Surrogacy : is it harder to relinquish genes?

Surrogacy has produced some positive outcomes creating an opportunity for otherwise childless couples to live their dream of parenthood. However it has also been problematic, particularly where the surrogate mother fails to relinquish a child born as a result of the surrogacy arrangement. This article examines whether a surrogate mother, who is genetically related to the child she delivers, is less likely to relinquish the child than one who has no genetic ties. An examination of empirical evidence provides support for this argument. Legislation and case law in three jurisdictions, Australia, the United States and the United Kingdom, is examined to determine which, if any, of these jurisdictions take into account the existence, or otherwise, of a genetic link between the surrogate mother and the child she bears. The article concludes that surrogacy legislation should, subject to exceptional circumstances, encourage surrogacy arrangements where the child and the surrogate are not genetically related.

Evidence for u.v. induction of CDKN2 mutations in melanoma cell lines

The CDKN2 gene, encoding the cyclin dependent kinase inhibitor p16, is a tumour suppressor gene involved in melanoma and maps to chromosome band 9p22. Mutations or interstitial deletions of this gene have been found both in the germline of familial melanoma cases and somatically in melanoma cell lines. Previous mutation analyses of melanoma cell lines have indicated a high frequency of C:G to T:A transitions, with all of these mutations occurring at dipyrimidine sites. Including three melanoma cell lines carrying tandem CC to TT mutations, the spectrum of mutations so far reported indicates a possible role for u.v. radiation in the mutagenesis of this gene in some tumours. To further examine this hypothesis we have characterised mutations of the CDKN2 gene in 30 melanoma cell lines. Nineteen lines carried complete or partial homozygous deletions of the gene. Of the remaining cell lines, eight were shown by direct sequencing of PCR products from exon 1 and exon 2 to carry a total of nine different mutations of CDKN2. Two cell lines carried tandem CC to TT mutations and a high rate of C:G to T:A transitions was observed. This study provides further evidence for the role of u.v. light in the genesis of melanoma, with one target being the CDKN2 tumour suppressor gene.

Analysis of the CDKN2A, CDKN2B and CDK4 genes in 48 Australian melanoma kindreds

Germline mutations within the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene and one of its targets, the cyclin dependent kinase 4 (CDK4) gene, have been identified in a proportion of melanoma kindreds. In the case of CDK4, only one specific mutation, resulting in the substitution of a cysteine for an arginine at codon 24 (R24C), has been found to be associated with melanoma. We have previously reported the identification of germline CDKN2A mutations in 7/18 Australian melanoma kindreds and the absence of the R24C CDK4 mutation in 21 families lacking evidence of a CDKN2A mutation. The current study represents an expansion of these efforts and includes a total of 48 melanoma families from Australia. All of these families have now been screened for mutations within CDKN2A and CDK4, as well as for mutations within the CDKN2A homolog and 9p21 neighbor, the CDKN2B gene, and the alternative exon 1 (E1beta) of CDKN2A. Families lacking CDKN2A mutations, but positive for a polymorphism(s) within this gene, were further evaluated to determine if their disease was associated with transcriptional silencing of one CDKN2A allele. Overall, CDKN2A mutations were detected in 3/30 (10%) of the new kindreds. Two of these mutations have been observed previously: a 24 bp duplication at the 5' end of the gene and a G to C transversion in exon 2 resulting in an M531 substitution. A novel G to A transition in exon 2, resulting in a D108N substitution was also detected. Combined with our previous findings, we have now detected germline CDKN2A mutations in 10/48 (21%) of our melanoma kindreds. In none of the 'CDKN2A-negative' families was melanoma found to segregate with either an untranscribed CDKN2A allele, an R24C CDK4 mutation, a CDKN2B mutation, or an E1beta mutation. The last three observations suggest that these other cell cycle control genes (or alternative gene products) are either not involved at all, or to any great extent, in melanoma predisposition.

Mutation analysis of the CDKN2A promoter in Australian melanoma families

Approximately 50% of all melanoma families worldwide show linkage to 9p21-22, but only about half of these have been shown to contain germ line CDKN2A mutations. It has been hypothesized that a proportion of these families carry mutations in the noncoding regions of CDKN2A. Several Canadian families have been reported to carry a mutation in the 5' UTR, at position -34 relative to the start site, which gives rise to a novel AUG translation initiation codon that markedly decreases translation from the wild-type AUG (Liu et al., 1999). Haplotype sharing in these Canadian families suggested that this mutation is of British origin. We sequenced 1,327 base pairs (bp) of CDKN2A, making up 1,116 bp of the 5' UTR and promoter, all of exon 1, and 61 bp of intron 1, in at least one melanoma case from 110 Australian families with three or more affected members known not to carry mutations within the p16 coding region. In addition, 431 bp upstream of the start codon was sequenced in an additional 253 affected probands from two-case melanoma families for which the CDKN2A mutation status was unknown. Several known polymorphisms at positions -33, -191, -493, and -735 were detected, in addition to four novel variants at positions 120, -252, -347, and -981 relative to the start codon. One of the probands from a two-case family was found to have the previously reported Q50R mutation. No family member was found to carry the mutation at position -34 or any other disease-associated mutation. For further investigation of noncoding CDKN2A mutations that may affect transcription, allele-specific expression analysis was carried out in 31 of the families with at least three affected members who showed either complete or "indeterminate" 9p haplotype sharing without CDKN2A exonic mutations. Reverse transcription polymerase chain reaction and automated sequencing showed expression of both CDKN2A alleles in all family members tested. The lack of CDKN2A promoter mutations and the absence of transcriptional silencing in the germ line of this cohort of families suggest that mutations in the promoter and 5' UTR play a very limited role in melanoma predisposition.

Evidence for three tumor suppressor loci on chromosome 9p involved in melanoma development

Cytogenetic and loss of heterozygosity (LOH) studies have long indicated the presence of a tumor suppressor gene (TSG) on 9p involved in the development of melanoma. Although LOH at 9p has been reported in approximately 60% of melanoma tumors, only 5-10% of these tumors have been shown to carry CDKN2A mutations, raising the possibility that another TSG involved in melanoma maps to chromosome 9p. To investigate this possibility, a panel of 37 melanomas derived from 35 individuals was analyzed for CDKN2A mutations by single-strand conformation polymorphism analysis and sequencing. The melanoma samples were then typed for 15 markers that map to 9p13-24 to investigate LOH trends in this region. In those tumors demonstrating retention of heterozygosity at markers flanking CDKN2A and LOH on one or both sides of the gene, multiplex microsatellite PCR was performed to rule out homozygous deletion of the region encompassing CDKN2A. CDKN2A mutations were found in tumors from 5 patients [5 (14%) of 35], 4 of which demonstrated LOH across the entire region examined. The remaining tumor with no observed LOH carried two point mutations, one on each allele. Although LOH was identified at one or more markers in 22 (59%) of 37 melanoma tumors corresponding to 20 (57%) of 35 individuals, only 11 tumors from 9 individuals [9 (26%) of 35] demonstrated LOH at D9S942 and D9S1748 the markers closest to CDKN2A. Of the remaining 11 tumors with LOH 9 demonstrated LOH at two or more contiguous markers either centromeric and/or telomeric to CDKN2A while retaining heterozygosity at several markers adjacent to CDKN2A. Multiplex PCR revealed one tumor carried a homozygous deletion extending from D9S1748 to the IFN-alpha locus. In the remaining eight tumors, multiplex PCR demonstrated that the observed heterozygosity was not attributable to homozygous deletion and stromal contamination at D9S1748, D9S942, or D9S974, as measured by comparative amplification strengths, which indicates that retention of heterozygosity with flanking LOH does not always indicate a homozygous deletion. This report supports the conclusions of previous studies that a least two TSGs involved in melanoma development in addition to CDKN2A may reside on chromosome 9p.

Chain scission resists for extreme ultraviolet lithography based on high performance polysulfone-containing polymers

A series of polymers with a comb architecture were prepared where the poly(olefin sulfone) backbone was designed to be highly sensitive to extreme ultraviolet (EUV) radiation, while the well-defined poly(methyl methacrylate) (PMMA) arms were incorporated with the aim of increasing structural stability. It is hypothesized that upon EUV radiation rapid degradation of the polysulfone backbone will occur leaving behind the well-defined PMMA arms. The synthesized polymers were characterised and have had their performance as chain-scission EUV photoresists evaluated. It was found that all materials possess high sensitivity towards degradation by EUV radiation (E0 in the range 4–6 mJ cm−2). Selective degradation of the poly(1-pentene sulfone) backbone relative to the PMMA arms was demonstrated by mass spectrometry headspace analysis during EUV irradiation and by grazing-angle ATR-FTIR. EUV interference patterning has shown that materials are capable of resolving 30 nm 1:1 line:space features. The incorporation of PMMA was found to increase the structural integrity of the patterned features. Thus, it has been shown that terpolymer materials possessing a highly sensitive poly(olefin sulfone) backbone and PMMA arms are able to provide a tuneable materials platform for chain scission EUV resists. These materials have the potential to benefit applications that require nanopattering, such as computer chip manufacture and nano-MEMS.

Achieving supply chain sustainability : the role of relationship management, culture and procurement form

In this research we examined, by means of case studies, the mechanisms by which relationships can be managed and by which communication and cooperation can be enhanced in developing sustainable supply chains. The research was predicated on the contention that the development of a sustainable supply chain depends, in part, on the transfer of knowledge and capabilities from the larger players in the supply chain. A sustainable supply chain requires proactive relationship management and the development of an appropriate organisational culture, and trust. By legitimising individuals’ expectations of the type of culture which is appropriate to their company and empowering employees to address mismatches that may occur, a situation can be created whereby the collaborating organisations develop their competences symbiotically and so facilitate a sustainable supply chain. Effective supply chain management enhances organisation performance and competitiveness through the management of operations across organisational boundaries. Relational contracting approaches facilitate the exchange of information and knowledge and build capacity in the supply chain, thus enhancing its sustainability. Relationship management also provides the conditions necessary for the development of collaborative and cooperative relationships However, often subcontractors and suppliers are not empowered to attend project meetings or to have direct communication with project based staff. With this being a common phenomenon in the construction industry, one might ask: what are the barriers to implementation of relationship management through the supply chain? In other words, the problem addressed in this research is the engagement of the supply chain through relationship management.

Aligning the drivers in the value chain - a new cane payment system for Mackay Sugar

For the 2005 season, Mackay Sugar and its growers agreed to implement a new cane payment system. The aim of the new system was to better align the business drivers between the mill and its growers and as a result improve business decision making. The technical basis of the new cane payment system included a fixed sharing of the revenue from sugar cane between the mill and growers. Further, the new system replaced the CCS formula with a new estimate of recoverable sugar (PRS) and introduced NIR for payment analyses. Significant mill and grower consultation processes led to the agreement to implement the new system in 2005 and this consultative approach has been reflected in two seasons of successful operation.

Competences and capabilities for innovation in supply chain relationships

There is little empirical research on the relational capabilities and competences in supply chain relationships, and the important links that exist between relational capabilities, competences and supply chain innovation. This study addresses some of that knowledge gap gained through a case study of the Australian freight services sector. Findings suggest that different competences developed by supply chain participants support different ways to enable operational effectiveness. Road freight businesses should acquire knowledge of how to select and manage inter-firm relationships that provide the greatest benefit, acquiring competences that either improve their current capabilities or assist them to explore strategies that ensure incremental innovation and supply chain performance objectives are met.

Triangular Linguistic Fuzzy based performance measurement model for supply chain to assess leanness attributes

Increasing global competitiveness worldwide has forced manufacturing organizations to produce high-quality products more quickly and at a competitive cost. In order to reach these goals, they need good quality components from suppliers at optimum price and lead time. This actually forced all the companies to adapt different improvement practices such as lean manufacturing, Just in Time (JIT) and effective supply chain management. Applying new improvement techniques and tools cause higher establishment costs and more Information Delay (ID). On the contrary, these new techniques may reduce the risk of stock outs and affect supply chain flexibility to give a better overall performance. But industry people are unable to measure the overall affects of those improvement techniques with a standard evaluation model .So an effective overall supply chain performance evaluation model is essential for suppliers as well as manufacturers to assess their companies under different supply chain strategies. However, literature on lean supply chain performance evaluation is comparatively limited. Moreover, most of the models assumed random values for performance variables. The purpose of this paper is to propose an effective supply chain performance evaluation model using triangular linguistic fuzzy numbers and to recommend optimum ranges for performance variables for lean implementation. The model initially considers all the supply chain performance criteria (input, output and flexibility), converts the values to triangular linguistic fuzzy numbers and evaluates overall supply chain performance under different situations. Results show that with the proposed performance measurement model, improvement area for each variable can be accurately identified.

Influence of physical and chemical parameters on the treatment of heavy metals in polluted stormwater using zeolite : A review

Zeolite-based technology can provide a cost effective solution for stormwater treatment for the removal of toxic heavy metals under increasing demand of safe water from alternative sources. This paper reviews the currently available knowledge relating to the effect of properties of zeolites such as pore size, surface area and Si:Al ratio and the physico-chemical conditions of the system such as pH, temperature, initial metal concentration and zeolite concentration on heavy metal removal performance. The primary aims are, to consolidate available knowledge and identify knowledge gaps. It was established that an in-depth understanding of operational issues such as, diffusion of metal ions into the zeolite pore structure, pore clogging, zeolite surface coverage by particulates in stormwater as well as the effect of pH on stormwater quality in the presence of zeolites is essential for developing a zeolite-based technology for the treatment of polluted stormwater. The optimum zeolite concentration to treat typical volumes of stormwater and initial heavy metal concentrations in stormwater should also be considered as operational issues in this regard. Additionally, leaching of aluminium and sodium ions from the zeolite structure to solution were identified as key issues requiring further research in the effort to develop cost effective solutions for the removal of heavy metals from stormwater.

Relationship management as a strategy for supply chain engagement in the civil engineering construction industry

Many studies into construction procurement methods reveal evidence of a need to change the culture and attitude in the construction industry, transition from traditional adversarial relationships to cooperative and collaborative relationships. At the same time there is also increasing concern and discussion on alternative procurement methods, involving a movement away from traditional procurement systems. Relational contracting approaches, such as partnering and relationship management, are business strategies that align the objectives of clients, commercial participants and stakeholders. It provides a collaborative environment and a framework for all participants to adapt their behaviour to project objectives and allows for engagement of those subcontractors and suppliers down the supply chain. The efficacy of relationship management in the client and contractor groups is proven and well documented. However, the industry has a history of slow implementation of relational contracting down the supply chain. Furthermore, there exists little research on relationship management conducted in the supply chain context. This research aims to explore the association between relational contracting structures and processes and supply chain sustainability in the civil engineering construction industry. It endeavours to shed light on the practices and prerequisites for relationship management implementation success and for supply sustainability to develop. The research methodology is a triangulated approach based on Cheung.s (2006) earlier research where questionnaire survey, interviews and case studies were conducted. This new research includes a face-to-face questionnaire survey that was carried out with 100 professionals from 27 contracting organisations in Queensland from June 2008 to January 2009. A follow-up survey sub-questionnaire, further examining project participants. perspectives was sent to another group of professionals (as identified in the main questionnaire survey). Statistical analysis including multiple regression, correlation, principal component factor analysis and analysis of variance were used to identify the underlying dimensions and test the relationships among variables. Interviews and case studies were conducted to assist in providing a deeper understanding as well as explaining findings of the quantitative study. The qualitative approaches also gave the opportunity to critique and validate the research findings. This research presents the implementation of relationship management from the contractor.s perspective. Findings show that the adaption of relational contracting approach in the supply chain is found to be limited; contractors still prefer to keep the suppliers and subcontractors at arm.s length. This research shows that the degree of match and mismatch between organisational structuring and organisational process has an impact on staff.s commitment level and performance effectiveness. Key issues affecting performance effectiveness and relationship effectiveness include total influence between parties, access to information, personal acquaintance, communication process, risk identification, timely problem solving and commercial framework. Findings also indicate that alliance and Early Contractor Involvement (ECI) projects achieve higher performance effectiveness at both short-term and long-term levels compared to projects with either no or partial relationship management adopted.

Errata supplement for QUT thesis 'Heavy vehicle suspensions : testing and analysis'

Errata supplement to QUT thesis: 'Heavy vehicle suspensions : testing and analysis'

Exploratory investigation of atmospheric total suspended particulate matter and heavy metals in urban air

Atmospheric concentration of total suspended particulate matter (TSP) and associated heavy metals are a great concern due to their adverse health impacts and contribution to stormwater pollution. This paper discusses the outcomes of a study which investigated the variation of atmospheric TSP and heavy metal concentrations with traffic and land use characteristics during weekdays and weekends. Data for this study was gathered from fifteen sites at the Gold Coast, Australia using a high volume air sampler. The study detected consistently high TSP concentrations during weekdays compared to weekends. This confirms the significant influence of traffic related sources on TSP loads during weekdays. Both traffic and land use related sources equally contribute to TSP during weekends. Almost all the measured heavy metals showed high concentration on weekdays compared to weekends indicating significant contributions from traffic related emissions. Among the heavy metals, Zn concentration was the highest followed by Pb. It is postulated that re-suspension of previously deposited reserves was the main Pb source. Soil related sources were the main contributors of Mn.

Apoptosis-related genes confer resistance to Fusarium wilt in transgenic ‘Lady Finger’ bananas

Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense (Foc), is one of the most devastating diseases of banana (Musa spp.). Apart from resistant cultivars, there are no effective control measures for the disease. We investigated whether the transgenic expression of apoptosis-inhibition related genes in banana could be used to confer disease resistance. Embryogenic cell suspensions of the banana cultivar, ‘Lady Finger’, were stably transformed with animal genes that negatively regulate apoptosis, namely Bcl-xL, Ced-9 and Bcl-2 3’ UTR, and independently transformed plant lines were regenerated for testing. Following a 12 week exposure to Foc race 1 in small-plant glasshouse bioassays, seven transgenic lines (2 x Bcl-xL, 3 x Ced-9 and 2 x Bcl-2 3’ UTR) showed significantly less internal and external disease symptoms than the wild-type susceptible ‘Lady Finger’ banana plants used as positive controls. Of these, one Bcl-2 3’ UTR line showed resistance that was equivalent to that of wild-type Cavendish bananas that were included as resistant negative controls. Further, the resistance of this line continued for 23 weeks post-inoculation at which time the experiment was terminated. Using TUNEL assays, Foc race 1 was shown to induce apoptosis-like features in the roots of wild-type ‘Lady Finger’ plants consistent with a necrotrophic phase in the lifecycle of this pathogen. This was further supported by the observed reduction of these effects in the roots of the resistant Bcl-2 3’ UTR transgenic line. This is the first report on the generation of transgenic banana plants with resistance to Fusarium wilt.