific linkage blocks, which have been conservatively inherited. A selective sweep analysis using microsatellite markers was performed using the members of OAC Bayfield’s pedigree to identify genomic regions that have retained a molecular selective signature through OAC Bayfield in the varieties derived from it. Overall, there was a high level of agreement between the identified quantitative trait loci (QTL) and the phenotypic traits that would have been expected to be under breeders’ selection.

A challenge in clinical medicine is that of correct diagnosis of disease. Medical researchers invest considerable time and effort to enhance accurate disease diagnosis. Diagnostic tests are important components in modern medical practice. The receiver operating characteristic (ROC) is a commonly used statistical tool for describing the discriminatory accuracy and performance of a diagnostic test. A popular summary index of discriminatory accuracy is the area under ROC curve (AUC). In the era of high-dimensional data, scientists are evaluating hundreds to multiple thousands of biomarkers simultaneously. A critical challenge is the combination of these markers into models that give insight into disease. In infectious disease, markers are often evaluated in the host as well as in the microorganism or virus causing infection, adding more complexity to the analysis. In addition to providing an improved understanding of factors associated with infection and disease development, combinations of relevant markers is important to diagnose and treat disease. Taken together, this presents many novel and major challenges to, and extends the role of, the statistical analyst. In this thesis, we will address the problem of how to select from multiple markers using existing methods. Logistic regression models offer a simple method for combining markers. We applied resampling methods (e.g., Cross-Validation and bootstrap) to adjust for overfitting associated with model selection. We simulated several multivariate models to evaluate the performance of the resampling approaches in this setting. We applied the methods to data collected from a study of tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) in Cape Town. Baseline levels of five biomarkers were evaluated and we used this dataset to evaluate whether a combination of these biomarkers could accurately discriminate between Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) and non TB-IRIS patients, applying AUC analysis and resampling methods. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2012.

KîîTharaka is a Bantu language spoken by a minority community in Kenya numbering about 120,000. Attitude markers belong to the broad category of ‘residue’ elements in language commonly called ‘discourse markers’. Alternative terms for discourse markers are: Discourse particles, discourse/speech modifiers, pragmatic markers, pragmatic particles, or discourse operators. As the term ‘attitude’ markers itself suggests, attitude markers may best be defined as a set of expressions in language which the speaker applies to clarify his or her feelings, emotions or views contained in the utterance being made. Attitude markers ‘amplify’ the speakers intended meaning. Moore (2001: 5) observes that English speakers use expressive verbs to convey attitudes to or about a state of affairs e.g. ‘apologize’, ‘appreciate’, ‘congratulate’, ‘deplore’, ‘detest’, ‘regret’, ‘thank’, and ‘welcome’. It is such kind of expressions that are investigated in this research on KîîTharaka. This dissertation highlights on this linguistic phenomenon with the view that to ignore the role played by attitude markers in communicating meaning in KîîTharaka may reduce the accuracy of the speaker’s or the writer’s intended message. Bearing in mind that attitude markers are similar to discourse markers in that both are not part of the conceptual (i.e. the referential) information of the speaker’s utterance, the critical distinction to be made between discourse markers and attitude markers is that unlike discourse markers, attitude markers do not function as connectives i.e. they do not primarily establish discourse cohesion. / Thesis (M.A.)-University of KwaZulu-Natal, Durban, 2009.

Methylmercury (MeHg) is a neurotoxic global pollutant that accumulates at high levels in predatory fish and marine mammals. The dietary intake of these animals is the main source of MeHg exposure in humans. At high levels, MeHg is known to damage the sensory and motor systems in both adults and children. Due to the complexity and inaccessibility of the central nervous system (CNS), early dysfunction is difficult to detect. Biochemical markers in the CNS have been used to identify MeHg neurotoxicity in animal models. Analogues of these biochemical targets are also present in peripheral blood tissue and may reflect early CNS dysfunction in human populations. The proposed peripheral biomarkers include (1) lymphocyte muscarinic acetylcholine (mACh) receptor, (2) serum cholinesterase (ChE) and (3) platelet monoamine oxidase (MAO). This thesis evaluates the effects of mercury (Hg) compounds on these CNS and peripheral biochemical markers in laboratory and epidemiological studies. In vitro studies showed that inorganic Hg (HgCl2) and MeHg inhibited mACh receptor binding in human, rat, and mouse brain tissue. Additionally, studies demonstrated that a low-level gestational exposure to MeHg reduced MAO activity in the developing embryo and in adult female offspring. Combined, these studies provide a framework for the assessment of biochemical targets of Hg compounds in humans. A cross sectional study was conducted to evaluate the association between peripheral biochemical markers and MeHg exposure in fish-eating adults (n=129) from Lac St-Pierre, Quebec. Blood-Hg concentrations were used as a marker of exposure and ranged from 0.2 to 17.0 mug/L. Multiple linear regression analysis demonstrated that both blood-Hg (p=0.011) and heavy smoking (p=0.001) were associated with reduced platelet-MAO activity. However, neither lymphocyte mACh receptor nor serum ChE was related to blood-Hg. These results suggest that exposure to MeHg may result in reduced plat

The biodiversity of Durban (eThekwini municipality) in KwaZulu Natal is primarily threatened by urbanization although other factors such as climate change and the spread of invasive species also pose a significant threat. Knowledge of what species exist within the city is important for biodiversity surveillance, detecting invasive taxa and uncovering cryptic species. Conducting a comprehensive biodiversity inventory is a daunting task, especially for hyperdiverse groups such as terrestrial arthropods, where closely related species can often only be separated by subtle morphological characters. This study investigated whether the barcoding marker, Cytochrome Oxidase C Subunit 1 (COI) can be used to efficiently and accurately delineate species of ants (family Formicidae) in comparison to traditional taxonomic approaches. The feasibility of DNA barcoding for assembling biodiversity inventories for urban areas which could be useful in conservation planning was also evaluated. A total of 619 individuals were sequenced from 23 geographic localities within the eThekwini region and surrounding regions. DNA barcoding revealed 80 provisional species/ “barcode clusters” or monophyletic lineages which could represent distinct species, while morphology revealed 51 different morphospecies. Extrapolation measures of species richness indicated that as many as 153 species of ants could occur in the city. Phylogenetic and phylogeographic analyses were performed on co-distributed species belonging to the genera Lepisiota, Camponotus, Pheidole and Pachycondyla to better understand the spatial distribution of genetic variability in the eThekwini region. Nuclear markers 18S rDNA and 28S rDNA were also sequenced and compared for a subsample of individuals from Camponotus and Pachycondyla. There was genetic variation at COI and the nuclear markers for each of the species examined. In order to fully elucidate the population genetic patterns which could be expected in eThekwini and surrounding regions, further sampling across more localities is essential. The use of more nuclear markers could also assist in uncovering these unique patterns of genetic variation in an urban setting. In this study, the utility of COI as a species diagnostic tool in ants was confirmed. The barcoding library constructed showed promise in highlighting reserves that should be preserved and possible cryptic speciation for further investigation. / M. Sc. University of KwaZulu-Natal, Durban 2014.

Soybean (Glycine max) is an important crop in the world in terms of total production and usage. It is also among the least diverse species. The main objectives of the present study were 1) to determine differences between ISSR and RAPD marker systems in detecting genetic variation in soybeans and 2) to identify and characterize accession- diagnostic molecular markers in G. max accessions. Genomic DNAs from 108 G. max accessions from 11 different gene pools were analyzed using several ISSR and RAPD primers. The levels of polymorphic loci detected with the two marker systems were in general moderate and similar.. Overall, 82% of genetic distance values were above 0.40 based on ISSR analysis. However, RAPD data revealed that the accessions from different countries are closely related with 64% genetic distance values below 0.40. The dendrograms constructed with ISSR data revealed that the South Korean accessions formed an out-group while the RAPD analysis showed that accessions from Sweden were separate from the other 10 gene pools. One variety-diagnostic marker generated with ISSR 5 primer was identified in the accession Kao Chien Tao from China. This marker was cloned, and sequenced. Although RAPD and ISSR marker systems detected similar levels of genetic variability, they target different regions of the soybean genome, resulting in different clustering of the 11 gene pools indicating different genetic relatedness among them. This finding demonstrates the usefulness of both marker systems in assessing diversity and relatedness among Glycine max gene pools.

Ovarian cancer has very high mortality because it is hard to diagnosis in early stages. Many ovarian cancer biomarkers (such as HE4, CA 125) are available and had been suggested as potential tools for early cancer detection. However, early cancer detection using serological markers will only become widely used if a new generation of sensors that can be handled in a clinical setting can be developed. A detection technology that is promising for miniaturization and integration in biomedical sensing devices is based on the phenomenon of the extraordinary light transmission (EOT) through arrays of nanoholes on metal films. EOT is an increase in light transmission observed at certain wavelengths that satisfy the surface plasmon resonance (SPR) condition of the nanostructure. The position of this resonance is affected by surface adsorption phenomenon, which is the basis for the biosensor. In this dissertation, the detection of the HE4 biomarker was demonstrated using EOT. The EOT-based detection was compared to two state-of-the-art analytical methods (ELISA and commercial SPR). Based on our experiments, it was found that ELISA has lowest detection limit, around 0.5 ng/mL for that particular protein (HE4). The detection limits for the commercial SPR, around 0.13 μg/mL was comparable to the nanohole-based detection limit, around 1.76 μg/mL. In contrast to ELISA, the SPR-based methods were label free, more time efficient, and more environmental friendly. An extra advantage of the nanohole scheme was that multiple samples could be analyzed simultaneously and in real time. Adsorption kinetic experiments were also performed to evaluate the rate constants of the HE4 binding to a surface coated with anti-HE4. The adsorption equilibrium constant for the HE4 – anti-HE4 system was determined to be (4.3 ± 2.1) x 107 M-1. / Graduate / 0487

In the bone marrow, CD34 is the best currently available marker of human multipotential stem cells and is downregulated upon the commitment of cells to the myeloid pathway. CD33 is the earliest marker of stem cell commitment to the myeloid lineage but is down-regulated as myeloid cells mature to granulocytes while expression is retained on monocytes, dendritic cells and macrophages. CD34 is a mucosialin and CD33 a member of the immunoglobulin superfamily. To determine the functions of CD34 and CD33 in early haematopoiesis, soluble forms of CD34 and CD33 have been constructed by PCR based construction of extracellular domain-IgGlFc (ECDFc) fusion plasmids. These chimaeric proteins have been used to define the ligand binding of CD33 and CD34 in a range of assay systems including: screening cell lines by immunofluorescence and iodination analysis; immunohistochemical staining; screening of cDNA libraries transiently expressed in COS cells by "panning" for ligands; and phosphorylation studies to assess the potential of phosphoproteins to regulate these molecules and their ligands in vitro. Iodination demonstrated that CD33 binds increasing numbers of ligands heterophilically on erythroleukemic (K562) and promonocytic (U937) cell lines at sizes ranging from 54-69Kd and 97-1 lOKd in a differentiation-dependent manner. CD33 was established to associate with several src-like kinases while Fc-CD33 precipitates phosphoproteins in the same region in KG-la, K562 and U937. Novel divalent-cation-dependent CD34 ligands of 66Kd and HOKd were isolated on HUVEC and both CD34 and Fc-CD34 precipitated phosphoproteins from HUVEC. From panning studies, Fc-CD33 demonstrated low levels of binding to ICAM-1 and a cDNA product sharing homology to the 3' end of dystrophin, termed here as apo-dystrophin-4. Apo-4 appears to give rise to two major proteins, at least one of which may provide an in vitro ligand for CD33 and contain a 3' enhancer. Models for both CD33 phosphoprotein and ligand binding behaviour are presented.

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