Clusterin facilitates COMMD1 and I-kB degradation to enhance NF-kB activity in prostate cancer cells

Secretory clusterin (sCLU) is a stress-activated, cytoprotective chaperone that confers broad-spectrum cancer treatment resistance, and its targeted inhibitor (OGX-011) is currently in phase II trials for prostate, lung, and breast cancer. However, the molecular mechanisms by which sCLU inhibits treatment-induced apoptosis in prostate cancer remain incompletely defined. We report that sCLU increases NF-κB nuclear translocation and transcriptional activity by serving as a ubiquitin-binding protein that enhances COMMD1 and I-κB proteasomal degradation by interacting with members of the SCF-βTrCP E3 ligase family. Knockdown of sCLU in prostate cancer cells stabilizes COMMD1 and I-κB, thereby sequestrating NF-κB in the cytoplasm and decreasing NF-κB transcriptional activity. Comparative microarray profiling of sCLU-overexpressing and sCLU-knockdown prostate cancer cells confirmed that the expression of many NF-κB–regulated genes positively correlates with sCLU levels. We propose that elevated levels of sCLU promote prostate cancer cell survival by facilitating degradation of COMMD1 and I-κB, thereby activating the canonical NF-κB pathway.

A rebirth of physical activity in parents : applying a theory-based approach

Physical inactivity is a serious concern both nationally and internationally. Despite the numerous benefits of performing regular physical activity, many individuals lead sedentary lifestyles. Of concern, though, is research showing that some population sub-groups are less likely to be active, such as parents of young children. Although there is a vast amount of research dedicated to understanding people.s physical activity-related behaviours, there is a paucity of research examining those factors that influence parental physical activity. More importantly, research applying theoretical models to understand physical activity decision-making among this at-risk population is limited. Given the current obesity epidemic, the decline in physical activity with parenthood, and the many social and health benefits associated with regular physical activity, it is important that adults with young children are sufficiently active. In light of the dearth of research examining parental physical activity and the scant research applying a theory-based approach to gain this understanding, the overarching aim of the current program of research was to adopt a mixed methods approach as well as use sound theoretical frameworks to understand the regular physical activity behaviour of mothers and fathers with young children. This program of research comprised of three distinct stages: a qualitative stage exploring individual, social, and psychological factors that influence parental regular physical activity (Stage 1); a quantitative stage identifying the important predictors of parental regular physical activity intentions and behaviour using sound theoretical frameworks and testing a single-item measure for assessing parental physical activity behaviour (Stage 2); and a qualitative stage exploring strategies for an intervention program aimed at increasing parental regular physical activity (Stage 3). As a thesis by publication, eight papers report the findings of this program of research; these papers are presented according to the distinct stages of investigation that guided this program of research. Stage One of the research program comprised a qualitative investigation using a focus group/interview methodology with parents of children younger than 5 years of age (N = 40; n = 21 mothers, n = 19 fathers) (Papers 1, 2, and 3). Drawing broadly on a social constructionist approach (Paper 1), thematic analytic methods revealed parents. understandings of physical activity (e.g., requires effort), patterns of physical activity-related behaviours (e.g., grab it when you can, declining physical activity habits), and how constructions of social role expectations might influence parents. physical activity decision making (e.g., creating an active family culture, guilt and selfishness). Drawing on the belief-based framework of the TPB (Paper 2), thematic content analytic methods revealed parents. commonly held beliefs about the advantages (e.g., improves parenting practices), disadvantages (e.g., interferes with commitments), barriers (e.g., time), and facilitators (e.g., social support) to performing regular physical activity. Parents. normative beliefs about social approval from important others or groups (e.g., spouse/partner) were also identified. Guided by theories of social support, Paper Three identified parents. perceptions about the specific social support dimensions that influence their physical activity decision making. Thematic content analysis identified instrumental (e.g., providing childcare, taking over chores), emotional (e.g., encouragement, companionship), and informational support (e.g., ideas and advice) as being important to the decision-making of parents in relation to their regular physical activity behaviour. The results revealed also that having support for being active is not straightforward (e.g., guilt-related issues inhibited the facilitative nature of social support for physical activity). Stage Two of the research program comprised a quantitative examination of parents. physical activity intentions and behaviour (Papers 4, 5, 6, and 7). Parents completed an extended TPB questionnaire at Time 1 (N = 580; n = 288 mothers, n = 292 fathers) and self-reported their physical activity at Time 2, 1 week later (N = 458; n = 252 mothers, n = 206 fathers). Paper Four revealed key behavioural (e.g., improving parenting practices), normative (e.g., people I exercise with), and control (e.g., lack of time) beliefs as significant independent predictors of parental physical activity. A test of the TPB augmented to include the constructs of self-determined motivation and planning was assessed in Paper Five. The findings revealed that the effect of self-determined motivation on intention was fully mediated by the TPB variables and the impact of intention on behaviour was partially mediated by the planning variables. Slight differences in the model.s motivational sequence between the sexes were also noted. Paper Six investigated, within a TPB framework, a range of social influences on parents. intentions to be active. For both sexes, attitude, perceived behavioural control, group norms, friend general support, and an active parent identity predicted intentions, with subjective norms and family support further predicting mothers. intentions and descriptive norms further predicting fathers. intentions. Finally, the measurement of parental physical activity was investigated in Paper Seven of Stage Two. The results showed that parents are at risk of low levels of physical activity, with the findings also revealing validation support for a brief single-item physical activity measure. Stage Three of the research program comprised a qualitative examination of parents. (N = 12; n = 6 mothers, n = 6 fathers) ideas for strategies that may be useful for developing and delivering an intervention program aimed at increasing parental physical activity (Paper 8). Parents revealed a range of strategies for what to include in a physical activity intervention designed for parents of young children. For example, parents identified persuasion and information type messages, problem-solving strategies that engage parents in generating a priority list of their lifestyle commitments, and behavioural modification techniques such as goal setting and incentives. Social intervention strategies (e.g., social comparison, counselling) and environmental approaches (e.g., community-based integrative parent/child programs) were also identified as was a skill-based strategy in helping parents generate a flexible life/family plan. Additionally, a range of strategies for how to best deliver a parental physical activity intervention was discussed. Taken as a whole, Paper Eight found that adopting a multifaceted approach in both the design and implementation of a resultant physical activity intervention may be useful in helping to increase parental physical activity. Overall, this program of research found support for parents as a unique group who hold both similar and distinctive perceptions about regular physical activity to the general adult population. Thus, these findings highlight the importance of targeting intervention strategies for parents of young children. Additionally, the findings suggest that it might also be useful to tailor some messages specifically to each sex. Effective promotion of physical activity in parents of young children is essential given the low rate of activity in this population. Results from this program of research highlight parents as an at-risk group for inactivity and provide an important first step in identifying the factors that influence both mothers. and fathers. physical activity decision making. These findings, in turn, provide a foundation on which to build effective intervention programs aimed at increasing parents. regular physical activity which is essential for ensuring the health and well-being of parents with young children.

Designerly analysis of a socio-physical design activity

The Making Design and Analysing Interaction track at the Participatory Innovation Conference calls for submissions from ‘Makers’ who will contribute examples of participatory innovation activities documented in video and ‘Analysts’ who will analyse those examples of participatory innovation activity. The aim of this paper is to open up for a discussion within the format of the track of the roles that designers could play in analysing the participatory innovation activities of others and to provide a starting point for this discussion through a concrete example of such ‘designerly analysis’. Designerly analysis opens new analytic frames for understanding participatory innovation and contributes to our understanding of design activities.

An investigation of commuter exposure to ultrafine particles in Sydney

Commuting in various transport modes represents an activity likely to incur significant exposure to traffic emissions. This study investigated the determinants and characteristics of exposure to ultrafine (< 100 nm) particles (UFPs) in four transport modes in Sydney, with a specific focus on exposure in automobiles, which remain the transport mode of choice for approximately 70% of Sydney commuters. UFP concentrations were measured using a portable condensation particle counter (CPC) inside five automobiles commuting on above ground and tunnel roadways, and in buses, ferries and trains. Determinant factors investigated included wind speed, cabin ventilation (automobiles only) and traffic volume. The results showed that concentrations varied significantly as a consequence of transport mode, vehicle type and ventilation characteristics. The effects of wind speed were minimal relative to those of traffic volume (especially heavy diesel vehicles) and cabin ventilation, with the latter proving to be a strong determinant of UFP ingress into automobiles. The effect of ~70 minutes of commuting on total daily exposure was estimated using a range of UFP concentrations reported for several microenvironments. A hypothetical Sydney resident commuting by automobile and spending 8.5 minutes of their day in the M5 East tunnel could incur anywhere from a lower limit of 3-11% to an upper limit of 37-69% of daily UFP exposure during a return commute, depending on the concentrations they encountered in other microenvironments, the type of vehicle they used and the ventilation setting selected. However, commute-time exposures at either extreme of the values presented are unlikely to occur in practice. The range of exposures estimated for other transport modes were comparable to those of automobiles, and in the case of buses, higher than automobiles.

Field study of air change and flow rate in six automobiles

For many people, a relatively large proportion of daily exposure to a multitude of pollutants may occur inside an automobile. A key determinant of exposure is the amount of outdoor air entering the cabin (i.e. air change or flow rate). We have quantified this parameter in six passenger vehicles ranging in age from 18 years to <1 year, at three vehicle speeds and under four different ventilation settings. Average infiltration into the cabin with all operable air entry pathways closed was between 1 and 33.1 air changes per hour (ACH) at a vehicle speed of 60 km/h, and between 2.6 and 47.3 ACH at 110 km/h, with these results representing the most (2005 Volkswagen Golf) and least air-tight (1989 Mazda 121) vehicles, respectively. Average infiltration into stationary vehicles parked outdoors varied between ~0 and 1.4 ACH and was moderately related to wind speed. Measurements were also performed under an air recirculation setting with low fan speed, while airflow rate measurements were conducted under two non-recirculate ventilation settings with low and high fan speeds. The windows were closed in all cases, and over 200 measurements were performed. The results can be applied to estimate pollutant exposure inside vehicles.

A fragment of the LG3 peptide of endorepellin is present in the urine of physically active mining workers : a potential marker of physical activity

Biomarker analysis has been implemented in sports research in an attempt to monitor the effects of exertion and fatigue in athletes. This study proposed that while such biomarkers may be useful for monitoring injury risk in workers, proteomic approaches might also be utilised to identify novel exertion or injury markers. We found that urinary urea and cortisol levels were significantly elevated in mining workers following a 12 hour overnight shift. These levels failed to return to baseline over 24h in the more active maintenance crew compared to truck drivers (operators) suggesting a lack of recovery between shifts. Use of a SELDI-TOF MS approach to detect novel exertion or injury markers revealed a spectral feature which was associated with workers in both work categories who were engaged in higher levels of physical activity. This feature was identified as the LG3 peptide, a C-terminal fragment of the anti-angiogenic / anti-tumourigenic protein endorepellin. This finding suggests that urinary LG3 peptide may be a biomarker of physical activity. It is also possible that the activity mediated release of LG3 / endorepellin into the circulation may represent a biological mechanism for the known inverse association between physical activity and cancer risk / survival.

The effect of lumbar support on the trunk muscle activity and pelvic tilt in a passenger vehicle car seat

In order to gain a competitive edge in the market, automotive manufacturers and automotive seat suppliers have identified seat ergonomics for further development to improve overall vehicle comfort. Adjustable lumbar support devices have been offered since long as comfort systems in either a 2-way or 4-way adjustable configuration, although their effect on lumbar strain is not well documented. The effect of a lumbar support on posture and muscular strain, and therefore the relationship between discomfort and comfort device parameter settings, requires clarification. The aim of this paper is to study the effect of a 4-way lumbar support on lower trunk and pelvis muscle activity, pelvic tilt and spine curvature during a car seating activity. 10 healthy subjects (5 m/f; age 19-39) performed a seating activity in a passenger vehicle with seven different static lumbar support positions. The lumbar support was tested in 3 different height positions in relation to the seatback surface centreline (high, centre, low), each having 2 depths positions (lumbar prominence). An extra depth position was added for the centre position. Posture data were collected using a VICON MX motion capture system and NORAXON DTS goniometers and inclinometer. A rigid-body model of an adjustable car seat with four-way adjustable lumbar support was constructed in UGS Siemens NX and connected to a musculoskeletal model of a seated-human, modelled in AnyBody. Wireless electromyography (EMG) was used to calibrate the musculoskeletal model and assess the relationship between (a) muscular strain and lumbar prominence (normal to seatback surface) respective to the lumbar height (alongside seatback surface), (b) hip joint moment and lumbar prominence (normal to seatback surface) respective to lumbar height (alongside seatback surface) and (c) pelvic tilt and lumbar prominence (normal to seatback surface) respective to the lumbar height (alongside seatback surface). This study was based on the assumption that the musculoskeletal human model was seated at the correct R-Point (SgRP), determined via the occupant packaging toolkit in the JACK digital human model. The effect of the interaction between the driver/car-seat has been investigated for factors resulting from the presence and adjustment of a 4-way lumbar support. The results obtained show that various seat adjustments, and driver’s lumbar supports can have complex influence on the muscle activation, joint forces and moments, all of which can affect the comfort perception of the driver. This study enables the automotive industry to optimise passenger vehicle seat development and design. It further more supports the evaluation of static postural and dynamic seat comfort in normal everyday driving tasks and can be applied for future car design to reduce investment and improve comfort.

Air Conditioning Systems : Design and Energy efficiency

Air conditioning systems have become an integral part of many modern buildings. Proper design and operation of air conditioning systems have significant impact not only on the energy use and greenhouse gas emissions from the buildings, but also on the thermal comfort and productivity of the occupants. In this paper, the purpose and need of installing air conditioning systems is first introduced. The methods used for the classification of air conditioning systems are then presented. This is followed by a discussion on the pros and cons of each type of the air conditioning systems, including both common and new air conditioning technologies. The procedures used to design air conditioning systems are also outlined, and the implications of air conditioning systems, including design, selection, operation and maintenance, on building energy efficiency is also discussed.

Energy use, indoor temperature and possible adaptation strategies for air-conditioned office buildings in face of global warming

This paper discusses and summarises a recent systematic study on the implication of global warming on air conditioned office buildings in Australia. Four areas are covered, including analysis of historical weather data, generation of future weather data for the impact study of global warming, projection of building performance under various global warming scenarios, and evaluation of various adaptation strategies under 2070 high global warming conditions. Overall, it is found that depending on the assumed future climate scenarios and the location considered, the increase of total building energy use for the sample Australian office building may range from 0.4 to 15.1%. When the increase of annual average outdoor temperature exceeds 2 °C, the risk of overheating will increase significantly. However, the potential overheating problem could be completely eliminated if internal load density is significantly reduced.

The introduction of an interactive teaching and learning activity (TLA) in class and its relationship to students’ learning-outcomes

In the university education arena, it is becoming apparent that traditional methods of conducting classes are not the most effective ways to achieve desired learning outcomes. The traditional class/method involves the instructor verbalizing information for passive, note-taking students who are assumed to be empty receptacles waiting to be filled with knowledge. This method is limited in its effectiveness, as the flow of information is usually only in one direction. Furthermore, “It has been demonstrated that students in many cases can recite and apply formulas in numerical problems, but the actual meaning and understanding of the concept behind the formula is not acquired (Crouch & Mazur)”. It is apparent that memorization is the main technique present in this approach. A more effective method of teaching involves increasing the students’ level of activity during, and hence their involvement in the learning process. This technique stimulates self- learning and assists in keeping these students’ levels of concentration more uniform. In this work, I am therefore interested in studying the influence of a particular TLA on students’ learning-outcomes. I want to foster high-level understanding and critical thinking skills using active learning (Silberman, 1996) techniques. The TLA in question aims to promote self-study by students and to expose them to a situation where their learning-outcomes can be tested. The motivation behind this activity is based on studies which suggest that some sensory modalities are more effective than others. Using various instruments for data collection and by means of a thorough analysis I present evidence of the effectiveness of this action research project which aims to improve my own teaching practices, with the ultimate goal of enhancing student’s learning.

Heat reject recovery in solar air conditioning

This study demonstrates the possibility of using an absorption chiller to produce chilled water for air conditioning, and at the same time recover the rejected heat producing domestic hot water. The absorption chiller considered for this application has been sized to suit a standard household and uses a solution of ammonia and water running on hot water at a temperature ranging from 80 - 120°C produced by thermal solar panels. The system consists of five main components: generator, rectifier, condenser, evaporator and absorber, and is divided in two sections at two different pressures. The section at higher pressure includes the generator, rectifier and condenser whereas the section at lower pressure includes the evaporator and the absorber. Heat in this type of system is usually rejected to the environment from the condenser, rectifier and absorber through a cooling tower or air cooler exchanger. In this paper we describe how to recover this heat to create domestic hot water by providing a quantitative evaluation of the amount of energy recovered by the proposed system, if used in the Australian region.