lacZ transduced human breast cancer xenografts as an in vivo model for the study of invasion and metastasis

A number of human cancer cell lines have been described as being invasive and metastatic in immune incompetent animals. However, it is difficult to assess metastatic spread of a subcutaneously injected or inoculated cell line, since an exact detection of all microfoci of human tumour cells in the animals by usual histological procedures would require extensive sectioning of the whole animal. To overcome this problem, we transduced human breast cancer cells with a replication-defective Moloney murine leukaemia retroviral vector (M-MuLV) containing both neo(R) (neomycin resistance) and lacZ genes. The resulting cell lines were selected for antibiotic (G418) resistance, and cell-sorted for lacZ expression. lacZ continued to be expressed in cultured cells for at least 20 passages without further G418 selection. The lacE gene codes for β-D-galactosidase, and cells expressing this gene stain blue with the chromogenic substrate X-gal. The lacZ-expressing cells retained the pre-transduction ability to traverse Matrigel in vitro, to form subcutaneous tumours in nude mice, and to grow invasively with the formation of metastases. X-gal staining showed high specificity, staining the tumour cells but not the surrounding mouse tissue on either whole tissue blocks or histological sections. The staining procedure was highly sensitive, allowing detection of microfoci of human cancer cells, and quantitative estimation of the metastatic capacity of the cells. These results indicate that lacZ transduction of human tumour cells is a powerful means of studying human cancer cell invasion and metastases in vivo.

Capital cost model for Robert evaporators

ROBERT EVAPORATORS in Australian sugar factories are traditionally constructed with 44.45 mm outside diameter stainless steel tubes of ~2 m length for all stages of evaporation. There are a few vessels with longer tubes (up to 2.8 m) and smaller and larger diameters (38.1 and 50.8 mm). Queensland University of Technology is undertaking a study to investigate the heat transfer performance of tubes of different lengths and diameters for the whole range of process conditions typically encountered in the evaporator set. Incorporation of these results into practical evaporator designs requires an understanding of the cost implications for constructing evaporator vessels with calandrias having tubes of different dimensions. Cost savings are expected for tubes of smaller diameter and longer length in terms of material, labour and installation costs in the factory. However these savings must be considered in terms of the heat transfer area requirements for the evaporation duty, which will likely be a function of the tube dimensions. In this paper a capital cost model is described which provides a relative cost of constructing and installing Robert evaporators of the same heating surface area but with different tube dimensions. Evaporators of 2000, 3000, 4000 and 5000 m2 are investigated. This model will be used in conjunction with the heat transfer efficiency data (when available) to determine the optimum tube dimensions for a new evaporator at a specified evaporation duty. Consideration is also given to other factors such as juice residence time (and implications for sucrose degradation and control) and droplet de-entrainment in evaporators of different tube dimensions.

Mechanical model and superelastic properties of carbon microcoils with circular cross-section

Here we report on an unconventional Ni-P alloy-catalyzed, high-throughput, highly reproducible chemical vapor deposition of ultralong carbon microcoils using acetylene precursor in the temperature range 700-750 °C. Scanning electron microscopy analysis reveals that the carbon microcoils have a unique double-helix structure and a uniform circular cross-section. It is shown that double-helix carbon microcoils have outstanding superelastic properties. The microcoils can be extended up to 10-20 times of their original coil length, and quickly recover the original state after releasing the force. A mechanical model of the carbon coils with a large spring index is developed to describe their extension and contraction. Given the initial coil parameters, this mechanical model can successfully account for the geometric nonlinearity of the spring constants for carbon micro- and nanocoils, and is found in a good agreement with the experimental data in the whole stretching process.

BIM for sustainable whole-of-life transport infrastructure asset management

The US National Institute of Standards and Technology (NIST) showed that, in 2004, owners and operations managers bore two thirds of the total industry cost burden from inadequate interoperability in construction projects from inception to operation, amounting to USD10.6 billion. Building Information Modelling (BIM) and similar tools were identified by Engineers Australia in 2005 as potential instruments to significantly reduce this sum, which in Australia could amount to total industry-wide cost burden of AUD12 billion. Public sector road authorities in Australia have a key responsibility in driving initiatives to reduce greenhouse gas emissions from the construction and operations of transport infrastructure. However, as previous research has shown the Environmental Impact Assessment process, typically used for project approvals and permitting based on project designs available at the consent stage, lacks Key Performance Indicators (KPIs) that include long-term impact factors and transfer of information throughout the project life cycle. In the building construction industry, BIM is widely used to model sustainability KPIs such as energy consumption, and integrated with facility management systems. This paper proposes that a similar use of BIM in early design phases of transport infrastructure could provide: (i) productivity gains through improved interoperability and documentation; (ii) the opportunity to carry out detailed cost-benefit analyses leading to significant operational cost savings; (iii) coordinated planning of street and highway lighting with other energy and environmental considerations; iv) measurable KPIs that include long-term impact factors which are transferable throughout the project life cycle; and (v) the opportunity for integrating design documentation with sustainability whole-of-life targets.

Untangling the evidence : introducing an empirical model for evidence-based library and information practice

Introduction This research is the first to investigate the experiences of teacher-librarians as evidence-based practice. An empirically derived model is presented in this paper. Method This qualitative study utilised the expanded critical incident approach, and investigated the real-life experiences of fifteen Australian teacher-librarians, through semi-structured interviews and inductive data analysis. Data collection utilised semi-structured interviews, on-site observations, journaling and the rubric for contextual information. These approaches allowed each of the interviewees to tell their own story and provided richness to the data. Analysis The analysis involved two types of data categorisation: binary and thematic. Binary classification was used to identify factual details. Thematic analysis involved categorising the emerging themes. Results An empirically derived model for evidence-based practice was devised and associated critical findings identified. The results demonstrate that evidence-based practice for teacher-librarians is a holistic practice. It is not a linear, step-by-step process. Conclusions This study is significant for teacher-librarians and library and information professionals as it provides new understanding of evidence-based practice.

Whole-genome multiparametric screening to identify modulators of epithelial-to-mesenchymal transition

Metastasis accounts for the poor prognosis of the majority of solid tumors. The phenotypic transition of nonmotile epithelial tumor cells to migratory and invasive “mesenchymal” cells (epithelial-to-mesenchymal transition [EMT]) enables the transit of cancer cells from the primary tumor to distant sites. There is no single marker of EMT; rather, multiple measures are required to define cell state. Thus, the multiparametric capability of high-content screening is ideally suited for the comprehensive analysis of EMT regulators. The aim of this study was to generate a platform to systematically identify functional modulators of tumor cell plasticity using the bladder cancer cell line TSU-Pr1-B1 as a model system. A platform enabling the quantification of key EMT characteristics, cell morphology and mesenchymal intermediate filament vimentin, was developed using the fluorescent whole-cell-tracking reagent CMFDA and a fluorescent promoter reporter construct, respectively. The functional effect of genome-wide modulation of protein-coding genes and miRNAs coupled with those of a collection of small-molecule kinase inhibitors on EMT was assessed using the Target Activation Bioapplication integrated in the Cellomics ArrayScan platform. Data from each of the three screens were integrated to identify a cohort of targets that were subsequently examined in a validation assay using siRNA duplexes. Identification of established regulators of EMT supports the utility of this screening approach and indicated capacity to identify novel regulators of this plasticity program. Pathway analysis coupled with interrogation of cancer-related expression profile databases and other EMT-related screens provided key evidence to prioritize further experimental investigation into the molecular regulators of EMT in cancer cells.

A constitutive model for mechanical response characterization of pumpkin peel and flesh tissues under tensile and compressive loadings

Enhancing quality of food products and reducing volume of waste during mechanical operations of food industry requires a comprehensive knowledge of material response under loadings. While research has focused on mechanical response of food material, the volume of waste after harvesting and during processing stages is still considerably high in both developing and developed countries. This research aims to develop and evaluate a constitutive model of mechanical response of tough skinned vegetables under postharvest and processing operations. The model focuses on both tensile and compressive properties of pumpkin flesh and peel tissues where the behaviours of these tissues vary depending on various factors such as rheological response and cellular structure. Both elastic and plastic response of tissue were considered in the modelling process and finite elasticity combined with pseudo elasticity theory was applied to generate the model. The outcomes were then validated using the published results of experimental work on pumpkin flesh and peel under uniaxial tensile and compression. The constitutive coefficients for peel under tensile test was α = 25.66 and β = −18.48 Mpa and for flesh α = −5.29 and β = 5.27 Mpa. under compression the constitutive coefficients were α = 4.74 and β = −1.71 Mpa for peel and α = 0.76 and β = −1.86 Mpa for flesh samples. Constitutive curves predicted the values of force precisely and close to the experimental values. The curves were fit for whole stress versus strain curve as well as a section of curve up to bio yield point. The modelling outputs had presented good agreement with the empirical values and the constructive curves exhibited a very similar pattern to the experimental curves. The presented constitutive model can be applied next to other agricultural materials under loading in future.

Model as you do : engaging an S-BPM vendor on process modelling in 3D virtual worlds

Accurate process model elicitation continues to be a time consuming task, requiring skill on the part of the interviewer to extract explicit and tacit process information from the interviewee. Many errors occur in this elicitation stage that would be avoided by better activity recall, more consistent specification methods and greater engagement in the elicitation process by interviewees. Metasonic GmbH has developed a process elicitation tool for their process suite. As part of a research engagement with Metasonic, staff from QUT, Australia have developed a 3D virtual world approach to the same problem, viz. eliciting process models from stakeholders in an intuitive manner. This book chapter tells the story of how QUT staff developed a 3D Virtual World tool for process elicitation, took the outcomes of their research project to Metasonic for evaluation, and finally, Metasonic’s response to the initial proof of concept.

Macro- and micronutrient disposition in an ex vivo model of extracorporeal membrane oxygenation

Background Extracorporeal membrane oxygenation (ECMO) circuits have been shown to sequester circulating blood compounds such as drugs based on their physicochemical properties. This study aimed to describe the disposition of macro- and micronutrients in simulated ECMO circuits. Methods Following baseline sampling, known quantities of macro- and micronutrients were injected post oxygenator into ex vivo ECMO circuits primed with the fresh human whole blood and maintained under standard physiologic conditions. Serial blood samples were then obtained at 1, 30 and 60 min and at 6, 12 and 24 h after the addition of nutrients, to measure the concentrations of study compounds using validated assays. Results Twenty-one samples were tested for thirty-one nutrient compounds. There were significant reductions (p < 0.05) in circuit concentrations of some amino acids [alanine (10%), arginine (95%), cysteine (14%), glutamine (25%) and isoleucine (7%)], vitamins [A (42%) and E (6%)] and glucose (42%) over 24 h. Significant increases in circuit concentrations (p < 0.05) were observed over time for many amino acids, zinc and vitamin C. There were no significant reductions in total proteins, triglycerides, total cholesterol, selenium, copper, manganese and vitamin D concentrations within the ECMO circuit over a 24-h period. No clear correlation could be established between physicochemical properties and circuit behaviour of tested nutrients. Conclusions Significant alterations in macro- and micronutrient concentrations were observed in this single-dose ex vivo circuit study. Most significantly, there is potential for circuit loss of essential amino acid isoleucine and lipid soluble vitamins (A and E) in the ECMO circuit, and the mechanisms for this need further exploration. While the reductions in glucose concentrations and an increase in other macro- and micronutrient concentrations probably reflect cellular metabolism and breakdown, the decrement in arginine and glutamine concentrations may be attributed to their enzymatic conversion to ornithine and glutamate, respectively. While the results are generally reassuring from a macronutrient perspective, prospective studies in clinical subjects are indicated to further evaluate the influence of ECMO circuit on micronutrient concentrations and clinical outcomes.

A framework for model integration and holistic modelling of socio-technical systems

This paper presents a layered framework for the purposes of integrating different Socio-Technical Systems (STS) models and perspectives into a whole-of-systems model. Holistic modelling plays a critical role in the engineering of STS due to the interplay between social and technical elements within these systems and resulting emergent behaviour. The framework decomposes STS models into components, where each component is either a static object, dynamic object or behavioural object. Based on existing literature, a classification of the different elements that make up STS, whether it be a social, technical or a natural environment element, is developed; each object can in turn be classified according to the STS elements it represents. Using the proposed framework, it is possible to systematically decompose models to an extent such that points of interface can be identified and the contextual factors required in transforming the component of one model to interface into another is obtained. Using an airport inbound passenger facilitation process as a case study socio-technical system, three different models are analysed: a Business Process Modelling Notation (BPMN) model, Hybrid Queue-based Bayesian Network (HQBN) model and an Agent Based Model (ABM). It is found that the framework enables the modeller to identify non-trivial interface points such as between the spatial interactions of an ABM and the causal reasoning of a HQBN, and between the process activity representation of a BPMN and simulated behavioural performance in a HQBN. Such a framework is a necessary enabler in order to integrate different modelling approaches in understanding and managing STS.

Testing times for the implementation of curriculum change: Analysis and extension of a curriculum change model

School curriculum change processes have traditionally been managed internally. However, in Queensland, Australia, as a response to the current high-stakes accountability regime, more and more principals are outsourcing this work to external change agents (ECAs). In 2009, one of the authors (a university lecturer and ECA) developed a curriculum change model (the Controlled Rapid Approach to Curriculum Change (CRACC)), specifically outlining the involvement of an ECA in the initiation phase of a school’s curriculum change process. The purpose of this paper is to extend the CRACC model by unpacking the implementation phase, drawing on data from a pilot study of a single school. Interview responses revealed that during the implementation phase, teachers wanted to be kept informed of the wider educational context; use data to constantly track students; relate pedagogical practices to testing practices; share information between departments and professional levels; and, own whole school performance. It is suggested that the findings would be transferable to other school settings and internal leadership of curriculum change. The paper also strikes a chord of concern – Do the responses from teachers operating in such an accountability regime live their professional lives within this corporate and globalised ideology whether they want to or not?

Effect of constitutive material models on seismic response of two-story reinforced concrete frame

This paper focuses on the finite element (FE) response sensitivity and reliability analyses considering smooth constitutive material models. A reinforced concrete frame is modeled for FE sensitivity analysis followed by direct differentiation method under both static and dynamic load cases. Later, the reliability analysis is performed to predict the seismic behavior of the frame. Displacement sensitivity discontinuities are observed along the pseudo-time axis using non-smooth concrete and reinforcing steel model under quasi-static loading. However, the smooth materials show continuity in response sensitivity at elastic to plastic transition points. The normalized sensitivity results are also used to measure the relative importance of the material parameters on the structural responses. In FE reliability analysis, the influence of smoothness behavior of reinforcing steel is carefully noticed. More efficient and reasonable reliability estimation can be achieved by using smooth material model compare with bilinear material constitutive model.

Soluble mediators in platelet concentrates modulate dendritic cell inflammatory responses in an experimental model of transfusion

The transfusion of platelet concentrates (PCs) is widely used to treat thrombocytopenia and severe trauma. Ex vivo storage of PCs is associated with a storage lesion characterized by partial platelet activation and the release of soluble mediators, such as soluble CD40 ligand (sCD40L), RANTES, and interleukin (IL)-8. An in vitro whole blood culture transfusion model was employed to assess whether mediators present in PC supernatants (PC-SNs) modulated dendritic cell (DC)-specific inflammatory responses (intracellular staining) and the overall inflammatory response (cytometric bead array). Lipopolysaccharide (LPS) was included in parallel cultures to model the impact of PC-SNs on cell responses following toll-like receptor-mediated pathogen recognition. The impact of both the PC dose (10%, 25%) and ex vivo storage period was investigated [day 2 (D2), day 5 (D5), day 7 (D7)]. PC-SNs alone had minimal impact on DC-specific inflammatory responses and the overall inflammatory response. However, in the presence of LPS, exposure to PC-SNs resulted in a significant dose associated suppression of the production of DC IL-12, IL-6, IL-1a, tumor necrosis factor-a (TNF-a), and macrophage inflammatory protein (MIP)-1b and storage-associated suppression of the production of DC IL-10, TNF-a, and IL-8. For the overall inflammatory response, IL-6, TNF-a, MIP-1a, MIP-1b, and inflammatory protein (IP)-10 were significantly suppressed and IL-8, IL-10, and IL-1b significantly increased following exposure to PC-SNs in the presence of LPS. These data suggest that soluble mediators present in PCs significantly suppress DC function and modulate the overall inflammatory response, particularly in the presence of an infectious stimulus. Given the central role of DCs in the initiation and regulation of the immune response, these results suggest that modulation of the DC inflammatory profile is a probable mechanism contributing to transfusion-related complications.

Whole-body cryotherapy (extreme cold air exposure) for preventing and treating muscle soreness after exercise in adults

Background Recovery strategies are often usedwith the intention of preventing orminimisingmuscle soreness after exercise. Whole-body cryotherapy, which involves a single or repeated exposure(s) to extremely cold dry air (below -100 °C) in a specialised chamber or cabin for two to four minutes per exposure, is currently being advocated as an effective intervention to reduce muscle soreness after exercise. Objectives To assess the effects (benefits and harms) of whole-body cryotherapy (extreme cold air exposure) for preventing and treating muscle soreness after exercise in adults. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, the British Nursing Index and the Physiotherapy Evidence Database. We also searched the reference lists of articles, trial registers and conference proceedings, handsearched journals and contacted experts. The searches were run in August 2015. Selection criteria We aimed to include randomised and quasi-randomised trials that compared the use of whole-body cryotherapy (WBC) versus a passive or control intervention (rest, no treatment or placebo treatment) or active interventions including cold or contrast water immersion, active recovery and infrared therapy for preventing or treating muscle soreness after exercise in adults. We also aimed to include randomised trials that compared different durations or dosages of WBC. Our prespecified primary outcomes were muscle soreness, subjective recovery (e.g. tiredness, well-being) and adverse effects. Data collection and analysis Two review authors independently screened search results, selected studies, assessed risk of bias and extracted and cross-checked data. Where appropriate, we pooled results of comparable trials. The random-effects model was used for pooling where there was substantial heterogeneity.We assessed the quality of the evidence using GRADE. Main results Four laboratory-based randomised controlled trials were included. These reported results for 64 physically active predominantly young adults (mean age 23 years). All but four participants were male. Two trials were parallel group trials (44 participants) and two were cross-over trials (20 participants). The trials were heterogeneous, including the type, temperature, duration and frequency of WBC, and the type of preceding exercise. None of the trials reported active surveillance of predefined adverse events. All four trials had design features that carried a high risk of bias, potentially limiting the reliability of their findings. The evidence for all outcomes was classified as ’very low’ quality based on the GRADE criteria. Two comparisons were tested: WBC versus control (rest or no WBC), tested in four studies; and WBC versus far-infrared therapy, also tested in one study. No studies compared WBC with other active interventions, such as cold water immersion, or different types and applications of WBC. All four trials compared WBC with rest or no WBC. There was very low quality evidence for lower self-reported muscle soreness (pain at rest) scores after WBC at 1 hour (standardised mean difference (SMD) -0.77, 95% confidence interval (CI) -1.42 to -0.12; 20 participants, 2 cross-over trials); 24 hours (SMD -0.57, 95%CI -1.48 to 0.33) and 48 hours (SMD -0.58, 95% CI -1.37 to 0.21), both with 38 participants, 2 cross-over studies, 1 parallel group study; and 72 hours (SMD -0.65, 95% CI -2.54 to 1.24; 29 participants, 1 cross-over study, 1 parallel group study). Of note is that the 95% CIs also included either no between-group differences or a benefit in favour of the control group. One small cross-over trial (9 participants) found no difference in tiredness but better well-being after WBC at 24 hours post exercise. There was no report of adverse events. One small cross-over trial involving nine well-trained runners provided very low quality evidence of lower levels of muscle soreness after WBC, when compared with infrared therapy, at 1 hour follow-up, but not at 24 or 48 hours. The same trial found no difference in well-being but less tiredness after WBC at 24 hours post exercise. There was no report of adverse events. Authors’ conclusions There is insufficient evidence to determine whether whole-body cryotherapy (WBC) reduces self-reportedmuscle soreness, or improves subjective recovery, after exercise compared with passive rest or no WBC in physically active young adult males. There is no evidence on the use of this intervention in females or elite athletes. The lack of evidence on adverse events is important given that the exposure to extreme temperature presents a potential hazard. Further high-quality, well-reported research in this area is required and must provide detailed reporting of adverse events.

Improving factory performance using an integrated sugar factory model

A whole of factory model of a raw sugar factory was developed in SysCAD software to assess and improve factory operations. The integrated sugar factory model ‘Sugar-SysCAD’ includes individual models for milling, heating and clarification, evaporation, crystallisation, steam cycle, sugar dryer and process and injection water circuits. These individual unit operation models can be either used as standalone models to optimise the unit operation or in the integrated mode to provide more accurate prediction of the effects of changes in any part of the process on the outputs of the whole factory process. Using the integrated sugar factory model, the effect of specific process operations can be understood and practical solutions can be determined to address process problems. The paper presents two factory scenarios to show the capabilities of the whole of factory model.