A population-specific HTR2B stop codon predisposes to severe impulsivity

Impulsivity, describing action without foresight, is an important feature of several psychiatric diseases, suicidality and violent behaviour. The complex origins of impulsivity hinder identification of the genes influencing it and the diseases with which it is associated. Here we perform exon-focused sequencing of impulsive individuals in a founder population, targeting fourteen genes belonging to the serotonin and dopamine domain. A stop codon in HTR2B was identified that is common (minor allele frequency > 1%) but exclusive to Finnish people. Expression of the gene in the human brain was assessed, as well as the molecular functionality of the stop codon, which was associated with psychiatric diseases marked by impulsivity in both population and family-based analyses. Knockout of Htr2b increased impulsive behaviours in mice, indicative of predictive validity. Our study shows the potential for identifying and tracing effects of rare alleles in complex behavioural phenotypes using founder populations, and indicates a role for HTR2B in impulsivity.

A robust methodology for developing an operational systems view of mine water interactions

The Minerals Council of Australia’s (MCA) Water Accounting Framework (WAF) is an industry lead initiative to enable cross company communication and comparisons of water management performance. The WAF consists of two models, the Input-Output Model that represents water interactions between an operation and its surrounding environment and the Operational Model that represents water interactions within an operation. Recently, MCA member companies have agreed to use the Input-Output Model to report on their external water interactions in Australian operations, with some adopting it globally. The next step will be to adopt the Operational Model. This will expand the functionality of the WAF from corporate reporting to allowing widespread identification of inefficiencies and to connect internal and external interactions. Implementing the WAF, particularly the Operational Model, is non-trivial. It can be particularly difficult for operations that are unfamiliar with the WAF definitions and methodology, lack information pertaining to flow volumes or contain unusual configurations. Therefore, there is a need to help industry with its implementation. This work presents a step-by-step guide to producing the Operational Model. It begins by describing a methodology for implementing the Operational Model by describing the identification of pertinent objects (stores, tasks and treatments), quantification of flows, aggregation of objects and production of reports. It then discusses how the Operational Model can represent a series of challenging scenarios and how it can be connected with Input-Output Model to improve water management.

Antisocial behaviour orders : Unanticipated directions in social network site development

Abstract: Social network technologies, as we know them today have become a popular feature of everyday life for many people. As their name suggests, their underlying premise is to enable people to connect with each other for a variety of purposes. These purposes however, are generally thought of in a positive fashion. Based on a multi-method study of two online environments, Habbo Hotel and Second Life, which incorporate social networking functionality, we she light on forms of what can be conceptualized as antisocial behaviours and the rationales for these. Such behaviours included: scamming, racist/homophobic attacks, sim attacks, avatar attacks, non-conformance to contextual norms, counterfeiting and unneighbourly behaviour. The rationales for sub behaviours included: profit, fun, status building, network disruption, accidental acts and prejudice. Through our analysis we are able to comment upon the difficulties of defining antisocial behaviour in such environments, particularly when such environments are subject to interpretation vis their use and expected norms. We also point to the problems we face in conducting our public and private lives given the role ICTs are playing in the convergence of these two spaces and also the convergence of ICTs themselves.

Best of breed IT strategy: an alternative to enterprise resource planning systems

Abstract - Enterprise Resource Planning (ERP) software has become the dominant strategic platform for supporting enterprise-wide business processes. However, single vendor ERP software systems have been criticised for not meeting specific organisation and industry requirements. An alternative approach ‘Best of Breed (BoB)’, integrates components of software from multiple standard package vendors, and in some cases custom components. The objective is to develop enterprise systems that are more closely aligned with the requirements of an organisation. Although this approach may not be common at present it is likely to grow in importance due to business needs and technology advances such as the componentisation of ERP software. A case study analysis of a BoB implementation at a global entertainment's company is used as a platform for the discussion of the issues associated with this strategy and a comparison is made with the single vendor ERP alternative. The analysis centres on the complexity of implementation, the differences in the levels of functionality and business fit and the maintenance requirements.

Social networking and digital gaming media convergence : Classification and its consequences for appropriation

Abstract Within the field of Information Systems, a good proportion of research is concerned with the work organisation and this has, to some extent, restricted the kind of application areas given consideration. Yet, it is clear that information and communication technology deployments beyond the work organisation are acquiring increased importance in our lives. With this in mind, we offer a field study of the appropriation of an online play space known as Habbo Hotel. Habbo Hotel, as a site of media convergence, incorporates social networking and digital gaming functionality. Our research highlights the ethical problems such a dual classification of technology may bring. We focus upon a particular set of activities undertaken within and facilitated by the space – scamming. Scammers dupe members with respect to their ‘Furni’, virtual objects that have online and offline economic value. Through our analysis we show that sometimes, online activities are bracketed off from those defined as offline and that this can be related to how the technology is classified by members – as a social networking site and/or a digital game. In turn, this may affect members’ beliefs about rights and wrongs. We conclude that given increasing media convergence, the way forward is to continue the project of educating people regarding the difficulties of determining rights and wrongs, and how rights and wrongs may be acted out with respect to new technologies of play online and offline.

ERP and best of breed : a comparative analysis

Enterprise Resource Planning (ERP) software is the dominant strategic platform for supporting enterprise-wide business processes. However, it has been criticised for being inflexible and not meeting specific organisation and industry requirements. An alternative, Best of Breed (BoB), integrates components of standard package and/or custom software. The objective is to develop enterprise systems that are more closely aligned with the business processes of an organisation. A case study of a BoB implementation facilitates a comparative analysis of the issues associated with this strategy and the single vendor ERP alternative. The paper illustrates the differences in complexity of implementation, levels of functionality, business process alignment potential and associated maintenance.

The automation of radiotherapy treatment planning assessment

Aim The assessment of treatment plans is an important component in the education of radiation therapists. The establishment of a grade for a plan is currently based on subjective assessment of a range of criteria. The automation of assessment could provide a number of advantages including faster feedback, reduced chance of human error, and simpler aggregation of past results. Method A collection of treatments planned by a cohort of 27 second year radiation therapy students were selected for quantitative evaluation. Treatment sites included the bladder, cervix, larynx, parotid and prostate, although only the larynx plans had been assessed in detail. The plans were designed with the Pinnacle system and exported using the DICOM framework. Assessment criteria included beam arrangement optimisation, volume contouring, target dose coverage and homogeneity, and organ-at-risk sparing. The in-house Treatment and Dose Assessor (TADA) software1 was evaluated for suitability in assisting with the quantitative assessment of these plans. Dose volume data were exported in per-student and per-structure data tables, along with beam complexity metrics, dose volume histograms, and reports on naming conventions. Results The treatment plans were exported and processed using TADA, with the processing of all 27 plans for each treatment site taking less than two minutes. Naming conventions were successfully checked against a reference protocol. Significant variations between student plans were found. Correlation with assessment feedback was established for the larynx plans. Conclusion The data generated could be used to inform the selection of future assessment criteria, monitor student development, and provide useful feedback to the students. The provision of objective, quantitative evaluations of plan quality would be a valuable addition to not only radiotherapy education programmes but also for staff development and potentially credentialing methods. New functionality within TADA developed for this work could be applied clinically to, for example, evaluate protocol compliance.

Chromosomal genotoxicity of nitrobenzene and benzonitrile

In order to investigate the chromosomal genotoxicity of nitrobenzene and benzonitrile, we studied the induction of micronuclei (MN) by these test compounds in V79 cells, as well as effects on the formation and stability of microtubules and on motor protein functions. No cytotoxicity was seen in V79 cell cultures in terms of Neutral red uptake after 18 h treatment with up to 1 mM nitrobenzene or 1 mM benzonitrile. Subsequently, a concentration range up to 100 μM was used in the experiments on induction of MN. Both test compounds exhibit a weak, but definitely positive test result compared to the solvent (DMSO) control. Minimal effect concentrations of nitrobenzene and benzonitrile appeared as low as 0.01 μM, and no-effect-concentrations were between 0.001 and 0.005 μM. Clearly enhanced MN rates were found at 0.1 μM and higher. Both, nitrobenzene and benzonitrile, induced mostly kinetochor (CREST)-positive micronuclei, thus characterising the chromosomal effects as aneugenic. In cell-free assays, a slight effect on tubulin assembly was observed at 1 mM nitrobenzene without addition of DMSO. Higher concentrations (5 mM) led to secondary effects. In presence of 1% DMSO, nitrobenzene exerted no detectable effect on tubulin assembly up to the solubility limit in water of about 15 mM. For benzonitrile in presence of DMSO, a clear dose-response of inhibition of tubulin assembly at 37°C was seen above the no-effect-concentration of 2 mM, with an IC50 of 13 mM and protein denaturation starting above a level of about 20 mM. The nature of the effects of nitrobenzene and benzonitrile on the association of tubulin to form microtubules was confirmed by electron microscopy. Treatment by either 5 mM nitrobenzene or 13 mM benzonitrile plus 1% DMSO left the microtubular structure intact whereas 5 mM nitrobenzene, in absence of DMSO, led to irregular cluster formations. The experiments demonstrate that both nitrobenzene and benzonitrile, in millimolar concentration ranges, may lead to interference with tubulin assembly in a cell-free system. The functionality of the tubulin-kinesin motor protein system was assessed using the microtubule gliding assay. Nitrobenzene affected the gliding velocity in a concentration-dependent manner, starting at about 7.5 μM and reaching complete inhibition of motility at 30 μM, whereas benzonitrile up to 200 μM did not affect the kinesin-driven gliding velocity. The micronucleus assay data demonstrate a chromosomal endpoint of genotoxicity of nitrobenzene and benzonitrile. Aneugenic effects of both compounds occur at remarkably low concentrations, with lowest-effect-concentrations being 0.1 μM. This points to the relevance of interactions with the cellular spindle apparatus.

Genotoxicity of inorganic mercury salts based on disturbed microtubule function

This study investigated the hypothesis that the chromosomal genotoxicity of inorganic mercury results from interaction(s) with cytoskeletal proteins. Effects of Hg2+ salts on functional activities of tubulin and kinesin were investigated by determining tubulin assembly and kinesin-driven motility in cell-free systems. Hg2+ inhibits microtubule assembly at concentrations above 1 μM, and inhibition is complete at about 10 μM. In this range, the tubulin assembly is fully (up to 6 μM) or partially (∼6-10 μM) reversible. The inhibition of tubulin assembly by mercury is independent of the anion, chloride or nitrate. The no-observed-effect- concentration for inhibition of microtubule assembly in vitro was 1 μM Hg2+, the IC50 5.8 μM. Mercury(II) salts at the IC 50 concentrations partly inhibiting tubulin assembly did not cause the formation of aberrant microtubule structures. Effects of mercury salts on the functionality of the microtubule motility apparatus were studied with the motor protein kinesin. By using a "gliding assay" mimicking intracellular movement and transport processes in vitro, HgCl2 affected the gliding velocity of paclitaxel-stabilised microtubules in a clear dose-dependent manner. An apparent effect is detected at a concentration of 0.1 μM and a complete inhibition is reached at 1 μM. Cytotoxicity of mercury chloride was studied in V79 cells using neutral red uptake, showing an influence above 17 μM HgCl2. Between 15 and 20 μM HgCl2 there was a steep increase in cell toxicity. Both mercury chloride and mercury nitrate induced micronuclei concentration-dependently, starting at concentrations above 0.01 μM. CREST analyses on micronuclei formation in V79 cells demonstrated both clastogenic (CREST-negative) and aneugenic effects of Hg2+, with some preponderance of aneugenicity. A morphological effect of high Hg2+ concentrations (100 μM HgCl2) on the microtubule cytoskeleton was verified in V79 cells by immuno-fluorescence staining. The overall data are consistent with the concept that the chromosomal genotoxicity could be due to interaction of Hg2+ with the motor protein kinesin mediating cellular transport processes. Interactions of Hg 2+ with the tubulin shown by in vitro investigations could also partly influence intracellular microtubule functions leading, together with the effects on the kinesin, to an impaired chromosome distribution as shown by the micronucleus test.

Supporting collaboration on very large-scale interactive wall surfaces

In this paper we describe CubIT, a multi-user presentation and collaboration system installed at the Queensland University of Technology’s (QUT) Cube facility. The ‘Cube’ is an interactive visualisation facility made up of five very large-scale interactive multi-panel wall displays, each consisting of up to twelve 55-inch multi-touch screens (48 screens in total) and massive projected display screens situated above the display panels. The paper outlines the unique design challenges, features, implementation and evaluation of CubIT. The system was built to make the Cube facility accessible to QUT’s academic and student population. CubIT enables users to easily upload and share their own media content, and allows multiple users to simultaneously interact with the Cube’s wall displays. The features of CubIT were implemented via three user interfaces, a multi-touch interface working on the wall displays, a mobile phone and tablet application and a web-based content management system. Each of these interfaces plays a different role and offers different interaction mechanisms. Together they support a wide range of collaborative features including multi-user shared workspaces, drag and drop upload and sharing between users, session management and dynamic state control between different parts of the system. The results of our evaluation study showed that CubIT was successfully used for a variety of tasks, and highlighted challenges with regards to user expectations regarding functionality as well as issues arising from public use.

Wrecking ball: could big tech firms ruin the Spotify party?

YouTube is contemplating the launch of a new music service. But how would such a service fare against established music services like Spotify, Rdio, and Pandora? All these services are referred to as “access-based music services”. They offer music listeners access to millions of songs they can listen to as much as they want for free (with advertising and only basic functionality) or for a monthly subscription fee (without advertising)...

The fatty acid synthase inhibitor triclosan : repurposing an anti-microbial agent for targeting prostate cancer

Inhibition of FASN has emerged as a promising therapeutic target in cancer, and numerous inhibitors have been investigated. However, severe pharmacological limitations have challenged their clinical testing. The synthetic FASN inhibitor triclosan, which was initially developed as a topical antibacterial agent, is merely affected by these pharmacological limitations. Yet, little is known about its mechanism in inhibiting the growth of cancer cells. Here we compared the cellular and molecular effects of triclosan in a panel of eight malignant and non-malignant prostate cell lines to the well-known FASN inhibitors C75 and orlistat, which target different partial catalytic activities of FASN. Triclosan displayed a superior cytotoxic profile with a several-fold lower IC50 than C75 or orlistat. Structure-function analysis revealed that alcohol functionality of the parent phenol is critical for inhibitory action. Rescue experiments confirmed that end product starvation was a major cause of cytotoxicity. Importantly, triclosan, C75 and orlistat induced distinct changes to morphology, cell cycle, lipid content and the expression of key enzymes of lipid metabolism, demonstrating that inhibition of different partial catalytic activities of FASN activates different metabolic pathways. These finding combined with its well-documented pharmacological safety profile make triclosan a promising drug candidate for the treatment of prostate cancer.

The OnTrack Diabetes web-based program for type 2 diabetes and dysphoria self-management: A randomized controlled trial protocol

Background: The prevalence of type 2 diabetes is rising with the majority of patients practicing inadequate disease self-management. Depression, anxiety, and diabetes-specific distress present motivational challenges to adequate self-care. Health systems globally struggle to deliver routine services that are accessible to the entire population, in particular in rural areas. Web-based diabetes self-management interventions can provide frequent, accessible support regardless of time and location Objective: This paper describes the protocol of an Australian national randomized controlled trial (RCT) of the OnTrack Diabetes program, an automated, interactive, self-guided Web program aimed to improve glycemic control, diabetes self-care, and dysphoria symptoms in type 2 diabetes patients. Methods: A small pilot trial is conducted that primarily tests program functionality, efficacy, and user acceptability and satisfaction. This is followed by the main RCT, which compares 3 treatments: (1) delayed program access: usual diabetes care for 3 months postbaseline followed by access to the full OnTrack Diabetes program; (2) immediate program: full access to the self-guided program from baseline onward; and (3) immediate program plus therapist support via Functional Imagery Training (FIT). Measures are administered at baseline and at 3, 6, and 12 months postbaseline. Primary outcomes are diabetes self-care behaviors (physical activity participation, diet, medication adherence, and blood glucose monitoring), glycated hemoglobin A1c (HbA1c) level, and diabetes-specific distress. Secondary outcomes are depression, anxiety, self-efficacy and adherence, and quality of life. Exposure data in terms of program uptake, use, time on each page, and program completion, as well as implementation feasibility will be conducted. Results: This trial is currently underway with funding support from the Wesley Research Institute in Brisbane, Australia. Conclusions: This is the first known trial of an automated, self-guided, Web-based support program that uses a holistic approach in targeting both type 2 diabetes self-management and dysphoria. Findings will inform the feasibility of implementing such a program on an ongoing basis, including in rural and regional locations.

Chondrocyte redifferentiation and construct mechanical property development in single-component photocrosslinkable hydrogels

Hydrogels are promising materials for cartilage repair, but the properties required for optimal functional outcomes are not yet known. In this study, we functionalized four materials that are commonly used in cartilage tissue engineering and evaluated them using in vitro cultures. Gelatin, hyaluronic acid, polyethylene glycol, and alginate were functionalized with methacrylic anhydride to make them photocrosslinkable. We found that the responses of encapsulated human chondrocytes were highly dependent on hydrogel type. Gelatin hydrogels supported cell proliferation and the deposition of a glycosaminoglycan rich matrix with significant mechanical functionality. However, cells had a dedifferentiated phenotype, with high expression of collagen type I. Chondrocytes showed the best redifferentiation in hyaluronic acid hydrogels, but the newly formed matrix was highly localized to the pericellular regions, and these gels degraded rapidly. Polyethylene glycol hydrogels, as a bioinert control, did not promote any strong responses. Alginate hydrogels did not support the deposition of new matrix, and the stiffness decreased during culture. The markedly different response of chondrocytes to these four photocrosslinkable hydrogels demonstrates the importance of material properties for chondrogenesis and extracellular matrix production, which are critical for effective cartilage repair.

Scheimpflug imaging of the post lens tear film during contact lens wear

A new imaging methodology is described to visualise the post lens tear film (PLTF) during contact lens wear. A rotating-Scheimpflug camera in combination with sodium fluorescein allows evaluation of the PLTF for different contact lens modalities, including mini-scleral, rigid gas permeable (RGP) and soft contact lenses. This imaging technique provides an extension of the instrument’s current functionality. The potential advantages and limitations of the technique are discussed.