Cytotoxic C20 diterpenoid alkaloids from the Australian endemic rainforest plant Anopterus macleayanus

In order to identify new anticancer compounds from nature, a prefractionated library derived from Australian endemic plants was generated and screened against the prostate cancer cell line LNCaP using a metabolic assay. Fractions from the seeds, leaves, and wood of Anopterus macleayanus showed cytotoxic activity and were subsequently investigated using a combination of bioassay-guided fractionation and mass-directed isolation. This led to the identification of four new diterpenoid alkaloids, 6α-acetoxyanopterine (1), 4′-hydroxy-6α-acetoxyanopterine (2), 4′-hydroxyanopterine (3), and 11α-benzoylanopterine (4), along with four known compounds, anopterine (5), 7β-hydroxyanopterine (6), 7β,4′-dihydroxyanopterine (7), and 7β-hydroxy-11α-benzoylanopterine (8); all compounds were purified as their trifluoroacetate salt. The chemical structures of 1–8 were elucidated after analysis of 1D/2D NMR and MS data. Compounds 1–8 were evaluated for cytotoxic activity against a panel of human prostate cancer cells (LNCaP, C4-2B, and DuCaP) and nonmalignant cell lines (BPH-1 and WPMY-1), using a live-cell imaging system and a metabolic assay. All compounds showed potent cytotoxicity with IC50 values of <400 nM; compound 1 was the most active natural product from this series, with an IC50 value of 3.1 nM toward the LNCaP cell line. The live-cell imaging assay on 1–8 showed a concentration- and time-dependent effect on the cell morphology and proliferation of LNCaP cells.

From vision to actions: Towards adaptive and autonomous humanoid robots

Although robotics research has seen advances over the last decades robots are still not in widespread use outside industrial applications. Yet a range of proposed scenarios have robots working together, helping and coexisting with humans in daily life. In all these a clear need to deal with a more unstructured, changing environment arises. I herein present a system that aims to overcome the limitations of highly complex robotic systems, in terms of autonomy and adaptation. The main focus of research is to investigate the use of visual feedback for improving reaching and grasping capabilities of complex robots. To facilitate this a combined integration of computer vision and machine learning techniques is employed. From a robot vision point of view the combination of domain knowledge from both imaging processing and machine learning techniques, can expand the capabilities of robots. I present a novel framework called Cartesian Genetic Programming for Image Processing (CGP-IP). CGP-IP can be trained to detect objects in the incoming camera streams and successfully demonstrated on many different problem domains. The approach requires only a few training images (it was tested with 5 to 10 images per experiment) is fast, scalable and robust yet requires very small training sets. Additionally, it can generate human readable programs that can be further customized and tuned. While CGP-IP is a supervised-learning technique, I show an integration on the iCub, that allows for the autonomous learning of object detection and identification. Finally this dissertation includes two proof-of-concepts that integrate the motion and action sides. First, reactive reaching and grasping is shown. It allows the robot to avoid obstacles detected in the visual stream, while reaching for the intended target object. Furthermore the integration enables us to use the robot in non-static environments, i.e. the reaching is adapted on-the- fly from the visual feedback received, e.g. when an obstacle is moved into the trajectory. The second integration highlights the capabilities of these frameworks, by improving the visual detection by performing object manipulation actions.

Health complaints and regulatory reform: Implications for vulnerable populations?

Complaints and disciplinary processes play a significant role in health professional regulation. Many countries are transitioning from models of self-regulation to greater external oversight through systems including meta regulation, responsive (risk–based) regulation, and “networked governance”. Such systems harness, in differing ways, public, private, professional and non-governmental bodies to exert influence over the conduct of health professionals and services. Interesting literature is emerging regarding complainants’ motivations and experiences, the impact of complaints processes on health professionals and identification of features such as complainant and health professional profiles, types of complaints and outcomes. This paper concentrates on studies identifying vulnerable groups and their participation in health care regulatory systems.

A comparison of international occupational therapy competencies : implications for Australian standards in the new millennium

Background/aim: A timely evaluation of the Australian Competency Standards for Entry-Level Occupational Therapists© (1994) was conducted. This thorough investigation comprised a literature review exploring the concept of competence and the applications of competency standards; systematic benchmarking of the Australian Occupational Therapy Competency Standards (OT AUSTRALIA, 1994) against other national and international competency standards and other affiliated documents, from occupational therapy and other cognate disciplines; and extensive nationwide consultation with the professional community. This paper explores and examines the similarities and disparities between occupational therapy competency standards documents available in English from Australia and other countries.----- Methods: An online search for national occupational therapy competency standards located 10 documents, including the Australian competencies.----- Results: Four 'frameworks' were created to categorise the documents according to their conceptual underpinnings: Technical-Prescriptive, Enabling, Educational and Meta-Cognitive. Other characteristics that appeared to impact the design, content and implementation of competency standards, including definitions of key concepts, authorship, national and cultural priorities, scope of services, intended use and review mechanisms, were revealed.----- Conclusion: The proposed 'frameworks' and identification of influential characteristics provided a 'lens' through which to understand and evaluate competency standards. While consistent application of and attention to some of these characteristics appear to consolidate and affirm the authority of competency standards, it is suggested that the national context should be a critical determinant of the design and content of the final document. The Australian Occupational Therapy Competency Standards (OT AUSTRALIA, 1994) are critiqued accordingly, and preliminary recommendations for revision are proposed.

A process for the management of physical infrastructure

Physical infrastructure assets are important components of our society and our economy. They are usually designed to last for many years, are expected to be heavily used during their lifetime, carry considerable load, and are exposed to the natural environment. They are also normally major structures, and therefore present a heavy investment, requiring constant management over their life cycle to ensure that they perform as required by their owners and users. Given a complex and varied infrastructure life cycle, constraints on available resources, and continuing requirements for effectiveness and efficiency, good management of infrastructure is important. While there is often no one best management approach, the choice of options is improved by better identification and analysis of the issues, by the ability to prioritise objectives, and by a scientific approach to the analysis process. The abilities to better understand the effect of inputs in the infrastructure life cycle on results, to minimise uncertainty, and to better evaluate the effect of decisions in a complex environment, are important in allocating scarce resources and making sound decisions. Through the development of an infrastructure management modelling and analysis methodology, this thesis provides a process that assists the infrastructure manager in the analysis, prioritisation and decision making process. This is achieved through the use of practical, relatively simple tools, integrated in a modular flexible framework that aims to provide an understanding of the interactions and issues in the infrastructure management process. The methodology uses a combination of flowcharting and analysis techniques. It first charts the infrastructure management process and its underlying infrastructure life cycle through the time interaction diagram, a graphical flowcharting methodology that is an extension of methodologies for modelling data flows in information systems. This process divides the infrastructure management process over time into self contained modules that are based on a particular set of activities, the information flows between which are defined by the interfaces and relationships between them. The modular approach also permits more detailed analysis, or aggregation, as the case may be. It also forms the basis of ext~nding the infrastructure modelling and analysis process to infrastructure networks, through using individual infrastructure assets and their related projects as the basis of the network analysis process. It is recognised that the infrastructure manager is required to meet, and balance, a number of different objectives, and therefore a number of high level outcome goals for the infrastructure management process have been developed, based on common purpose or measurement scales. These goals form the basis of classifYing the larger set of multiple objectives for analysis purposes. A two stage approach that rationalises then weights objectives, using a paired comparison process, ensures that the objectives required to be met are both kept to the minimum number required and are fairly weighted. Qualitative variables are incorporated into the weighting and scoring process, utility functions being proposed where there is risk, or a trade-off situation applies. Variability is considered important in the infrastructure life cycle, the approach used being based on analytical principles but incorporating randomness in variables where required. The modular design of the process permits alternative processes to be used within particular modules, if this is considered a more appropriate way of analysis, provided boundary conditions and requirements for linkages to other modules, are met. Development and use of the methodology has highlighted a number of infrastructure life cycle issues, including data and information aspects, and consequences of change over the life cycle, as well as variability and the other matters discussed above. It has also highlighted the requirement to use judgment where required, and for organisations that own and manage infrastructure to retain intellectual knowledge regarding that infrastructure. It is considered that the methodology discussed in this thesis, which to the author's knowledge has not been developed elsewhere, may be used for the analysis of alternatives, planning, prioritisation of a number of projects, and identification of the principal issues in the infrastructure life cycle.

Mesenchymal stem cells

Cell based therapies as they apply to tissue engineering and regenerative medicine, require cells capable of self renewal and differentiation, and a prerequisite is to be able to prepare an effective dose of ex vivo expanded cells for autologous transplants. The in vivo identification of a source of physiologically relevant cell types suitable for cell therapies therefore figures as an integral part of tissue engineering. Stem cells serve as a reserve for biological repair, having the potential to differentiate into a number of specialised cell types within the body; they therefore represent the most useful candidates for cell based therapies. The primary goal of stem cell research is to produce cells that are both patient specific, as well as having properties suitable for the specific conditions for which they are intended to remedy. From a purely scientific perspective, stem cells allow scientists to gain a deeper understanding of developmental biology and regenerative therapies. Stem cells have acquired a number of uses for applications in regenerative medicine, immunotherapy, gene therapy, but it is in the area of tissue engineering that they generate most excitement, primarily as a result of their capacity for self-renewal and pluripotency. A unique feature of stem cells is their ability to maintain an uncommitted quiescent state in vivo and then, once triggered by conditions such as disease, injury or natural wear or tear, serve as a reservoir and natural support system to replenish lost cells. Although these cells retain the plasticity to differentiate into various tissues, being able to control this differentiation process is still one of the biggest challenges facing stem cell research. In an effort to harness the potential of these cells a number of studies have been conducted using both embryonic/foetal and adult stem cells. The use of embryonic stem cells (ESC) have been hampered by strong ethical and political concerns, this despite their perceived versatility due to their pluripotency. Ethical issues aside, other concerns raised with ESCs relates to the possibility of tumorigenesis, immune rejection and complications with immunosuppressive therapies, all of which adds layers of complications to the application ESC in research and which has led to the search for alternative sources for stem cells. The adult tissues in higher organisms harbours cells, termed adult stem cells, and these cells are reminiscent of unprogrammed stem cells. A number of sources of adult stem cells have been described. Bone marrow is by far the most accessible source of two potent populations of adult stem cells, namely haematopoietic stem cells (HSCs) and bone marrow mesenchymal stem cells (BMSCs). Autologously harvested adult stem cells can, in contrast to embryonic stem cells, readily be used in autografts, since immune rejection is not an issue; and their use in scientific research has not attracted the ethical concerns which have been the case with embryonic stem cells. The major limitation to their use, however, is the fact that adult stem cells are exceedingly rare in most tissues. This fact makes identifying and isolating these cells problematic; bone marrow being perhaps the only notable exception. Unlike the case of HSCs, there are as yet no rigorous criteria for characterizing MSCs. Changing acuity about the pluripotency of MSCs in recent studies has expanded their potential application; however, the underlying molecular pathways which impart the features distinctive to MSCs remain elusive. Furthermore, the sparse in vivo distribution of these cells imposes a clear limitation to their study in vitro. Also, when MSCs are cultured in vitro, there is a loss of the in vivo microenvironment, resulting in a progressive decline in proliferation potential and multipotentiality. This is further exacerbated with increased passage numbers in culture, characterized by the onset of senescence related changes. As a consequence, it is necessary to establish protocols for generating large numbers of MSCs but without affecting their differentiation potential. MSCs are capable of differentiating into mesenchymal tissue lineages, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Recent findings indicate that adult bone marrow may also contain cells that can differentiate into the mature, nonhematopoietic cells of a number of tissues, including cells of the liver, kidney, lung, skin, gastrointestinal tract, and myocytes of heart and skeletal muscle. MSCs can readily be expanded in vitro and can be genetically modified by viral vectors and be induced to differentiate into specific cell lineages by changing the microenvironment–properties which makes these cells ideal vehicles for cellular gene therapy. MSCs can also exert profound immunosuppressive effects via modulation of both cellular and innate immune pathways, and this property allows them to overcome the issue of immune rejection. Despite the many attractive features associated with MSCs, there are still many hurdles to overcome before these cells are readily available for use in clinical applications. The main concern relates to in vivo characterization and identification of MSCs. The lack of a universal biomarker, sparse in vivo distribution, and a steady age related decline in their numbers, makes it an obvious need to decipher the reprogramming pathways and critical molecular players which govern the characteristics unique to MSCs. This book presents a comprehensive insight into the biology of adult stem cells and their utility in current regeneration therapies. The adult stem cell populations reviewed in this book include bone marrow derived MSCs, adipose derived stem cells (ASCs), umbilical cord blood stem cells, and placental stem cells. The features such as MSC circulation and trafficking, neuroprotective properties, and the nurturing roles and differentiation potential of multiple lineages have been discussed in details. In terms of therapeutic applications, the strengths of MSCs have been presented and their roles in disease treatments such as osteoarthritis, Huntington’s disease, periodontal regeneration, and pancreatic islet transplantation have been discussed. An analysis comparing osteoblast differentiation of umbilical cord blood stem cells and MSCs has been reviewed, as has a comparison of human placental stem cells and ASCs, in terms of isolation, identification and therapeutic applications of ASC in bone, cartilage regeneration, as well as myocardial regeneration. It is my sincere hope that this book will update the reader as to the research progress of MSC biology and potential use of these cells in clinical applications. It will be the best reward to all contributors of this book, if their efforts herein may in some way help the readers in any part of their study, research, and career development.

Value-adding to cellulosic ethanol: Lignin polymers

Lignocellulosic waste materials are the most promising feedstock for generation of a renewable, carbon-neutral substitute for existing liquid fuels. The development of value-added products from lignin will greatly improve the economics of producing liquid fuels from biomass. This review gives an outline of lignin chemistry, describes the current processes of lignocellulosic biomass fractionation and the lignin products obtained through these processes, then outlines current and potential value-added applications of these products, in particular as components of polymer composites. Research highlights The use of lignocellulosic biomass to produce platform chemicals and industrial products enhances the sustainability of natural resources and improves environmental quality by reducing greenhouse and toxic emissions. In addition, the development of lignin based products improves the economics producing liquid transportation fuel from lignocellulosic feedstock. Value adding can be achieved by converting lignin to functionally equivalent products that rely in its intrinsic properties. This review outlines lignin chemistry and some potential high value products that can be made from lignin. Keywords: Lignocellulose materials; Lignin chemistry; Application

Variables governing the dynamics of attacker-defender systems in team sport

This project was a step forward in the examination and identification of key variables on the perception, decision making and action of team sport athletes through theoretical insights provided by the ecological dynamics perspective. The methodology drew on experiential knowledge of elite coaches to drive further empirical investigation into the specific task, environmental and personal constraints that shape the behaviour of athletes in specific performance contexts. The thesis has provided an effective rationale for further investigation into the emergent perception, decision making and action demanded of athletes in these unpredictable, fluent, fast-paced environments.

A Kallikrein 15 (KLK15) single nucleotide polymorphism located close to a novel exon shows evidence of association with poor ovarian cancer survival

KLK15 over-expression is reported to be a significant predictor of reduced progression-free survival and overall survival in ovarian cancer. Our aim was to analyse the KLK15 gene for putative functional single nucleotide polymorphisms (SNPs) and assess the association of these and KLK15 HapMap tag SNPs with ovarian cancer survival. Results In silico analysis was performed to identify KLK15 regulatory elements and to classify potentially functional SNPs in these regions. After SNP validation and identification by DNA sequencing of ovarian cancer cell lines and aggressive ovarian cancer patients, 9 SNPs were shortlisted and genotyped using the Sequenom iPLEX Mass Array platform in a cohort of Australian ovarian cancer patients (N = 319). In the Australian dataset we observed significantly worse survival for the KLK15 rs266851 SNP in a dominant model (Hazard Ratio (HR) 1.42, 95% CI 1.02-1.96). This association was observed in the same direction in two independent datasets, with a combined HR for the three studies of 1.16 (1.00-1.34). This SNP lies 15bp downstream of a novel exon and is predicted to be involved in mRNA splicing. The mutant allele is also predicted to abrogate an HSF-2 binding site. Conclusions We provide evidence of association for the SNP rs266851 with ovarian cancer survival. Our results provide the impetus for downstream functional assays and additional independent validation studies to assess the role of KLK15 regulatory SNPs and KLK15 isoforms with alternative intracellular functional roles in ovarian cancer survival.

An ingenious decision support system for remote health monitoring of pregnant women

Maternal deaths have been a critical issue for women living in rural and remote areas. The need to travel long distances, the shortage of primary care providers such as physicians, specialists and nurses, and the closing of small hospitals have been problems identified in many rural areas. Some research work has been undertaken and a few techniques have been developed to remotely measure the physiological condition of pregnant women through sophisticated ultrasound equipment. There are numerous ways to reduce maternal deaths, and an important step is to select the right approaches to achieving this reduction. One such approach is the provision of decision support systems in rural and remote areas. Decision support systems (DSSs) have already shown a great potential in many health fields. This thesis proposes an ingenious decision support system (iDSS) based on the methodology of survey instruments and identification of significant variables to be used in iDSS using statistical analysis. A survey was undertaken with pregnant women and factorial experimental design was chosen to acquire sample size. Variables with good reliability in any one of the statistical techniques such as Chi-square, Cronbach’s á and Classification Tree were incorporated in the iDSS. The decision support system was developed with significant variables such as: Place of residence, Seeing the same doctor, Education, Tetanus injection, Baby weight, Previous baby born, Place of birth, Assisted delivery, Pregnancy parity, Doctor visits and Occupation. The ingenious decision support system was implemented with Visual Basic as front end and Microsoft SQL server management as backend. Outcomes of the ingenious decision support system include advice on Symptoms, Diet and Exercise to pregnant women. On conditional system was sent and validated by the gynaecologist. Another outcome of ingenious decision support system was to provide better pregnancy health awareness and reduce long distance travel, especially for women in rural areas. The proposed system has qualities such as usefulness, accuracy and accessibility.

Spatial variation of particle number concentration in school microscale environment

There is significant toxicological evidence of the effects of ultrafine particles (<100nm) on human health (WHO 2005). Studies show that the number concentration of particles has been associated with adverse human health effects (Englert 2004). This work is part of a major study called ‘Ultrafine Particles form Traffic Emissions and Children’s Health’ (UPTECH), which seeks to determine the effect of the exposure to traffic related ultrafine particles on children’s health in schools (http://www.ilaqh.qut.edu.au/Misc/UPT ECH%20Home.htm). Quantification of spatial variation of particle number concentration (PNC) in a microscale environment and identification of the main affecting parameters and their contribution levels are the main aims of this analysis.

Career counseling people of African ancestry

One of the most important challenges facing the career counseling profession is developing effective strategies to counsel racially diverse individuals. Understanding the role of racial factors in career counseling requires an understanding of the impact of race on the development and identification of career concerns (Leong & Hartung, 1997 ). This chapter invites an understanding of career counseling with a focus on people of African ancestry. There is scant literature on the career development and career counseling of people of African ancestry including African Americans. This paucity of literature is explained, in part, by the fact that people of African ancestry have unique histories of being excluded from a broad range of human services, including career counseling. This chapter considers career counseling with people of African ancestry. First, the chapter explores how the African cultural belief of Ubuntu may influence individuals and then considers its possible influence on career counseling. Second,the chapter considers how cultural contexts may impact on the career counseling of individuals of African ancestry, specifically African Americans and African immigrants. Finally, social justice and narrative approaches to career counseling are examined as a means to address the needs of people of African ancestry in a range of cultural settings.

An ingenuous Decision Support System (iDSS) approach for remote area pregnant women

This paper addresses development of an ingenious decision support system (iDSS) based on the methodology of survey instruments and identification of significant variables to be used in iDSS using statistical analysis. A survey was undertaken with pregnant women and factorial experimental design was chosen to acquire sample size. Variables with good reliability in any one of the statistical techniques such as Chi-square, Cronbach’s α and Classification Tree were incorporated in the iDSS. The ingenious decision support system was implemented with Visual Basic as front end and Microsoft SQL server management as backend. Outcome of the ingenious decision support system include advice on Symptoms, Diet and Exercise to pregnant women.

How the environment affects opportunity recognition by entrepreneurs at the bottom of the pyramid

There is an army of bottom of the pyramid entrepreneurs (BOPE) who have the potential to transform developing economies, if they can identify and exploit business opportunities. BOPE could have unidentified resources that could lead to the recognition of radical new opportunities. This study paper asks how environmental factors and identification of resources affect Opportunity Recognition by BOP entrepreneurs in developing economies. To investigate this research question we conduct a literature review and plan semi-structured interviews of existing and nascent entrepreneurs in the largest and arguably the poorest country in Africa, the Democratic Republic of the Congo. In this paper we review the context of BOPE and describe the methodology we will use to gather and analyse data. Finally, we describe our access to suitable respondents for this study and how it will be conducted.

Novel keratins identified by quantitative proteomic analysis as the major cytoskeletal proteins of equine (Equus caballus) hoof lamellar tissue

The dermo-epidermal interface that connects the equine distal phalanx to the cornified hoof wall withstands great biomechanical demands, but is also a region where structural failure often ensues as a result of laminitis. The cytoskeleton in this region maintains cell structure and facilitates intercellular adhesion, making it likely to be involved in laminitis pathogenesis, although it is poorly characterized in the equine hoof lamellae. The objective of the present study was to identify and quantify the cytoskeletal proteins present in the epidermal and dermal lamellae of the equine hoof by proteomic techniques. Protein was extracted from the mid-dorsal epidermal and dermal lamellae from the front feet of 5 Standardbred geldings and 1 Thoroughbred stallion. Mass spectrometry-based spectral counting techniques, PAGE, and immunoblotting were used to identify and quantify cytoskeletal proteins, and indirect immunofluorescence was used for cellular localization of K14 and K124 (where K refers to keratin). Proteins identified by spectral counting analysis included 3 actin microfilament proteins; 30 keratin proteins along with vimentin, desmin, peripherin, internexin, and 2 lamin intermediate filament proteins; and 6 tubulin microtubule proteins. Two novel keratins, K42 and K124, were identified as the most abundant cytoskeletal proteins (22.0 ± 3.2% and 23.3 ± 4.2% of cytoskeletal proteins, respectively) in equine hoof lamellae. Immunoreactivity to K14 was localized to the basal cell layer, and that to K124 was localized to basal and suprabasal cells in the secondary epidermal lamellae. Abundant proteins K124, K42, K14, K5, and α1-actin were identified on 1- and 2-dimensional polyacrylamide gels and aligned with the results of previous studies. Results of the present study provide the first comprehensive analysis of cytoskeletal proteins present in the equine lamellae by using mass spectrometry-based techniques for protein quantification and identification.