984 resultados para Onuchic, Nelson


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Leukocytes are critical effectors of inflammation and tumor biology. Chemokine-like factors produced by such inflammatory sites are key mediators of tumor growth that activate leukocytic recruitment and tumor infiltration and suppress immune surveillance. Here we report that the endocrine peptide hormone, relaxin, is a regulator of leukocyte biology with properties important in recruitment to sites of inflammation. This study uses the human monocytic cell line THP-1 and normal human peripheral blood mononuclear cells to define a novel role for relaxin in regulation of leukocyte adhesion and migration. Our studies indicate that relaxin promotes adenylate cyclase activation, substrate adhesion, and migratory capacity of mononuclear leukocytes through a relaxin receptor LGR7-dependent mechanism. Relaxin-stimulated cAMP accumulation was observed to occur primarily in non-adherent cells. Relaxin stimulation results in increased substrate adhesion and increased migratory activity of leukocytes. In addition, relaxin-stimulated substrate adhesion resulted in enhanced chemotaxis to monocyte chemoattractant protein-1. These responses in THP-1 and peripheral blood mononuclear cells are relaxin dose-dependent and proportional to cAMP accumulation. We further demonstrate that LGR7 is critical for mediating these biological responses by use of RNA interference lentiviral short hairpin constructs. In summary, we provide evidence that relaxin is a novel leukocyte stimulatory agent with properties affecting adhesion and chemomigration

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Hexachlorobenzene (HCB) is a persistent environmental contaminant that has the potential to interfere with steroid hormone regulation. The prostate requires precise control by androgens to regulate its growth and function. To determine if HCB impacts androgen action in the prostate, we used a number of methods. Our in vitro cell-culture-based assay used a firefly luciferase reporter gene driven by an androgen-responsive promoter. In the presence of dihydrotestosterone, low concentrations (0.5-5 nM) of HCB increased the androgen-responsive production of firefly luciferase and high concentrations of HCB (> 10 microM) suppressed this transcriptional activity. Results from a binding assay showed no evidence of affinity between HCB and the androgen receptor. We also tested HCB for in vivo effects using transgenic mice in which the transgene was a prostate-specific, androgen-responsive promoter upstream of a chloramphenicol acetyl transferase (CAT) reporter gene. In 4-week-old mice, the proportion of dilated prostate acini, a marker of sexual maturity, increased in the low HCB dose group and decreased in the high HCB dose mice. In the 8-week-old mice, there was a significant decrease in both CAT activity and prostate weight upon exposure to 20 mg/kg/day HCB. Therefore, in vitro and in vivo data suggest that HCB weakly agonizes androgen action, and consequently, low levels of HCB enhanced androgen action but high levels of HCB interfered. Environmental contaminants have been implicated in the rising incidence of prostate cancer, and insight into the mechanisms of endocrine disruption will help to clarify their role.

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Cell-cell and cell-matrix interactions play a major role in tumor morphogenesis and cancer metastasis. Therefore, it is crucial to create a model with a biomimetic microenvironment that allows such interactions to fully represent the pathophysiology of a disease for an in vitro study. This is achievable by using three-dimensional (3D) models instead of conventional two-dimensional (2D) cultures with the aid of tissue engineering technology. We are now able to better address the complex intercellular interactions underlying prostate cancer (CaP) bone metastasis through such models. In this study, we assessed the interaction of CaP cells and human osteoblasts (hOBs) within a tissue engineered bone (TEB) construct. Consistent with other in vivo studies, our findings show that intercellular and CaP cell-bone matrix interactions lead to elevated levels of matrix metalloproteinases, steroidogenic enzymes and the CaP biomarker, prostate specific antigen (PSA); all associated with CaP metastasis. Hence, it highlights the physiological relevance of this model. We believe that this model will provide new insights for understanding of the previously poorly understood molecular mechanisms of bone metastasis, which will foster further translational studies, and ultimately offer a potential tool for drug screening. © 2010 Landes Bioscience.

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Burkholderia pseudomallei, the causative agent of melioidosis is associated with soil. This study used a geographic information system (GIS) to determine the spatial distribution of clinical cases of melioidosis in the endemic suburban region of Townsville in Australia. A total of 65 cases over the period 1996–2008 were plotted using residential address. Two distinct groupings were found. One was around the base of a hill in the city centre and the other followed the old course of a major waterway in the region. Both groups (accounting for 43 of the 65 cases examined) are in areas expected to have particularly wet topsoils following intense rainfall, due to soil type or landscape position.

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The dominant economic paradigm currently guiding industry policy making in Australia and much of the rest of the world is the neoclassical approach. Although neoclassical theories acknowledge that growth is driven by innovation, such innovation is exogenous to their standard models and hence often not explored. Instead the focus is on the allocation of scarce resources, where innovation is perceived as an external shock to the system. Indeed, analysis of innovation is largely undertaken by other disciplines, such as evolutionary economics and institutional economics. As more has become known about innovation processes, linear models, based on research and development or market demand, have been replaced by more complex interactive models which emphasise the existence of feedback loops between the actors and activities involved in the commercialisation of ideas (Manley 2003). Currently dominant among these approaches is the national or sectoral innovation system model (Breschi and Malerba 2000; Nelson 1993), which is based on the notion of increasingly open innovation systems (Chesbrough, Vanhaverbeke, and West 2008). This chapter reports on the ‘BRITE Survey’ funded by the Cooperative Research Centre for Construction Innovation which investigated the open sectoral innovation system operating in the Australian construction industry. The BRITE Survey was undertaken in 2004 and it is the largest construction innovation survey ever conducted in Australia. The results reported here give an indication of how construction innovation processes operate, as an example that should be of interest to international audiences interested in construction economics. The questionnaire was based on a broad range of indicators recommended in the OECD’s Community Innovation Survey guidelines (OECD/Eurostat 2005). Although the ABS has recently begun to undertake regular innovation surveys that include the construction industry (2006), they employ a very narrow definition of the industry and only collect very basic data compared to that provided by the BRITE Survey, which is presented in this chapter. The term ‘innovation’ is defined here as a new or significantly improved technology or organisational practice, based broadly on OECD definitions (OECD/Eurostat 2005). Innovation may be technological or organisational in nature and it may be new to the world, or just new to the industry or the business concerned. The definition thus includes the simple adoption of existing technological and organisational advancements. The survey collected information about respondents’ perceptions of innovation determinants in the industry, comprising various aspects of business strategy and business environment. It builds on a pilot innovation survey undertaken by PricewaterhouseCoopers (PWC) for the Australian Construction Industry Forum on behalf of the Australian Commonwealth Department of Industry Tourism and Resources, in 2001 (PWC 2002). The survey responds to an identified need within the Australian construction industry to have accurate and timely innovation data upon which to base effective management strategies and public policies (Focus Group 2004).

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Sustainability decisions and their impacts may be among the greatest challenges facing the world in the 21st century (Davos 2000). Apart from adaptation on the part of established organizations these challenges are arguably going to require solutions developed by new actors However, young ventures have only recently begun generating research interest within sustainability literature (Shepherd et al. 2009). In particular, little is known about resource behaviours of these ventures and how they adapt to substantial resource constraints. One promising theory that has been identified as a way that some entrepreneurs manage constraints is bricolage: a construct defined as “making do by applying combinations of the resources at hand to new problems and opportunities” (Baker and Nelson 2005: 333). Bricolage may be critical as the means of continued venture success as these ventures are frequently developed in severe resource constraint, owing to higher levels of technical sophistication (Rothaermel and Deeds 2006). Further, they are often developed by entrepreneurs committed to personal and social goals of resourcefulness, including values that focus on conservation rather than consumption of resources (Shepherd et al. 2009). In this paper, using seven novel cases of high potential sustainability firms from CAUSEE we consider how constraints impact resource behaviours and further illustrate and extend bricolage domains previously developed by Baker and Nelson (2005) with recommendations for theory and practice provided.

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The importance of the first year experience (FYE) to success at university is well documented and supported with the transition into university regarded as crucial. While there is also support for the notion that a successful FYE should have a whole-of-institution focus and models have been proposed, many institutions still face challenges in achieving institution-wide FYE program implementation. This paper discusses the origins, theoretical and empirical bases and structure of an institution-wide approach to the FYE. It uses a case study of the Transitions In Project (TIP) at the Queensland University of Technology to illustrate how institution-wide FYE program implementation can be achieved and sustained. TIP had four inter-related projects focussing on at-risk students, first year curriculum, learning resources and staff development. The key aim of TIP was to identify good practice and institutionalise it in a sustainable way. The degree of success in achieving this is evaluated.

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Objectives To explore the extent of and factors associated with male residents who change wandering status post nursing home admission. Design Longitudinal design with secondary data analyses. Admissions over a 4-year period were examined using repeat assessments with the Minimum Data Set (MDS) to formulate a model understanding the development of wandering behavior. Setting One hundred thirty-four Veterans Administration (VA) nursing homes throughout the United States. Participants: Included 6673 residents admitted to VA nursing homes between October 2000 and October 2004. Measurements MDS variables (cognitive impairment, mood, behavior problems, activities of daily living and wandering) included ratings recorded at residents’ admission to the nursing home and a minimum of two other time points at quarterly intervals. Results The majority (86%) of the sample were classified as non wanderers at admission and most of these (94%) remained non wanderers until discharge or the end of the study. Fifty one per cent of the wanderers changed status to non wanderers with 6% of these residents fluctuating in status more than two times. Admission variables associated with an increased risk of changing status from non-wandering to wandering included older age, greater cognitive impairment, more socially inappropriate behavior, resisting care, easier distractibility, and needing less help with personal hygiene. Requiring assistance with locomotion and having three or more medical comorbidities were associated with a decreased chance of changing from non-wandering to wandering status. Conclusion A resident’s change from non-wandering to wandering status may reflect an undetected medical event that affects cognition, but spares mobility.

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There is widespread recognition that higher education institutions (HEIs) must actively support commencing students to ensure equity in access to the opportunities afforded by higher education. This role is particularly critical for students who because of educational, cultural or financial disadvantage or because they are members of social groups currently under-represented in higher education, may require additional transitional support to “level the playing field.” The challenge faced by HEIs is to provide this “support” in a way that is integrated into regular teaching and learning practices and reaches all commencing students. The Student Success Program (SSP) is an intervention in operation at the Queensland University of Technology (QUT) designed to identify and support those students deemed to be at risk of disengaging from their learning and their institution. Two sets of evidence of the impact of the SSP are presented: First, its expansion (a) from a one-faculty pilot project (Nelson, Duncan & Clarke, 2009) to all faculties and (b) into a variety of applications mirroring the student life cycle; and second, an evaluation of the impact of the SSP on students exposed to it. The outcomes suggest that: the SSP is an example of good practice that can be successfully applied to a variety of learning contexts and student enrolment situations; and the impact of the intervention on student persistence is sustained for at least 12 months and positively influences student retention. It is claimed that the good practice evidenced by the SSP is dependent on its integration into the broader First Year Experience Program at QUT as an example of transition pedagogy in action.

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About 1.6 million students currently study outside their home country. Despite this, and the fact that Australia, the United States, the United Kingdom and many of the other host countries of international students are themselves extremely culturally diverse communities, business education remains essentially mono-cultural in form and Anglo American in content. Whilst it is true that these international students may want to understand the "Western" way of doing things, they may not be familiar or comfortable with the processes used to facilitate learning. This paper explores a project undertaken to create a tool that provides essential pre-orientation information and advice to students before they leave home. Where cultural adjustment is required, catching students before departure is a very effective time to introduce key information about lifestyle, culture and approaches to teaching and learning that would assist students with the complex and difficult adjustment to studying abroad, so that they could make a smoother transition to their new place of learning. Welcome to Studying Business at QUT is a Data DVD with 19 short videos capturing a student perspective on life and study. Forty percent of the content is related to living and studying and includes sections on accommodation, lifestyle, food and transport etc., and 60% takes an in-depth look at studying business, featuring students and academics talking about issues such as assessment, academic writing and working in groups. This paper outlines the process of developing the DVD and the range of issues addressed.

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As higher education institutions respond to government targets to widen participation, their student populations will become increasingly diverse, and the issues around student success and retention will be more closely scrutinised. The concept of student engagement is a key factor in student achievement and retention and Australasian institutions have a range of initiatives aimed at monitoring and intervening with students who are at risk of disengaging. Within the widening participation agenda, it is absolutely critical that these initiatives are designed to enable success for all students, particularly those for whom social and cultural disadvantage have been a barrier. Consequently, for the sector, initiatives of this type must be consistent with the concept of social justice and a set of principles would provide this foundation. This session will provide an opportunity for participants to examine a draft set of principles and to discuss their potential value for the participants’ institutional contexts.

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The emerging theory of ‘bricolage’ as a resource behaviour represents an attempt to address the central entrepreneurship research problem of making systematic sense of entrepreneurs that sometimes manage to create significant new economic activity under what appears to be severe resource constraints (Baker & Nelson 2005). However, despite growing interest in bricolage there is little large scale empirical evidence about the effectiveness and outcomes of using bricolage processes while developing innovative outcomes in nascent and young firms. In this research we test bricolage using different forms of innovation using data from the Comprehensive Australian Study of Entrepreneurial Emergence (CAUSEE) project. Our results indicate overall positive results of bricolage with all forms of innovativeness. A discussion of the results and recommended future research is provided.

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This protocol represents an attempt to assist in the instruction of teamwork assessment for first-year students across QUT. We anticipate that teaching staff will view this protocol as a generic resource in teamwork instruction, processes and evaluation. Teamwork has been acknowledged as a problematic practice at QUT while existing predominantly in importance amongst graduate capabilities for all students at this institution. This protocol is not an extensive document on the complexities and dynamics of teamwork processes, but instead presents itself as a set of best practice guidelines and recommendations to assist in team design, development, management, support and assessment. It is recommended that this protocol be progressively implemented across QUT, not only to attain teamwork teaching consistency, but to address and deal with the misconceptions and conflict around the importance of the teamwork experience. The authors acknowledge the extensive input and contributions from a Teamwork Steering Committee selected from academic staff and administrative members across the institution. As well, we welcome feedback and suggestions to both fine tune and make inclusive those strategies that staff believe add to optimal teamwork outcomes.