The proximal first exon architecture of the murine ghrelin gene is highly similar to its human orthologue

BACKGROUND: The murine ghrelin gene (Ghrl), originally sequenced from stomach tissue, contains five exons and a single transcription start site in a short, 19 bp first exon (exon 0). We recently isolated several novel first exons of the human ghrelin gene and found evidence of a complex transcriptional repertoire. In this report, we examined the 5' exons of the murine ghrelin orthologue in a range of tissues using 5' RACE. -----FINDINGS: 5' RACE revealed two transcription start sites (TSSs) in exon 0 and four TSSs in intron 0, which correspond to 5' extensions of exon 1. Using quantitative, real-time RT-PCR (qRT-PCR), we demonstrated that extended exon 1 containing Ghrl transcripts are largely confined to the spleen, adrenal gland, stomach, and skin. -----CONCLUSION: We demonstrate that multiple transcription start sites are present in exon 0 and an extended exon 1 of the murine ghrelin gene, similar to the proximal first exon organisation of its human orthologue. The identification of several transcription start sites in intron 0 of mouse ghrelin (resulting in an extension of exon 1) raises the possibility that developmental-, cell- and tissue-specific Ghrl mRNA species are created by employing alternative promoters and further studies of the murine ghrelin gene are warranted.

Lesser-known worlds : bridging the telematic flows with located human experience through game design

This paper represents a new theorization of the role of location-based games (LBGs) as potentially playing specific roles in peoples’ access to the culture of cities [22]. A LBG is a game that employs mobile technologies as tools for game play in real world environments. We argue that as a new genre in the field of mobile entertainment, research in this area tends to be preoccupied with the newness of the technology and its commercial possibilities. However, this overlooks its potential to contribute to cultural production. We argue that the potential to contribute to cultural production lies in the capacity of these experiences to enhance relationships between specific groups and new urban spaces. Given that developers can design LBGs to be played with everyday devices in everyday environments, what new creative opportunities are available to everyday people?

Maintaining human agency in the design on context-aware systems : Design games in a dental surgery

This paper describes a series of design games, specifically aimed at exploring shifts in human agency in order to inform the design of context-aware applications. The games focused on understanding information handling issues in dental practice with participants from a university dental school playing an active role in the activities. Participatory design activities help participants to reveal potential implicit technical resources that can be presented explicitly in technologies in order to assist humans in managing their interactions with and amidst technical systems gracefully.

Ex vivo investigation of novel wound healing therapies and development of a 3-D human skin equivalent wound model

It has previously been found that complexes comprised of vitronectin and growth factors (VN:GF) enhance keratinocyte protein synthesis and migration. More specifically, these complexes have been shown to significantly enhance the migration of dermal keratinocytes derived from human skin. In view of this, it was thought that these complexes may hold potential as a novel therapy for healing chronic wounds. However, there was no evidence indicating that the VN:GF complexes would retain their effect on keratinocytes in the presence of chronic wound fluid. The studies in this thesis demonstrate for the first time that the VN:GF complexes not only stimulate proliferation and migration of keratinocytes, but also these effects are maintained in the presence of chronic wound fluid in a 2-dimensional (2-D) cell culture model. Whilst the 2-D culture system provided insights into how the cells might respond to the VN:GF complexes, this investigative approach is not ideal as skin is a 3-dimensional (3-D) tissue. In view of this, a 3-D human skin equivalent (HSE) model, which reflects more closely the in vivo environment, was used to test the VN:GF complexes on epidermopoiesis. These studies revealed that the VN:GF complexes enable keratinocytes to migrate, proliferate and differentiate on a de-epidermalised dermis (DED), ultimately forming a fully stratified epidermis. In addition, fibroblasts were seeded on DED and shown to migrate into the DED in the presence of the VN:GF complexes and hyaluronic acid, another important biological factor in the wound healing cascade. This HSE model was then further developed to enable studies examining the potential of the VN:GF complexes in epidermal wound healing. Specifically, a reproducible partial-thickness HSE wound model was created in fully-defined media and monitored as it healed. In this situation, the VN:GF complexes were shown to significantly enhance keratinocyte migration and proliferation, as well as differentiation. This model was also subsequently utilized to assess the wound healing potential of a synthetic fibrin-like gel that had previously been demonstrated to bind growth factors. Of note, keratinocyte re-epitheliasation was shown to be markedly improved in the presence of this 3-D matrix, highlighting its future potential for use as a delivery vehicle for the VN:GF complexes. Furthermore, this synthetic fibrin-like gel was injected into a 4 mm diameter full-thickness wound created in the HSE, both keratinocytes and fibroblasts were shown to migrate into this gel, as revealed by immunofluorescence. Interestingly, keratinocyte migration into this matrix was found to be dependent upon the presence of the fibroblasts. Taken together, these data indicate that reproducible wounds, as created in the HSEs, provide a relevant ex vivo tool to assess potential wound healing therapies. Moreover, the models will decrease our reliance on animals for scientific experimentation. Additionally, it is clear that these models will significantly assist in the development of novel treatments, such as the VN:GF complexes and the synthetic fibrin-like gel described herein, ultimately facilitating their clinical trial in the treatment of chronic wounds.

SNP technologies for drug discovery : a current review

Single nucleotide polymorphisms (SNPs) are unique genetic differences between individuals that contribute in significant ways to the determination of human variation including physical characteristics like height and appearance as well as less obvious traits such as personality, behaviour and disease susceptibility. SNPs can also significantly influence responses to pharmacotherapy and whether drugs will produce adverse reactions. The development of new drugs can be made far cheaper and more rapid by selecting participants in drug trials based on their genetically determined response to drugs. Technology that can rapidly and inexpensively genotype thousands of samples for thousands of SNPs at a time is therefore in high demand. With the completion of the human genome project, about 12 million true SNPs have been identified to date. However, most have not yet been associated with disease susceptibility or drug response. Testing for the appropriate drug response SNPs in a patient requiring treatment would enable individualised therapy with the right drug and dose administered correctly the first time. Many pharmaceutical companies are also interested in identifying SNPs associated with polygenic traits so novel therapeutic targets can be discovered. This review focuses on technologies that can be used for genotyping known SNPs as well as for the discovery of novel SNPs associated with drug response.

Computational power meets human contact

This chapter traces the development of the global digital storytelling movement from its origins in California to its adoption by the BBC in the UK and its subsequent dispersal around the world. It identifies the foundational practices, uneven development and diffusion, and emergent practices internationally.

Social justice and high-quality human services : visioning the place of a contemporary professional association

The current world situation is plagued by “wicked problems” and a widespread sense of “things are going to get worse”. We confront the almost imponderable consequences of global habitat destruction and climate change, as well as the meltdown of the financial markets with their largely yet to be seen damage to the “real economy”. These things will have considerable negative impacts on the social system and people's lives, particularly the disadvantaged and socially excluded, and require innovative policy and program responses delivered by caring, intelligent, and committed practitioners. These gargantuan issues put into perspective the difficulties that confront social, welfare, and community work today. Yet, in times of trouble, social work and human services tend to do well. For example, although Australian Social Workers and Welfare and Community Workers have experienced phenomenal job growth over the past 5 years, they also have good prospects for future growth and above average salaries in the seventh and sixth deciles, respectively (Department of Education, Employment and Workplace Relations, 2008). I aim to examine the host of reasons why the pursuit of social justice and high-quality human services is difficult to attain in today's world and then consider how the broadly defined profession of social welfare practitioners may collectively take action to (a) respond in ways that reassert our role in compassionately assisting the downtrodden and (b) reclaim the capacity to be a significant body of professional expertise driving social policy and programs. For too long social work has responded to the wider factors it confronts through a combination of ignoring them, critiquing from a distance, and concentrating on the job at hand and our day-to-day responsibilities. Unfortunately, “holding the line” has proved futile and, little by little, the broad social mandate and role of social welfare has altered until, currently, most social programs entail significant social surveillance of troublesome or dangerous groups, rather than assistance. At times it almost seems like the word “help” has been lost in the political and managerial lexicon, replaced by “manage” and “control”. Our values, beliefs, and ethics are under real threat as guiding principles for social programs.

A cluster-randomised intervention trial against Schistosoma japonicum in the Peoples' Republic of China: bovine and human transmission

Background Zoonotic schistosomiasis japonica is a major public health problem in China. Bovines, particularly water buffaloes, are thought to play a major role in the transmission of schistosomiasis to humans in China. Preliminary results (1998–2003) of a praziquantel (PZQ)-based pilot intervention study we undertook provided proof of principle that water buffaloes are major reservoir hosts for S. japonicum in the Poyang Lake region, Jiangxi Province. Methods and Findings Here we present the results of a cluster-randomised intervention trial (2004–2007) undertaken in Hunan and Jiangxi Provinces, with increased power and more general applicability to the lake and marshlands regions of southern China. The trial involved four matched pairs of villages with one village within each pair randomly selected as a control (human PZQ treatment only), leaving the other as the intervention (human and bovine PZQ treatment). A sentinel cohort of people to be monitored for new infections for the duration of the study was selected from each village. Results showed that combined human and bovine chemotherapy with PZQ had a greater effect on human incidence than human PZQ treatment alone. Conclusions The results from this study, supported by previous experimental evidence, confirms that bovines are the major reservoir host of human schistosomiasis in the lake and marshland regions of southern China, and reinforce the rationale for the development and deployment of a transmission blocking anti-S. japonicum vaccine targeting bovines.

Regulating Multi-National Corporations Through State-Based Laws : Problems with Enforcing Human Rights Under The Alien Tort Statute

Under the Alien Tort Statute United States of America (“America”) Federal Courts have the jurisdiction to hear claims for civil wrongs, committed against non-American citizens, which were perpetrated outside America’s national borders. The operation of this law has confronted American Federal Courts with difficulties on how to manage conflicts between American executive foreign policy and judicial interpretations of international law. Courts began to pass judgment over conduct which was approved by foreign governments. Then in 2005 the American Supreme Court wound back the scope of the Alien Tort Statute. This article will review the problems with the expansion of the Alien Tort Statute and the reasons for its subsequent narrowing.

The comprehensive Australian Study of entrepreneurial emergence (CAUSEE) high potential nascent entrepreneurs : some preliminary findings

Principal Topic The Comprehensive Australian Study of Entrepreneurial Emergence (CAUSEE) represents the first Australian study to employ and extend the longitudinal and large scale systematic research developed for the Panel Study of Entrepreneurial Dynamics (PSED) in the US (Gartner, Shaver, Carter and Reynolds, 2004; Reynolds, 2007). This research approach addresses several shortcomings of other data sets including under coverage; selection bias; memory decay and hindsight bias, and lack of time separation between the assessment of causes and their assumed effects (Johnson et al 2006; Davidsson 2006). However, a remaining problem is that any a random sample of start-ups will be dominated by low potential, imitative ventures. In recognition of this issue CAUSEE supplemented PSED-type random samples with theoretically representative samples of the 'high potential' emerging ventures employing a unique methodology using novel multiple screening criteria. We define new ''high-potential'' ventures as new entrepreneurial innovative ventures with high aspirations and potential for growth. This distinguishes them from those ''lifestyle'' imitative businesses that start small and remain intentionally small (Timmons, 1986). CAUSEE is providing the opportunity to explore, for the first time, if process and outcomes of high potentials differ from those of traditional lifestyle firms. This will allows us to compare process and outcome attributes of the random sample with the high potential over sample of new firms and young firms. The attributes in which we will examine potential differences will include source of funding, and internationalisation. This is interesting both in terms of helping to explain why different outcomes occur but also in terms of assistance to future policymaking, given that high growth potential firms are increasingly becoming the focus of government intervention in economic development policies around the world. The first wave of data of a four year longitudinal study has been collected using these samples, allowing us to also provide some initial analysis on which to continue further research. The aim of this paper therefore is to present some selected preliminary results from the first wave of the data collection, with comparisons of high potential with lifestyle firms. We expect to see owing to greater resource requirements and higher risk profiles, more use of venture capital and angel investment, and more internationalisation activity to assist in recouping investment and to overcome Australia's smaller economic markets Methodology/Key Propositions In order to develop the samples of 'high potential' in the NF and YF categories a set of qualification criteria were developed. Specifically, to qualify, firms as nascent or young high potentials, we used multiple, partly compensating screening criteria related to the human capital and aspirations of the founders as well as the novelty of the venture idea, and venture high technology. A variety of techniques were also employed to develop a multi level dataset of sources to develop leads and firm details. A dataset was generated from a variety of websites including major stakeholders including the Federal and State Governments, Australian Chamber of Commerce, University Commercialisation Offices, Patent and Trademark Attorneys, Government Awards and Industry Awards in Entrepreneurship and Innovation, Industry lead associations, Venture Capital Association, Innovation directories including Australian Technology Showcase, Business and Entrepreneurs Magazines including BRW and Anthill. In total, over 480 industry, association, government and award sources were generated in this process. Of these, 74 discrete sources generated high potentials that fufilled the criteria. 1116 firms were contacted as high potential cases. 331 cases agreed to participate in the screener, with 279 firms (134 nascents, and 140 young firms) successfully passing the high potential criteria. 222 Firms (108 Nascents and 113 Young firms) completed the full interview. For the general sample CAUSEE conducts screening phone interviews with a very large number of adult members of households randomly selected through random digit dialing using screening questions which determine whether respondents qualify as 'nascent entrepreneurs'. CAUSEE additionally targets 'young firms' those that commenced trading from 2004 or later. This process yielded 977 Nascent Firms (3.4%) and 1,011 Young Firms (3.6%). These were directed to the full length interview (40-60 minutes) either directly following the screener or later by appointment. The full length interviews were completed by 594 NF and 514 YF cases. These are the cases we will use in the comparative analysis in this report. Results and Implications The results for this paper are based on Wave one of the survey which has been completed and the data obtained. It is expected that the findings will assist in beginning to develop an understanding of high potential nascent and young firms in Australia, how they differ from the larger lifestyle entrepreneur group that makes up the vast majority of the new firms created each year, and the elements that may contribute to turning high potential growth status into high growth realities. The results have implications for Government in the design of better conditions for the creation of new business, firms who assist high potentials in developing better advice programs in line with a better understanding of their needs and requirements, individuals who may be considering becoming entrepreneurs in high potential arenas and existing entrepreneurs make better decisions.

Human resource management and innovation: what are knowledge-intensive firms doing?

An undeniable shift in focus from traditional production companies to Knowledge-Intensive Firms (KIFs) poses challenges for academics and practioners alike. In particular, effective management of an organization's human resources has become a critical issue for ensuring sustained innovation capacity. The relationship between Human Resource Management (HRM) in KIFs is however still a largely unexplored arena. The objective of this paper is to explore this relationship in an effort to identify HRM practices that support innovation. To this end, the paper includes reviews of the literature relevant to HRM and innovation in KIFs and four case studies from companies in Denmark and Australia that have been recognized for excellence in innovation. On the basis of content analyses conducted on the case data, some preliminary conclusions are posited regarding the role of HRM in KIFs. More specifically, the findings from this study suggest that while there are commonalities between HRM practices in traditional manufacturing companies and KIFs, there are also important differences, especially in terms of staffing practices. The paper contributes by offering recommendations for management of HRM in innovative KIFs and potential avenues for research to further develop our understanding of how HRM can support innovation in KIFs.

Regulation of human stem cell research in Australia

Australia is currently well placed to contribute to the global growth of human stem cell research. However, as the science has progressed, authorities have had to deal with the ongoing challenges of regulating such a fast moving field of scientific endeavour. Australia’s past and current approach to regulating the use of embryos in human embryonic stem cell research provides an insight into how Australia may continue to adapt to future regulatory challenges presented by human stem cell research. In the broader context, a number of issues have been identified that may impact upon the success of future human stem cell research in Australia.

Commercialisation of regenerative human tissue : Regulation and reform in Australia and England, Wales and Northern Ireland

The commercialisation of therapeutic products containing regenerative human tissue is regulated by the common law, statute and ethical guidelines in Australia and England, Wales and Northern Ireland. This article examines the regulatory regimes in these jurisdictions and considers whether reform is required to both support scientific research and ensure conformity with modern social views on medical research and the use of human tissue. The authors consider the crucial role of informed consent in striking the balance between the interests of researchers and the interests of the public.

Development of a biaxial compression device for biological samples : preliminary experimental results for a closed cell foam

Biological tissues are subjected to complex loading states in vivo and in order to define constitutive equations that effectively simulate their mechanical behaviour under these loads, it is necessary to obtain data on the tissue's response to multiaxial loading. Single axis and shear testing of biological tissues is often carried out, but biaxial testing is less common. We sought to design and commission a biaxial compression testing device, capable of obtaining repeatable data for biological samples. The apparatus comprised a sealed stainless steel pressure vessel specifically designed such that a state of hydrostatic compression could be created on the test specimen while simultaneously unloading the sample along one axis with an equilibrating tensile pressure. Thus a state of equibiaxial compression was created perpendicular to the long axis of a rectangular sample. For the purpose of calibration and commissioning of the vessel, rectangular samples of closed cell ethylene vinyl acetate (EVA) foam were tested. Each sample was subjected to repeated loading, and nine separate biaxial experiments were carried out to a maximum pressure of 204 kPa (30 psi), with a relaxation time of two hours between them. Calibration testing demonstrated the force applied to the samples had a maximum error of 0.026 N (0.423% of maximum applied force). Under repeated loading, the foam sample demonstrated lower stiffness during the first load cycle. Following this cycle, an increased stiffness, repeatable response was observed with successive loading. While the experimental protocol was developed for EVA foam, preliminary results on this material suggest that this device may be capable of providing test data for biological tissue samples. The load response of the foam was characteristic of closed cell foams, with consolidation during the early loading cycles, then a repeatable load-displacement response upon repeated loading. The repeatability of the test results demonstrated the ability of the test device to provide reproducible test data and the low experimental error in the force demonstrated the reliability of the test data.

Variations in MIMO-OFDM channel capacity due to random human movement in an indoor environment

Channel measurements and simulations have been carried out to observe the effects of pedestrian movement on multiple-input multiple-output orthogonal frequency division multiplexing (MIMO-OFDM) channel capacity. An in-house built MIMO-OFDM packet transmission demonstrator equipped with four transmitters and four receivers has been utilized to perform channel measurements at 5.2 GHz. Variations in the channel capacity dynamic range have been analysed for 1 to 10 pedestrians and different antenna arrays (2 × 2, 3 × 3 and 4 × 4). Results show a predicted 5.5 bits/s/Hz and a measured 1.5 bits/s/Hz increment in the capacity dynamic range with the number of pedestrian and the number of antennas in the transmitter and receiver array.