Investigation of structural requirements of anticancer activity at the paclitaxel/tubulin binding site using CoMFA and CoMSIA

CoMFA and CoMSIA analysis were utilized in this investigation to define the important interacting regions in paclitaxel/tubulin binding site and to develop selective paclitaxel-like active compounds. The starting geometry of paclitaxel analogs was taken from the crystal structure of docetaxel. A total of 28 derivatives of paclitaxel were divided into two groups—a training set comprising of 19 compounds and a test set comprising of nine compounds. They were constructed and geometrically optimized using SYBYL v6.6. CoMFA studies provided a good predictability (q2 = 0.699, r2 = 0.991, PC = 6, S.E.E. = 0.343 and F = 185.910). They showed the steric and electrostatic properties as the major interacting forces whilst the lipophilic property contribution was a minor factor for recognition forces of the binding site. These results were in agreement with the experimental data of the binding activities of these compounds. Five fields in CoMSIA analysis (steric, electrostatic, hydrophobic, hydrogen-bond acceptor and donor properties) were considered contributors in the ligand–receptor interactions. The results obtained from the CoMSIA studies were: q2 = 0.535, r2 = 0.983, PC = 5, S.E.E. = 0.452 and F = 127.884. The data obtained from both CoMFA and CoMSIA studies were interpreted with respect to the paclitaxel/tubulin binding site. This intuitively suggested where the most significant anchoring points for binding affinity are located. This information could be used for the development of new compounds having paclitaxel-like activity with new chemical entities to overcome the existing pharmaceutical barriers and the economical problem associated with the synthesis of the paclitaxel analogs. These will boost the wide use of this useful class of compounds, i.e. in brain tumors as the most of the present active compounds have poor blood–brain barrier crossing ratios and also, various tubulin isotypes has shown resistance to taxanes and other antimitotic agents.

Social networking sites and participatory reluctance: A case study of Gaydar, user resistance and interface rejection

This article conceptualises ‘participatory reluctance’ as a particular orientation to social media that problematises binarised notions of connection and disconnection in social networking sites. It qualitatively examines how the concept has functioned within gay men’s social networking service, Gaydar, among 18- to 28-year-old users of the site in Brisbane, Australia. Participatory reluctance is shown to be a central aspect of the culture of this space, fostered among the studied demographic by the convergence of the growing global push for marriage equality and increasing normalisation of the kinds of gay male identities commonly adopted among this group, with three key factors rooted primarily in Gaydar’s design: (1) young users’ perceptions of the site as a space for procuring casual sex; (2) their perceptions of the imagined user as embodying existing stereotypes of gay masculinity, and; (3) a lack of genuine alternatives in terms of niche digital spaces for gay men’s social networking.

User centred engineering in automotive design: A shift from technology-driven product development

The research assessed how best to transition engineering-based automotive firms towards more customer-orientated design and development approaches, whilst identifying the main barriers and concerns facing such a shift. The research investigates the ability of a firm to empower individual engineers with user centred design tools traditionally used by designers, whilst understanding the company-wide needs to facilitate their implementation.

Investigating in-domain data requirements for PLDA training

This paper analyzes the limitations upon the amount of in- domain (NIST SREs) data required for training a probabilistic linear discriminant analysis (PLDA) speaker verification system based on out-domain (Switchboard) total variability subspaces. By limiting the number of speakers, the number of sessions per speaker and the length of active speech per session available in the target domain for PLDA training, we investigated the relative effect of these three parameters on PLDA speaker verification performance in the NIST 2008 and NIST 2010 speaker recognition evaluation datasets. Experimental results indicate that while these parameters depend highly on each other, to beat out-domain PLDA training, more than 10 seconds of active speech should be available for at least 4 sessions/speaker for a minimum of 800 speakers. If further data is available, considerable improvement can be made over solely out-domain PLDA training.

Colonoscopy requirements of population screening for colorectal cancer in New Zealand

Aim: To estimate the colonoscopy burden of introducing population screening for colorectal cancer in New Zealand. Methods: Screening for colorectal cancer using biennial immunochemical faecal occult blood tests offered to people aged 50-74 years of age was modelled using population estimates from Statistics New Zealand for 2011-2031. Modelling to determine colonoscopy requirements was based on participation and test positivity rates from published results of screening programmes. Estimates of the number of procedures required for ongoing adenoma surveillance were calculated using screening literature results of adenoma yield, and New Zealand Guidelines for Adenoma Surveillance. Sensitivity analysis was undertaken on key parameters. Results: For a test positivity of 6.4%, biennial screening using immunochemical faecal occult blood testing with a 60% participation rate, would require 18,000 colonoscopies nationally, increasing to 28,000 by 2031. The majority of procedures are direct referrals from a positive FOBT, with surveillance colonoscopy numbers building over time. Conclusion: Colonoscopy requirements for immunochemical faecal occult blood based population screening for colorectal cancer are high. Significant expansion of services is required and careful management of surveillance procedures to ensure timely delivery of initial colonoscopies whilst maintaining symptomatic services. A model re-run informed by data from the screening pilot will allow improved estimates for the New Zealand setting.

Introduction to the Proceedings of the Workshop on User-Focused Service Engineering, Consumption and Aggregation (USECA) 2011

The first User-Focused Service Engineering, Consumption and Aggregation workshop (USECA) in 2011 was held in conjunction with the WISE 2011 conference in Sydney, Australia. Web services and related technology are a widely accepted standard architectural paradigm for application development. The idea of reusing existing software components to build new applications has been well documented and supported for the world of enterprise computing and professional developers. However, this powerful idea has not been transferred to end-users who have limited or no computing knowledge. The current methodologies, models, languages and tools developed for Web service composition are suited to IT professionals and people with years of training in computing technologies. It is still hard to imagine any of these technologies being used by business professionals, as opposed to computing professionals. © 2013 Springer-Verlag.

Compensation or consideration for a statutory right of user?

Section 180 of the Property Law Act 1974 (Qld) makes provision for an applicant to seek a statutory right of user over a neighbour’s property where such right of use is reasonably necessary in the interests of effective use in any reasonable manner of the dominant land. A key issue in an application under s 180 is compensation. Unfortunately, while s 180 expressly contemplates that an order for compensation will include provision for payment of compensation to the owner of servient land there are certain issues that are less clear. One of these is the basis for determination of the amount of compensation. In this regard, s 180(4)(a) provides that, in making an order for a statutory right of user, the court: (a) shall, except in special circumstances, include provision for payment by the applicant to such person or persons as may be specified in the order of such amount by way of compensation or consideration as in the circumstances appears to the court to be just The operation of this statutory provision was considered by de Jersey CJ (as he then was) in Peulen v Agius [2015] QSC 137.

Perceived quality of e‐health services: A conceptual scale development of e‐health service quality based on the C‐OAR‐SE approach

Purpose Health service quality is an important determinant for health service satisfaction and behavioral intentions. The purpose of this paper is to investigate requirements of e‐health services and to develop a measurement model to analyze the construct of “perceived e‐health service quality.” Design/methodology/approach The paper adapts the C‐OAR‐SE procedure for scale development by Rossiter. The focal aspect is the “physician‐patient relationship” which forms the core dyad in the healthcare service provision. Several in‐depth interviews were conducted in Switzerland; first with six patients (as raters), followed by two experts of the healthcare system (as judges). Based on the results and an extensive literature research, the classification of object and attributes is developed for this model. Findings The construct e‐health service quality can be described as an abstract formative object and is operationalized with 13 items: accessibility, competence, information, usability/user friendliness, security, system integration, trust, individualization, empathy, ethical conduct, degree of performance, reliability, and ability to respond. Research limitations/implications Limitations include the number of interviews with patients and experts as well as critical issues associated with C‐OAR‐SE. More empirical research is needed to confirm the quality indicators of e‐health services. Practical implications Health care providers can utilize the results for the evaluation of their service quality. Practitioners can use the hierarchical structure to measure service quality at different levels. The model provides a diagnostic tool to identify poor and/or excellent performance with regard to the e‐service delivery. Originality/value The paper contributes to knowledge with regard to the measurement of e‐health quality and improves the understanding of how customers evaluate the quality of e‐health services.

An analysis of user engagement in student Facebook groups

Analysing the engagement of students in university-based Facebook groups can shed light on the nature of their learning experience and highlight leverage points to build on student success. While post-semester surveys and demographic participation data can highlight who was involved and how they subsequently felt about the experience, these techniques do not necessarily reflect real-time engagement. One way to gain insight into in-situ student experiences is by categorising the original posts and comments into predetermined frameworks of learning. This paper offers a systematic method of coding Facebook contributions within various engagement categories: motivation, discourse, cognition and emotive responses.

Irrational addicts and responsible pleasure seekers: Constructions of the drug user

Historically, drug use has been understood as a problem of epidemiology, psychiatry, physiology, and criminality requiring legal and medical governance. Consequently drug research tends to be underpinned by an imperative to better govern, and typically proposes policy interventions to prevent or solve drug problems. We argue that categories of ‘addictive’ and ‘recreational’ drug use are discursive forms of governance that are historically, politically and socially contingent. These constructions of the drug problem shape what drug users believe about themselves and how they enact these beliefs in their drug use practices. Based on qualitative interviews with young illicit drug users in Brisbane, Australia, this paper uses Michel Foucault’s concept of governmentality to provide insights into how the governance of illicit drugs intersects with self-governance to create a drug user self. We propose a reconceptualisation of illicit drug use that takes into account the contingencies and subjective factors that shape the drug experience. This allows for an understanding of the relationships between discourses, policies, and practices in constructions of illicit drug users.

Tissue requirements for establishing long-term CD4+ T cell-mediated immunity following Leishmania donovani infection

Organ-specific immunity is a feature of many infectious diseases, including visceral leishmaniasis caused by Leishmania donovani. Experimental visceral leishmaniasis in genetically susceptible mice is characterized by an acute, resolving infection in the liver and chronic infection in the spleen. CD4+ T cell responses are critical for the establishment and maintenance of hepatic immunity in this disease model, but their role in chronically infected spleens remains unclear. In this study, we show that dendritic cells are critical for CD4+ T cell activation and expansion in all tissue sites examined. We found that FTY720-mediated blockade of T cell trafficking early in infection prevented Ag-specific CD4+ T cells from appearing in lymph nodes, but not the spleen and liver, suggesting that early CD4+ T cell priming does not occur in liver-draining lymph nodes. Extended treatment with FTY720 over the first month of infection increased parasite burdens, although this associated with blockade of lymphocyte egress from secondary lymphoid tissue, as well as with more generalized splenic lymphopenia. Importantly, we demonstrate that CD4+ T cells are required for the establishment and maintenance of antiparasitic immunity in the liver, as well as for immune surveillance and suppression of parasite outgrowth in chronically infected spleens. Finally, although early CD4+ T cell priming appeared to occur most effectively in the spleen, we unexpectedly revealed that protective CD4+ T cell-mediated hepatic immunity could be generated in the complete absence of all secondary lymphoid tissues.

Relationships between user experience and intuitiveness of visual and physical interactions

This paper investigates the effects of experience on the intuitiveness of physical and visual interactions performed by airport security screeners. Using portable eye tracking glasses, 40 security screeners were observed in the field as they performed search, examination and interface interactions during airport security x-ray screening. Data from semi structured interviews was used to further explore the nature of visual and physical interactions. Results show there are positive relationships between experience and the intuitiveness of visual and physical interactions performed by security screeners. As experience is gained, security screeners are found to perform search, examination and interface interactions more intuitively. In addition to experience, results suggest that intuitiveness is affected by the nature and modality of activities performed. This inference was made based on the dominant processing styles associated with search and examination activities. The paper concludes by discussing the implications that this research has for the design of visual and physical interfaces. We recommend designing interfaces that build on users’ already established intuitive processes, and that reduce the cognitive load incurred during transitions between visual and physical interactions.

Delegation of access in an Information Accountability Framework for eHealth

Shared eHealth records systems offer promising benefits for improving healthcare through high availability of information and improved decision making; however, their uptake has been hindered by concerns over the privacy of patient information. To address these privacy concerns while balancing the requirements of healthcare professionals to have access to the information they need to provide appropriate care, the use of an Information Accountability Framework (IAF) has been proposed. For the IAF and so called Accountable-eHealth systems to become a reality, the framework must provide for a diverse range of users and use cases. The initial IAF model did not provide for more diverse use cases including the need for certain users to delegate access to another user in the system to act on their behalf while maintaining accountability. In this paper, we define the requirements for delegation of access in the IAF, how such access policies would be represented in the Framework, and implement and validate an expanded IAF model.

The right to a voice and the fight to be heard: The experience of being an ESL user in Australia

This paper focuses on the fundamental right to be heard, that is, the right to have one’s voice heard and listened to – to impose reception (Bourdieu, 1977). It focuses on the ways that non-mainstream English is heard and received in Australia, where despite public policy initiatives around equal opportunity, language continues to socially disadvantage people (Burridge & Mulder, 1998). English is the language of the mainstream and most people are monolingually English (Ozolins, 1993). English has no official status yet it remains dominant and its centrality is rarely challenged (Smolicz, 1995). This paper takes the position that the lack of language engagement in mainstream Australia leads to linguistic desensitisation. Writing in the US context where English is also the unofficial norm, Lippi-Green (1997) maintains that discrimination based on speech features or accent is commonly accepted and widely perceived as appropriate. In Australia, non-standard forms of English are often disparaged or devalued because they do not conform to the ‘standard’ (Burridge & Mulder, 1998). This paper argues that talk cannot be taken for granted: ‘spoken voices’ are critical tools for representing the self and negotiating and manifesting legitimacy within social groups (Miller, 2003). In multicultural, multilingual countries like Australia, the impact of the spoken voice, its message and how it is heard are critical tools for people seeking settlement, inclusion and access to facilities and services. Too often these rights are denied because of the way a person sounds. This paper reports a study conducted with a group that has been particularly vulnerable to ongoing ‘panics’ about language – international students. International education is the third largest revenue source for Australia (AEI, 2010) but has been beset by concerns from academics (Auditor-General, 2002) and the media about student language levels and falling work standards (e.g. Livingstone, 2004). Much of the focus has been high-stakes writing but with the ascendancy of project work in university assessment and the increasing emphasis on oracy, there is a call to recognise the salience of talk, especially among students using English as a second language (ESL) (Kettle & May, 2012). The study investigated the experiences of six international students in a Master of Education course at a large metropolitan university. It utilised data from student interviews, classroom observations, course materials, university policy documents and media reports to examine the ways that speaking and being heard impacted on the students’ learning and legitimacy in the course. The analysis drew on Fairclough’s (2003) model of the dialectical-relational Critical Discourse Analysis (CDA) to analyse the linguistic, discursive and social relations between the data texts and their conditions of production and interpretation, including the wider socio-political discourses on English, language difference, and second language use. The interests of the study were if and how discourses of marginalisation and discrimination manifested and if and how students recognised and responded to them pragmatically. Also how they juxtaposed with and/or contradicted the official rhetoric about diversity and inclusion. The underpinning rationale was that international students’ experiences can provide insights into the hidden politics and practices of being heard and afforded speaking rights as a second language speaker in Australia.

Deriatives disclosure in corporate annual reports: bank analysts; perceptions of usefulness

Responding to mixed evidence on the decision-usefulness of annual report disclosures for derivative financial instruments to capital market participants, and concerns identified by practice, this paper examines usefulness in a direct study of user perceptions. Interviews with analysts from Australia’s four major banks reveal essential usefulness, limited by the disclosures’ failure to reflect companies’ actual use of derivatives throughout the period, and inability of users to understand companies’ off-balance sheet risk and risk management practices from information considered generic and boilerplate. The research complements and extends existing archival and survey research and provides new evidence suggesting low-cost ways for increasing usefulness. It supports the International Accounting Standards Board’s disclosure recommendations in its recent Discussion Paper: A Review of the Conceptual Framework for Financial Reporting, but, at the same time, highlights that for these proposed measures to be successful in relation to IFRS 7, they may need to address other issues. The research increases knowledge of the informational requirements of lenders, an important class of financial information user, and supports calls from practice for companies to improve their disclosure of material economic risks.