A novel chemo–mechano–biological model of arterial tissue growth and remodelling

Arterial growth and remodelling (GandR) is mediated by vascular cells in response to their chemical and mechanical environment. To date, mechanical and biochemical stimuli tend to be modelled separately, however this ignores their complex interplay. Here, we present a novel mathematical model of arterial chemo–mechano–biology. We illustrate its application to the development of an inflammatory aneurysm in the descending human aorta. The arterial wall is modelled as a bilayer cylindrical non–linear elastic membrane, which is internally pressurized and axially stretched. The medial degradation that accompanies aneurysm development is driven by an inflammatory response. Collagen remodelling is simulated by adaption of the natural reference configuration of constituents; growth is simulated by changes in normalised mass–densities. We account for the distribution of attachment stretches that collagen fibres are configured to the matrix and, innovatively, allow this distribution to remodel. This enables the changing functional role of the adventitia to be simulated. Fibroblast-mediated collagen growth is represented using a biochemical pathway model: a system of coupled non-linear ODEs governs the evolution of fibroblast properties and levels of key biomolecules under the regulation of Transforming Growth Factor (TGF)-β, a key promoter of matrix deposition. Given physiologically realistic targets, different modes of aneurysm development can be captured, while the predicted evolution of biochemical variables is qualitatively consistent with trends observed experimentally. Interestingly, we observe that increasing the levels of collagen–promoting TGF-β results in arrest of aneurysm growth, what seems to be consistent with experimental evidence. We conclude that this novel Chemo–Mechano–Biological (CMB) mathematical model has the potential to provide new mechanobiological insight into vascular disease progression and therapy.</p

Statistical Optimization of Process Variables for Antibiotic Activity of Xenorhabdus bovienii

The production of secondary metabolites with antibiotic properties is a common characteristic to entomopathogenic bacteria Xenorhabdus spp. These metabolites not only have diverse chemical structures but also have a wide range of bioactivities of medicinal and agricultural interests. Culture variables are critical to the production of secondary metabolites of microorganisms. Manipulating culture process variables can promote secondary metabolite biosynthesis and thus facilitate the discovery of novel natural products. This work was conducted to evaluate the effects of five process variables (initial pH, medium volume, rotary speed, temperature, and inoculation volume) on the antibiotic production of Xenorhabdus bovienii YL002 using response surface methodology. A 25–1 factorial central composite design was chosen to determine the combined effects of the five variables, and to design a minimum number of experiments. The experimental and predicted antibiotic activity of X. bovienii YL002 was in close agreement. Statistical analysis of the results showed that initial pH, medium volume, rotary speed and temperature had a significant effect (P<0.05) on the antibiotic production of X. bovienii YL002 at their individual level; medium volume and rotary speed showed a significant effect at a combined level and was most significant at an individual level. The maximum antibiotic activity (287.5 U/mL) was achieved at the initial pH of 8.24, medium volume of 54 mL in 250 mL flask, rotary speed of 208 rpm, temperature of 32.0°C and inoculation volume of 13.8%. After optimization, the antibiotic activity was improved by 23.02% as compared with that of unoptimized conditions

Multicenter phase II trial of accelerated cisplatin and high-dose epirubicin followed by surgery or radiotherapy in patients with stage IIIa non-small-cell lung cancer with mediastinal lymph node involvement (N2-disease)

To assess the therapeutic activity of accelerated cisplatin and high-dose epirubicin with erythropoietin and G-CSF support as induction therapy for patients with stage IIIa-N2 non-small-cell lung cancer (NSCLC). Patients with stage IIIa-N2 NSCLC were enrolled in a phase II trial. They received cisplatin 60 mg m−2 and epirubicin 135 mg m−2 every 2 weeks for three courses combined with erythropoietin and G-CSF. Depending on results of clinical response to induction therapy and restaging, patients were treated with surgery or radiotherapy. In total, 61 patients entered from March 2001 to April 2004. During 169 courses of induction chemotherapy, National Cancer Institute of Canada (NCI-C) grade III/IV leucocytopenia was reported in 35 courses (20.7%), NCI-C grade III/IV thrombocytopenia in 26 courses (15.4%) and NCI-C grade III/IV anaemia in six courses (3.6%). Main cause of cisplatin dose reduction was nephrotoxicity (12 courses). Most patients received three courses. There were no chemotherapy-related deaths. Three patients were not evaluable for clinical response. Twenty-eight patients had a partial response (48.3%, 95% CI: 36–61.1%), 24 stable disease and six progressive disease. After induction therapy, 30 patients underwent surgery; complete resection was achieved in 19 procedures (31.1%). Radical radiotherapy was delivered to 25 patients (41%). Six patients were considered unfit for further treatment. Median survival for all patients was 18 months. Response rate of accelerated cisplatin and high-dose epirubicin as induction chemotherapy for stage IIIa-N2 NSCLC patients is not different from more commonly used cisplatin-based regimen

Detection and impacts of leakage from sub-seafloor deep geological carbon dioxide storage

Fossil fuel power generation and other industrial emissions of carbon dioxide are a threat to global climate1, yet many economies will remain reliant on these technologies for several decades2. Carbon dioxide capture and storage (CCS) in deep geological formations provides an effective option to remove these emissions from the climate system3. In many regions storage reservoirs are located offshore4, 5, over a kilometre or more below societally important shelf seas6. Therefore, concerns about the possibility of leakage7, 8 and potential environmental impacts, along with economics, have contributed to delaying development of operational CCS. Here we investigate the detectability and environmental impact of leakage from a controlled sub-seabed release of CO2. We show that the biological impact and footprint of this small leak analogue (&lt;1 tonne CO2 d?1) is confined to a few tens of metres. Migration of CO2 through the shallow seabed is influenced by near-surface sediment structure, and by dissolution and re-precipitation of calcium carbonate naturally present in sediments. Results reported here advance the understanding of environmental sensitivity to leakage and identify appropriate monitoring strategies for full-scale carbon storage operations

National Guidelines for Digital Modelling

These National Guidelines and Case Studies for Digital Modelling are the outcomes from one of a number of Building Information Modelling (BIM)-related projects undertaken by the CRC for Construction Innovation. Since the CRC opened its doors in 2001, the industry has seen a rapid increase in interest in BIM, and widening adoption. These guidelines and case studies are thus very timely, as the industry moves to model-based working and starts to share models in a new context called integrated practice. Governments, both federal and state, and in New Zealand are starting to outline the role they might take, so that in contrast to the adoption of 2D CAD in the early 90s, we ensure that a national, industry-wide benefit results from this new paradigm of working. Section 1 of the guidelines give us an overview of BIM: how it affects our current mode of working, what we need to do to move to fully collaborative model-based facility development. The role of open standards such as IFC is described as a mechanism to support new processes, and make the extensive design and construction information available to asset operators and managers. Digital collaboration modes, types of models, levels of detail, object properties and model management complete this section. It will be relevant for owners, managers and project leaders as well as direct users of BIM. Section 2 provides recommendations and guides for key areas of model creation and development, and the move to simulation and performance measurement. These are the more practical parts of the guidelines developed for design professionals, BIM managers, technical staff and ‘in the field’ workers. The guidelines are supported by six case studies including a summary of lessons learnt about implementing BIM in Australian building projects. A key aspect of these publications is the identification of a number of important industry actions: the need for BIM-compatible product information and a national context for classifying product data; the need for an industry agreement and setting process-for-process definition; and finally, the need to ensure a national standard for sharing data between all of the participants in the facility-development process

Towards sustainable facilities management

About 1 per cent of all Australian commercial building stock is new each year. This means that if new building works are relied on to provide significant change in the sustainability of the stock, then it will take many years before a significant impact is achieved. Fortunately, commercial buildings are refurbished at relatively frequent intervals, so their rate of improvement is much faster than the rate of new construction. However, there are other drivers which could lead to significant improvements in our building stock. These fall under the aegis of facilities management (FM). In this chapter, FM is defined to cover the entire project life cycle after handover from the initial construction. This includes not only the day-today operations involved in running a facility, but also major refurbishments and upgrades. Sustainable FM is a process that manages the efficient operation of facilities in support of service delivery, operational life cycle costs and the use of resources, and minimizes their impact on built environment

Towards digital facility modelling for Sydney Opera House using IFC and semantic web technology

The challenges of maintaining a building such as the Sydney Opera House are immense and are dependent upon a vast array of information. The value of information can be enhanced by its currency, accessibility and the ability to correlate data sets (integration of information sources). A building information model correlated to various information sources related to the facility is used as definition for a digital facility model. Such a digital facility model would give transparent and an integrated access to an array of datasets and obviously would support Facility Management processes. In order to construct such a digital facility model, two state-of-the-art Information and Communication technologies are considered: an internationally standardized building information model called the Industry Foundation Classes (IFC) and a variety of advanced communication and integration technologies often referred to as the Semantic Web such as the Resource Description Framework (RDF) and the Web Ontology Language (OWL). This paper reports on some technical aspects for developing a digital facility model focusing on Sydney Opera House. The proposed digital facility model enables IFC data to participate in an ontology driven, service-oriented software environment. A proof-of-concept prototype has been developed demonstrating the usability of IFC information to collaborate with Sydney Opera House’s specific data sources using semantic web ontologies

Sequence Analysis of Insecticidal Genes from Xenorhabdus nematophilus PMFI296

Three strains of Xenorhabdus nematophilus showed insecticidal activity when fed to Pieris brassicae (cabbage white butterfly) larvae. From one of these strains (X. nematophilus PMFI296) a cosmid genome library was prepared in Escherichia coli and screened for oral insecticidal activity. Two overlapping cosmid clones were shown to encode insecticidal proteins, which had activity when expressed in E. coli (50% lethal concentration [LC(50)] of 2 to 6 μg of total protein/g of diet). The complete sequence of one cosmid (cHRIM1) was obtained. On cHRIM1, five genes (xptA1, -A2, -B1, -C1, and -D1) showed homology with up to 49% identity to insecticidal toxins identified in Photorhabdus luminescens, and also a smaller gene (chi) showed homology to a putative chitinase gene (38% identity). Transposon mutagenesis of the cosmid insert indicated that the genes xptA2, xptD1, and chi were not important for the expression of insecticidal activity toward P. brassicae. One gene (xptA1) was found to be central for the expression of activity, and the genes xptB1 and xptC1 were needed for full activity. The location of these genes together on the chromosome and therefore present on a single cosmid insert probably accounted for the detection of insecticidal activity in this E. coli clone. Although multiple genes may be needed for full activity, E. coli cells expressing the xptA1 gene from the bacteriophage lambda P(L) promoter were shown to have insecticidal activity (LC(50) of 112 μg of total protein/g of diet). This is contrary to the toxin genes identified in P. luminescens, which were not insecticidal when expressed individually in E. coli. High-level gene expression and the use of a sensitive insect may have aided in the detection of insecticidal activity in the E. coli clone expressing xptA1. The location of these toxin genes and the chitinase gene and the presence of mobile elements (insertion sequence) and tRNA genes on cHRIM1 indicates that this region of DNA represents a pathogenicity island on the genome of X. nematophilus PMFI296