The active site residue V266 of Chlamydial HtrA is critical for substrate binding during both in vitro and in vivo conditions

HtrA is a complex, multimeric chaperone and serine protease important for the virulence and survival of many bacteria. Chlamydia trachomatis is an obligate, intracellular bacterial pathogen that is responsible for severe disease pathology. C. trachomatis HtrA (CtHtrA) has been shown to be highly expressed in laboratory models of disease. In this study, molecular modelling of CtHtrA protein active site structure identified putative S1-S3 subsite residues I242, I265, and V266. These residues were altered by site-directed mutagenesis, and these changes were shown to considerably reduce protease activity on known substrates and resulted in a narrower and distinct range of substrates compared to wild type. Bacterial two-hybrid analysis revealed that CtHtrA is able to interact in vivo with a broad range of protein sequences with high affinity. Notably, however, the interaction was significantly altered in 35 out of 69 clones when residue V266 was mutated, indicating that this residue has an important function during substrate binding.

Solving tri-diagonal linear systems using field programmable gate arrays

In this paper, we present the outcomes of a project on the exploration of the use of Field Programmable Gate Arrays(FPGAs) as co-processors for scientific computation. We designed a custom circuit for the pipelined solving of multiple tri-diagonal linear systems. The design is well suited for applications that require many independent tri diagonal system solves, such as finite difference methods for solving PDEs or applications utilising cubic spline interpolation. The selected solver algorithm was the Tri Diagonal Matrix Algorithm (TDMA or Thomas Algorithm). Our solver supports user specified precision thought the use of a custom floating point VHDL library supporting addition, subtraction, multiplication and division. The variable precision TDMA solver was tested for correctness in simulation mode. The TDMA pipeline was tested successfully in hardware using a simplified solver model. The details of implementation, the limitations, and future work are also discussed.

Human papillomavirus prevalence, viral load and pre-cancerous lesions of the cervix in women initiating highly active antiretroviral therapy in South Africa : a cross-sectional study

Background Cervical cancer and infection with human immunodeficiency virus (HIV) are both important public health problems in South Africa (SA). The aim of this study was to determine the prevalence of cervical squamous intraepithelial lesions (SILs), high-risk human papillomavirus (HR-HPV), HPV viral load and HPV genotypes in HIV positive women initiating anti-retroviral (ARV) therapy. Methods A cross-sectional survey was conducted at an anti-retroviral (ARV) treatment clinic in Cape Town, SA in 2007. Cervical specimens were taken for cytological analysis and HPV testing. The Digene Hybrid Capture 2 (HC2) test was used to detect HR-HPV. Relative light units (RLU) were used as a measure of HPV viral load. HPV types were determined using the Roche Linear Array HPV Genotyping test. Crude associations with abnormal cytology were tested and multiple logistic regression was used to determine independent risk factors for abnormal cytology. Results The median age of the 109 participants was 31 years, the median CD4 count was 125/mm3, 66.3% had an abnormal Pap smear, the HR-HPV prevalence was 78.9% (Digene), the median HPV viral load was 181.1 RLU (HC2 positive samples only) and 78.4% had multiple genotypes. Among women with abnormal smears the most prevalent HR-HPV types were HPV types 16, 58 and 51, all with a prevalence of 28.5%. On univariate analysis HR-HPV, multiple HPV types and HPV viral load were significantly associated with the presence of low and high-grade SILs (LSIL/HSIL). The multivariate logistic regression showed that HPV viral load was associated with an increased odds of LSIL/HSIL, odds ratio of 10.7 (95% CI 2.0 – 57.7) for those that were HC2 positive and had a viral load of ≤ 181.1 RLU (the median HPV viral load), and 33.8 (95% CI 6.4 – 178.9) for those that were HC2 positive with a HPV viral load > 181.1 RLU. Conclusion Women initiating ARVs have a high prevalence of abnormal Pap smears and HR-HPV. Our results underscore the need for locally relevant, rigorous screening protocols for the increasing numbers of women accessing ARV therapy so that the benefits of ARVs are not partially offset by an excess risk in cervical cancer.

Effect of Australia's walk to work day campaign on adults' active commuting and physical activity behavior

Purpose. To determine whether Australia's Walk to Work Day media campaign resulted in behavioural change among targeted groups. Methods. Pre- and postcampaign telephone surveys of a cohort of adults aged 18 to 65 years (n = 1100, 55% response rate) were randomly sampled from Australian major melropolitan areas. Tests for dependent samples were applied (McNemax chi(2) or paired t-test). Results. Among participants who did not usually actively commute to work was a significant decrease in car only use an increase in walking combined with public transport. Among those who were employed was a significant increase in total time walking (+16 min/wk; t [780] = 2.04, p < .05) and in other moderate physical activity (+120 min/wk; t [1087] = 4.76, p < .005), resulting in a significant decrease in the proportion who were inactive (chi(2) (1) = 6.1, p < .05). Conclusion. Although nonexperimental, the Walk to Work Day initiative elicited short-term changes in targeted behaviors among target groups. Reinforcement by integrating worksite health promotion strategies may be required for sustained effects.

Solving tri-diagonal linear systems using field programmable gate arrays

In this paper, we present the outcomes of a project on the exploration of the use of Field Programmable Gate Arrays (FPGAs) as co-processors for scientific computation. We designed a custom circuit for the pipelined solving of multiple tri-diagonal linear systems. The design is well suited for applications that require many independent tri-diagonal system solves, such as finite difference methods for solving PDEs or applications utilising cubic spline interpolation. The selected solver algorithm was the Tri-Diagonal Matrix Algorithm (TDMA or Thomas Algorithm). Our solver supports user specified precision thought the use of a custom floating point VHDL library supporting addition, subtraction, multiplication and division. The variable precision TDMA solver was tested for correctness in simulation mode. The TDMA pipeline was tested successfully in hardware using a simplified solver model. The details of implementation, the limitations, and future work are also discussed.

Mobility and active ageing in suburban environments : findings from in-depth interviews and person-based GPS tracking

Background. Governments face a significant challenge to ensure that community environments meet the mobility needs of an ageing population. Therefore, it is critical to investigate the effect of suburban environments on the choice of transportation and its relation to participation and active ageing. Objective. This research explores if and how suburban environments impact older people’s mobility and their use of different modes of transport. Methods. Data derived from GPS tracking, travel diaries, brief questionnaires, and semistructured interviews were gathered from thirteen people aged from 56 to 87 years, living in low-density suburban environments in Brisbane, Australia. Results. The suburban environment influenced the choice of transportation and out-of-home mobility. Both walkability and public transportation (access and usability) impact older people’s transportation choices. Impracticality of active and public transportation within suburban environments creates car dependency in older age. Conclusion. Suburban environments often create barriers to mobility, which impedes older people’s engagement in their wider community and ability to actively age in place. Further research is needed to develop approaches towards age-friendly suburban environments which will encourage older people to remain active and engaged in older age.

How do older adults respond to Active Australia physical activity questions? Lessons from cognitive interviews

The aim of this study was to examine older adults’ understanding and interpretation of a validated questionnaire for physical activity surveillance, the Active Australia Survey (AAS). To address this aim, cognitive interviewing techniques were used during face-to-face semi-structured interviews with 44 adults aged 65-89 years. Qualitative data analysis revealed that participants were confused with questionnaire phrasing, misunderstood the scope of activities to include in answers, and misunderstood the time frame of activities to report. They also struggled to accurately estimate the frequency and duration of their activities. Our findings suggest that AAS questions may be interpreted differently by older adults than intended by survey developers. Findings also suggest that older adults use a range of methods for calculating PA frequency and duration. The issues revealed in this study may be useful for adapting AAS for use in older community-dwelling adults.

Active versus passive screen time for young children

In this paper, we report some initial findings from our investigations into the Australian Government’s Longitudinal Study of Australian Children dataset. It is revealed that the majority of Australian children are exceeding the government’s Screen Time recommendations and that most of their screen time is spent as TV viewing, as opposed to video game play or computer use. In light of this finding,we review the body of research surrounding children’s engagement in Screen Time activities and the associated positive and negative effects. Based on existing evidence,we define two categories of Screen Time—Active Screen Time and Passive Screen Time. It is proposed that this distinction provides a more accurate classification of Screen Time and a more informative lens through which to consider the associated benefits and detrimental effects for young children.

Assessment bias : physical activity questionnaire assessment inadvertently influences patients’ desire to be ‘more physically active’

Evaluating physical activity is important for public health population research and evaluating lifestyle interventions among targeted groups. Self-reported questionnaires are frequently used to evaluate physical activity in a variety of contexts where resource or pragmatic limitations prohibit the use of more sophisticated approaches. However, prior research in the use of other patient reported outcomes in healthcare settings has highlighted that simply completing a questionnaire may change a patients’ behaviour or responses to subsequent questions. This methodology study aimed to examine whether completing a standard physical activity questionnaire altered patients responses to two related questions a) whether they are ‘sufficiently physically active’ and b) whether they desire ‘to be more physically active.’

Signaling of receptor tyrosine kinases in the nucleus

Since the discovery of the first receptor tyrosine kinase (RTK) proteins in the late 1970s and early 1980s, many scientists have explored the functions of these important cell signaling molecules. The finding that these proteins are often deregulated or mutated in diseases such as cancers and diabetes, together with their potential as clinical therapeutic targets, has further highlighted the necessity for understanding the signaling functions of these important proteins. The mechanisms of RTK regulation and function have been recently reviewed by Lemmon & Schlessinger (2010) but in this review we instead focus on the results of several recent studies that show receptor tyrosine kinases can function from subcellular localisations, including in particular the nucleus, in addition to their classical plasma membrane location. Nuclear localisation of receptor tyrosine kinases has been demonstrated to be important for normal cell function but is also believed to contribute to the pathogenesis of several human diseases.

Exo1 plays a major role in DNA end resection in humans and influences double-strand break repair and damage signaling decisions

The resection of DNA double-strand breaks (DSBs) to generate ssDNA tails is a pivotal event in the cellular response to these breaks. In the two-step model of resection, primarily elucidated in yeast, initial resection by Mre11-CtIP is followed by extensive resection by two distinct pathways involving Exo1 or BLM/WRN-Dna2. However, resection pathways and their exact contributions in humans in vivo are not as clearly worked out as in yeast. Here, we examined the contribution of Exo1 to DNA end resection in humans in vivo in response to ionizing radiation (IR) and its relationship with other resection pathways (Mre11-CtIP or BLM/WRN). We find that Exo1 plays a predominant role in resection in human cells along with an alternate pathway dependent on WRN. While Mre11 and CtIP stimulate resection in human cells, they are not absolutely required for this process and Exo1 can function in resection even in the absence of Mre11-CtIP. Interestingly, the recruitment of Exo1 to DNA breaks appears to be inhibited by the NHEJ protein Ku80, and the higher level of resection that occurs upon siRNA-mediated depletion of Ku80 is dependent on Exo1. In addition, Exo1 may be regulated by 53BP1 and Brca1, and the restoration of resection in BRCA1-deficient cells upon depletion of 53BP1 is dependent on Exo1. Finally, we find that Exo1-mediated resection facilitates a transition from ATM- to ATR-mediated cell cycle checkpoint signaling. Our results identify Exo1 as a key mediator of DNA end resection and DSB repair and damage signaling decisions in human cells.

The predictors of active ageing of older Australians : the triple a study

The concept of older adults contributing to society in a meaningful way has been termed ‘active ageing’. Active ageing reflects changes in prevailing theories of social and psychological aspects of ageing, with a focus on individuals' strengths as opposed to their deficits or pathology. In order to explore predictors of active ageing, the Australian Active Ageing (Triple A) project group undertook a national postal survey of participants over the age of 50 years recruited randomly through their 2004 membership of a large Australia-wide senior's organisation. The survey comprised 178 items covering paid and voluntary work, learning, social, spiritual, emotional, health and home, life events and demographic items. A 45% response rate (2655 returned surveys) reflected an expected balance of gender, age and geographic representation of participants. The data were analysed using data mining techniques to represent generalizations on individual situations. Data mining identifies the valid, novel, potentially useful and understandable patterns and trends in data. The results based on the clustering mining technique indicate that physical and emotional health combined with the desire to learn were the most significant factors when considering active ageing. The findings suggest that remaining active in later life is not only directly related to the maintenance of emotional and physical health, but may be significantly intertwined with the opportunity to engage in on-going learning activities that are relevant to the individual. The findings of this study suggest that practitioners and policy makers need to incorporate older peoples' learning needs within service and policy framework developments.

Active text perception for mobile robots

Our everyday environment is full of text but this rich source of information remains largely inaccessible to mobile robots. In this paper we describe an active text spotting system that uses a small number of wide angle views to locate putative text in the environment and then foveates and zooms onto that text in order to improve the reliability of text recognition. We present extensive experimental results obtained with a pan/tilt/zoom camera and a ROS-based mobile robot operating in an indoor environment.