Implication of 3D culture system for study of prostate cancer (CaP) mediated bone metastasis

Introduction : For the past decade, three dimensional (3D) culture has served as a foundation for regenerative medicine study. With an increasing awareness of the importance of cell-cell and cell-extracellular matrix interactions which are lacking in 2D culture system, 3D culture system has been employed for many other applications namely cancer research. Through development of various biomaterials and utilization of tissue engineering technology, many in vivo physiological responses are now better understood. The cellular and molecular communication of cancer cells and their microenvironment, for instance can be studied in vitro in 3D culture system without relying on animal models alone. Predilection of prostate cancer (CaP) to bone remains obscure due to the complexity of the mechanisms and lack of proper model for the studies. In this study, we aim to investigate the interaction between CaP cells and osteoblasts simulating the natural bone metastasis. We also further investigate the invasiveness of CaP cells and response of androgen sensitve CaP cells, LNCaP to synthetic androgen.----- Method : Human osteoblast (hOB) scaffolds were prepared by seeding hOB on medical grade polycaprolactone-tricalcium phosphate (mPLC-TCP) scaffolds and induced to produce bone matrix. CaP cell lines namely wild type PC3 (PC3-N), overexpressed prostate specific antigen PC3 (PC3k3s5) and LNCaP were seeded on hOB scaffolds as co-cultures. Morphology of cells was examined by Phalloidin-DAPI and SEM imaging. Gelatin zymography was performed on the 48 hours conditioned media (CM) from co-cultures to determine matrix metalloproteinase (MMP) activity. Gene expression of hOB/LNCaP co-cultures which were treated for 48 hours with 1nM synthetic androgen R1881 were analysed by quantitative real time PCR (qRT-PCR).----- Results : Co-culture of PCC/hOB revealed that the morphology of PCCs on the tissue engineered bone matrix varied from homogenous to heterogenous clusters. Enzymatically inactive pro-MMP2 was detected in CM from hOBs and PCCs cultured on scaffolds. Elevation in MMP9 activity was found only in hOB/PC3N co-culture. hOB/LNCaP co-culture showed increase in expression of key enzymes associated with steroid production which also corresponded to an increase in prostate specific antigen (PSA) and MMP9.----- Conclusions : Upregulation of MMP9 indicates involvement of ECM degradation during cancer invasion and bone metastases. Expression of enzymes involved in CaP progression, PSA, which is not expressed in osteoblasts, demonstrates that crosstalk between PCCs and osteoblasts may play a part in the aggressiveness of CaP. The presence of steroidogenic enzymes, particularly, RDH5, in osteoblasts and stimulated expression in co-culture, may indicate osteoblast production of potent androgens, fuelling cancer cell proliferation. Based on these results, this practical 3D culture system may provide greater understanding into CaP mediated bone metastasis. This allows the role of the CaP/hOB interaction with regards to invasive property and steroidogenesis to be further explored.

Off-world robotic excavation for Large-scale habitat construction and resource extraction

This paper describes technologies we have developed to perform autonomous large-scale off-world excavation. A scale dragline excavator of size similar to that required for lunar excavation was made capable of autonomous control. Systems have been put in place to allow remote operation of the machine from anywhere in the world. Algorithms have been developed for complete autonomous digging and dumping of material taking into account machine and terrain constraints and regolith variability. Experimental results are presented showing the ability to autonomously excavate and move large amounts of regolith and accurately place it at a specified location.

Teachers’ understanding of school connectedness : implications for the development and implementation of school based injury prevention strategies

Aim: Worldwide, injury is the leading cause of death and disability for young people. Injuries among young people are commonly associated with risk taking behaviour, including violence and transport risks, which often occur in the context of alcohol use. The school environment has been identified as having a significant role in shaping adolescent behaviour. In particular, school connectedness, the degree to which adolescents feel that they belong and are accepted at school, has been shown to be an important protective factor. Strategies for increasing school connectedness may therefore be effective in reducing risk taking and associated injury. Prior to developing connectedness strategies, it is important to understand the perspectives of those in the school regarding the construct and how it is realised in the school context. The aim of this research was to understand teachers’ perspectives of school connectedness, the strategies they employ to connect with students, and their perceptions of school connectedness as a strategy for risk taking and injury prevention. Method: In depth interviews of approximately 45 minutes duration were conducted with 13 Health and PE teachers and support staff from 2 high schools in Southeast Queensland, Australia. Additionally, 6 focus group workshop discussions were held with 35 Education department employees (5-6 per group), including teachers from 15 Southeast Queensland high schools. Results: Participants were found to place strong importance on the development of connectedness among students, including those at risk for problem behaviour. Strategies used to promote connectedness included building trust, taking an interest in each student and being available to talk to, and finding something positive for students to succeed at. Teachers identified strategies as being related to decreased risk taking behavior. Teacher training on school connectedness was perceived as an important and useful inclusion in a school based injury prevention program. Conclusions: The established link between increased school connectedness and decreased problem behaviour has implications for school based strategies designed to decrease adolescent risk taking behaviour and associated injury. Targeting school connectedness as a point of intervention, in conjunction with individual attitude and behaviour change programs, may be an effective injury prevention strategy.

Evolution of life drama program

Life Drama is a program of drama-based experiential learning activities involving groups of community leaders and members. The three-year project evolved from a theatre-in-education approach to an intercultural theatre approach incorporating Papua New Guinean performance traditions. It involved Australian, English and Papua New Guinean researchers at four key sites: Tari, Southern Highlands Province; Port Moresby, National Capital District; Madang, Madang Province; and Karkar Island, Madang Province. The project was innovative in a number of ways, including: a Participatory Action Research approach, involving community leaders at various levels as co-researchers; a participatory theatre approach as opposed to a performance approach; emphasis on sexual health promotion and HIV prevention through an experiential learning paradigm; addressing the norms and realities of the community rather than targeting only individual behaviour; an International Theatre Research Laboratory to explore the fusion of traditional cultural elements with contemporary health promotion aims; and an innovative method-assemblage approach to collecting and triangulating quantitative, qualitative, and performative data. The project attracted over $350,000 in funding and support from the Australian Research Council, National AIDS Secretariat in PNG, and private sector and non-government partners. Findings were presented at various conferences and symposia including the annual Medical Symposium in Wewak (2010), the triennial Research in Drama Education conference in Exeter (2011), and the International Research in Drama Education conference (Sydney 2009 and Limerick 2012). A number of peer-reviewed journal articles have been published. Elements of the program have been incorporated into the University of Goroka's compulsory HIV awareness program for undergraduate students. A national dissemination strategy for Life Drama in Papua New Guinea is now underway, with seed funding of AUD$74,000 from the National AIDS Council Secretariat, PNG.

Fast fourier analysis of structural organization in decellularized cartilage-on-bone laminates

Denaturation of tissues can provide a unique biological environment for regenerative medicine application only if minimal disruption of their microarchitecture is achieved during the decellularization process. The goal is to keep the structural integrity of such a construct as functional as the tissues from which they were derived. In this work, cartilage-on-bone laminates were decellularized through enzymatic, non-ionic and ionic protocols. This work investigated the effects of decellularization process on the microarchitecture of cartiligous extracellular matrix; determining the extent of how each process deteriorated the structural organization of the network. High resolution microscopy was used to capture cross-sectional images of samples prior to and after treatment. The variation of the microarchitecture was then analysed using a well defined fast Fourier image processing algorithm. Statistical analysis of the results revealed how significant the alternations among aforementioned protocols were (p < 0.05). Ranking the treatments by their effectiveness in disrupting the ECM integrity, they were ordered as: Trypsin> SDS> Triton X-100.

Anisotropy of articular cartilage reflects the ECM gradient architecture : Hough-Radon Transform Analysis

Tissue-specific extracellular matrix (ECM) is known to be an ideal bioscaffold to inspire the future of regenerative medicine. It holds the secret of how nature has developed such an organization of molecules into a unique functional complexity. This work exploited an innovative image processing algorithm and high resolution microscopy associated with mechanical analysis to establish a correlation between the gradient organization of cartiligous ECM and its anisotropic biomechanical response. This was hypothesized to be a reliable determinant that can elucidate how microarchitecture interrelates with biomechanical properties. Hough-Radon transform of the ECM cross-section images revealed its conformational variation from tangential interface down to subchondral region. As the orientation varied layer by layer, the anisotropic mechanical response deviated relatively. Although, results were in good agreement (Kendall's tau-b > 90%), there were evidences proposing that alignment of the fibrous network, specifically in middle zone, is not as random as it was previously thought.

Report on the AIDS Vaccine 2008 Conference

The "AIDS Vaccine 2008" Conference was held in Cape Town, South Africa (October 13 to 16, 2008) and organized, under the aegis of the Global HIV Vaccine Enterprise, by Dr. Lynn Morris (Chair of the Conference) National Institute of Communicable Diseases; Dr. Koleka Mlisana from CAPRISA, University KwaZulu-Natal, Durban, Dr. Glenda Gray from Perinatal HIV Research Unit, University Witwatersrand, Johannesburg and Dr. Carolyn Williamson from Institute of Infectious Diseses. and Molecular Medicine, UCT, Cape Town (Co-Chairs of the Conference). Since the first AIDS Vaccine conference, organized in Paris in 2000, this was the first time it was held outside of the U.S. and Europe, and involved nearly 1,000 participants. Besides three Plenary Sessions with ten state-of-the-art plenary lectures and one Keynote Lecture given by Dr. A.S. Fauci (Director of NIAID, NIH, USA), the Conference was organized in nine oral sessions, four poster discussion groups covering a wide spectrum of scientific information relating to HIV vaccine research and development. Moreover three Symposia, two Special Sessions, one Roundtable as well as two Debates were held, the latter focusing on current controversial topics. The conference opening was memorable for a number of reasons: among these was the presence of South Africa's new Minister of Health, Barbara Hogan who, in her first speech in a major forum as a senior member of the SA Government, affirmed that HIV causes AIDS, and that the search for a vaccine is of paramount importance to SA and the rest of the world. A scientific summary of the Conference is reported in the present article, divided into four major topics: (1) vaccine concepts and design; (2) T-cell immunology and innate immunity; (3) B-cell immunology, neutralizing antibodies and mucosal immunology; and (4) clinical trials. © 2009 Landes Bioscience.

Indigenous Australian women and work : an historical context

The aim of this on-going research is to interrogate the era of colonialism in Australia (1896-1966) and the denial of paid employment of Aboriginal women. The 1897 Aborigines Protection and the Restriction of the Sale of Opium Act witnessed thousands of Aboriginal people placed on Government run reserves and missions. This resulted in all aspects of their lives being controlled through state mechanisms. Under various Acts of Parliament, Aboriginal women were sent to privately owned properties to be utilised as ‘domestic servants’ through a system of forced indentured labour, which continued until the 1970’s. This paper discusses the hidden histories of these women through the use of primary sources documents including records from the Australian Department of Native Affairs and Department of Home and Health. This social history research reveals that the practice of removing Aboriginal women from their families at the age of 12 or 13 and to white families was more common practice than not. These women were often: not paid, worked up to 15 hour days, not allowed leave and subjected to many forms of abuse. Wages that were meant to be paid were re-directed to other others, including the Government. Whilst the retrieval of these ‘stolen wages’ is now an on-going issue resulting in the Queensland Government in 2002 offering AUS $2,000 to $4,000 in compensation for a lifetime of work, Aboriginal women were also asked to waive their legal right to further compensation. There are few documented histories of these Aboriginal women as told through the archives. This hidden Aboriginal Australian women’s history needs to be revealed to better understand the experiences and depth of misappropriation of Aboriginal women as domestic workers. In doing so, it also reveals a more accurate reflection of women’s work in Australia.

International hermelin brain tumor symposium on matricellular proteins in normal and cancer cell-matrix interactions

The second of the Hermelin Brain Tumor Center Symposia was held once again at Henry Ford Hospital in Detroit, Michigan on October 24th and 25th, 2003. A public conference was held on the 24th while a closed-door session took place on the 25th. The purpose of these symposia is to bring together experts in a particular field of study with the aim to share information with each other and the public, but then to meet privately to present novel data, hold discussions, and share concepts. While the interaction is intended to benefit all involved, the incentive is the expectation that the shared information will aid researchers at the Hermelin Brain Tumor Center in their quest to identify potential therapeutic targets and explore translational therapeutic strategies for the treatment of patients suffering nervous system tumors...

Modeling of protein signaling networks in clinical proteomics

Molecular interactions that underlie pathophysiological states are being elucidated using techniques that profile proteomicend points in cellular systems. Within the field of cancer research, protein interaction networks play pivotal roles in the establishment and maintenance of the hallmarks of malignancy, including cell division, invasion, and migration. Multiple complementary tools enable a multifaceted view of how signal protein pathway alterations contribute to pathophysiological states.One pivotal technique is signal pathway profiling of patient tissue specimens. This microanalysis technology provides a proteomic snapshot at one point in time of cells directly procured from the native context of a tumor micro environment. To study the adaptive patterns of signal pathway events over time, before and after experimental therapy, it is necessary to obtain biopsies from patients before, during, and after therapy. A complementary approach is the profiling of cultured cell lines with and without treatment. Cultured cell models provide the opportunity to study short-term signal changes occurring over minutes to hours. Through this type of system, the effects of particular pharmacological agents may be used to test the effects of signal pathway inhibition or activation on multiple endpoints within a pathway. The complexity of the data generated has necessitated the development of mathematical models for optimal interpretation of interrelated signaling pathways. In combination,clinical proteomic biopsy profiling, tissue culture proteomic profiling, and mathematical modeling synergistically enable a deeper understanding of how protein associations lead to disease states and present new insights into the design of therapeutic regimens.

Introduction : At the Intersection of Entrepreneurship and Human Resource Management

In recent years there has been a growing literature on human resource management (HRM) and smaller firms which has also encompassed firms that are growing and entrepreneurial. For example we have seen a special edition of Entrepreneurship Theory and Practice (Katz et al., 2000), two of Human Resource Management Review (Baron, 2003; Barrett and Mayson, 2006) and one of Human Resource Management (Huselid, 2003; Tansky and Heneman, 2003), with another of Human Resource Management (to be edited by Ribeiro, Roig and Tansky) scheduled for publication in 2010. In addition, symposia on the topic have been undertaken at the Academy of Management in 2005 (organized by Mayson) and in 2004 (organized by Hayton). Papers dealing with issues of HRM for new, small, growing and/or entrepreneurial firms have been presented at a range of different conferences, whether they are management oriented such as the Academy of Management (AoM) and its regional variants (for example, the British Academy of Management (BAM) or the Australian and New Zealand Academy of Management (ANZAM)), entrepreneurially focused ones like the Babson College Entrepreneurship Research conference or ones focused specifically on smaller firms such as the conferences of the Institute for Small Business and Entrepreneurship (ISBE) in the UK or the International Council for Small Business (ICSB) and its regional affiliates. With all these papers and all this discussion is there anything left to say? Well yes, we think there is and we are...

Cardiovascular diseases and vulnerable plaques: data, modeling, predictions and clinical applications PREFACE

Introduction Two symposia on “cardiovascular diseases and vulnerable plaques” Cardiovascular disease (CVD) is the leading cause of death worldwide. Huge effort has been made in many disciplines including medical imaging, computational modeling, bio- mechanics, bioengineering, medical devices, animal and clinical studies, population studies as well as genomic, molecular, cellular and organ-level studies seeking improved methods for early detection, diagnosis, prevention and treatment of these diseases [1-14]. However, the mechanisms governing the initiation, progression and the occurrence of final acute clinical CVD events are still poorly understood. A large number of victims of these dis- eases who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs [8,9]. Most cardiovascular diseases are associated with vulnerable plaques. A grand challenge here is to develop new imaging techniques, predictive methods and patient screening tools to identify vulnerable plaques and patients who are more vulnerable to plaque rupture and associated clinical events such as stroke and heart attack, and recommend proper treatment plans to prevent those clinical events from happening. Articles in this special issue came from two symposia held recently focusing on “Cardio-vascular Diseases and Vulnerable Plaques: Data, Modeling, Predictions and Clinical Applications.” One was held at Worcester Polytechnic Institute (WPI), Worcester, MA, USA, July 13-14, 2014, right after the 7th World Congress of Biomechanics. This symposium was endorsed by the World Council of Biomechanics, and partially supported by a grant from NIH-National Institute of Biomedical Image and Bioengineering. The other was held at Southeast University (SEU), Nanjing, China, April 18-20, 2014.

Introducing the multi-faceted teaching experiment

A mathematics classroom is comprised of many mathematicians with varying understanding of mathematics knowledge, including the teacher, students and sometimes researchers. To align with this conceptualisation of knowledge and understanding, the multi-faceted teaching experiment will be introduced as an approach to study all classroom participants’ interactions with the shared knowledge of mathematics. Drawing on the experiences of a large curriculum project, it is claimed that, unlike a multi-tiered teaching experiment, the multi-faceted teaching experiment provides a research framework that allows for the study of mathematicians’ building of knowledge in a classroom without privileging the experience of any one participant.