Mutations in cardiac T-Box Factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy

The T-box family transcription factor gene TBX20 acts in a conserved regulatory network, guiding heart formation and patterning in diverse species. Mouse Tbx20 is expressed in cardiac progenitor cells, differentiating cardiomyocytes, and developing valvular tissue, and its deletion or RNA interference-mediated knockdown is catastrophic for heart development. TBX20 interacts physically, functionally, and genetically with other cardiac transcription factors, including NKX2-5, GATA4, and TBX5, mutations of which cause congenital heart disease (CHD). Here, we report nonsense (Q195X) and missense (I152M) germline mutations within the T-box DNA-binding domain of human TBX20 that were associated with a family history of CHD and a complex spectrum of developmental anomalies, including defects in septation, chamber growth, and valvulogenesis. Biophysical characterization of wild-type and mutant proteins indicated how the missense mutation disrupts the structure and function of the TBX20 T-box. Dilated cardiomyopathy was a feature of the TBX20 mutant phenotype in humans and mice, suggesting that mutations in developmental transcription factors can provide a sensitized template for adult-onset heart disease. Our findings are the first to link TBX20 mutations to human pathology. They provide insights into how mutation of different genes in an interactive regulatory circuit lead to diverse clinical phenotypes, with implications for diagnosis, genetic screening, and patient follow-up.

Ultimate load behaviour of box-columns under combined loading of axial compression and torsion

This paper describes a study of the theoretical and experimental behaviour of box-columns of varying b/t ratios under loadings of axial compression and torsion and their combinations. Details of the testing rigs and the testing methods, the results obtained such as the load-deflection curves and the interaction diagrams, and experimental observations regarding the behaviour of box-models and the types of local plastic mechanisms associated with each type of loading are presented. A simplified rigid-plastic analysis is carried out to study the collapse behaviour of box-columns under these loadings, based on the observed plastic mechanisms, and the results are compared with those of experiments.

Heat-producing crust regulation of subsurface temperatures : a stochastic model re-evaluation of the geothermal potential in western Queensland, Australia

A large subsurface, elevated temperature anomaly is well documented in Central Australia. High Heat Producing Granites (HHPGs) intersected by drilling at Innamincka are often assumed to be the dominant cause of the elevated subsurface temperatures, although their presence in other parts of the temperature anomaly has not been confirmed. Geological controls on the temperature anomaly remain poorly understood. Additionally, methods previously used to predict temperature at 5 km depth in this area are simplistic and possibly do not give an accurate representation of the true distribution and magnitude of the temperature anomaly. Here we re-evaluate the geological controls on geothermal potential in the Queensland part of the temperature anomaly using a stochastic thermal model. The results illustrate that the temperature distribution is most sensitive to the thermal conductivity structure of the top 5 km. Furthermore, the results indicate the presence of silicic crust enriched in heat producing elements between and 40 km.

The effects of hot and cold temperatures on emergency hospital admissions in Brisbane, Australia

As Earth's climate is rapidly changing, the impact of ambient temperature on health outcomes has attracted increasing attention in the recent time. Considerable number of excess deaths has been reported because of exposure to ambient hot and cold temperatures. However, relatively little research has been conducted on the relation between temperature and morbidity. The aim of this study was to characterize the relationship between both hot and cold temperatures and emergency hospital admissions in Brisbane, Australia, and to examine whether the relation varied by age and socioeconomic factors. It aimed to explore lag structures of temperature–morbidity association for respiratory causes, and to estimate the magnitude of emergency hospital admissions for cardiovascular diseases attributable to hot and cold temperatures for the large contribution of both diseases to the total emergency hospital admissions. A time series study design was applied using routinely collected data of daily emergency hospital admissions, weather and air pollution variables in Brisbane during 1996–2005. Poisson regression model with a distributed lag non-linear structure was adopted to assess the impact of temperature on emergency hospital admissions after adjustment for confounding factors. Both hot and cold effects were found, with higher risk of hot temperatures than that of cold temperatures. Increases in mean temperature above 24.2oC were associated with increased morbidity, especially for the elderly ≥ 75 years old with the largest effect. The magnitude of the risk estimates of hot temperature varied by age and socioeconomic factors. High population density, low household income, and unemployment appeared to modify the temperature–morbidity relation. There were different lag structures for hot and cold temperatures, with the acute hot effect within 3 days after hot exposure and about 2-week lagged cold effect on respiratory diseases. A strong harvesting effect after 3 days was evident for respiratory diseases. People suffering from cardiovascular diseases were found to be more vulnerable to hot temperatures than cold temperatures. However, more patients admitted for cardiovascular diseases were attributable to cold temperatures in Brisbane compared with hot temperatures. This study contributes to the knowledge base about the association between temperature and morbidity. It is vitally important in the context of ongoing climate change. The findings of this study may provide useful information for the development and implementation of public health policy and strategic initiatives designed to reduce and prevent the burden of disease due to the impact of climate change.

The role of Y-box binding protein 1 in prostate cancer

This thesis examined the possible role of Y-box binding protein 1 (YBX1) in prostate cancer aggression and spread. Novel roles were uncovered for YBX1 in the regulation of several genes previously implicated in prostate cancer, as well as showing an effect for YBX1 in increasing tumour cell invasion and movement and reciprocal regulation of androgen-regulated gene networks. In addition, it was found that Y-box 1 regulated several other well-known cancer genes implicated in breast and other cancers. The work performed in this thesis has strengthened the foundations for pursuing YBX1 as a possible central target molecule in prostate cancer therapeutics.

Extreme temperatures and paediatric emergency department admissions

Background Children are particularly vulnerable to the effects of extreme temperatures. Objective To examine the relationship between extreme temperatures and paediatric emergency department admissions (EDAs) in Brisbane, Australia, during 2003–2009. Methods A quasi-Poisson generalised linear model combined with a distributed lag non-linear model was used to examine the relationships between extreme temperatures and age-, gender- and cause-specific paediatric EDAs, while controlling for air pollution, relative humidity, day of the week, influenza epidemics, public holiday, season and long-term trends. The model residuals were checked to identify whether there was an added effect due to heat waves or cold spells. Results There were 131 249 EDAs among children during the study period. Both high (RR=1.27; 95% CI 1.12 to 1.44) and low (RR=1.81; 95% CI 1.66 to 1.97) temperatures were significantly associated with an increase in paediatric EDAs in Brisbane. Male children were more vulnerable to temperature effects. Children aged 0–4 years were more vulnerable to heat effects and children aged 10–14 years were more sensitive to both hot and cold effects. High temperatures had a significant impact on several paediatric diseases, including intestinal infectious diseases, respiratory diseases, endocrine, nutritional and metabolic diseases, nervous system diseases and chronic lower respiratory diseases. Low temperatures were significantly associated with intestinal infectious diseases, respiratory diseases and endocrine, nutritional and metabolic diseases. An added effect of heat waves on childhood chronic lower respiratory diseases was seen, but no added effect of cold spells was found. Conclusions As climate change continues, children are at particular risk of a variety of diseases which might be triggered by extremely high temperatures. This study suggests that preventing the effects of extreme temperature on children with respiratory diseases might reduce the number of EDAs.

Active security in multiparty computation over black-box groups

Most previous work on unconditionally secure multiparty computation has focused on computing over a finite field (or ring). Multiparty computation over other algebraic structures has not received much attention, but is an interesting topic whose study may provide new and improved tools for certain applications. At CRYPTO 2007, Desmedt et al introduced a construction for a passive-secure multiparty multiplication protocol for black-box groups, reducing it to a certain graph coloring problem, leaving as an open problem to achieve security against active attacks. We present the first n-party protocol for unconditionally secure multiparty computation over a black-box group which is secure under an active attack model, tolerating any adversary structure Δ satisfying the Q 3 property (in which no union of three subsets from Δ covers the whole player set), which is known to be necessary for achieving security in the active setting. Our protocol uses Maurer’s Verifiable Secret Sharing (VSS) but preserves the essential simplicity of the graph-based approach of Desmedt et al, which avoids each shareholder having to rerun the full VSS protocol after each local computation. A corollary of our result is a new active-secure protocol for general multiparty computation of an arbitrary Boolean circuit.

An overview of Australian intrans*igence : a systemic Pandora’s Box

Despite the fact that Australia is a socially progressive country and boasts one of the largest Gender Dysphoria Clinics in the Southern Hemisphere, delivering services for almost four decades, Australian Governments fail to arrive at any consensus on the legal and human rights approaches to Trans*people. The subsequent lack of recognition does little more than increase the levels of frustration of and the continued discrimination to Trans*people, including adverse mental health problems, in this country. The purpose of this presentation is to provide an overview of the Australian systems that govern Trans*people and to identify how Trans*identities are manipulated in our Federal system of government; a system which offers little to protect the human rights of Trans*people. In order to contextualise the Australian situation, I commence with a brief description on the layers of government which will include how Australian Trans*people are currently protected under the law in those jurisdictions. I then present some of the impracticalities endured by the transitioning individual (single or married) including change of documentation and legal gender status before, during and after surgical transition for both those born on and off shore. This presentation will also include discussion of legislation that has been described by Trans*advocates as “Gesture”, “Cart before the Horse” and “Harmful”. I will conclude with a way forward by suggesting the development of a coordinated all of government approach in consultation with key stakeholders for “Trans* Friendly Legislation” to improve the human and legal rights, and ultimately the health and wellbeing of Australian Trans*identities.

“Creep-out” versus “gross-out” : horror movies at the Australian Box Office

Australia is a difficult market for horror movies. Particularly in recent years, Australia has been regarded as a graveyard for many horror films released theatrically. This is not to say that Australians have not enjoyed the occasional scary movie on the big screen. But what types of horror films have been popular with Australian audiences at the box-office remains poorly understood. Horror films revolve around monsters, the fear of death and the transgression of boundaries, and they aim to scare audiences through ‘gross-out’ or ‘creep-out’ factors (some combine both). The former refers to shocking and graphic portrayals of gore and violence – as seen in the sadistic torture of backpackers in Hostel (Eli Roth, 2005), which depicts limbs being hacked off and eyes being cut from nerve endings. The latter refers to the crafting of fear through mood and suspense without explicit bloodshed, achieved brilliantly in The Sixth Sense’s (M Night Shyamalan, 1999) chilling encounters with ‘dead people’. In creep-out films, it is often what viewers don’t see that is most disturbing. Using an analysis of the top fifty films each year at the Australian box office from 1992 to 2012, this article identifies the most successful horror movies over this period to ascertain what types of horror movies – with reference to creep-out and gross-out factors – have been most popular with domestic audiences.

Conservation and divergence of four kiwifruit SVP-like MADS-box genes suggest distinct roles in kiwifruit bud dormancy and flowering

MADS-box genes similar to Arabidopsis SHORT VEGETATIVE PHASE (SVP) have been implicated in the regulation of flowering in annual species and bud dormancy in perennial species. Kiwifruit (Actinidia spp.) are woody perennial vines where bud dormancy and out-growth affect flower development. To determine the role of SVP-like genes in dormancy and flowering of kiwifruit, four MADS-box genes with homology to Arabidopsis SVP, designated SVP1, SVP2, SVP3, and SVP4, have been identified and analysed in kiwifruit and functionally characterized in Arabidopsis. Phylogenetic analysis indicate that these genes fall into different sub-clades within the SVP-like gene group, suggesting distinct functions. Expression was generally confined to vegetative tissues, and increased transcript accumulation in shoot buds over the winter period suggests a role for these genes in bud dormancy. Down-regulation before flower differentiation indicate possible roles as floral repressors. Over-expression and complementation studies in Arabidopsis resulted in a range of floral reversion phenotypes arising from interactions with Arabidopsis MADS-box proteins, but only SVP1 and SVP3 were able to complement the svp mutant. These results suggest that the kiwifruit SVP-like genes may have distinct roles during bud dormancy and flowering.

Assessing the threshold temperatures among different age and cause-of-deaths

The relationship between temperature and mortality is non-linear and the effect estimates depend on the threshold temperatures selected. However, little is known about whether threshold temperatures differ with age or cause of deaths in the Southern Hemisphere. We conducted polynomial distributed lag non-linear models to assess the threshold temperatures for mortality from all ages (Dall), aged from 15 to 64 (D15-64), 65- 84(D65-84), ≥85 years (D85+), respiratory (RD) and cardiovascular diseases (CVD) in Brisbane, Australia, 1996–2004. We examined both hot and cold thresholds, and the lags of up to 15 days for cold effects and 3 days for hot effects. Results show that for the current day, the cold threshold was 20°C and the hot threshold was 28°C for the groups of Dall, D15-64 and D85+. The cold threshold was higher (23°C) for the group of D65-84 and lower (21°C) for the group of CVD. The hot threshold was higher (29°C) for the group of D65-84 and lower (27°C) for the group of RD. Compared to the current day, for the cold effects of up to 15-day lags, the threshold was lower for the group of D15-64, and the thresholds were higher for the groups of D65-84, D85+, RD and CVD; while for the hot effects of 3-day lags, the threshold was higher for the group of D15-64 and the thresholds were lower for the groups of D65-84 and RD. Temperature thresholds appeared to differ with age and death categories. The elderly and deaths from RD and CVD were more sensitive to temperature stress than the adult group. These findings may have implications in the assessment of temperature-related mortality and development of weather/health warning systems.

Increased size selectivity of Si quantum dots on SiC at low substrate temperatures : an ion-assisted self-organization approach

A simple, effective, and innovative approach based on ion-assisted self-organization is proposed to synthesize size-selected Si quantum dots (QDs) on SiC substrates at low substrate temperatures. Using hybrid numerical simulations, the formation of Si QDs through a self-organization approach is investigated by taking into account two distinct cases of Si QD formation using the ionization energy approximation theory, which considers ionized in-fluxes containing Si3+ and Si1+ ions in the presence of a microscopic nonuniform electric field induced by a variable surface bias. The results show that the highest percentage of the surface coverage by 1 and 2 nm size-selected QDs was achieved using a bias of -20 V and ions in the lowest charge state, namely, Si1+ ions in a low substrate temperature range (227-327 °C). As low substrate temperatures (≤500 °C) are desirable from a technological point of view, because (i) low-temperature deposition techniques are compatible with current thin-film Si-based solar cell fabrication and (ii) high processing temperatures can frequently cause damage to other components in electronic devices and destroy the tandem structure of Si QD-based third-generation solar cells, our results are highly relevant to the development of the third-generation all-Si tandem photovoltaic solar cells.

On secure multi-party computation in black-box groups

We study the natural problem of secure n-party computation (in the passive, computationally unbounded attack model) of the n-product function f G (x 1,...,x n ) = x 1 ·x 2 ⋯ x n in an arbitrary finite group (G,·), where the input of party P i is x i  ∈ G for i = 1,...,n. For flexibility, we are interested in protocols for f G which require only black-box access to the group G (i.e. the only computations performed by players in the protocol are a group operation, a group inverse, or sampling a uniformly random group element). Our results are as follows. First, on the negative side, we show that if (G,·) is non-abelian and n ≥ 4, then no ⌈n/2⌉-private protocol for computing f G exists. Second, on the positive side, we initiate an approach for construction of black-box protocols for f G based on k-of-k threshold secret sharing schemes, which are efficiently implementable over any black-box group G. We reduce the problem of constructing such protocols to a combinatorial colouring problem in planar graphs. We then give two constructions for such graph colourings. Our first colouring construction gives a protocol with optimal collusion resistance t < n/2, but has exponential communication complexity O(n*2t+1^2/t) group elements (this construction easily extends to general adversary structures). Our second probabilistic colouring construction gives a protocol with (close to optimal) collusion resistance t < n/μ for a graph-related constant μ ≤ 2.948, and has efficient communication complexity O(n*t^2) group elements. Furthermore, we believe that our results can be improved by further study of the associated combinatorial problems.

A gray-box neural network-based model identification and fault estimation scheme for nonlinear dynamic systems

A novel gray-box neural network model (GBNNM), including multi-layer perception (MLP) neural network (NN) and integrators, is proposed for a model identification and fault estimation (MIFE) scheme. With the GBNNM, both the nonlinearity and dynamics of a class of nonlinear dynamic systems can be approximated. Unlike previous NN-based model identification methods, the GBNNM directly inherits system dynamics and separately models system nonlinearities. This model corresponds well with the object system and is easy to build. The GBNNM is embedded online as a normal model reference to obtain the quantitative residual between the object system output and the GBNNM output. This residual can accurately indicate the fault offset value, so it is suitable for differing fault severities. To further estimate the fault parameters (FPs), an improved extended state observer (ESO) using the same NNs (IESONN) from the GBNNM is proposed to avoid requiring the knowledge of ESO nonlinearity. Then, the proposed MIFE scheme is applied for reaction wheels (RW) in a satellite attitude control system (SACS). The scheme using the GBNNM is compared with other NNs in the same fault scenario, and several partial loss of effect (LOE) faults with different severities are considered to validate the effectiveness of the FP estimation and its superiority.

Activation of forkhead box O transcription factors by oncogenic BRAF promotes p21cip1-dependent senescence

Oncogene-induced senescence (OIS) is a potent tumor-suppressive mechanism that is thought to come at the cost of aging. The Forkhead box O (FOXO) transcription factors are regulators of life span and tumor suppression. However, whether and how FOXOs function in OIS have been unclear. Here, we show a role for FOXO4 in mediating senescence by the human BRAFV600E oncogene, which arises commonly in melanoma. BRAFV600E signaling through mitogen-activated protein kinase/extracellular signal-regulated kinase kinase resulted in increased reactive oxygen species levels and c-Jun NH 2 terminal kinase-mediated activation of FOXO4 via its phosphorylation on Thr223, Ser226, Thr447, and Thr451. BRAFV600E-induced FOXO4 phosphorylation resulted in p21cip1-mediated cell senescence independent of p16 ink4a or p27kip1. Importantly, melanocyte-specific activation of BRAFV600E in vivo resulted in the formation of skin nevi expressing Thr223/Ser226-phosphorylated FOXO4 and elevated p21cip1. Together, these findings support a model in which FOXOs mediate a trade-off between cancer and aging.