Search

ABSTRACT Air samples of particulate matter (PM) with an aerodynamic diameter less than 10 µm (P[M.sub.10]) were collected from six sites in Bangkok, Thailand, using high-volume air samplers. Daily samples [...]

Abstract 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, K-ras 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 proto-oncoprotein 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 K-ras 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.

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]

Ambient Volatile Organic Compounds (VOCs) were examined in a heavy traffic urban area in Bangkok, Thailand, on focusing monoaromatic compounds of benzene, toluene, ethylbenzene, m-, p- and o-xylene (BTEX). Passive samplers were used to measure ambient BTEX concentrations in the environment close to very congested roads. Prior to the measurement, the validity of passive sampler performance was investigated to be acceptable for actual use. The monitoring was made five times on weekly basis in April-June in 2003. It was observed that averages of BTEX concentrations were as follows: 12.7 μg m-3 for benzene, 72.8 μg m-3 for toluene, 6.0 μg m-3 for ethylbenzene, 25.7 μg m-3 for m-, p-xylene and 13.6 μg m-3 for o-xylene. They are considered to be at very high concentration levels compared to other countries. Their distributions seemed to be in the form of logarithmic normal distribution. On the other hand, cluster analysis suggested that ambient BTEX in this study were derived from automobile exhaust gases. [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]

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]

Indoor nitrogen dioxide exposure has been associated with respiratory symptoms in children in many studies, but in Australia, levels and sources of nitrogen dioxide in homes have not been well-characterized. Therefore, as part of a larger indoor environmental study, conducted in the Latrobe Valley, Victoria, nitrogen dioxide was monitored using passive samplers in 80 homes. Samples were collected on five occasions over one year. Mean indoor levels were higher than outdoor levels, and a seasonal variation was evident, with highest levels recorded in winter. The overall median level was 11.6 µg/m³ (6.0 ppb), ranging from <0.7 to 246 µg/m³ (128 ppb). Major indoor nitrogen dioxide sources were: gas stoves, vented gas heaters, and smoking. Some 67% of variation in indoor nitrogen dioxide levels could be explained by presence of major sources, house age, and outdoor levels. Gas stoves were the main contributors. [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]