Turbulent velocity and suspended sediment concentration measurements in an urban environment of the Brisbane River Flood Plain at Gardens Point on 12-13 January 2011

The flood flow in urbanised areas constitutes a major hazard to the population and infrastructure as seen during the summer 2010-2011 floods in Queensland (Australia). Flood flows in urban environments have been studied relatively recently, although no study considered the impact of turbulence in the flow. During the 12-13 January 2011 flood of the Brisbane River, some turbulence measurements were conducted in an inundated urban environment in Gardens Point Road next to Brisbane's central business district (CBD) at relatively high frequency (50 Hz). The properties of the sediment flood deposits were characterised and the acoustic Doppler velocimeter unit was calibrated to obtain both instantaneous velocity components and suspended sediment concentration in the same sampling volume with the same temporal resolution. While the flow motion in Gardens Point Road was subcritical, the water elevations and velocities fluctuated with a distinctive period between 50 and 80 s. The low frequency fluctuations were linked with some local topographic effects: i.e, some local choke induced by an upstream constriction between stairwells caused some slow oscillations with a period close to the natural sloshing period of the car park. The instantaneous velocity data were analysed using a triple decomposition, and the same triple decomposition was applied to the water depth, velocity flux, suspended sediment concentration and suspended sediment flux data. The velocity fluctuation data showed a large energy component in the slow fluctuation range. For the first two tests at z = 0.35 m, the turbulence data suggested some isotropy. At z = 0.083 m, on the other hand, the findings indicated some flow anisotropy. The suspended sediment concentration (SSC) data presented a general trend with increasing SSC for decreasing water depth. During a test (T4), some long -period oscillations were observed with a period about 18 minutes. The cause of these oscillations remains unknown to the authors. The last test (T5) took place in very shallow waters and high suspended sediment concentrations. It is suggested that the flow in the car park was disconnected from the main channel. Overall the flow conditions at the sampling sites corresponded to a specific momentum between 0.2 to 0.4 m2 which would be near the upper end of the scale for safe evacuation of individuals in flooded areas. But the authors do not believe the evacuation of individuals in Gardens Point Road would have been safe because of the intense water surges and flow turbulence. More generally any criterion for safe evacuation solely based upon the flow velocity, water depth or specific momentum cannot account for the hazards caused by the flow turbulence, water depth fluctuations and water surges.

Scaling analysis of the thermal boundary layer adjacent to an abruptly heated inclined flat plate

The natural convection thermal boundary layer adjacent to an abruptly heated inclined flat plate is investigated through a scaling analysis and verified by numerical simulations. In general, the development of the thermal flow can be characterized by three distinct stages, i.e. a start-up stage, a transitional stage and a steady state stage. Major scales including the flow velocity, flow development time, and the thermal and viscous boundary layer thicknesses are established to quantify the flow development at different stages and over a wide range of flow parameters. Details of the scaling analysis and the numerical procedures are described in this paper.

FGFR2 mutations are rare across histologic subtypes of ovarian cancer

OBJECTIVE: Ovarian cancer is the leading cause of death from gynecologic malignancies in the Western world. Fibroblast growth factor receptor (FGFR) signaling has been implicated to play a role in ovarian tumorigenesis. Mutational activation of one member of this receptor family, FGFR2, is a frequent event in endometrioid endometrial cancer. Given the similarities in the histologic and molecular genetics of ovarian and endometrial cancers, we hypothesized that activating FGFR2 mutations may occur in a subset of endometrioid ovarian tumors, and possibly other histotypes. METHODS: Six FGFR2 exons were sequenced in 120 primary ovarian tumors representing the major histologic subtypes. RESULTS: FGFR2 mutation was detected at low frequency in endometrioid (1/46, 2.2%) and serous (1/41, 2.4%) ovarian cancer. No mutations were detected in clear cell, mucinous, or mixed histology tumors or in the ovarian cancer cell lines tested. Functional characterization of the FGFR2 mutations confirmed that the mutations detected in ovarian cancer result in receptor activation. CONCLUSIONS: Despite the low incidence of FGFR2 mutations in ovarian cancer, the two FGFR2 mutations identified in ovarian tumors (S252W, Y376C) overlap with the oncogenic mutations previously identified in endometrial tumors, suggesting activated FGFR2 may contribute to ovarian cancer pathogenesis in a small subset of ovarian tumors.

Gatekeeping, gatewatching, real-time feedback : new challenges for Journalism

How bloggers and other independent online commentators criticise, correct, and otherwise challenge conventional journalism has been known for years, but has yet to be fully accepted by journalists; hostilities between the media establishment and the new generation of citizen journalists continue to flare up from time to time. The old gatekeeping monopoly of the mass media has been challenged by the new practice of gatewatching: by individual bloggers and by communities of commentators which may not report the news first-hand, but curate and evaluate the news and other information provided by official sources, and thus provide an important service. And this now takes place ever more rapidly, almost in real time: using the latest social networks, which disseminate, share, comment, question, and debunk news reports within minutes, and using additional platforms that enable fast and effective ad hoc collaboration between users. When hundreds of volunteers can prove within a few days that a German minister has been guilty of serious plagiarism, when the world first learns of earthquakes and tsunamis via Twitter – how does journalism manage to keep up?

Evidence for CRHR1 in multiple sclerosis using supervised machine learning and meta-analysis in 12 566 individuals

The primary genetic risk factor in multiple sclerosis (MS) is the HLA-DRB1*1501 allele; however, much of the remaining genetic contribution to MS has yet to be elucidated. Several lines of evidence support a role for neuroendocrine system involvement in autoimmunity which may, in part, be genetically determined. Here, we comprehensively investigated variation within eight candidate hypothalamic-pituitary-adrenal (HPA) axis genes and susceptibility to MS. A total of 326 SNPs were investigated in a discovery dataset of 1343 MS cases and 1379 healthy controls of European ancestry using a multi-analytical strategy. Random Forests, a supervised machine-learning algorithm, identified eight intronic SNPs within the corticotrophin-releasing hormone receptor 1 or CRHR1 locus on 17q21.31 as important predictors of MS. On the basis of univariate analyses, six CRHR1 variants were associated with decreased risk for disease following a conservative correction for multiple tests. Independent replication was observed for CRHR1 in a large meta-analysis comprising 2624 MS cases and 7220 healthy controls of European ancestry. Results from a combined meta-analysis of all 3967 MS cases and 8599 controls provide strong evidence for the involvement of CRHR1 in MS. The strongest association was observed for rs242936 (OR = 0.82, 95% CI = 0.74-0.90, P = 9.7 × 10-5). Replicated CRHR1 variants appear to exist on a single associated haplotype. Further investigation of mechanisms involved in HPA axis regulation and response to stress in MS pathogenesis is warranted. © The Author 2010. Published by Oxford University Press. All rights reserved.

Scheduling a flow-shop with combined buffer conditions

In this paper, No-Wait, No-Buffer, Limited-Buffer, and Infinite-Buffer conditions for the flow-shop problem (FSP) have been investigated. These four different buffer conditions have been combined to generate a new class of scheduling problem, which is significant for modelling many real-world scheduling problems. A new heuristic algorithm is developed to solve this strongly NP-hard problem. Detailed numerical implementations have been analysed and promising results have been achieved.

Transition to intensive care nursing: A state-wide, workplace centred program-12 years on

In November 1999, the Queensland Health (QH) Transition to Practice Nurse Education Program - Intensive Care (TPNEP-IC) was initiated in QH Intensive Care Units (ICUs) across Queensland. This 12-month, state-wide, workplace based education program has set minimum standards for intensive care nursing education and therefore minimum standards for intensive care nursing practice in QH. In the 12 years of operation, 824 nurses have completed TPNEP-IC, 761 achieving academic credit status and 453 utilising this academic credit status to undertake postgraduate study in critical/intensive care nursing at three Queensland universities. These outcomes were achieved through the appointment of nurse educators within ICUs who, through a united and strong commitment to this state-wide approach formed collaborative professional networks, which resulted in the development, implementation and maintenance of the program. Furthermore, these networks enabled a framework of support for discussion and dissemination of evidence based practice, to endorse quality processes for TPNEP-IC and to nurture leadership potential among educators. Challenges to overcome included obtaining adequate resources to support all aspects of the program, gaining local management and administrative support, and embedding TPNEP-IC within ICU culture. The 12 years of operation of the program have demonstrated its long term sustainability. The program is being launched through a new blended learning approach utilising e-learning strategies. To capitalise on the current success, a strong commitment by all stakeholders will be required to ensure the ongoing sustainability of the program.

Start Smart : QUT’s trial support program for commencing undergraduate students who have not completed year 12 in the past two years

Commencing students in undergraduate degrees who identify as mature age students experience particular issues when faced with enrolment into university as an adult learner (Bird & Morgan, 2003). In line with QUT’s commitment to “supporting all commencing students to adjust successfully to study at QUT by providing a strong transition experience” (QUT, 2008, 6.2.1), the Start Smart trial program was developed and implemented for Semester 1, 2012. The Start Smart trial program consists of an orientation event, wrapped around and supported by existing First Year Experience (FYE) and Retention strategies within QUT, namely the Student Success Program (SSP) and the Peer Programs Strategy (PPS). This report examines the motivations for designing a program as a response to the needs of a cohort that are unique amongst all commencing undergraduate students. Participants will be asked to consider the implications of delivering special and unique orientation events to specific cohorts, and the long term sustainability of such programs within their own university structures.

The roles of the preproghrelin-derived peptides - ghrelin, desacyl ghrelin and obestatin - in prostate cancer

Prostate cancer is the second most common cause of cancer related deaths in Western men. Despite the significant improvements in current treatment techniques, there is no cure for advanced metastatic, castrate-resistant disease. Early detection and prevention of progression to a castrate-resistant state may provide new strategies to improve survival. A number of growth factors have been shown to act in an autocrine/paracrine manner to modulate prostate cancer tumour growth. Our laboratory has previously shown that ghrelin and its receptors (the functional GHS-R1a and the non-functional GHS-R1b) are expressed in prostate cancer specimens and cell lines. We have shown that ghrelin increases cell proliferation in the PC3 and LNCaP prostate cancer cell lines through activation of ERK1/2, suggesting that ghrelin could regulate prostate cancer cell growth and play a role in the progression of the disease. Ghrelin is a 28 amino-acid peptide hormone, identified to be the natural ligand of the growth hormone secretagogue receptor (GHS-R1a). It is well characterised as a growth hormone releasing and as an orexigenic peptide that stimulates appetite and feeding and regulates energy expenditure and bodyweight. In addition to its orexigenic properties, ghrelin has been shown to play a regulatory role in a number of systems, including the reproductive, immune and cardiovascular systems and may play a role in a number of pathological conditions such as chronic heart failure, anorexia, cachexia, obesity, diabetes and cancer. In cancer, ghrelin and its receptor are expressed in a range of tumours and cancer cell lines and ghrelin has been demonstrated to modulate cell proliferation, apoptosis, migration and invasion in some cell types. The ghrelin gene (GHRL) encodes preproghrelin peptide, which is processed to produce three currently known functional peptides - ghrelin, desacyl ghrelin and obestatin. Prohormone convertases (PCs) have been shown to cleave the preproghrelin peptide into two primary products - the 28 amino acid peptide, ghrelin, and the remaining 117 amino acid C-terminal peptide, C-ghrelin. C-ghrelin can then be further processed to produce the 23 amino acid peptide, obestatin. Ghrelin circulates in two different forms - an octanoylated form (known as ghrelin) and a non-octanoylated form, desacyl ghrelin. The unique post-translational addition of octanoic acid to the serine 3 residue of the propeptide chain to form acylated ghrelin is catalysed by ghrelin O-acyltransferase (GOAT). This modification is necessary for binding of ghrelin to its only known functional receptor, the GHS-R1a. As desacyl ghrelin cannot bind and activate the GHS-R1a, it was initially thought to be an inactive peptide, despite the fact that it circulates at much higher levels than ghrelin. Further research has demonstrated that desacyl ghrelin is biologically active and shares some of the actions of ghrelin, as well as having some opposing and distinct roles. Interestingly, both ghrelin and desacyl ghrelin have been shown to modulate apoptosis, cell differentiation and proliferation in some cell types, and to stimulate cell proliferation through activation of ERK1/2 and PI3K/Akt pathways. The third known peptide product of the ghrelin preprohormone, obestatin, was initially thought to oppose the actions of ghrelin in appetite regulation and food intake and to mediate its effects through the G protein-coupled receptor 39 (GPR39). Subsequent research failed to reproduce the initial findings, however, and the possible anorexigenic effects of obestatin, as well as the identity of its receptor, remain unclear. Obestatin plays some important physiological roles, including roles in improving memory, the inhibition of thirst and anxiety, increased secretion of pancreatic juice, and regulation of cell proliferation, survival, apoptosis and differentiation. Preliminary studies have also shown that obestatin stimulates cell proliferation in some cell types through activation of ERK1/2, Akt and PKC pathways. Overall, however, at the commencement of this PhD project, relatively little was known regarding the functions and mechanisms of action of the preproghrelin-derived functional peptides in modulating prostate cancer cell proliferation. The roles of obestatin, and desacyl ghrelin as potential growth factors had not previously been investigated, and the potential expression and regulation of the preproghrelin processing enzymes, GOAT and prohormone convertases was unknown in prostate cancer cell lines. Therefore, the overall objectives of this study were to: 1. investigate the effects of obestatin on cell proliferation and signaling in prostate cancer cell lines 2. compare the effects of desacyl ghrelin and ghrelin on cell proliferation and signaling in prostate cancer cell lines 3. investigate whether prostate cancer cell lines possess the necessary enzymatic machinery to produce ghrelin and desacyl ghrelin and if these peptides can regulate GOAT expression Our laboratory has previously shown that ghrelin stimulates cell proliferation in the PC3 and LNCaP prostate cancer cell line through activation of the ERK1/2 pathway. In this study it has been demonstrated that treatments with either ghrelin, desacyl ghrelin or obestatin over 72 hours significantly increased cell proliferation in the PC3 prostate cancer cell line but had no significant effect in the RWPE-1 transformed normal prostate cell line. Ghrelin (1000nM) stimulated cell proliferation in the PC3 prostate cancer cell line by 31.66 6.68% (p<0.01) with the WST-1 method, and 13.55 5.68% (p<0.05) with the CyQUANT assay. Desacyl ghrelin (1000nM) increased cell proliferation in PC3 cells by 21.73 2.62% (p<0.01) (WST-1), and 15.46 7.05% (p<0.05) (CyQUANT) above untreated control. Obestatin (1000nM) induced a 28.37 7.47% (p<0.01) (WST-1) and 12.14 7.47% (p<0.05) (CyQUANT) significant increase in cell proliferation in the PC3 prostate cancer cell line. Ghrelin and desacyl ghrelin treatments stimulated Akt and ERK phosphorylation across a range of concentrations (p<0.01). Obestatin treatment significantly stimulated Akt, ERK and PKC phosphorylation (p<0.05). Through the use of specific inhibitors, the MAPK inhibitor U0126 and the Akt1/2 kinase inhibitor, it was demonstrated that ghrelin- and obestatin-induced cell proliferation in the PC3 prostate cancer cell line is mediated through activation of ERK1/2 and Akt pathways. Although desacyl ghrelin significantly stimulated Akt and ERK phosphorylation, U0126 failed to prevent desacyl ghrelin-induced cell proliferation suggesting ghrelin and desacyl ghrelin might act through different mechanisms to increase cell proliferation. Ghrelin and desacyl ghrelin have shown a proliferative effect in osteoblasts, pancreatic -cells and cardiomyocytes through activation of ERK1/2 and PI3K/Akt pathways. Here it has been shown that ghrelin and its non-acylated form exert the same function and stimulate cell proliferation in the PC3 prostate cancer cell line through activation of the Akt pathway. Ghrelin-induced proliferation was also mediated through activation of the ERK1/2 pathway, however, desacyl ghrelin seems to stimulate cell proliferation in an ERK1/2-independent manner. As desacyl ghrelin does not bind and activate GHSR1a, the only known functional ghrelin receptor, the finding that both ghrelin and desacyl ghrelin stimulate cell proliferation in the PC3 cell line suggests that these peptides could be acting through the yet unidentified alternative ghrelin receptor in this cell type. Obestatin treatment also stimulated PKC phosphorylation, however, a direct role for this pathway in stimulating cell proliferation could not be proven using available PKC pathway inhibitors, as they caused significant cell death over the extended timeframe of the cell proliferation assays. Obestatin has been shown to stimulate cell proliferation through activation of PKC isoforms in human retinal epithelial cells and in the human gastric cancer cell line KATO-III. We have demonstrated that all of the prostate-derived cell lines examined (PC3, LNCaP, DU145, 22Rv1, RWPE-1 and RWPE-2) expressed GOAT and at least one of the prohormone convertases, which are known to cleave the proghrelin peptide, PC1/3, PC2 and furin, at the mRNA level. These cells, therefore, are likely to possess the necessary machinery to cleave the preproghrelin protein and to produce the mature ghrelin and desacyl ghrelin peptides. In addition to prohormone convertases, the presence of octanoic acid is essential for acylated ghrelin production. In this study octanoic acid supplementation significantly increased cell proliferation in the PC3 prostate cancer cell line by over 20% compared to untreated controls (p<0.01), but surprisingly, not in the DU145, LNCaP or 22Rv1 prostate cancer cell lines or in the RWPE-1 and RWPE-2 prostate-derived cell lines. In addition, we demonstrated that exogenous ghrelin induced a statistically significant two-fold decrease in GOAT mRNA expression in the PC3 cell line (p<0.05), suggesting that ghrelin could pontentially downregulate its own acylation and, therefore, regulate the balance between ghrelin and desacyl ghrelin. This was not observed, however, in the DU145 and LNCaP prostate cancer cell lines. The GOAT-ghrelin system represents a direct link between ingested nutrients and regulation of ghrelin production and the ghrelin/desacyl ghrelin ratio. Regulation of ghrelin acylation is a potentially attractive and desirable tool for the development of better therapies for a number of pathological conditions where ghrelin has been shown to play a key role. The finding that desacyl ghrelin stimulates cell proliferation in the PC3 prostate cancer cell line, and responds to ghrelin in the same way, suggests that this cell line expresses an alternative ghrelin receptor. Although all the cell lines examined expressed both GHS-R1a and GHS-R1b mRNA, it remains uncertain whether these cell lines express the unidentified alternative ghrelin receptor. It is possible that the varied responses seen could be due to the expression of different ghrelin receptors in different cell lines. In addition to GOAT, prohormone convertases and octanoic acid availability may regulate the production of different peptides from the ghrelin preprohormone. The studies presented in this thesis provide significant new information regarding the roles and mechanisms of action of the preproghrelin-derived peptides, ghrelin, desacyl ghrelin and obestatin, in modulating prostate cancer cell line proliferation. A number of key questions remain to be resolved, however, including the identification of the alternative ghrelin/desacyl ghrelin receptor, the identification of the obestatin receptor, a clarification of the signaling mechanisms which mediate cell proliferation in response to obestatin treatment and a better understanding of the regulation at both the gene and post-translational levels of functional peptide generation. Further studies investigating the role of the ghrelin axis using in vivo prostate cancer models may be warranted. Until these issues are determined, the potential for the ghrelin axis, to be recognised as a novel useful target for therapy for cancer or other pathologies will be uncertain.

A framework for life cycle cost estimation of a product family at the early stage of product development

A cost estimation method is required to estimate the life cycle cost of a product family at the early stage of product development in order to evaluate the product family design. There are difficulties with existing cost estimation techniques in estimating the life cycle cost for a product family at the early stage of product development. This paper proposes a framework that combines a knowledge based system and an activity based costing techniques in estimating the life cycle cost of a product family at the early stage of product development. The inputs of the framework are the product family structure and its sub function. The output of the framework is the life cycle cost of a product family that consists of all costs at each product family level and the costs of each product life cycle stage. The proposed framework provides a life cycle cost estimation tool for a product family at the early stage of product development using high level information as its input. The framework makes it possible to estimate the life cycle cost of various product family that use any types of product structure. It provides detailed information related to the activity and resource costs of both parts and products that can assist the designer in analyzing the cost of the product family design. In addition, it can reduce the required amount of information and time to construct the cost estimation system.