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.

The transition from isolated, rural contexts to boarding school: Can school physical education play a part?

This study considers the transition of children from rurally isolated schooling environments to boarding school contexts. There is an assumption that these transitions are often carried out with little fuss. Moreover; there is some evidence to show this transition is beneficial to both child and school. However, contrary data suggest that parents of such children are deeply concerned about this transition from a sport and physical education perspective (Wright et al., 1998). This study attempts to address this under-researched area. Data were gathered using semi-structured interviews with teachers, children and parents in an isolated schooling context, and with teachers and children from a boarding school in a regional Queensland centre. Some videotape data of children in physical education and sporting contexts were also collected. The data indicate that the transition from rural contexts to highly competitive boarding school environments is relatively smooth, with physical education and sport being significant contributors to this process.

Students’ well-being and social connections

Description of Workshop/Poster Presentation This presentation will showcase CORE Connections – ‘Creating Opportunities for Resilience and Engagement’ – which is a whole-school approach to mental health promotion. While initially designed to prevent adolescent depression and substance abuse, current thinking suggests that competency enhancement (e.g., autonomy, competence, supportive networks) more widely improves students’ well-being, educational engagement, and learning outcomes. In the presentation, we will provide an overview of the CORE project, describe the CORE intervention, which is conceptualized as a dynamic and penetrating process of social practices, present some preliminary findings from the pilot phase of CORE, and conclude our presentation with an interactive section with the participants. This project will highlight a wellness focus that addresses social engagement within whole school cultures. Purpose of the Presentation Student mental and physical well-being has gained increasing attention. Our presentation will introduce the CORE project, which has a potential to decrease student depression, anxiety, and substance use, and to increase student self-esteem and learning outcomes. In this vein, our presentation will raise the public awareness of the salient role of social connection in student well-being. Specifically, a group of presenters will discuss the impact of social connection on students’ anxiety, mathematics achievement, and perceived racial discrimination. • We will present participants with an alternative way to conceptualize and approach mental health promotion within a school context. In contrast to prescribed programs that are commonly used in today’s schools, CORE is a whole-school approach that is flexibly integrated into all aspects of the classroom and school environment. Our aim is to illustrate the intervention principles of CORE while highlighting examples of mental health outcomes/transformation. • Underutilized in mental health promotion research, social network analysis provides critical information in understanding relationships between social cohesion (e.g., a student’s connectedness to others) and mental health outcomes. This session will showcase how focusing on and strengthening social connections in and out of school can contribute to student well-being, achievement, and mental health. Educational Objectives By the end of the presentation, participants will • obtain a general overview of the CORE program, • understand how psychological health and school performance relate to student well-being, • and understand how social connections in and out of school can contribute to student well-being. Interactive / Participatory Component We will invite audience members to discuss inhibitors and contributors to student well-being and the best ways for schools to help students feel safe, connected, and valued. Presentation Key Points • Overview of the CORE project • Theorization of social connection • Some empirical studies emerging from CORE • Presenter-audience interaction Evidence of Relevance and Utility to Participants Potential participants are adults with significant relationships with students, either as family members, community neighbors, educators, scholars, service providers, or policy makers. Our presentation will inspire these significant adults to construct a welcoming society to help improve student well-being.

Reducing environmental pressures of road building

Although road construction and use provides significant economic and social benefits its environmental impact is of growing concern. Roads are one of the greatest greenhouse gas contributors both directly through fossil energy consumed in mining, transporting, earthworks, and paving work, along with in-direct emissions from road use by vehicles. This discussion paper will outline opportunities within the Australian context for reducing environmental pressure in road building and consider the future environmental impacts of road projects.

Working the story : News curation in social media as a second save of citizen journalism

For the first decade of its existence, the concept of citizen journalism has described an approach which was seen as a broadening of the participant base in journalistic processes, but still involved only a comparatively small subset of overall society – for the most part, citizen journalists were news enthusiasts and “political junkies” (Coleman, 2006) who, as some exasperated professional journalists put it, “wouldn’t get a job at a real newspaper” (The Australian, 2007), but nonetheless followed many of the same journalistic principles. The investment – if not of money, then at least of time and effort – involved in setting up a blog or participating in a citizen journalism Website remained substantial enough to prevent the majority of Internet users from engaging in citizen journalist activities to any significant extent; what emerged in the form of news blogs and citizen journalism sites was a new online elite which for some time challenged the hegemony of the existing journalistic elite, but gradually also merged with it. The mass adoption of next-generation social media platforms such as Facebook and Twitter, however, has led to the emergence of a new wave of quasi-journalistic user activities which now much more closely resemble the “random acts of journalism” which JD Lasica envisaged in 2003. Social media are not exclusively or even predominantly used for citizen journalism; instead, citizen journalism is now simply a by-product of user communities engaging in exchanges about the topics which interest them, or tracking emerging stories and events as they happen. Such platforms – and especially Twitter with its system of ad hoc hashtags that enable the rapid exchange of information about issues of interest – provide spaces for users to come together to “work the story” through a process of collaborative gatewatching (Bruns, 2005), content curation, and information evaluation which takes place in real time and brings together everyday users, domain experts, journalists, and potentially even the subjects of the story themselves. Compared to the spaces of news blogs and citizen journalism sites, but also of conventional online news Websites, which are controlled by their respective operators and inherently position user engagement as a secondary activity to content publication, these social media spaces are centred around user interaction, providing a third-party space in which everyday as well as institutional users, laypeople as well as experts converge without being able to control the exchange. Drawing on a number of recent examples, this article will argue that this results in a new dynamic of interaction and enables the emergence of a more broadly-based, decentralised, second wave of citizen engagement in journalistic processes.

The future of roads: How road agencies are facing a conflicted future

Although road construction and use provides significant economic and social benefits, its environmental impact is of growing concern. Roads are one of the greatest greenhouse gas contributors, both directly through fossil energy consumed in mining, transporting, earthworks and paving work, and through the emissions from road use by vehicles. Further,according to the Australian Government, when combined with expected population growth and internal migration,expected changes in temperature and rainfall are expected to increase road maintenance costs. This discussion paper will outline opportunities within the Australian context for reducing environmental and carbon pressure from road building, and provide a framework for considering the potential pressures that will affect the resilience of roads to the impacts of climate change and oil vulnerability.

The future of roads: Reducing environmental pressures and the management of carbon

Although road construction and use provides significant economic and social benefits, its environmental impact is of growing concern. Roads are one of the greatest greenhouse gas contributors, both directly through fossil energy consumed in mining, transporting, earthworks and paving work, plus the emissions from road use by vehicles. Further, according to the Australian Government, when combined with forecast population growth, internal migration and changes in temperature and rainfall, these are expected to increase road maintenance costs. This discussion paper outlines opportunities within the Australian context for reducing environmental and carbon pressure from road building, and provides a framework for considering the potential future pressures that will affect the resilience of roads to the impacts of climate change and oil vulnerability. Seven strategic areas are outlined for further investigation, including a guide to carbon management for road agencies covering planning, funding, procurement, delivery and maintenance of roads.

Socioeconomic inequalities in diet and bodyweight: Evidence, causes, and intervention options

Diets low in fruits, vegetables, and whole grains, and high in saturated fat, salt, and sugar are the major contributors to the burden of chronic diseases globally. Previous research, and studies in this issue of Public Health Nutrition (PHN), show that unhealthy diets are more commonly observed among socioeconomically disadvantaged groups, and are key contributors to their higher rates of chronic disease. Most research examining socioeconomic inequalities in diet and bodyweight has been descriptive, and has focused on identifying the nature, extent, and direction of the inequalities. These types of studies are clearly necessary and important. We need however to move beyond description of the problem and focus much more on the question of why inequalities in diet and bodyweight exist. Furthering our understanding of this question will provide the necessary evidence-base to develop effective interventions to reduce the inequalities. The challenge of tackling dietary inequalities however doesn’t finish here: a maximally effective approach will also require equity-based policies that address the unequal population-distribution of social and economic resources, which is the fundamental root-cause of dietary and bodyweight inequalities.

Incentives for global public health: Patent law and access to essential medicines

This portrait of the global debate over patent law and access to essential medicines focuses on public health concerns about HIV/AIDS, malaria, tuberculosis, the SARS virus, influenza, and diseases of poverty. The essays explore the diplomatic negotiations and disputes in key international fora, such as the World Trade Organization, the World Health Organization and the World Intellectual Property Organization. Drawing upon international trade law, innovation policy, intellectual property law, health law, human rights and philosophy, the authors seek to canvass policy solutions which encourage and reward worthwhile pharmaceutical innovation while ensuring affordable access to advanced medicines. A number of creative policy options are critically assessed, including the development of a Health Impact Fund, prizes for medical innovation, the use of patent pools, open-source drug development and forms of 'creative capitalism'.

Intellectual property and emerging technologies: The new biology

This unique and comprehensive collection investigates the challenges posed to intellectual property by recent paradigm shifts in biology. It explores the legal ramifications of emerging technologies, such as genomics, synthetic biology, stem cell research, nanotechnology, and biodiscovery. Extensive contributions examine recent controversial court decisions in patent law – such as Bilski v. Kappos, and the litigation over Myriad’s patents in respect of BRCA1 and BRCA2 – while other papers explore sui generis fields, such as access to genetic resources, plant breeders' rights, and traditional knowledge. The collection considers the potential and the risks of the new biology for global challenges – such as access to health-care, the protection of the environment and biodiversity, climate change, and food security. It also considers Big Science projects – such as biobanks, the 1000 Genomes Project, and the Doomsday Vault. The inter-disciplinary research brings together the work of scholars from Australia, Canada, Europe, the UK and the US and involves not only legal analysis of case law and policy developments, but also historical, comparative, sociological, and ethical methodologies. Intellectual Property and Emerging Technologies will appeal to policy-makers, legal practitioners, business managers, inventors, scientists and researchers.

Patent law and biological inventions

In response to scientific breakthroughs in biotechnology, the development of new technologies, and the demands of a hungry capitalist marketplace, patent law has expanded to accommodate a range of biological inventions. There has been much academic and public debate as to whether gene patents have a positive impact upon research and development, health-care, and the protection of the environment. In a satire of prevailing patenting practices, the English poet and part-time casino waitress, Donna MacLean, sought a patent application - GB0000180.0 - in respect of herself. She explained that she had satisfied the usual patent criteria - in that she was novel, inventive, and useful: It has taken 30 years of hard labor for me to discover and invent myself, and now I wish to protect my invention from unauthorized exploitation, genetic or otherwise. I am new: I have led a private existence and I have not made the invention of myself public. I am not obvious (2000: 18). MacLean said she had many industrial applications. 'For example, my genes can be used in medical research to extremely profitable ends - I therefore wish to have sole control of my own genetic material' (2000: 18). She observed in an interview: 'There's a kind of unpleasant, grasping, greedy atmosphere at the moment around the mapping of the human genome ... I wanted to see if a human being could protect their own genes in law' (Meek, 2000). This special issue of Law in Context charts a new era in the long-standing debate over biological inventions. In the wake of the expansion of patentable subject matter, there has been great strain placed upon patent criteria - such as 'novelty', 'inventive step', and 'utility'. Furthermore, there has been a new focus upon legal doctrines which facilitate access to patented inventions - like the defence of experimental use, the 'Bolar' exception, patent pooling, and compulsory licensing. There has been a concerted effort to renew patent law with an infusion of ethical principles dealing with informed consent and benefit sharing. There has also been a backlash against the commercialisation of biological inventions, and a call by some activists for the abolition of patents on genetic inventions. This collection considers a wide range of biological inventions - ranging from micro-organisms, plants and flowers and transgenic animals to genes, express sequence tags, and research tools, as well as genetic diagnostic tests and pharmaceutical drugs. It is thus an important corrective to much policy work, which has been limited in its purview to merely gene patents and biomedical research. This collection compares and contrasts the various approaches of a number of jurisdictions to the legal problems in respect of biological inventions. In particular, it looks at the complexities of the 1998 European Union Directive on the Legal Protection of Biotechnological Inventions, as well as decisions of member states, such as the Netherlands, and peripheral states, like Iceland. The edition considers US jurisprudence on patent law and policy, as well as recent developments in Canada. It also focuses upon recent developments in Australia - especially in the wake of parallel policy inquiries into gene patents and access to genetic resources.

Submission to Inquiry into School Libraries and Teacher Librarians

We welcome the opportunity to contribute to the Department of Education, Employment and Workplace Relations (DEEWR) Inquiry into School Libraries and Teacher Librarians. We thank the Federal Government for the recognition that the Building the Education Revolution (BER) is not just about physical infrastructure. We are pleased that the Government has responded to calls from the library and information sector for a review focusing on school libraries and teacher librarians. The Australian Library and Information Association (ALIA) is the peak body representing the library and information services sector. It represents 6000 members, the library and information profession, Australian library and information services, and the interests of over 12 million library users. ALIA is committed to promoting the free flow of information and ideas in the interest of all Australians and a thriving culture, economy and democracy. We support the development of a 21st century information infrastructure with libraries as the conduit for a sustainable knowledge economy. This submission strongly supports the separate submission from the Australian School Library Association (ASLA) with whom ALIA works in partnership on issues concerning school libraries and teacher librarians. Other contributors to this submission include the ALIA Schools Group, the joint ALIA/ASLA Policy Advisory Group, and current practitioners. ALIA and ASLA are looking forward to working with the Federal Government on implementing the Inquiry recommendations.

Cultural adaptation and resilience: Controversies, issues and emerging models

What enables people to bounce back from stressful experiences? How do certain individuals maintain a sense of purpose and direction over the long term, even in the face of adversity? This is the first book to move beyond childhood and adolescence to explore resilience across the lifespan. Coverage ranges from genetic and physiological factors through personal, family, organizational, and community processes. Contributors examine how resilience contributes to health and well-being across the adult life cycle; why—and what happens when—resilience processes fail; ethnic and cultural dimensions of resilience; and ways to enhance adult resilience, including reviews of exemplary programs.

Resilience: A new definition of health for people and communities

What enables people to bounce back from stressful experiences? How do certain individuals maintain a sense of purpose and direction over the long term, even in the face of adversity? This is the first book to move beyond childhood and adolescence to explore resilience across the lifespan. Coverage ranges from genetic and physiological factors through personal, family, organizational, and community processes. Contributors examine how resilience contributes to health and well-being across the adult life cycle; why—and what happens when—resilience processes fail; ethnic and cultural dimensions of resilience; and ways to enhance adult resilience, including reviews of exemplary programs.

Empirical investigation of factors contributing to the psychological safety climate on construction sites

Employees’ safety climate perceptions dictate their safety behavior because individuals act based on their perceptions of reality. Extensive empirical research in applied psychology has confirmed this relationship. However, rare efforts have been made to investigate the factors contributing to a favorable safety climate in construction research. As an initial effort to address the knowledge gap, this paper examines factors contributing to a psychological safety climate, an operationalization of a safety climate at the individual level, and, hence, the basic element of a safety climate at higher levels. A multiperspective framework of contributors to a psychological safety climate is estimated by a structural equation modeling technique using individual questionnaire responses from a random sample of construction project personnel. The results inform management of three routes to psychological safety climate: a client’s proactive involvement in safety management, a workforce-friendly workplace created by the project team, and transformational supervisors’ communication about safety matters with the workforce. This paper contributes to the field of construction engineering and management by highlighting a broader contextual influence in a systematic formation of psychological safety climate perceptions.