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Purpose – The purpose of this study is to unravel the mystery of Level of Development (LOD) as frequently referred to in Building Information Modelling (BIM) delivery documents. LOD is a key parameter for describing digital content in a BIM context. It is seen as an important vehicle for specifying information exchange throughout a facility’ life cycle. However, hitherto, there has been little research examining how, beyond the theoretical concept, LOD can be applied and smartly utilised in practice. This study seeks to unravel the concept and reveal new insights into its application from a design management perspective. Design/methodology/approach – Following a literature and document review, two small-scale case projects were identified. The first was – to temper the state-of-the-art theory and understand what happens in practice today – discovery led. The second was – to drill down to the core of LOD utilisation to support planned model progression and test a plausible novel methodology to automate associated workflow – theory led. Findings – Results suggest that a lack of consistent understanding and utilisation exists and particular LOD errors are highlighted, but, moreover, LOD can be so much more useful if integrated into a BIM-like workflow. Consequently, a new method of automatically comparing planned model progression with the current state of the model is presented. Practical implications – Advancement of the understanding of the concept and application of LOD and its usefulness has significant implications for designing information management research. Originality/value – Fresh insights into LOD, concept and application are presented. The emerging proposed utilisation framework is novel and targets removal of known labour-intensive activities associated with LOD matrices whilst facilitating rich reuse of efficient model progression knowledge. [ABSTRACT FROM AUTHOR]

Background: Alterations in gene splicing occur in human sporadic colorectal cancer (CRC) and may contribute to tumour progression. The K-ras proto-oncogene encodes two splice variants, Kras 4A and 4B, and K-ras activating mutations which jointly affect both isoforms are prevalent in CRC. Past studies have established that splicing of both the K-ras oncogene and proto-oncogene is altered in CRC in favour of K-ras 4B. The present study addressed whether the K-Ras 4A protooncoprotein can suppress tumour development in the absence of its oncogenic allele, utilising the ApcMin/+ (Min) mouse that spontaneously develops intestinal tumours that do not harbour K-ras activating mutations, and the K-rastmΔ4A/tmΔ4A mouse that can express the K-ras 4B splice variant only. By this means tumorigenesis in the small intestine was compared between ApcMin/+, K-ras+/+ and ApcMin/+, K-rastmΔ4A/tmΔ4A mice that can, and cannot, express the K-ras 4A proto-oncoprotein respectively. Methods: The relative levels of expression of the K-ras splice variants in normal small intestine and small intestinal tumours were quantified by real-time RT-qPCR analysis. Inbred (C57BL/6) ApcMin/+, K-ras+/+ and ApcMin/+, K-rastmΔ4A/tmΔ4A mice were generated and the genotypes confirmed by PCR analysis. Survival of stocks was compared by the Mantel-Haenszel test, and tumour number and area compared by Student's t-test in outwardly healthy mice at approximately 106 and 152 days of age. DNA sequencing of codons 12, 13 and 61 was performed to confirm the intestinal tumours did not harbour a K-ras activating mutation. Results: The K-ras 4A transcript accounted for about 50% of K-ras expressed in the small intestine of both wild-type and Min mice. Tumours in the small intestine of Min mice showed increased levels of K-ras 4B transcript expression, but no appreciable change in K-ras 4A transcript levels. No Kras activating mutations were detected in 27 intestinal tumours derived from Min and compound mutant Min mice. K-Ras 4A deficiency did not affect mouse survival, or tumour number, size or histopathology. Conclusion: The K-Ras 4A proto-oncoprotein does not exhibit tumour suppressor activity in the small intestine, even though the K-ras 4A/4B ratio is reduced in adenomas lacking K-ras activating mutations. [ABSTRACT FROM AUTHOR]

In mammals, the three classical ras genes encode four highly homologous proteins, N-Ras, H-Ras, and the isoforms K-Ras 4A and 4B. Previous studies have shown that K-ras is essential for mouse development and that while K-ras 4A and 4B are expressed during development, K-ras 4A expression is regulated temporally and spatially and occurs in adult kidney, intestine, stomach, and liver. In the present study, the pattern of K-ras 4A expression was examined in a wide range of wild-type adult mouse tissues, and gene targeting was used to generate K-ras 4A-deficient mice to examine its role in development. It was found that K-ras 4A is also expressed in uterus, lung, pancreas, salivary glands, seminal vesicles, bone marrow cells, and cecum, where it was the major K-Ras isoform expressed. Mating between K-ras[sup tmΔ4A/+] mice produced viable K-ras[sup tmΔ4A/tmΔ4A] offspring with the expected Mendelian ratios of inheritance, and these mice expressed the K-ras 4B splice variant only. K-ras[sup tmΔ4A/tmΔ4A] mice were fertile and showed no histopathological abnormalities on inbred (129/Ola) or crossbred (129/Ola × C57BL/6) genetic backgrounds. The results demonstrate that K-Ras 4A, like H- and N-Ras, is dispensable for normal mouse development, at least in the presence of functional K-Ras 4B. [ABSTRACT FROM AUTHOR]

Focuses on a study which assessed the effect of Smad4 and Apc genotypes in carcinogen-induced pancreatic lesions in the mouse. List of genes identified as mutated in pancreatic cancer; Information on adenomatous polyposis coli; Way in which the role of SMAD4 in colorectal tumor progression was established.

Tumour suppressor genes prevent cancer development. They can be identified by studying humans, but a full understanding of the mechanisms of their action requires the production of animal models. Mice with mutations in tumour suppressor genes can be produced by gene targeting. The phenotypic consequences of tumour suppressor gene mutations in mice and humans show parallels and contrasts, and both can contribute to the elucidation of disease processes. [ABSTRACT FROM AUTHOR]

Defects of mismatch repair are thought to be responsible for carcinogenesis in hereditary non-polyposis colorectal cancer and about 15% of sporadic colon cancers. The phenotype is seen as microsatellite instability and is known to be caused either by mutations in mismatch repair genes or by aberrant methylation of these genes stabilizing their downregulation. Lack of repair of microsatellite sequence errors, created during replication, leads to a mutation-prone phenotype. Where mutations occur within mononucleotide tracts within exons they cause translation frameshifts, premature cessation of translation and abnormal protein expression. Such mutations have been observed in the TGFβRII, BAX, IGFIIR, MSH3 and MSH6 genes in colon and other cancers. We describe here frameshift mutations affecting the gene for the methyl-CpG binding thymine glycosylase, MBD4, in over 40% of microsatellite unstable sporadic colon cancers. The mutations all appear heterozygous but their location would ensure truncation of the protein between the methyl-CpG binding and glycosylase domains, thus potentially generating a dominant negative effect. It is thus possible that such mutations enhance mutation frequency at other sites in these tumours. A suggestion has been made that MBD4 (MED1) mutations may lead to an increased rate of microsatellite instability but this mechanism appears unlikely due to the nature of mutations we have found. [ABSTRACT FROM AUTHOR]

The indoor environment of 80 houses in the Latrobe Valley, Victoria, Australia was assessed during six visits performed bi-monthly over a period of one year. Children between 7 and 14 years of age residing in the houses were included, result ing in 148 study children, 53 of whom were asthmatic. A respiratory health questionnaire was completed and skin prick tests performed. Significant risk factors for asthma were: exposure to a gas stove (OR=3.I5, 95% CI 1.28-7.72), and indoor pets (OR= 2.68, 95% CI 1.07-6.70). Exposure to airborne Aspergillus spores {+10 CFU/m&sup1, OR =1.51, 95% CI 1.05-2.18) was a risk factor for atopy, while exposure to a gas stove (OR=2.32, 95% CI 1.04-5.18) was a risk factor for respiratory symptoms. In conclusion, exposure to gas stoves, fungal spores and pets in the home were identified as statistically significant risk factors for respiratory health in children. [ABSTRACT FROM AUTHOR]

We wish to construct a mouse model for the human inherited disease cystic fibrosis. We describe here the successful targeting in embryonal stem cells of the murine homologue ( Cftr) of the cystic fibrosis transmembrane conductance regulator gene, as the first critical step towards this end. The targeting event precisely disrupts exon 10, the site of the major mutation in patients with cystic fibrosis. The targeted cells are pluripotent and competent to form chimaeras. [ABSTRACT FROM AUTHOR]

The derivation of a karyotypically normal embryonal stem (ES) cell line, E14, from inner cell masses (ICMs) isolated by immunosurgery from 129/Ola late mouse blastocysts is described. Disaggregated ICMs were cultured on mitotically-arrested fibroblast feeder layers in droplets of medium conditioned with Buffalo rat liver (BRL) cells under oil. BRL-conditioned medium inhibits the differentiation of established embryonal carcinoma (EC) and ES cell lines which can be maintained indefinitely in the complete absence of feeder cells (Smith and Hooper 1987). At clonal densities, however, a combination of BRL-conditioned medium and a feeder layer was most effective in preventing the differentiation of E14 cells. This effect was less pronounced at higher passage suggesting it may be particularly important to use a combination in the early stages of isolation. Once established, E14 has been maintained in BRL-conditioned medium alone. In non-conditioned medium on agarose, E14 cells formed embryoid bodies which when allowed to reattach differentiated into a wide variety of tissues. An HPRT-deficient sub line of E14, E14TG2a, has been demonstrated to form germline chimaeras with high efficiency after injection into blastocysts (Hooper et al. 1987). The modifications to the ES cell isolation procedure described here may improve the efficiency with which karyotypically normal lines can be derived. [ABSTRACT FROM AUTHOR]

Immunosurgical isolation of inner cell masses (ICMs) from sheep embryos was most efficient at the expanded, zona-intact blastocyst stage (day 7 to 8 post oestrus) before migration of endoderm cells beyond the boundary of the ICM across the blastocoelic surface of the trophectoderm. When cultured under conditions which allow the isolation of embryonal stem (ES) cell lines from mouse ICMs, sheep ICMs attached, spread and developed areas of both ES cell-like and endoderm-like cells. After prolonged culture only endoderm-like cells were evident. The implications for the isolation of ES cell lines from sheep embryos and possible species-specific requirements are discussed. [ABSTRACT FROM AUTHOR]

Airborne viable and total fungal spores were sampled inside and outside 80 houses in the Latrobe Valley, Victoria, Australia as part of a larger indoor environmental study. Each residence was visited six times over a period of 1 year for sample collection, and fungal spore samples were collected from at least three indoor sites and from an outdoor site. Viable spores were sampled using an Andersen sampler, while total spores were assessed using a Burkard spore trap. Identification of fungal colonies to genera level was performed in two seasons; winter and late spring. The most common fungal genera/groups were Cladosporium, Penicillium, and yeasts, both indoors and outdoors in winter and late spring. Outdoor levels were higher than those indoors throughout the year, and a significant seasonal variation in spore levels was seen both indoors and outdoors with overall maxima in summer. Contrary to this trend, the levels of Aspergillus, yeasts, Cephalosporium and Gliocladium were higher in winter. Most fungal genera were found in greater concentrations outdoors compared to indoors, but Penicillium was more common indoors. Outdoor spore levels were a significant influence on indoor levels, but seasonal differences suggest that other influences are important. [ABSTRACT FROM AUTHOR]

The building permission process is to a large extent an analogue process where much information is handled in paper format or as pdf files. With the ongoing digitalisation in society, there is a potential to automate this process by integrating Building Information Models (BIM) of planned buildings and geospatial data to check if a building conforms to the building permission regulations. In this study, an inventory of which regulations in the (Swedish) detailed development plans that can be automatically checked or supported by 3D visualisation was conducted. Then, two of these regulations, the building height and the building footprint area, were studied in detail to find to which extent they can be automatically checked by integration of BIM and geospatial data. In addition, a feasibility study of one visual criterion was conducted. One concern when automating the building permission process is the variability of content within the Industry Foundation Classes (IFC) data model. Variations in modelling methods and model content leads to differences in IFC models' content and structure; these differences complicate automated processes. To facilitate automated processes, requirements on the production of IFC models for building permission applications could be defined in the form of model view definitions or delivery specifications. [ABSTRACT FROM AUTHOR]

A flow injection method was developed for the determination of palladium, based on the reaction of palladium with DBOK-chlorophosphonazo with a detection limit of 0.07 μg/mL and a linear calibration range from 0.1 to 3.2 μg/mL of palladium. The reaction product has a maximum absorption at 630 nm. The method was applied to determine Pd2+ in catalysts and in anode mud samples. The relative error is less than 3% and the recovery of palladium is in the range 95% to 105% [ABSTRACT FROM AUTHOR]