Inactivation of the Huntington's disease gene (Hdh) impairs anterior streak formation and early patterning of the mouse embryo

Background Huntingtin, the HD gene encoded protein mutated by polyglutamine expansion in Huntington's disease, is required in extraembryonic tissues for proper gastrulation, implicating its activities in nutrition or patterning of the developing embryo. To test these possibilities, we have used whole mount in situ hybridization to examine embryonic patterning and morphogenesis in homozygous Hdhex4/5 huntingtin deficient embryos. Results In the absence of huntingtin, expression of nutritive genes appears normal but E7.0–7.5 embryos exhibit a unique combination of patterning defects. Notable are a shortened primitive streak, absence of a proper node and diminished production of anterior streak derivatives. Reduced Wnt3a, Tbx6 and Dll1 expression signify decreased paraxial mesoderm and reduced Otx2 expression and lack of headfolds denote a failure of head development. In addition, genes initially broadly expressed are not properly restricted to the posterior, as evidenced by the ectopic expression of Nodal, Fgf8 and Gsc in the epiblast and T (Brachyury) and Evx1 in proximal mesoderm derivatives. Despite impaired posterior restriction and anterior streak deficits, overall anterior/posterior polarity is established. A single primitive streak forms and marker expression shows that the anterior epiblast and anterior visceral endoderm (AVE) are specified. Conclusion Huntingtin is essential in the early patterning of the embryo for formation of the anterior region of the primitive streak, and for down-regulation of a subset of dynamic growth and transcription factor genes. These findings provide fundamental starting points for identifying the novel cellular and molecular activities of huntingtin in the extraembryonic tissues that govern normal anterior streak development. This knowledge may prove to be important for understanding the mechanism by which the dominant polyglutamine expansion in huntingtin determines the loss of neurons in Huntington's disease.

Domestication to crop improvement: Genetic resources for sorghum and saccharum (Andropogoneae)

Background Both sorghum (Sorghum bicolor) and sugarcane (Saccharum officinarum) are members of the Andropogoneae tribe in the Poaceae and are each other's closest relatives amongst cultivated plants. Both are relatively recent domesticates and comparatively little of the genetic potential of these taxa and their wild relatives has been captured by breeding programmes to date. This review assesses the genetic gains made by plant breeders since domestication and the progress in the characterization of genetic resources and their utilization in crop improvement for these two related species. Genetic Resources The genome of sorghum has recently been sequenced providing a great boost to our knowledge of the evolution of grass genomes and the wealth of diversity within S. bicolor taxa. Molecular analysis of the Sorghum genus has identified close relatives of S. bicolor with novel traits, endosperm structure and composition that may be used to expand the cultivated gene pool. Mutant populations (including TILLING populations) provide a useful addition to genetic resources for this species. Sugarcane is a complex polyploid with a large and variable number of copies of each gene. The wild relatives of sugarcane represent a reservoir of genetic diversity for use in sugarcane improvement. Techniques for quantitative molecular analysis of gene or allele copy number in this genetically complex crop have been developed. SNP discovery and mapping in sugarcane has been advanced by the development of high-throughput techniques for ecoTILLING in sugarcane. Genetic linkage maps of the sugarcane genome are being improved for use in breeding selection. The improvement of both sorghum and sugarcane will be accelerated by the incorporation of more diverse germplasm into the domesticated gene pools using molecular tools and the improved knowledge of these genomes.

Approximate Membership Localization within a Web-Based Join Framework

In this paper, we propose a search-based approach to join two tables in the absence of clean join attributes. Non-structured documents from the web are used to express the correlations between a given query and a reference list. To implement this approach, a major challenge we meet is how to efficiently determine the number of times and the locations of each clean reference from the reference list that is approximately mentioned in the retrieved documents. We formalize the Approximate Membership Localization (AML) problem and propose an efficient partial pruning algorithm to solve it. A study using real-word data sets demonstrates the effectiveness of our search-based approach, and the efficiency of our AML algorithm.

Responsibility to Protect and Sovereignty

The responsibility to protect ('R2P') principle articulates the obligations of the international community to prevent conflict occurring, to intervene in conflicts, and to assist in rebuilding after conflicts. The doctrine is about protecting civilians in armed conflicts from four mass atrocity crimes: genocide, war crimes, crimes against humanity and ethnic cleansing. This book examines interventions in East Timor, Sri Lanka, Sudan and Kosovo. The chapters explore and question UN debates with respect to the doctrine both before and after its adoption in 2005; contrasting state attitudes to international military intervention; and what takes place after intervention. It also discusses the ability of the Security Council to access reliable information and credible and transparent processes to enable it to make a determination on the occurrence of atrocities in a Member State. Questioning whether there is a need to find a closer operational link between the responsibilities to prevent and react and a normative link between R2P and principles of international law, the contributions examine the effectiveness of the framework of R2P for international decision-making in response to mass atrocity crimes and ask how an international system to deal with threats and mass atrocities can be developed in the absence of a central authority. This book will be valuable to those interested in international law, human rights, and security, peace and conflict studies

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.

A theory of waste behaviour in the construction industry

Levels of waste within the construction industry need to be reduced for environmental and economic reasons. Changing people's wasteful behaviour can make a significant contribution. This paper describes a research project that used Ajzen's 'theory of planned behaviour' to investigate the attitudinal forces that shape behaviour at the operative level. It concludes that operatives see waste as an inevitable by-product of construction activity. Attitudes towards waste management are not negative, although they are pragmatic and impeded by perceptions of a lack of managerial commitment. Waste management is perceived as a low project priority, and there is an absence of appropriate resources and incentives to support it. A theory of waste behaviour is proposed for the construction industry, and recommendations are made to help managers improve operatives' attitudes towards waste.

Online geographic information systems for improving health planning practice : lessons learned from the case study of Logan-Beaudesert, Australia

This study examines the impact of utilising a Decision Support System (DSS) in a practical health planning study. Specifically, it presents a real-world case of a community-based initiative aiming to improve overall public health outcomes. Previous studies have emphasised that because of a lack of effective information, systems and an absence of frameworks for making informed decisions in health planning, it has become imperative to develop innovative approaches and methods in health planning practice. Online Geographical Information Systems (GIS) has been suggested as one of the innovative methods that will inform decision-makers and improve the overall health planning process. However, a number of gaps in knowledge have been identified within health planning practice: lack of methods to develop these tools in a collaborative manner; lack of capacity to use the GIS application among health decision-makers perspectives, and lack of understanding about the potential impact of such systems on users. This study addresses the abovementioned gaps and introduces an online GIS-based Health Decision Support System (HDSS), which has been developed to improve collaborative health planning in the Logan-Beaudesert region of Queensland, Australia. The study demonstrates a participatory and iterative approach undertaken to design and develop the HDSS. It then explores the perceived user satisfaction and impact of the tool on a selected group of health decision makers. Finally, it illustrates how decision-making processes have changed since its implementation. The overall findings suggest that the online GIS-based HDSS is an effective tool, which has the potential to play an important role in the future in terms of improving local community health planning practice. However, the findings also indicate that decision-making processes are not merely informed by using the HDSS tool. Instead, they seem to enhance the overall sense of collaboration in health planning practice. Thus, to support the Healthy Cities approach, communities will need to encourage decision-making based on the use of evidence, participation and consensus, which subsequently transfers into informed actions.

A longitudinal study of corporate earnings guidance in Australia’s continuous disclosure environment

Since the introduction of a statutory‐backed continuous disclosure regime (CDR) in 1994, regulatory reforms have significantly increased litigation risk in Australia for failure to disclose material information or for false and misleading disclosure. However, there is almost no empirical research on the impact of the reforms on corporate disclosure behaviour. Motivated by the absence of research and using management earnings forecasts (MEFs) as a disclosure proxy, this study examines (1) why managers issue earnings forecasts, (2) what firm‐specific factors influence MEF characteristics, and (3) how MEF behaviour changes as litigation risk increases. Based on theories in information economics, a theoretical framework for MEF behaviour is formulated which includes antecedent influencing factors related to firms‟ internal and external environments. Applying this framework, hypotheses are developed and tested using multivariate models and a large sample of hand-collected MEFs (7,213) issued by top 500 ASX-listed companies over the 1994 to 2008 period. The results reveal strong support for the hypotheses. First, MEFs are issued to reduce information asymmetry, litigation risk and signal superior performance. Second, firms with better financial performance, smaller earnings changes, and lower operating uncertainty provide better quality MEFs. Third, forecast frequency and quality (accuracy, timeliness and precision) noticeably improve as litigation risk increases. However, managers appear to be still reluctant to disclose earnings forecasts when there are large earnings changes, and an asymmetric treatment of news type continues to prevail (a good news bias). Thus, the findings generally provide support for the effectiveness of the CDR regulatory reforms in improving disclosure behaviour and will be valuable to market participants and corporate regulators in understanding the implications of management forecasting decisions and areas for further improvement.

The flammability of metallic materials in normal and reduced gravity

Metallic materials exposed to oxygen-enriched atmospheres – as commonly used in the medical, aerospace, aviation and numerous chemical processing industries – represent a significant fire hazard which must be addressed during design, maintenance and operation. Hence, accurate knowledge of metallic materials flammability is required. Reduced gravity (i.e. space-based) operations present additional unique concerns, where the absence of gravity must also be taken into account. The flammability of metallic materials has historically been quantified using three standardised test methods developed by NASA, ASTM and ISO. These tests typically involve the forceful (promoted) ignition of a test sample (typically a 3.2 mm diameter cylindrical rod) in pressurised oxygen. A test sample is defined as flammable when it undergoes burning that is independent of the ignition process utilised. In the standardised tests, this is indicated by the propagation of burning further than a defined amount, or „burn criterion.. The burn criterion in use at the onset of this project was arbitrarily selected, and did not accurately reflect the length a sample must burn in order to be burning independent of the ignition event and, in some cases, required complete consumption of the test sample for a metallic material to be considered flammable. It has been demonstrated that a) a metallic material.s propensity to support burning is altered by any increase in test sample temperature greater than ~250-300 oC and b) promoted ignition causes an increase in temperature of the test sample in the region closest to the igniter, a region referred to as the Heat Affected Zone (HAZ). If a test sample continues to burn past the HAZ (where the HAZ is defined as the region of the test sample above the igniter that undergoes an increase in temperature of greater than or equal to 250 oC by the end of the ignition event), it is burning independent of the igniter, and should be considered flammable. The extent of the HAZ, therefore, can be used to justify the selection of the burn criterion. A two dimensional mathematical model was developed in order to predict the extent of the HAZ created in a standard test sample by a typical igniter. The model was validated against previous theoretical and experimental work performed in collaboration with NASA, and then used to predict the extent of the HAZ for different metallic materials in several configurations. The extent of HAZ predicted varied significantly, ranging from ~2-27 mm depending on the test sample thermal properties and test conditions (i.e. pressure). The magnitude of the HAZ was found to increase with increasing thermal diffusivity, and decreasing pressure (due to slower ignition times). Based upon the findings of this work, a new burn criterion requiring 30 mm of the test sample to be consumed (from the top of the ignition promoter) was recommended and validated. This new burn criterion was subsequently included in the latest revision of the ASTM G124 and NASA 6001B international test standards that are used to evaluate metallic material flammability in oxygen. These revisions also have the added benefit of enabling the conduct of reduced gravity metallic material flammability testing in strict accordance with the ASTM G124 standard, allowing measurement and comparison of the relative flammability (i.e. Lowest Burn Pressure (LBP), Highest No-Burn Pressure (HNBP) and average Regression Rate of the Melting Interface(RRMI)) of metallic materials in normal and reduced gravity, as well as determination of the applicability of normal gravity test results to reduced gravity use environments. This is important, as currently most space-based applications will typically use normal gravity information in order to qualify systems and/or components for reduced gravity use. This is shown here to be non-conservative for metallic materials which are more flammable in reduced gravity. The flammability of two metallic materials, Inconel® 718 and 316 stainless steel (both commonly used to manufacture components for oxygen service in both terrestrial and space-based systems) was evaluated in normal and reduced gravity using the new ASTM G124-10 test standard. This allowed direct comparison of the flammability of the two metallic materials in normal gravity and reduced gravity respectively. The results of this work clearly show, for the first time, that metallic materials are more flammable in reduced gravity than in normal gravity when testing is conducted as described in the ASTM G124-10 test standard. This was shown to be the case in terms of both higher regression rates (i.e. faster consumption of the test sample – fuel), and burning at lower pressures in reduced gravity. Specifically, it was found that the LBP for 3.2 mm diameter Inconel® 718 and 316 stainless steel test samples decreased by 50% from 3.45 MPa (500 psia) in normal gravity to 1.72 MPa (250 psia) in reduced gravity for the Inconel® 718, and 25% from 3.45 MPa (500 psia) in normal gravity to 2.76 MPa (400 psia) in reduced gravity for the 316 stainless steel. The average RRMI increased by factors of 2.2 (27.2 mm/s in 2.24 MPa (325 psia) oxygen in reduced gravity compared to 12.8 mm/s in 4.48 MPa (650 psia) oxygen in normal gravity) for the Inconel® 718 and 1.6 (15.0 mm/s in 2.76 MPa (400 psia) oxygen in reduced gravity compared to 9.5 mm/s in 5.17 MPa (750 psia) oxygen in normal gravity) for the 316 stainless steel. Reasons for the increased flammability of metallic materials in reduced gravity compared to normal gravity are discussed, based upon the observations made during reduced gravity testing and previous work. Finally, the implications (for fire safety and engineering applications) of these results are presented and discussed, in particular, examining methods for mitigating the risk of a fire in reduced gravity.

Negative affect-induced food intake in non-dieting women is reward driven and associated with restrained-disinhibited eating subtype

In humans the presence of negative affect is thought to promote food intake, but there is widespread variability. Susceptibility to negative affect-induced eating may depend on trait eating behaviours, notably ‘emotional eating’, ‘restrained eating’ and ‘disinhibited eating’, but the evidence is not consistent. In the present study, 30 non-obese, non-dieting women were given access to palatable food whilst in a state of negative or neutral affect, induced by a validated autobiographical recall technique. As predicted, food intake was higher in the presence of negative affect; however, this effect was moderated by the pattern of eating behaviour traits and enhanced wanting for the test food. Specifically, the High Restraint-High Disinhibition subtype in combination with higher scores on emotional eating and food wanting was able to predict negative-affect intake (adjusted R2 = .61). In the absence of stress, individuals who are both restrained and vulnerable to disinhibited eating are particularly susceptible to negative affect food intake via stimulation of food wanting. Identification of traits that predispose individuals to overconsume and a more detailed understanding of the specific behaviours driving such overconsumption may help to optimise strategies to prevent weight gain.

The impact of taxes on optimal portfolio choice : an Australian study

Taxes are an important component of investing that is commonly overlooked in both the literature and in practice. For example, many understand that taxes will reduce an investment’s return, but less understood is the risk-sharing nature of taxes that also reduces the investment’s risk. This thesis examines how taxes affect the optimal asset allocation and asset location decision in an Australian environment. It advances the model of Horan & Al Zaman (2008), improving the method by which the present value of tax liabilities are calculated, by using an after-tax risk-free discount rate, and incorporating any new or reduced tax liabilities generated into its expected risk and return estimates. The asset allocation problem is examined for a range of different scenarios using Australian parameters, including different risk aversion levels, personal marginal tax rates, investment horizons, borrowing premiums, high or low inflation environments, and different starting cost bases. The findings support the Horan & Al Zaman (2008) conclusion that equities should be held in the taxable account. In fact, these findings are strengthened with most of the efficient frontier maximising equity holdings in the taxable account instead of only half. Furthermore, these findings transfer to the Australian case, where it is found that taxed Australian investors should always invest into equities first through the taxable account before investing in super. However, untaxed Australian investors should invest their equity first through superannuation. With borrowings allowed in the taxable account (no borrowing premium), Australian taxed investors should hold 100% of the superannuation account in the risk-free asset, while undertaking leverage in the taxable account to achieve the desired risk-return. Introducing a borrowing premium decreases the likelihood of holding 100% of super in the risk-free asset for taxable investors. The findings also suggest that the higher the marginal tax rate, the higher the borrowing premium in order to overcome this effect. Finally, as the investor’s marginal tax rate increases, the overall allocation to equities should increase due to the increased risk and return sharing caused by taxation, and in order to achieve the same risk/return level as the lower taxation level, the investor must take on more equity exposure. The investment horizon has a minimal impact on the optimal allocation decision in the absence of factors such as mean reversion and human capital.

Room ventilation and the risk of airborne infection transmission in three health care settings within a large teaching hospital

Background: Room ventilation is a key determinant of airborne disease transmission. Despite this, ventilation guidelines in hospitals are not founded on robust scientific evidence related to prevention of airborne transmission. Methods: We sought to assess the effect of ventilation rates on influenza, tuberculosis (TB) and rhinovirus infection risk within three distinct rooms in a major urban hospital; a Lung Function Laboratory, Emergency Department (ED) Negative-pressure Isolation Room and an Outpatient Consultation Room were investigated. Air exchange rate measurements were performed in each room using CO2 as a tracer. Gammaitoni and Nucci’s model was employed to estimate infection risk. Results: Current outdoor air exchange rates in the Lung Function Laboratory and ED Isolation Room limited infection risks to between 0.1 and 3.6%. Influenza risk for individuals entering an Outpatient Consultation Room after an infectious individual departed ranged from 3.6 to 20.7%, depending on the duration for which each person occupied the room. Conclusions: Given the absence of definitive ventilation guidelines for hospitals, air exchange measurements combined with modelling afford a useful means of assessing, on a case-by-case basis, the suitability of room ventilation at preventing airborne disease transmission.

Interactions between pedestrians and cyclists in the city centre

The city centre represents a complex environment for cycling with large volumes of pedestrians and motorised vehicles and frequent signalised intersections. Much of the previous literature has focused on cyclist-motor vehicle interactions because of the safety implications for cyclists, but there is increasing concern from pedestrians about the threats they perceive from cyclists. In the absence of objective data, this has the potential to lead to restrictions on cyclist access and behaviour. This presentation reports the development of a method to study the extent of cycling in the city centre and the frequency and nature of interactions between cyclists and pedestrians. Queensland is one of the few Australian jurisdictions that permits adults to cycle on the footpath and this was also of interest. 1992 cyclists were observed at six locations in the Brisbane city centre, during 7-9am, 9-11am, 2-4pm and 4-6pm on four weekdays in October 2010. The majority (85.5%) of cyclists were male, and 21.8% rode on the footpath. Females were more likely to travel on the footpath than males. One or more pedestrians were within 1m for 18.1% of observed cyclists, and one or more pedestrians were within 5m for 39.1% of observed cyclists. There were few conflicts, defined as an occasion where if no one took evasive action a collision would occur, between cyclists and pedestrians or vehicles (1.1% and 0.6% respectively) but they were more common for adolescents and riders not wearing (or not fastening) helmets.

Writing the self : the emergence of a dialogic space

While much narrative inquiry is concerned with issues of self and identity, doing study on the processes (the how) of self-making offers ongoing challenges to methodology. This article explores the creation of a dialogic space that assisted young adolescents to write about themselves and their daily lives using email journals as an alternative to face-to-face interviews. With the researcher acting as a listener-responder, and in the absence of researcher-designed questions, a dynamic field was opened up for participant-led self-making to emerge over a six month period of self-reflective written expression. The article describes a shared email relationship based on a dialogic pattern of thinking, writing, listening and response intended to foster participants’ voices as ontological narratives of self. Findings show the use of email journals created a synergy for self-disclosure and a safe space for self-expression where the willingness of participants to be themselves was encouraged. The self-representations of a specific group of gifted young adolescents thus emerged as written versions of “who” they are —offering data that differs from interview approaches and contributing to discussion of the value of ontology narratives.