The effect of dialect mismatch on likelihood-maximising speech enhancement for noise-robust speech recognition

Traditional speech enhancement methods optimise signal-level criteria such as signal-to-noise ratio, but these approaches are sub-optimal for noise-robust speech recognition. Likelihood-maximising (LIMA) frameworks are an alternative that optimise parameters of enhancement algorithms based on state sequences generated for utterances with known transcriptions. Previous reports of LIMA frameworks have shown significant promise for improving speech recognition accuracies under additive background noise for a range of speech enhancement techniques. In this paper we discuss the drawbacks of the LIMA approach when multiple layers of acoustic mismatch are present – namely background noise and speaker accent. Experimentation using LIMA-based Mel-filterbank noise subtraction on American and Australian English in-car speech databases supports this discussion, demonstrating that inferior speech recognition performance occurs when a second layer of mismatch is seen during evaluation.

Molecular markers of obesity and diabetes

Recently it has been shown that the consumption of a diet high in saturated fat is associated with impaired insulin sensitivity and increased incidence of type 2 diabetes. In contrast, diets that are high in monounsaturated fatty acids (MUFAs) or polyunsaturated fatty acids (PUFAs), especially very long chain n-3 fatty acids (FAs), are protective against disease. However, the molecular mechanisms by which saturated FAs induce the insulin resistance and hyperglycaemia associated with metabolic syndrome and type 2 diabetes are not clearly defined. It is possible that saturated FAs may act through alternative mechanisms compared to MUFA and PUFA to regulate of hepatic gene expression and metabolism. It is proposed that, like MUFA and PUFA, saturated FAs regulate the transcription of target genes. To test this hypothesis, hepatic gene expression analysis was undertaken in a human hepatoma cell line, Huh-7, after exposure to the saturated FA, palmitate. These experiments showed that palmitate is an effective regulator of gene expression for a wide variety of genes. A total of 162 genes were differentially expressed in response to palmitate. These changes not only affected the expression of genes related to nutrient transport and metabolism, they also extend to other cellular functions including, cytoskeletal architecture, cell growth, protein synthesis and oxidative stress response. In addition, this thesis has shown that palmitate exposure altered the expression patterns of several genes that have previously been identified in the literature as markers of risk of disease development, including CVD, hypertension, obesity and type 2 diabetes. The altered gene expression patterns associated with an increased risk of disease include apolipoprotein-B100 (apo-B100), apo-CIII, plasminogen activator inhibitor 1, insulin-like growth factor-I and insulin-like growth factor binding protein 3. This thesis reports the first observation that palmitate directly signals in cultured human hepatocytes to regulate expression of genes involved in energy metabolism as well as other important genes. Prolonged exposure to long-chain saturated FAs reduces glucose phosphorylation and glycogen synthesis in the liver. Decreased glucose metabolism leads to elevated rates of lipolysis, resulting in increased release of free FAs. Free FAs have a negative effect on insulin action on the liver, which in turn results in increased gluconeogenesis and systemic dyslipidaemia. It has been postulated that disruption of glucose transport and insulin secretion by prolonged excessive FA availability might be a non-genetic factor that has contributed to the staggering rise in prevalence of type 2 diabetes. As glucokinase (GK) is a key regulatory enzyme of hepatic glucose metabolism, changes in its activity may alter flux through the glycolytic and de novo lipogenic pathways and result in hyperglycaemia and ultimately insulin resistance. This thesis investigated the effects of saturated FA on the promoter activity of the glycolytic enzyme, GK, and various transcription factors that may influence the regulation of GK gene expression. These experiments have shown that the saturated FA, palmitate, is capable of decreasing GK promoter activity. In addition, quantitative real-time PCR has shown that palmitate incubation may also regulate GK gene expression through a known FA sensitive transcription factor, sterol regulatory element binding protein-1c (SREBP-1c), which upregulates GK transcription. To parallel the investigations into the mechanisms of FA molecular signalling, further studies of the effect of FAs on metabolic pathway flux were performed. Although certain FAs reduce SREBP-1c transcription in vitro, it is unclear whether this will result in decreased GK activity in vivo where positive effectors of SREBP-1c such as insulin are also present. Under these conditions, it is uncertain if the inhibitory effects of FAs would be overcome by insulin. The effects of a combination of FAs, insulin and glucose on glucose phosphorylation and metabolism in cultured primary rat hepatocytes at concentrations that mimic those in the portal circulation after a meal was examined. It was found that total GK activity was unaffected by an increased concentration of insulin, but palmitate and eicosapentaenoic acid significantly lowered total GK activity in the presence of insulin. Despite the fact that total GK enzyme activity was reduced in response to FA incubation, GK enzyme translocation from the inactive, nuclear bound, to active, cytoplasmic state was unaffected. Interestingly, none of the FAs tested inhibited glucose phosphorylation or the rate of glycolysis when insulin is present. These results suggest that in the presence of insulin the levels of the active, unbound cytoplasmic GK are sufficient to buffer a slight decrease in GK enzyme activity and decreased promoter activity caused by FA exposure. Although a high fat diet has been associated with impaired hepatic glucose metabolism, there is no evidence from this thesis that FAs themselves directly modulate flux through the glycolytic pathway in isolated primary hepatocytes when insulin is also present. Therefore, although FA affected expression of a wide range of genes, including GK, this did not affect glycolytic flux in the presence of insulin. However, it may be possible that a saturated FA-induced decrease in GK enzyme activity when combined with the onset of insulin resistance may promote the dys-regulation of glucose homeostasis and the subsequent development of hyperglycaemia, metabolic syndrome and type 2 diabetes.

Post-tensioning and its effect on multi-level formwork load distribution

Multi-level concrete buildings requrre substantial temporary formwork structures to support the slabs during construction. The primary function of this formwork is to safely disperse the applied loads so that the slab being constructed, or the portion of the permanent structure already constructed, is not overloaded. Multi-level formwork is a procedure in which a limited number of formwork and shoring sets are cycled up the building as construction progresses. In this process, each new slab is supported by a number of lower level slabs. The new slab load is, essentially, distributed to these supporting slabs in direct proportion to their relative stiffness. When a slab is post-tensioned using draped tendons, slab lift occurs as a portion of the slab self-weight is balanced. The formwork and shores supporting that slab are unloaded by an amount equivalent to the load balanced by the post-tensioning. This produces a load distribution inherently different from that of a conventionally reinforced slab. Through , theoretical modelling and extensive on-site shore load measurement, this research examines the effects of post-tensioning on multilevel formwork load distribution. The research demonstrates that the load distribution process for post-tensioned slabs allows for improvements to current construction practice. These enhancements include a shortening of the construction period; an improvement in the safety of multi-level form work operations; and a reduction in the quantity of form work materials required for a project. These enhancements are achieved through the general improvement in safety offered by post-tensioning during the various formwork operations. The research demonstrates that there is generally a significant improvement in the factors of safety over those for conventionally reinforced slabs. This improvement in the factor of safety occurs at all stages of the multi-level formwork operation. The general improvement in the factors of safety with post-tensioned slabs allows for a shortening of the slab construction cycle time. Further, the low level of load redistribution that occurs during the stripping operations makes post-tensioned slabs ideally suited to reshoring procedures. Provided the overall number of interconnected levels remains unaltered, it is possible to increase the number of reshored levels while reducing the number of undisturbed shoring levels without altering the factors of safety, thereby, reducing the overall quantity of formwork and shoring materials.