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.

Stop lecturing me, I want to learn

Re-evaluation of pedagogical practice is driving learning design at Queensland University of Technology. One objective is to support approaches to increase student engagement and attendance in physical and virtual learning spaces through opportunities for active and problem-based learning. This paper provides an overview and preliminary evaluation of the pilot of one of these initiatives, the Open Web Lecture (OWL), a new web-based student response application that seamlessly integrates a virtual learning environment within a physical learning space.

‘It's the end of the university as we know it (and I feel fine)’: the Generation Y student in higher education discourse

This paper examines discussions of Generation Y within higher education discourse, arguing the sector’s use of the term to describe students is misguided for three reasons. First, portraying students as belonging to Generation Y homogenises people undertaking higher education as young, middle-class and technologically literate. Second, speaking of Generation Y students allows constructivism to be reinvented as a ‘new’ learning and teaching philosophy. Third, the Generation Y university student has become a central figure in concerns about technology’s role in learning and teaching. While the notion of the ‘Generation Y student’ creates the illusion that higher education institutions understand their constituents, ultimately, it is of little value in explaining young adults’ educational experiences.

Peer state assessment of TxDOT maintenance program and practices, part I : workshop findings and recommendations

To assess and improve their practices, and thus ensure the future excellence of the Texas highway system, the Texas Department of Transportation (TxDOT) sought a forum in which experts from other State Departments of Transportation could evaluate the TxDOT maintenance program and practices based on their expertise. To meet this need, a Peer State Review of TxDOT Maintenance Practices project was organized and conducted by the Center for Transportation Research (CTR) at The University of Texas at Austin. CTR researchers, along with TxDOT staff, conducted a workshop to present TxDOT’s maintenance practices to the visiting peer reviewers and invite their feedback. Directors of maintenance from six different states—California, Kansas, Georgia, Missouri, North Carolina, and Washington—participated in the workshop. CTR and TxDOT worked together to design a questionnaire with 15 key questions to capture the peers’ opinions on maintenance program and practices. This paper compiles and summarizes this information. The examination results suggested that TxDOT should use a more state-wide approach to funding and planning, in addition to funding and planning for each district separately. Additionally, the peers recommended that criteria such as condition and level of service of the roadways be given greater weight in the funding allocation than lane miles or vehicle miles traveled (VMT). The Peer Reviewers also determined that TxDOT maintenance employee experience and communications were strong assets. Additional strengths included the willingness of TxDOT to invite peer reviews of their practices and a willingness to consider opportunities for improvement.

"My friend was over the alcohol limit, so I asked him not to drive" : Young females intervening in alcohol-impaired driving

Potential to strengthen a commitment to intervene within a friendship group: – all knew the other passengers, – 3 in 4 discussed intervening with other passengers, – expectations of friends was a key predictive factor. - young women have potential and willingness to intervene in their friends’ drink driving behaviour - majority of campaigns and strategies to reduce alcohol related crashes target the driver however it is arguable that some strategies should target the young female passenger.

Then I let you

In this video, a male voice recites a teenage love poem. Words flash on screen in time with the spoken words. Sometimes the two sets of words match, and sometimes they differ. This work examines processes of signification. It emphasizes disruption and disconnection as fundamental and generative operations in making meaning. Extending on post-structural and deconstructionist ideas, this work questions the relationship between written and spoken words. By actively disrupting the sincerity of a teenage love poem, it questions the sites and mechanisms of comprehension, poetry and signification.

Weighted LDA techniques for I-vector based speaker verification

This paper introduces the Weighted Linear Discriminant Analysis (WLDA) technique, based upon the weighted pairwise Fisher criterion, for the purposes of improving i-vector speaker verification in the presence of high intersession variability. By taking advantage of the speaker discriminative information that is available in the distances between pairs of speakers clustered in the development i-vector space, the WLDA technique is shown to provide an improvement in speaker verification performance over traditional Linear Discriminant Analysis (LDA) approaches. A similar approach is also taken to extend the recently developed Source Normalised LDA (SNLDA) into Weighted SNLDA (WSNLDA) which, similarly, shows an improvement in speaker verification performance in both matched and mismatched enrolment/verification conditions. Based upon the results presented within this paper using the NIST 2008 Speaker Recognition Evaluation dataset, we believe that both WLDA and WSNLDA are viable as replacement techniques to improve the performance of LDA and SNLDA-based i-vector speaker verification.

Evaluation of the Type I child car restraints fitting service in WA

Child passenger injury remains a major road safety issue despite advances in biomechanical understanding and child restraint design. In Australia, one intervention with parents to encourage universal and consistent use of the most appropriate restraint as well as draw their attention to critical aspects of installation is the RoadWise Type 1 Child Car Restraints Fitting Service, WA. A mixed methods evaluation of this service was conducted in early 2010. Evaluation results suggest that it has been effective in ensuring good quality training of child restraint fitters. In addition, stakeholder and user satisfaction with the Service is high, with participants agreeing that the Service is valuable to the community, and fitters regarding the training course, materials and post-training support as effective. However, a continuing issue for interventions of this type is whether the parents who need them perceive this need. Evidence from the evaluation suggests that only about 25% of parents who could benefit from the Service actually use it. This may be partly due to parental perceptions that such services are not necessary or relevant to them, or to overconfidence about the ease of installing restraints correctly. Thus there is scope for improving awareness of the Service amongst groups most likely to benefit from it (e.g. new parents) and for alerting parents to the importance of correct installation and getting their self-installed restraints checked. Efforts to inform and influence parents should begin when their children are very young, preferably at or prior to birth and/or before the parent installs the first restraint.

Do you see what I mean? charting changing representations and receptions of the disabled body in contemporary and pop cultural performance

The meaning of the body emerges through acts of seeing, looking and staring in daily and dramatic performances. Acts that are, as Maike Bleeker argues1, bound up with the scopic rules, regimes and narratives that apply in specific cultures at specific times. In Western culture, the disabled body has been seen as a sign of defect, deficiency, fear, shame or stigma. Disabled artists – Mat Fraser, Bill Shannon, Aaron Williamson, Katherine Araniello, Liz Crow and Ju Gosling – have attempted, via performances that co-opt conventional images of the disabled body, to challenge dominant ways of representing and responding such bodies from within. In this paper, I consider what happens when non-disabled artists co-opt images of the disabled body to draw attention to, affirm, and even exoticise, eroticise or beautify, other modalities of or desires for difference. As Carrie Sandahl has noted2, the signs, symbols and somatic idiosyncrasies of the disabled body are, today, transported or translated into theatre, film and television as a metaphor or "master trope" for every body’s experience of difference. This happens in performance art (Guillermo Gomez-Pena’s use of a wheelchair in Chamber of Confessions), performance (Marie Chouinard's use of crutches, canes and walkers to represent dancers’ experience of becoming different or mutant during training in bODY rEMIX /gOLDBERG vARIATIONS), and pop culture (characters in wheelchairs in Glee or Oz). In this paper, I chart changing representations and receptions of the disabled body in such contexts. I use analysis of this cultural shift as a starting point for a re-consideration of questions about whether a face-toface encounter with a disabled body is in fact a privileged site for the emergence of a politics, and whether co-opting disability as a metaphor for a range of difference differences reduces its currency as a category around which a specific group might mobilise a politics.

Gold coating of silica and zinc oxide nanoparticles by the surface reduction of gold(I) chloride

The possibility of a surface inner sphere electron transfer mechanism leading to the coating of gold via the surface reduction of gold(I) chloride on metal and semi-metal oxide nanoparticles was investigated. Silica and zinc oxide nanoparticles are known to have very different surface chemistry, potentially leading to a new class of gold coated nanoparticles. Monodisperse silica nanoparticles were synthesised by the well known Stöber protocol in conjunction with sonication. The nanoparticle size was regulated solely by varying the amount of ammonia solution added. The presence of surface hydroxyl groups was investigated by liquid proton NMR. The resultant nanoparticle size was directly measured by the use of TEM. The synthesised silica nanoparticles were dispersed in acetonitrile (MeCN) and added to a bis acetonitrile gold(I) co-ordination complex [Au(MeCN)2]+ in MeCN. The silica hydroxyl groups were deprotonated in the presence of MeCN generating a formal negative charge on the siloxy groups. This allowed the [Au(MeCN)2]+ complex to undergo ligand exchange with the silica nanoparticles, which formed a surface co-ordination complex with reduction to gold(0), that proceeded by a surface inner sphere electron transfer mechanism. The residual [Au(MeCN)2]+ complex was allowed to react with water, disproportionating into gold(0) and gold(III) respectively, with gold(0) being added to the reduced gold already bound on the silica surface. The so-formed metallic gold seed surface was found to be suitable for the conventional reduction of gold(III) to gold(0) by ascorbic acid. This process generated a thin and uniform gold coating on the silica nanoparticles. This process was modified to include uniformly gold coated composite zinc oxide nanoparticles (Au@ZnO NPs) using surface co-ordination chemistry. AuCl dissolved in acetonitrile (MeCN) supplied chloride ions which were adsorbed onto ZnO NPs. The co-ordinated gold(I) was reduced on the ZnO surface to gold(0) by the inner sphere electron transfer mechanism. Addition of water disproportionated the remaining gold(I) to gold(0) and gold(III). Gold(0) bonded to gold(0) on the NP surface with gold(III) was reduced to gold(0) by ascorbic acid (ASC), which completed the gold coating process. This gold coating process of Au@ZnO NPs was modified to incorporate iodide instead of chloride. ZnO NPs were synthesised by the use of sodium oxide, zinc iodide and potassium iodide in refluxing basic ethanol with iodide controlling the presence of chemisorbed oxygen. These ZnO NPs were treated by the addition of gold(I) chloride dissolved in acetonitrile leaving chloride anions co-ordinated on the ZnO NP surface. This allowed acetonitrile ligands in the added [Au(MeCN)2]+ complex to surface exchange with adsorbed chloride from the dissolved AuCl on the ZnO NP surface. Gold(I) was then reduced by the surface inner sphere electron transfer mechanism. The presence of the reduced gold on the ZnO NPs allowed adsorption of iodide to generate a uniform deposition of gold onto the ZnO NP surface without the use of additional reducing agents or heat.