Chlamydial infection of immune cells : altered function and implications for disease

Chlamydia trachomatis is an obligate intracellular bacterial pathogen that infects the genital and ocular mucosa of humans, causing infections that can lead to pelvic inflammatory disease, infertility, and blinding trachoma. C. pneumoniae is a respiratory pathogen that is the cause of 12–15% of community-acquired pneumonia. Both chlamydial species were believed to be restricted to the epithelia of the genital, ocular, and respiratory mucosa; however, increasing evidence suggests that both these pathogens can be isolated from peripheral blood of both healthy individuals and patients with inflammatory conditions such as coronary artery disease and asthma. Chlamydia can also be isolated from brain tissues of patients with degenerative neurological disorders such as Alzheimer’s disease and multiple sclerosis, and also from certain lymphomas. An increasing number of in vitro studies suggest that some chlamydial species can infect immune cells, at least at low levels. These infections may alter immune cell function in a way that promotes chlamydial persistence in the host and contributes to the progression of several chronic inflammatory diseases. In this paper, we review the evidence for the growth of Chlamydia in immune cells, particularly monocytes/macrophages and dendritic cells, and describe how infection may affect the function of these cells.

Multiple human single-stranded DNA binding proteins function in genome maintenance : structural, biochemical and functional analysis

DNA exists predominantly in a duplex form that is preserved via specific base pairing. This base pairing affords a considerable degree of protection against chemical or physical damage and preserves coding potential. However, there are many situations, e.g. during DNA damage and programmed cellular processes such as DNA replication and transcription, in which the DNA duplex is separated into two singlestranded DNA (ssDNA) strands. This ssDNA is vulnerable to attack by nucleases, binding by inappropriate proteins and chemical attack. It is very important to control the generation of ssDNA and protect it when it forms, and for this reason all cellular organisms and many viruses encode a ssDNA binding protein (SSB). All known SSBs use an oligosaccharide/oligonucleotide binding (OB)-fold domain for DNA binding. SSBs have multiple roles in binding and sequestering ssDNA, detecting DNA damage, stimulating strand-exchange proteins and helicases, and mediation of protein–protein interactions. Recently two additional human SSBs have been identified that are more closely related to bacterial and archaeal SSBs. Prior to this it was believed that replication protein A, RPA, was the only human equivalent of bacterial SSB. RPA is thought to be required for most aspects of DNA metabolism including DNA replication, recombination and repair. This review will discuss in further detail the biological pathways in which human SSBs function.

Noise robust voice activity detection using features extracted from the time-domain autocorrelation function

This paper presents a method of voice activity detection (VAD) for high noise scenarios, using a noise robust voiced speech detection feature. The developed method is based on the fusion of two systems. The first system utilises the maximum peak of the normalised time-domain autocorrelation function (MaxPeak). The second zone system uses a novel combination of cross-correlation and zero-crossing rate of the normalised autocorrelation to approximate a measure of signal pitch and periodicity (CrossCorr) that is hypothesised to be noise robust. The score outputs by the two systems are then merged using weighted sum fusion to create the proposed autocorrelation zero-crossing rate (AZR) VAD. Accuracy of AZR was compared to state of the art and standardised VAD methods and was shown to outperform the best performing system with an average relative improvement of 24.8% in half-total error rate (HTER) on the QUT-NOISE-TIMIT database created using real recordings from high-noise environments.

Development of the response coefficient-root function method for the transient vibration serviceability design of flat concrete floors

The vibration serviceability limit state is an important design consideration for two-way, suspended concrete floors that is not always well understood by many practicing structural engineers. Although the field of floor vibration has been extensively developed, at present there are no convenient design tools that deal with this problem. Results from this research have enabled the development of a much-needed, new method for assessing the vibration serviceability of flat, suspended concrete floors in buildings. This new method has been named, the Response Coefficient-Root Function (RCRF) method. Full-scale, laboratory tests have been conducted on a post-tensioned floor specimen at Queensland University of Technology’s structural laboratory. Special support brackets were fabricated to perform as frictionless, pinned connections at the corners of the specimen. A series of static and dynamic tests were performed in the laboratory to obtain basic material and dynamic properties of the specimen. Finite-element-models have been calibrated against data collected from laboratory experiments. Computational finite-element-analysis has been extended to investigate a variety of floor configurations. Field measurements of floors in existing buildings are in good agreement with computational studies. Results from this parametric investigation have led to the development of new approach for predicting the design frequencies and accelerations of flat, concrete floor structures. The RCRF method is convenient tool to assist structural engineers in the design for the vibration serviceability limit-state of in-situ concrete floor systems.

Review of the under the limit drink driving rehabilitation program

The combination of alcohol and driving is a major health and economic burden to most communities in industrialised countries. The total cost of crashes for Australia in 1996 was estimated at approximately 15 billion dollars and the costs for fatal crashes were about 3 billion dollars (BTE, 2000). According to the Bureau of Infrastructure, Transport and Regional Development and Local Government (2009; BITRDLG) the overall cost of road fatality crashes for 2006 $3.87 billion, with a single fatal crash costing an estimated $2.67 million. A major contributing factor to crashes involving serious injury is alcohol intoxication while driving. It is a well documented fact that consumption of liquor impairs judgment of speed, distance and increases involvement in higher risk behaviours (Waller, Hansen, Stutts, & Popkin, 1986a; Waller et al., 1986b). Waller et al. (1986a; b) asserts that liquor impairs psychomotor function and therefore renders the driver impaired in a crisis situation. This impairment includes; vision (degraded), information processing (slowed), steering, and performing two tasks at once in congested traffic (Moskowitz & Burns, 1990). As BAC levels increase the risk of crashing and fatality increase exponentially (Department of Transport and Main Roads, 2009; DTMR). According to Compton et al. (2002) as cited in the Department of Transport and Main Roads (2009), crash risk based on probability, is five times higher when the BAC is 0.10 compared to a BAC of 0.00. The type of injury patterns sustained also tends to be more severe when liquor is involved, especially with injuries to the brain (Waller et al., 1986b). Single and Rohl (1997) reported that 30% of all fatal crashes in Australia where alcohol involvement was known were associated with Breadth Analysis Content (BAC) above the legal limit of 0.05gms/100ml. Alcohol related crashes therefore contributes to a third of the total cost of fatal crashes (i.e. $1 billion annually) and crashes where alcohol is involved are more likely to result in death or serious injury (ARRB Transport Research, 1999). It is a major concern that a drug capable of impairment such as is the most available and popular drug in Australia (Australian Institute of Health and Welfare, 2007; AIHW). According to the AIHW (2007) 89.9% of the approximately 25,000 Australians over the age of 14 surveyed had consumed at some point in time, and 82.9% had consumed liquor in the previous year. This study found that 12.1% of individuals admitted to driving a motor vehicle whilst intoxicated. In general males consumed more liquor in all age groups. In Queensland there were 21503 road crashes in 2001, involving 324 fatalities and the largest contributing factor was alcohol and or drugs (Road Traffic Report, 2001). 23438 road crashes in 2004, involving 289 fatalities and the largest contributing factor was alcohol and or drugs (DTMR, 2009). Although a number of measures such as random breath testing have been effective in reducing the road toll (Watson, Fraine & Mitchell, 1995) the recidivist drink driver remains a serious problem. These findings were later supported with research by Leal, King, and Lewis (2006). This Queensland study found that of the 24661 drink drivers intercepted in 2004, 3679 (14.9%) were recidivists with multiple drink driving convictions in the previous three years covered (Leal et al., 2006). The legal definition of the term “recidivist” is consistent with the Transport Operations (Road Use Management) Act (1995) and is assigned to individuals who have been charged with multiple drink driving offences in the previous five years. In Australia relatively little attention has been given to prevention programs that target high-risk repeat drink drivers. However, over the last ten years a rehabilitation program specifically designed to reduce recidivism among repeat drink drivers has been operating in Queensland. The program, formally known as the “Under the Limit” drink driving rehabilitation program (UTL) was designed and implemented by the research team at the Centre for Accident Research and Road Safety in Queensland with funding from the Federal Office of Road Safety and the Institute of Criminology (see Sheehan, Schonfeld & Davey, 1995). By 2009 over 8500 drink-drivering offenders had been referred to the program (Australian Institute of Crime, 2009).

Correlations between designability and various structural characteristics of protein lattice models

Using six kinds of lattice types (4×4 ,5×5 , and6×6 square lattices;3×3×3 cubic lattice; and2+3+4+3+2 and4+5+6+5+4 triangular lattices), three different size alphabets (HP ,HNUP , and 20 letters), and two energy functions, the designability of proteinstructures is calculated based on random samplings of structures and common biased sampling (CBS) of proteinsequence space. Then three quantities stability (average energy gap),foldability, and partnum of the structure, which are defined to elucidate the designability, are calculated. The authors find that whatever the type of lattice, alphabet size, and energy function used, there will be an emergence of highly designable (preferred) structure. For all cases considered, the local interactions reduce degeneracy and make the designability higher. The designability is sensitive to the lattice type, alphabet size, energy function, and sampling method of the sequence space. Compared with the random sampling method, both the CBS and the Metropolis Monte Carlo sampling methods make the designability higher. The correlation coefficients between the designability, stability, and foldability are mostly larger than 0.5, which demonstrate that they have strong correlation relationship. But the correlation relationship between the designability and the partnum is not so strong because the partnum is independent of the energy. The results are useful in practical use of the designability principle, such as to predict the proteintertiary structure.

Infinite-horizon policy-gradient estimation

Gradient-based approaches to direct policy search in reinforcement learning have received much recent attention as a means to solve problems of partial observability and to avoid some of the problems associated with policy degradation in value-function methods. In this paper we introduce GPOMDP, a simulation-based algorithm for generating a biased estimate of the gradient of the average reward in Partially Observable Markov Decision Processes (POMDPs) controlled by parameterized stochastic policies. A similar algorithm was proposed by Kimura, Yamamura, and Kobayashi (1995). The algorithm's chief advantages are that it requires storage of only twice the number of policy parameters, uses one free parameter β ∈ [0,1) (which has a natural interpretation in terms of bias-variance trade-off), and requires no knowledge of the underlying state. We prove convergence of GPOMDP, and show how the correct choice of the parameter β is related to the mixing time of the controlled POMDP. We briefly describe extensions of GPOMDP to controlled Markov chains, continuous state, observation and control spaces, multiple-agents, higher-order derivatives, and a version for training stochastic policies with internal states. In a companion paper (Baxter, Bartlett, & Weaver, 2001) we show how the gradient estimates generated by GPOMDP can be used in both a traditional stochastic gradient algorithm and a conjugate-gradient procedure to find local optima of the average reward. ©2001 AI Access Foundation and Morgan Kaufmann Publishers. All rights reserved.