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.

Implementing value management as a decision-making tool in the design stages of design and build construction projects : a methodology for improved cost optimization

Value Management (VM) has been proven to provide a structured framework, together with other supporting tools and techniques, that facilitate effective decision-making in many types of projects, thus achieving ‘best value’ for clients. One of the major success factors of VM in achieving better project objectives for clients is through the provision of beneficial input by multi-disciplinary team members being involved in critical decision-making discussions during the early stage of construction projects. This paper describes a doctoral research proposal based on the application of VM in design and build construction projects, especially focusing on the design stage. The research aims to study the effects of implementing VM in design and build construction projects, in particular how well the methodology addresses issues related to cost overruns resulting from poor coordination and overlooking of critical constructability issues amongst team members in construction projects in Malaysia. It is proposed that through contractors’ early involvement during the design stage, combined with the use of the VM methodology, particularly as a decision-making tool, better optimization of construction cost can be achieved, thus promoting more efficient and effective constructability. The main methods used in this research involve a thorough literature study, semi-structured interviews, and a survey of major stakeholders, a detailed case study and a VM workshop and focus group discussions involving construction professionals in order to explore and possibly develop a framework and a specific methodology for the facilitating successful application of VM within design and build construction projects.

Stabilization mechanisms of soil organic matter: Implications for C-saturation of soils

The relationship between soil structure and the ability of soil to stabilize soil organic matter (SOM) is a key element in soil C dynamics that has either been overlooked or treated in a cursory fashion when developing SOM models. The purpose of this paper is to review current knowledge of SOM dynamics within the framework of a newly proposed soil C saturation concept. Initially, we distinguish SOM that is protected against decomposition by various mechanisms from that which is not protected from decomposition. Methods of quantification and characteristics of three SOM pools defined as protected are discussed. Soil organic matter can be: (1) physically stabilized, or protected from decomposition, through microaggregation, or (2) intimate association with silt and clay particles, and (3) can be biochemically stabilized through the formation of recalcitrant SOM compounds. In addition to behavior of each SOM pool, we discuss implications of changes in land management on processes by which SOM compounds undergo protection and release. The characteristics and responses to changes in land use or land management are described for the light fraction (LF) and particulate organic matter (POM). We defined the LF and POM not occluded within microaggregates (53-250 mum sized aggregates as unprotected. Our conclusions are illustrated in a new conceptual SOM model that differs from most SOM models in that the model state variables are measurable SOM pools. We suggest that physicochemical characteristics inherent to soils define the maximum protective capacity of these pools, which limits increases in SOM (i.e. C sequestration) with increased organic residue inputs.

The role of sulphates and organic vapours in growth of newly formed particles in a eucalypt forest

The influence of biogenic particle formation on climate is a well recognised phenomenon. To understand the mechanisms underlying the biogenic particle formation, determining the chemical composition of the new particles and therefore the species that drive the particle production is of utmost importance. Due to the very small amount of mass involved, indirect approaches are frequently used to infer the composition. We present here the results of such an indirect approach by simultaneously measuring volatile and hygroscopic properties of newly formed particles in a forest environment. It is shown that the particles are composed of both sulphates and organics, with the amount of sulphate component strongly depending on the available gas-phase sulphuric acid, and the organic components having the same volatility and hygroscopicity as photooxidation products of a monoterpene such as α-pinene. Our findings agree with a two-step process through nucleation and cluster formation followed by simultaneous growth by condensation of sulphates and organics that take the particles to climatically relevant sizes.

Surface modification of alumina nanofibres for the selective adsorption of alachlor and imazaquin herbicides

The effective removal of pollutants using a thermally and chemically stable substrate that has controllable absorption properties is a goal of water treatment. In this study, the surfaces of thin alumina (γ-Al2O3) nanofibres were modified by the grafting either of two organosilane agents, 3-chloro-propyl-triethoxysilane (CPTES) and octyl-triethoxysilane (OTES). These modified materials were then trialed as absorbents for the removal of two herbicides, alachlor and imazaquin from water. The formation of organic groups during the functionalisation process established super hydrophobic sites on the surfaces of the nanofibres. This super hydrophobic group is a kind of protruding adsorption site which facilitates the intimate contact with the pollutants. OTES grafted substrate were shown to be more selective for alachlor while imazaquin selectivity is shown by the CPTES grafted substrate. Kinetics studies revealed that imazaquin was rapidly adsorbed on CPTES-modified surfaces. However, the adsorption of alachlor by OTES grafted surface was achieved more slowly.

Characterisation of organoclays and adsorption of p-nitrophenol : environmental application

Organoclays were synthesised through ion exchange of a single surfactant for sodium ions, and characterised by a range of method including X-ray diffraction (XRD), BET, X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM). The change in surface properties of montmorillonite and organoclays intercalated with the surfactant, tetradecyltrimethylammonium bromide (TDTMA) were determined using XRD through the change in basal spacing and the expansion occurred by the adsorbed p-nitrophenol. The changes of interlayer spacing were observed in TEM. In addition, the surface measurement such as specific surface area and pore volume was measured and calculated using BET method, this suggested the loaded surfactant is highly important to determine the sorption mechanism onto organoclays. The collected results of XPS provided the chemical composition of montmorillonite and organoclays, and the high-resolution XPS spectra offered the chemical states of prepared organoclays with binding energy. Using TGA and FT-IR, the confirmation of intercalated surfactant was investigated. The collected data from various techniques enable an understanding of the changes in structure and surface properties. This study is of importance to provide mechanisms for the adsorption of organic molecules, especially in contaminated environmental sites and polluted waters.

Depth of focus and visual acuity with primary and secondary spherical aberration

It is known that the depth of focus (DOF) of the human eye can be affected by the higher order aberrations. We estimated the optimal combinations of primary and secondary Zernike spherical aberration to expand the DOF and evaluated their efficiency in real eyes using an adaptive optics system. The ratio between increased DOF and loss of visual acuity was used as the performance indicator. The results indicate that primary or secondary spherical aberration alone shows similar effectiveness in extending the DOF. However, combinations of primary and secondary spherical aberration with different signs provide better efficiency for expanding the DOF. This finding suggests that the optimal combinations of primary and secondary spherical aberration may be useful in the design of optical presbyopic corrections. © 2011 Elsevier Ltd. All rights reserved.

Thermal stability of the ‘cave’ mineral brushite CaHPO4•2H2O -mechanism of formation and decomposition

Thermogravimetry combined with evolved gas mass spectrometry has been used to ascertain the stability of the ‘cave’ mineral brushite. X-ray diffraction shows that brushite from the Jenolan Caves is very pure. Thermogravimetric analysis coupled with ion current mass spectrometry shows a mass loss at 111°C due to loss of water of hydration. A further decomposition step occurs at 190°C with the conversion of hydrogen phosphate to a mixture of calcium ortho-phosphate and calcium pyrophosphate. TG-DTG shows the mineral is not stable above 111°C. A mechanism for the formation of brushite on calcite surfaces is proposed, and this mechanism has relevance to the formation of brushite in urinary tracts.

The evaluation of new and isotopically labeled isoindoline nitroxides and an azaphenalene nitroxide for EPR oximetry

Isoindoline nitroxides are potentially useful probes for viable biological systems, exhibiting low cytotoxicity, moderate rates of biological reduction and favorable Electron Paramagnetic Resonance (EPR) characteristics. We have evaluated the anionic (5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl; CTMIO), cationic (5-(N,N,N-trimethylammonio)-1,1,3,3-tetramethylisoindolin-2-yloxyl iodide, QATMIO) and neutral (1,1,3,3-tetramethylisoindolin-2-yloxyl; TMIO) nitroxides and their isotopically labeled analogs ((2)H(12)- and/or (2)H(12)-(15)N-labeled) as potential EPR oximetry probes. An active ester analogue of CTMIO, designed to localize intracellularly, and the azaphenalene nitroxide 1,1,3,3-tetramethyl-2,3-dihydro-2-azaphenalen-2-yloxyl (TMAO) were also studied. While the EPR spectra of the unlabeled nitroxides exhibit high sensitivity to O(2) concentration, deuteration resulted in a loss of superhyperfine features and a subsequent reduction in O(2) sensitivity. Labeling the nitroxides with (15)N increased the signal intensity and this may be useful in decreasing the detection limits for in vivo measurements. The active ester nitroxide showed approximately 6% intracellular localization and low cytotoxicity. The EPR spectra of TMAO nitroxide indicated an increased rigidity in the nitroxide ring, due to dibenzo-annulation.

Crisis communication under transformative change : the emergent context and roles of primary and secondary organisations

In an era of complex challenges that draw sustained media attention and entangle multiple organisational actors, this thesis addresses the gap between current trends in society and business, and existing scholarship in public relations and crisis communication. By responding to calls from crisis communication researchers to develop theory (Coombs, 2006a), to examine the interdependencies of crises (Seeger, Sellnow, & Ulmer, 1998), and to consider variation in crisis response (Seeger, 2002), this thesis contributes to theory development in crisis communication and public relations. Through transformative change, this thesis extends existing scholarship built on a preservation or conservation logic where public relations is used to maintain stability by incrementally responding to changes in an organisation‘s environment (Cutlip, Center, & Broom, 2006; Everett, 2001; Grunig, 2000; Spicer, 1997). Based on the opportunity to contribute to ongoing theoretical development in the literature, the overall research problem guiding this thesis asks: How does transformative change during crisis influence corporate actors’ communication? This thesis adopts punctuated equilibrium theory, which describes change as alternating between long periods of stability and short periods of revolutionary or transformative change (Gersick, 1991; Romanelli & Tushman, 1994; Siggelkow, 2002; Tushman, Newman, & Romanelli, 1986; Tushman & Romanelli, 1985). As a theory for change, punctuated equilibrium provides an opportunity to examine public relations and transformative change, building on scholarship that is based primarily on incremental change. Further, existing scholarship in public relations and crisis communication focuses on the actions of single organisations in situational or short-term crisis events. Punctuated equilibrium theory enables the study of multiple crises and multiple organisational responses during transformative change. In doing so, punctuated equilibrium theory provides a framework to explain both the context for transformative change and actions or strategies enacted by organisations during transformative change (Tushman, Newman, & Romanelli, 1986; Tushman & Romanelli, 1985; Tushman, Virany, & Romanelli, 1986). The connections between context and action inform the research questions that guide this thesis: RQ1: What symbolic and substantive strategies persist and change as crises develop from situational events to transformative and multiple linked events? RQ2: What features of the crisis context influence changes in symbolic and substantive strategies? To shed light on these research questions, the thesis adopts a qualitative approach guided by process theory and methods to explicate the events, sequences and activities that were essential to change (Pettigrew, 1992; Van de Ven, 1992). Specifically, the thesis draws on an alternative template strategy (Langley, 1999) that provides several alternative interpretations of the same events (Allison, 1971; Allison & Zelikow, 1999). Following Allison (1971) and Allison and Zelikow (1999), this thesis uses three alternative templates of crisis or strategic response typologies to construct three narratives using media articles and organisational documents. The narratives are compared to identify and draw out different patterns of crisis communication strategies that operate within different crisis contexts. The thesis is based on the crisis events that affected three organisations within the pharmaceutical industry for four years. The primary organisation is Merck, as its product recall crisis triggered transformative change affecting, in different ways, the secondary organisations of Pfizer and Novartis. Three narratives are presented based on the crisis or strategic response typologies of Coombs (2006b), Allen and Caillouet (1994), and Oliver (1991). The findings of this thesis reveal different stories about crisis communication under transformative change. By zooming in to a micro perspective (Nicolini, 2009) to focus on the crisis communication and actions of a single organisation and zooming out to a macro perspective (Nicolini, 2009) to consider multiple organisations, new insights about crisis communication, change and the relationships among multiple organisations are revealed at context and action levels. At the context level, each subsequent narrative demonstrates greater connections among multiple corporate actors. By zooming out from Coombs‘ (2006b) focus on single organisations to consider Allen and Caillouet‘s (1994) integration of the web of corporate actors, the thesis demonstrates how corporate actors add accountability pressures to the primary organisation. Next, by zooming further out to the macro perspective by considering Oliver‘s (1991) strategic responses to institutional processes, the thesis reveals a greater range of corporate actors that are caught up in the process of transformative change and accounts for their varying levels of agency over their environment. By zooming in to a micro perspective and out to a macro perspective (Nicolini, 2009) across alternative templates, the thesis sheds light on sequences, events, and actions of primary and secondary organisations. Although the primary organisation remains the focus of sustained media attention across the four-year time frame, the secondary organisations, even when one faced a similar starting situation to the primary organisation, were buffered by the process of transformative change. This understanding of crisis contexts in transforming environments builds on existing knowledge in crisis communication. At the action level, the thesis also reveals different interpretations from each alternative template. Coombs‘ (2006b) narrative shows persistence in the primary organisation‘s crisis or strategic responses over the four-year time frame of the thesis. That is, the primary organisation consistently applies a diminish crisis response. At times, the primary organisation drew on denial responses when corporate actors questioned its legitimacy or actions. To close the crisis, the primary organisation uses a rebuild crisis posture (Coombs, 2006). These finding are replicated in Allen and Caillouet‘s (1994) narrative, noting this template‘s limitation to communication messages only. Oliver‘s (1991) narrative is consistent with Coombs‘ (2006b) but also demonstrated a shift from a strategic response that signals conformity to the environment to one that signals more active resistance to the environment over time. Specifically, the primary organisation‘s initial response demonstrates conformity but these same messages were used some three years later to set new expectations in the environment in order to shape criteria and build acceptance for future organisational decisions. In summary, the findings demonstrate the power of crisis or strategic responses when considered over time and in the context of transformative change. The conclusions of this research contribute to scholarship in the public relations and management literatures. Based on the significance of organisational theory, the primary contribution of the theory relates to the role of interorganisational linkages or legitimacy buffers that form during the punctuation of equilibrium. The network of linkages among the corporate actors are significant also to the crisis communication literature as they form part of the process model of crisis communication under punctuated equilibrium. This model extends existing research that focuses on crisis communication of single organisations to consider the emergent context that incorporates secondary organisations as well as the localised contests of legitimacy and buffers from regulatory authorities. The thesis also provides an empirical base for punctuated equilibrium in public relations and crisis communication, extending Murphy‘s (2000) introduction of the theory to the public relations literature. In doing this, punctuated equilibrium theory reinvigorates theoretical development in crisis communication by extending existing scholarship around incrementalist approaches and demonstrating how public relations works in the context of transformative change. Further research in this area could consider using alternative templates to study transformative change caused by a range of crisis types from natural disasters to product tampering, and to add further insight into the dynamics between primary and secondary organisations. This thesis contributes to practice by providing guidelines for crisis response strategy selection and indicators related to the emergent context for crises under transformative change that will help primary and secondary organisations‘ responses to crises.

The beliefs which motivate young male and female drivers to speed : a comparison of low and high intenders

In Australia, young drivers aged 17 to 24 years, and particularly males, have the highest risk of being involved in a fatal crash. Investigation of young drivers’ beliefs allows for a greater understanding of their involvement in risky behaviours, such as speeding, as beliefs are associated with intentions, the antecedent to behaviour. The theory of planned behaviour (TPB) was used to conceptualise beliefs using a scenario based questionnaire distributed to licensed drivers (N = 398). The questionnaire measured individual’s beliefs and intentions to speed in a particular situation. Consistent with a TPB-based approach, the beliefs of those with low intentions to speed (‘low intenders’) were compared with the beliefs of those with high intentions (‘high intenders’) with such comparisons conducted separately for males and females. Overall, significant differences in the beliefs held by low and high intenders and for both females and males were found. Specifically, for females, it was found that high intenders were significantly more likely to perceive advantages of speeding, less likely to perceive disadvantages, and more likely to be encouraged to speed on familiar and inappropriately signed roads than female low intenders. Females, however, did not differ in their perceptions of support from friends, with all females reporting some level of disapproval from most friends and all females (i.e., low and high intenders) reporting approval to speed from their male friends. The results for males revealed that high intenders were significantly more likely to speed on familiar and inappropriately signed roads as well as having greater perceptions of support from all friends, except from those friends with whom they worked. Low and high intending males did not differ in their perceptions of the advantages and disadvantages of speeding, with the exception of feelings of excitement whereby high intenders reported speeding to be more exciting than low intenders. The findings are discussed in terms of how they may directly inform the content of mass media and public education campaigns aimed at encouraging young drivers to slow down.

Numerical exploration of plastic deformation mechanisms of copper nanowires with surface defects

Based on the molecular dynamics simulation, plastic deformation mechanisms associated with the zigzag stress curves in perfect and surface defected copper nanowires under uniaxial tension are studied. In our previous study, it has found that the surface defect exerts larger influence than the centro-plane defect, and the 45o surface defect appears as the most influential surface defect. Hence, in this paper, the nanowire with a 45o surface defect is chosen to investigate the defect’s effect to the plastic deformation mechanism of nanowires. We find that during the plastic deformation of both perfect and defected nanowires, decrease regions of the stress curve are accompanied with stacking faults generation and migration activities, but during stress increase, the structure of the nanowire appears almost unchanged. We also observe that surface defects have obvious influence on the nanowire’s plastic deformation mechanisms. In particular, only two sets of slip planes are found to be active and twins are also observed in the defected nanowire.

Developing a knowledge base for enterprise system success: the role of management and operational staff

Knowledge base is one of the emerging concepts in the Knowledge Management area. As there exists no agreed- upon standard definition of a knowledge base, this paper defines a knowledge base in terms of our research of Enterprise Systems (ES). The knowledge base is defined with reference to Learning Network Theory. Using this theoretical framework, we investigate the roles of management and operational staff in organisations and how their interactions can create a better ES-knowledge base to contribute to ES success. We focus on the post- implementation phase of ES as part of the ES lifecycle. Our findings will facilitate future research directions and contribute to better understandings of how the knowledge base can be integrated and how this integration leads to Enterprise System success.