Identification of eusynstyelamide B as a potent cell cycle inhibitor following the generation and screening of an ascidian-derived extract library using a real time cell analyzer

Ascidians are marine invertebrates that have been a source of numerous cytotoxic compounds. Of the first six marine-derived drugs that made anticancer clinical trials, three originated from ascidian specimens. In order to identify new anti-neoplastic compounds, an ascidian extract library (143 samples) was generated and screened in MDA-MB-231 breast cancer cells using a real-time cell analyzer (RTCA). This resulted in 143 time-dependent cell response profiles (TCRP), which are read-outs of changes to the growth rate, morphology, and adhesive characteristics of the cell culture. Twenty-one extracts affected the TCRP of MDA-MB-231 cells and were further investigated regarding toxicity and specificity, as well as their effects on cell morphology and cell cycle. The results of these studies were used to prioritize extracts for bioassay-guided fractionation, which led to the isolation of the previously identified marine natural product, eusynstyelamide B (1). This bis-indole alkaloid was shown to display an IC50 of 5 μM in MDA-MB-231 cells. Moreover, 1 caused a strong cell cycle arrest in G2/M and induced apoptosis after 72 h treatment, making this molecule an attractive candidate for further mechanism of action studies.

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.

Simulation-based density estimation for time series using covariate data

This paper proposes a simulation-based density estimation technique for time series that exploits information found in covariate data. The method can be paired with a large range of parametric models used in time series estimation. We derive asymptotic properties of the estimator and illustrate attractive finite sample properties for a range of well-known econometric and financial applications.

Obesity and hypertension have differing oxidant handling molecular pathways in age-related chronic kidney disease

Chronic kidney disease (CKD) in ageing is a burden on health systems worldwide. Rat models of age-related CKD linked with obesity and hypertension were used to investigate alterations in oxidant handling and energy metabolism to identify gene targets or markers for age-related CKD. Young adult (3 months) and old (21–24 months) spontaneously-hypertensive (SHR), normotensive Wistar-Kyoto (WKY) and Wistar rats (normotensive, obese in ageing) were compared for renal functional and physiological parameters, renal fibrosis and inflammation, oxidative stress (hemeoxygenase-1/HO-1), apoptosis and cell injury (including Bax:Bcl-2), phosphorylated and non-phosphorylated forms of oxidant and energy sensing proteins (p66Shc, AMPK), signal transduction proteins (ERK1/2, PKB), and transcription factors (NF-κB, FoxO1). All old rats were normoglycemic. Renal fibrosis, tubular epithelial apoptosis, interstitial macrophages and myofibroblasts (all p < 0.05), p66Shc/phospho-p66 (p < 0.05), Bax/Bcl-2 ratio (p < 0.05) and NF-κB expression (p < 0.01) were highest in old obese Wistars. Expression of phospho-FoxO/FoxO was elevated in old Wistars (p < 0.001) and WKYs (p < 0.01). SHRs had high levels in young and old rats. Expression of PKB, phospho-PKB, ERK1/2 and phospho-ERK1/2 were significantly elevated in all aged animals. These results suggest that obesity and hypertension have differing oxidant handling and signalling pathways that act in the pathogenesis of age-related CKD

“Conversations Before the End of Time” : Refuturing Applications of a New Media Praxis

This chapter examines how the methods, outcomes and transformative potentials of my new media arts praxis have been understood by a range of critical commentators from disciplinary perspectives outside of my own ‘home territory’ of media arts. By drawing upon perspectives from Human Computer Interface Design, Engineering, Sustainability Design, Tertiary Education, Communication Design and Public Librarianship I demonstrate how ideas from my arts disciplines have had tangible ‘external’ significance and application.

Thrust allocation with linear constrained quadratic cost function

In this paper, a method of thrust allocation based on a linearly constrained quadratic cost function capable of handling rotating azimuths is presented. The problem formulation accounts for magnitude and rate constraints on both thruster forces and azimuth angles. The advantage of this formulation is that the solution can be found with a finite number of iterations for each time step. Experiments with a model ship are used to validate the thrust allocation system.

Healthcare-associated infections in Australia : time for national surveillance

Abstract Objective. Healthcare-associated infection (HAI) surveillance programs are critical for infection prevention. Australia does not have a comprehensive national HAI surveillance program. The purpose of this paper is to provide an overview of established international and Australian statewide HAI surveillance programs and recommend a pathway for the development of a national HAI surveillance program in Australia. Methods. This study examined existing HAI surveillance programs through a literature review, a review of HAI surveillance program documentation, such as websites, surveillance manuals and data reports and direct contact with program representatives. Results. Evidence from international programs demonstrates national HAI surveillance reduces the incidence of HAIs. However, the current status of HAI surveillance activity in Australian states is disparate, variation between programs is not well understood, and the quality of data currently used to compose national HAI rates is uncertain. Conclusions. There is a need to develop a well-structured, evidence-based national HAI program in Australia to meet the increasing demand for validated reliable national HAI data. Such a program could be leveraged off the work of existing Australian and international programs.

A Memetic Algorithm for the location-based continuously operating reference stations placement problem in Network Real-Time Kinematic

Network Real-Time Kinematic (NRTK) is a technology that can provide centimeter-level accuracy positioning services in real time, and it is enabled by a network of Continuously Operating Reference Stations (CORS). The location-oriented CORS placement problem is an important problem in the design of a NRTK as it will directly affect not only the installation and operational cost of the NRTK, but also the quality of positioning services provided by the NRTK. This paper presents a Memetic Algorithm (MA) for the location-oriented CORS placement problem, which hybridizes the powerful explorative search capacity of a genetic algorithm and the efficient and effective exploitative search capacity of a local optimization. Experimental results have shown that the MA has better performance than existing approaches. In this paper we also conduct an empirical study about the scalability of the MA, effectiveness of the hybridization technique and selection of crossover operator in the MA.

Real-time price based home energy management scheduler

With the recent development of advanced metering infrastructure, real-time pricing (RTP) scheme is anticipated to be introduced in future retail electricity market. This paper proposes an algorithm for a home energy management scheduler (HEMS) to reduce the cost of energy consumption using RTP. The proposed algorithm works in three subsequent phases namely real-time monitoring (RTM), stochastic scheduling (STS) and real-time control (RTC). In RTM phase, characteristics of available controllable appliances are monitored in real-time and stored in HEMS. In STS phase, HEMS computes an optimal policy using stochastic dynamic programming (SDP) to select a set of appliances to be controlled with an objective of the total cost of energy consumption in a house. Finally, in RTC phase, HEMS initiates the control of the selected appliances. The proposed HEMS is unique as it intrinsically considers uncertainties in RTP and power consumption pattern of various appliances. In RTM phase, appliances are categorized according to their characteristics to ease the control process, thereby minimizing the number of control commands issued by HEMS. Simulation results validate the proposed method for HEMS.

A review of preschool children's physical activity and sedentary time using objective measures

CONTEXT: Identifying current physical activity levels and sedentary time of preschool children is important for informing government policy and community initiatives. This paper reviewed studies reporting on physical activity and time spent sedentary among preschool-aged children (2-5 years) using objective measures. EVIDENCE ACQUISITION: Databases were searched for studies published up to and including April 2013 that reported on, or enabled the calculation of, the proportion of time preschool children spent sedentary and in light- and moderate to vigorous-intensity physical activity. A total of 40 publications met the inclusion criteria for physical activity and 31 met the inclusion criteria for sedentary time. Objective measures included ActiGraph, Actiwatch, Actical, Actiheart, and RT3 accelerometers, direct observation, and Quantum XL telemetry heart rate monitoring. Data were analyzed in May 2013. EVIDENCE SYNTHESIS: Considerable variation in prevalence estimates existed. The proportion of time children spent sedentary ranged from 34% to 94%. The time spent in light-intensity physical activity and moderate to vigorous-intensity physical activity ranged from 4% to 33% and 2% to 41%, respectively. CONCLUSIONS: The considerable variation of prevalence estimates makes it difficult to determine the "true" prevalence of physical activity and sedentary time in preschool children. Future research should aim to reduce inconsistencies in the employed methodologies to better understand preschoolers' physical activity levels and sedentary behavior.

Development of realistic design fire time-temperature curves for the testing of cold-formed steel wall system

Fire resistance rating of light gauge steel frame (LSF) wall systems is obtained from fire tests based on the standard fire time-temperature curve. However, fire severity has increased in modern buildings due to higher fuel loads as a result of modern furniture and light weight constructions that make use of thermoplastics materials, synthetic foams and fabrics. Some of these materials are high in calorific values and increase both the spread of fire growth and heat release rate, thus increasing the fire severity beyond that of the standard fire curve. Further, the standard fire curve does not include a decay phase that is present in natural fires. Despite the increasing usage of LSF walls, their behaviour in real building fires is not fully understood. This paper presents the details of a research study aimed at developing realistic design fire curves for use in the fire tests of LSF walls. It includes a review of the characteristics of building fires, previously developed fire time-temperature curves, computer models and available parametric equations. The paper highlights that real building fire time-temperature curves depend on the fuel load representing the combustible building contents, ventilation openings and thermal properties of wall lining materials, and provides suitable values of many required parameters including fuel loads in residential buildings. Finally, realistic design fire time-temperature curves simulating the fire conditions in modern residential buildings are proposed for the testing of LSF walls.

Configuring retroreflective markings to enhance the night-time conspicuity of road workers

This study investigated whether the night-time conspicuity of road workers can be enhanced by positioning retroreflective strips on the moveable joints in patterns that convey varying degrees of biological motion. Participants were 24 visually normal adults (12 young M = 26.8 years; 12 older M = 72.9 years). Visual acuity, contrast sensitivity and glare sensitivity were recorded for each participant. Experimenters acting as road workers walked in place on a closed road circuit within simulated road work sites, facing either the oncoming driver or the roadway (presenting sideways to the driver) and wearing one of four clothing conditions: (i) standard road worker vest; (ii) standard vest plus thigh-mounted retroreflective strips; (iii) standard vest plus retroreflective strips on ankles and knees; (iv) standard vest plus retroreflective strips positioned on the extremities in a configuration that conveyed biological motion (“biomotion”). As they drove along the closed road participants were instructed to press a button to indicate when they first recognized that a road worker was present. The results demonstrated that regardless of the direction of walking, road workers wearing biomotion clothing were recognized at significantly (p < 0.05) longer distances (3×), relative to the standard vest alone. Response distances were significantly shorter for the older drivers. Contrast sensitivity was a better predictor of the ability to recognize road workers than was visual acuity or glare sensitivity. We conclude that adding retroreflective strips in the biomotion configuration can significantly improve road worker conspicuity regardless of the road worker's orientation and the age of the driver.

Differential effects of refractive blur on day and night-time driving performance

Purpose To investigate the effect of different levels of refractive blur on real-world driving performance measured under day and nighttime conditions. Methods Participants included 12 visually normal, young adults (mean age = 25.8 ± 5.2 years) who drove an instrumented research vehicle around a 4 km closed road circuit with three different levels of binocular spherical refractive blur (+0.50 diopter sphere [DS], +1.00 DS, +2.00 DS) compared with a baseline condition. The subjects wore optimal spherocylinder correction and the additional blur lenses were mounted in modified full-field goggles; the order of testing of the blur conditions was randomized. Driving performance was assessed in two different sessions under day and nighttime conditions and included measures of road signs recognized, hazard detection and avoidance, gap detection, lane-keeping, sign recognition distance, speed, and time to complete the course. Results Refractive blur and time of day had significant effects on driving performance (P < 0.05), where increasing blur and nighttime driving reduced performance on all driving tasks except gap judgment and lane keeping. There was also a significant interaction between blur and time of day (P < 0.05), such that the effects of blur were exacerbated under nighttime driving conditions; performance differences were evident even for +0.50 DS blur relative to baseline for some measures. Conclusions The effects of blur were greatest under nighttime conditions, even for levels of binocular refractive blur as low as +0.50 DS. These results emphasize the importance of accurate and up-to-date refractive correction of even low levels of refractive error when driving at night.

A time for everything : reviewing an institution’s virtual learning environment

This paper outlines a review carried out at Queensland University of Technology (QUT) in 2013 to identify the extent to which the centrally supported virtual learning environment met current and future learning and teaching needs. A range of consultation and investigation activities occurred from May to November to encourage open stakeholder feedback as well as to allow for reflection on alternative digital technologies, systems and strategies. This resulted in the development of nine recommendations, which, following a planning phase, will commence being implemented from mid-2014.