DNA adduction by the potent carcinogen aflatoxin B1 : mechanistic studies

Aflatoxin B1, a potently carcinogenic fungal metabolite, is converted to the biologically active form by chemical oxidation using dimethyldioxirane and enzymatically by cytochrome P450 mixed-function oxidases. Both processes give rise to mixtures of the exo- and endo-8,9-epoxides. Methanolysis studies reveal exclusive trans opening of both epoxides under neutral conditions in CH3OH and CH3OH/H2O mixtures; an SN2 mechanism is postulated. Under acidic conditions, the exo isomer gives mixtures of trans and cis solvolysis products, suggesting that the reaction is, at least in part, SN1; the endo isomer gives only the trans product. The exo isomer reacts with DNA by attack of the nitrogen atom at the 7 position of guanine on C8 of the epoxide to give the trans adduct; the endo epoxide fails to form an adduct at this or any other site in DNA. The exo isomer is strongly mutagenic in a base-pair reversion assay employing Salmonella typhimurium; the endo isomer is essentially nonmutagenic. Aflatoxin B1 and its derivatives intercalate in DNA. These results are consistent with a mechanism in which intercalation of the exo epoxide optimally orients the epoxide for an SN2 reaction with guanine but intercalation of the endo isomer places the epoxide in an orientation which precludes reaction. Thus, while the exo epoxide is a potent mutagen, the endo epoxide fails to react with DNA.

Evolution to a chronic disease niche correlates with increased sensitivity to tryptophan availability for the obligate intracellular bacterium Chlamydia pneumoniae

The chlamydiae are obligate intracellular parasites that have evolved specific interactions with their various hosts and host cell types to ensure their successful survival and consequential pathogenesis. The species Chlamydia pneumoniae is ubiquitous, with serological studies showing that most humans are infected at some stage in their lifetime. While most human infections are asymptomatic, C. pneumoniae can cause more-severe respiratory disease and pneumonia and has been linked to chronic diseases such as asthma, atherosclerosis, and even Alzheimer's disease. The widely dispersed animal-adapted C. pneumoniae strains cause an equally wide range of diseases in their hosts. It is emerging that the ability of C. pneumoniae to survive inside its target cells, including evasion of the host's immune attack mechanisms, is linked to the acquisition of key metabolites. Tryptophan and arginine are key checkpoint compounds in this host-parasite battle. Interestingly, the animal strains of C. pneumoniae have a slightly larger genome, enabling them to cope better with metabolite restrictions. It therefore appears that as the evolutionarily more ancient animal strains have evolved to infect humans, they have selectively become more "susceptible" to the levels of key metabolites, such as tryptophan. While this might initially appear to be a weakness, it allows these human C. pneumoniae strains to exquisitely sense host immune attack and respond by rapidly reverting to a persistent phase. During persistence, they reduce their metabolic levels, halting progression of their developmental cycle, waiting until the hostile external conditions have passed before they reemerge.

One-step homogeneous C-reactive protein assay for saliva

Background: Cardiovascular disease is the leading cause of death in the world. Human C-reactive protein (CRP) has been used in the risk assessment of coronary events. Human saliva mirrors the body's health and well-being and is non-invasive, easy to collect and ideal for third world countries as well as for large patient screening. The aim was to establish a saliva CRP reference range and to demonstrate the clinical utility of salivary CRP levels in assessing the coronary events in a primary health care setting. Methods: We have used a homogeneous bead based assay to detect CRP levels in human saliva. We have developed a rapid 15 min (vs 90 min), sequential, one-step assay to detect CRP in saliva. Saliva was collected from healthy volunteers (n = 55, ages 20-70 years) as well as from cardiac patients (n = 28, ages 43-86 years). Results: The assay incubation time was optimised from 90 min to 15 mm and generated a positive correlation (n = 29, range 10-2189 pg/mL, r2 = 0.94; Passing Bablok slope 0.885. Intercept 0, p>0.10), meaning we could decrease the incubation time and produce equivalent results with confidence. The mean CRP level in the saliva of healthy human volunteers was 285 pg/mL and in cardiac patients was 1680 pg/mL (p<0.01). Analysis of CRP concentrations in paired serum and saliva samples from cardiac patients gave a positive correlation (r2 = 0.84, p<0.001) and the salivary CRP concentration capable of distinguishing healthy from diseased patients. Conclusions: The results suggest that this minimally invasive, rapid and sensitive assay will be useful in large patient screening studies for risk assessment of coronary events. (C) 2011 Elsevier B.V. All rights reserved.

Get a life? The impact of the European working time directive : the case of UK senior doctors

This paper seeks to identify the effect of the implementation of the European Working Time Directive (EWTD) on the working hours of UK doctors. The Labour Force Survey is used to compare the working hours of doctors with a variety of control groups before and after the implementation of the directive. The controls include those unconstrained by the directive and doctor counterparts working in Europe. We use differences-in-differences and matching methods to estimate the impact of this natural experiment, distinguishing between the anticipation and enactment of the EWTD. We find that the legislation reduced the hours of senior doctors by around 8 hours in total including the component attributable to anticipation effects and allowing for (exogenously set) rising wages.

Epigenetics and migraine; complex mitochondrial interactions contributing to disease susceptibility

Migraine is a common neurological disorder classified by the World Health Organisation (WHO) as one of the top twenty most debilitating diseases in the developed world. Current therapies are only effective for a proportion of sufferers and new therapeutic targets are desperately needed to alleviate this burden. Recently the role of epigenetics in the development of many complex diseases including migraine has become an emerging topic. By understanding the importance of acetylation, methylation and other epigenetic modifications, it then follows that this modification process is a potential target to manipulate epigenetic status with the goal of treating disease. Bisulphite sequencing and methylated DNA immunoprecipitation have been used to demonstrate the presence of methylated cytosines in the human D-loop of mitochondrial DNA (mtDNA), proving that the mitochondrial genome is methylated. For the first time, it has been shown that there is a difference in mtDNA epigenetic status between healthy controls and those with disease, especially for neurodegenerative and age related conditions. Given co-morbidities with migraine and the suggestive link between mitochondrial dysfunction and the lowered threshold for triggering a migraine attack, mitochondrial methylation may be a new avenue to pursue. Creative thinking and new approaches are needed to solve complex problems and a systems biology approach, where multiple layers of information are integrated is becoming more important in complex disease modelling.

Nornalup Bushfire Research - BAL40 House

For Construction - Architectural drawing package. House designed to AS3959:2009 Bushfire Attack Level 40. QUT-Client Agreement 100% Research (HERDC definition of Research).

Ausma Bushfire Research - BAL40 House

Construction drawings for Built work of Architecture. Completed July 2013. House designed to AS3959:2009 Bushfire Attack Level 40. 100% Commercial Research Project (HERDC Definition of Research)

Multi-ciphersuite security of the Secure Shell (SSH) protocol

The Secure Shell (SSH) protocol is widely used to provide secure remote access to servers, making it among the most important security protocols on the Internet. We show that the signed-Diffie--Hellman SSH ciphersuites of the SSH protocol are secure: each is a secure authenticated and confidential channel establishment (ACCE) protocol, the same security definition now used to describe the security of Transport Layer Security (TLS) ciphersuites. While the ACCE definition suffices to describe the security of individual ciphersuites, it does not cover the case where parties use the same long-term key with many different ciphersuites: it is common in practice for the server to use the same signing key with both finite field and elliptic curve Diffie--Hellman, for example. While TLS is vulnerable to attack in this case, we show that SSH is secure even when the same signing key is used across multiple ciphersuites. We introduce a new generic multi-ciphersuite composition framework to achieve this result in a black-box way.

With budget cuts coming, ABC and SBS stand divided

Did SBS chief executive Michael Ebeid score a well-timed free kick or an own goal in his attack on the ABC this week? The ABC recently secured the free-to-air television rights for the Asian Cup football tournament to be held in Australia early next year, together with tonight’s match between the Socceroos and Japan. A lower bid by SBS – still in some circles fondly known as the “Soccer Broadcasting Service” – was rejected, dealing a significant blow to the smaller public broadcaster. The ABC was reportedly asked to make a bid by Football Federation Australia. The FFA presumably believes the ABC’s coverage will attract larger audiences to the game. This is despite SBS’s long-term success with the sport. It should not be forgotten, however, that while SBS has largely been defined by its long connection with the world game, ABC was the home of football from the late 1950s until the 1980s. But the stoush is only partly about football. It was surely no coincidence that it comes on the eve of the government’s formal announcement of the size of the cuts to public broadcasting...

Acoustic identification of 12 species of echolocating bat by discriminant function analysis and artificial neural networks

We recorded echolocation calls from 14 sympatric species of bat in Britain. Once digitised, one temporal and four spectral features were measured from each call. The frequency-time course of each call was approximated by fitting eight mathematical functions, and the goodness of fit, represented by the mean-squared error, was calculated. Measurements were taken using an automated process that extracted a single call from background noise and measured all variables without intervention. Two species of Rhinolophus were easily identified from call duration and spectral measurements. For the remaining 12 species, discriminant function analysis and multilayer back-propagation perceptrons were used to classify calls to species level. Analyses were carried out with and without the inclusion of curve-fitting data to evaluate its usefulness in distinguishing among species. Discriminant function analysis achieved an overall correct classification rate of 79% with curve-fitting data included, while an artificial neural network achieved 87%. The removal of curve-fitting data improved the performance of the discriminant function analysis by 2 %, while the performance of a perceptron decreased by 2 %. However, an increase in correct identification rates when curve-fitting information was included was not found for all species. The use of a hierarchical classification system, whereby calls were first classified to genus level and then to species level, had little effect on correct classification rates by discriminant function analysis but did improve rates achieved by perceptrons. This is the first published study to use artificial neural networks to classify the echolocation calls of bats to species level. Our findings are discussed in terms of recent advances in recording and analysis technologies, and are related to factors causing convergence and divergence of echolocation call design in bats.

Split leverage : attacking the confidentiality of linked databases by partitioning

This article considers the risk of disclosure in linked databases when statistical analysis of micro-data is permitted. The risk of disclosure needs to be balanced against the utility of the linked data. The current work specifically considers the disclosure risks in permitting regression analysis to be performed on linked data. A new attack based on partitioning of the database is presented.

Protecting encrypted cookies from compression side-channel attacks

Compression is desirable for network applications as it saves bandwidth; however, when data is compressed before being encrypted, the amount of compression leaks information about the amount of redundancy in the plaintext. This side channel has led to successful CRIME and BREACH attacks on web traffic protected by the Transport Layer Security (TLS) protocol. The general guidance in light of these attacks has been to disable compression, preserving confidentiality but sacrificing bandwidth. In this paper, we examine two techniques - heuristic separation of secrets and fixed-dictionary compression|for enabling compression while protecting high-value secrets, such as cookies, from attack. We model the security offered by these techniques and report on the amount of compressibility that they can achieve.

A lucky break : contingency in the storied worlds of prickly pear

In July 1926, the science behind biological control transitioned from an experimental method to a trusted policy tool in invasive species management. In local storytelling, historical writing and scientific analysis, the ‘lucky’ discovery of the South American Cactoblastis cactorum moth was a watershed moment for scientists concerned with prickly pear, Opuntia and Nopalea spp. Within 10 years, Queensland declared itself pest free. Overnight success is the climax in this tale's narrative arc. Articulating this introduction as a ‘lucky break’ worked to stabilize the narrative of human control in the agricultural environments of post-colonial Queensland, and, in doing so, consolidated biological control as critical management technique. I argue that ‘luck’ elides the assemblage of elements and actors necessary to enable this change, allowing settlers to distance themselves from the responsibility for disruptions associated with nineteenth-century plant transfers. To challenge the rhetorical function of luck, three episodes of contingency are discussed: (1) transnational mobility of things and knowledge, (2) the unpredictable adaptation of insect diet, and; (3) human vectors in industrialized insect–plant complexes. There are important distinguishing differences between luck and contingency, which I frame as a critical analytical tool for understanding the political role of non-humans, in the storied worlds of science in prickly pear land.

Acoustic identification of twelve species of echolocating bat by discriminant function analysis and artificial neural networks

We recorded echolocation calls from 14 sympatric species of bat in Britain. Once digitised, one temporal and four spectral features were measured from each call. The frequency-time course of each call was approximated by fitting eight mathematical functions, and the goodness of fit, represented by the mean-squared error, was calculated. Measurements were taken using an automated process that extracted a single call from background noise and measured all variables without intervention. Two species of Rhinolophus were easily identified from call duration and spectral measurements. For the remaining 12 species, discriminant function analysis and multilayer back-propagation perceptrons were used to classify calls to species level. Analyses were carried out with and without the inclusion of curve-fitting data to evaluate its usefulness in distinguishing among species. Discriminant function analysis achieved an overall correct classification rate of 79% with curve-fitting data included, while an artificial neural network achieved 87%. The removal of curve-fitting data improved the performance of the discriminant function analysis by 2 %, while the performance of a perceptron decreased by 2 %. However, an increase in correct identification rates when curve-fitting information was included was not found for all species. The use of a hierarchical classification system, whereby calls were first classified to genus level and then to species level, had little effect on correct classification rates by discriminant function analysis but did improve rates achieved by perceptrons. This is the first published study to use artificial neural networks to classify the echolocation calls of bats to species level. Our findings are discussed in terms of recent advances in recording and analysis technologies, and are related to factors causing convergence and divergence of echolocation call design in bats.

Correcting flaws in Mitchell’s analysis of EPBC

Efficient error-Propagating Block Chaining (EPBC) is a block cipher mode intended to simultaneously provide both confidentiality and integrity protection for messages. Mitchell’s analysis pointed out a weakness in the EPBC integrity mechanism that can be used in a forgery attack. This paper identifies and corrects a flaw in Mitchell’s analysis of EPBC, and presents other attacks on the EPBC integrity mechanism.