Relaxin stimulates leukocyte adhesion and migration through a relaxin receptor LGR7-dependent mechanism

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

Sensitivity of the lane change test as a measure of in-vehicle system demand

The Lane Change Test (LCT) is one of the growing number of methods developed to quantify driving performance degradation brought about by the use of in-vehicle devices. Beyond its validity and reliability, for such a test to be of practical use, it must also be sensitive to the varied demands of individual tasks. The current study evaluated the ability of several recent LCT lateral control and event detection parameters to discriminate between visual-manual and cognitive surrogate In-Vehicle Information System tasks with different levels of demand. Twenty-seven participants (mean age 24.4 years) completed a PC version of the LCT while performing visual search and math problem solving tasks. A number of the lateral control metrics were found to be sensitive to task differences, but the event detection metrics were less able to discriminate between tasks. The mean deviation and lane excursion measures were able to distinguish between the visual and cognitive tasks, but were less sensitive to the different levels of task demand. The other LCT metrics examined were less sensitive to task differences. A major factor influencing the sensitivity of at least some of the LCT metrics could be the type of lane change instructions given to participants. The provision of clear and explicit lane change instructions and further refinement of its metrics will be essential for increasing the utility of the LCT as an evaluation tool.

An empirical test of causal relationships of factors affecting ICT adoption for building project management : an Indian SME case study

Purpose - Building project management (BPM) requires effective coordination and collaboration between multiple project team organisations which can be achieved by real time information flow between all participants. In the present scenario, this can be achieved by the use of information communication technologies (ICT). The purpose of this paper is to present part of a research project conducted to study the causal relationships between factors affecting ICT adoption for BPM by small and medium enterprises. Design/methodology/approach - This paper discusses structural equation modelling (SEM) analysis conducted to test the causal relationships between quantitative factors. Data for quantitative analysis were gathered through a questionnaire survey conducted in the Indian construction industry. Findings - SEM analysis results help in demonstrating that an increased and matured use of ICT for general administration within the organisation would lead to: an improved ICT infrastructure within the organisation; development of electronic databases; and a staff that is confident of using information technology (IT) tools. In such a scenario, staff would use advanced software and IT technologies for project management (PM) processes and that would lead to an increased adoption of ICT for PM processes. But, for general administration also, ICT adoption would be enhanced if the organisation is interacting more with geographically separated agencies and senior management perceives that significant benefits would accrue by adoption of ICT. All the factors are inter-related and their effect cannot be maximized in isolation. Originality/value - The results provide direction to building project managements for strategically adopting the effective use of ICT within their organisations and for BPM general.

Settlement geography of African refugee communities in Southeast Queensland : an analysis of residential distribution and secondary migration

Before 2001, most Africans immigrating to Australia were white South Africans and Zimbabweans who arrived as economic and family-reunion migrants (Cox, Cooper & Adepoju, 1999). Black African communities are a more recent addition to the Australian landscape, with most entering Australia as refugees after 2001. African refugees are a particularly disadvantaged immigrant group, which the Department of Immigration and Multicultural Affairs (in the Community Relations Commission of New South Wales, 2006) suggests require high levels of settlement support (p.23). Decision makers and settlement service providers need to have settlement data on the communities so that they can be effective in planning, budgeting and delivering support where it is most needed. Settlement data are also useful for determining the challenges that these communities face in trying to establish themselves in resettlement. There has been no verification of existing secondary data sources, however, or previous formal study of African refugee settlement geography in Southeast Queensland. This research addresses the knowledge gap by using a mixed-method approach to identify and describe the distribution and population size of eight African communities in Southeast Queensland, examine secondary migration patterns in these communities and assess the relationship between these geographic features and housing, a critical factor in successful settlement. Significant discrepancies exist between the primary data gathered in the study and existing secondary data relating to population size and distribution of the communities. Results also reveal a tension between the socio-cultural forces and the housing and economic imperatives driving secondary migration in the communities, and a general lack of engagement by African refugees with structured support networks. These findings have a wide range of implications for policy and for groups that provide settlement support to these communities.

Migration of breast cancer cells : understanding the roles of volume exclusion and cell-to-cell adhesion

We study MCF-7 breast cancer cell movement in a transwell apparatus. Various experimental conditions lead to a variety of monotone and nonmonotone responses which are difficult to interpret. We anticipate that the experimental results could be caused by cell-to-cell adhesion or volume exclusion. Without any modeling, it is impossible to understand the relative roles played by these two mechanisms. A lattice-based exclusion process random-walk model incorporating agent-to-agent adhesion is applied to the experimental system. Our combined experimental and modeling approach shows that a low value of cell-to-cell adhesion strength provides the best explanation of the experimental data suggesting that volume exclusion plays a more important role than cell-to-cell adhesion. This combined experimental and modeling study gives insight into the cell-level details and design of transwell assays.

Assessment of pile driving refusal using the standard test (SPT)

The design of driven pile foundations involves an iterative process requiring an initial estimate of the refusal level to determine the depth of boreholes for subsequent analyses. Current procedures for determining borehole depths incorporate parameters typically unknown at the investigation stage. Thus, a quantifiable procedure more applicable at this preliminary stage would provide greater confidence in estimating the founding level of driven piles. This paper examines the effectiveness of the Standard Penetration Test (SPT) in directly estimating driven pile refusal levels. A number of significant correlations were obtained between SPT information and pile penetration records demonstrating the potential application of the SPT. Results indicated pile penetration was generally best described as a function of both the pile toe and cumulative shaft SPT values. The influence of the toe SPT increased when piles penetrated rock. A refusal criteria was established from the results to guide both the estimation of borehole depths and likely pile lengths during the design stage.

Mechanistic investigations into interactions between IGF-I and IGFBPs and their impact on facilitating cell migration on vitronectin

Numerous studies have reported links between insulin-like growth factors (IGFs) and the extra-cellular matrix protein vitronectin (VN). We ourselves have reported that IGF-I binds to VN via IGF-binding proteins (IGFBPs) to stimulate HaCaT and MCF-7 cell migration. Here, we detail the functional evaluation of IGFBP-1, -2, -3, -4 and -6 in the presence and absence of IGF-I and VN. The data presented here, combined with our prior data on IGFBP-5, suggest that IGFBP-3, -4 and -5 are the most effective at stimulating cell migration in combination with IGF-I and VN. In addition, we demonstrate that different regions within IGFBP-3 and -4 are critical for complex formation. Furthermore, we examine whether multi-protein complexes of IGF-I and IGFBPs associated with fibronectin and collagen IV are also able to enhance functional biological responses.

Corneal confocal microscopy : a novel noninvasive test to diagnose and stratify the severity of human diabetic neuropathy

OBJECTIVE: The accurate quantification of human diabetic neuropathy is important to define at-risk patients, anticipate deterioration, and assess new therapies. ---------- RESEARCH DESIGN AND METHODS: A total of 101 diabetic patients and 17 age-matched control subjects underwent neurological evaluation, neurophysiology tests, quantitative sensory testing, and evaluation of corneal sensation and corneal nerve morphology using corneal confocal microscopy (CCM). ---------- RESULTS: Corneal sensation decreased significantly (P = 0.0001) with increasing neuropathic severity and correlated with the neuropathy disability score (NDS) (r = 0.441, P < 0.0001). Corneal nerve fiber density (NFD) (P < 0.0001), nerve fiber length (NFL), (P < 0.0001), and nerve branch density (NBD) (P < 0.0001) decreased significantly with increasing neuropathic severity and correlated with NDS (NFD r = −0.475, P < 0.0001; NBD r = −0.511, P < 0.0001; and NFL r = −0.581, P < 0.0001). NBD and NFL demonstrated a significant and progressive reduction with worsening heat pain thresholds (P = 0.01). Receiver operating characteristic curve analysis for the diagnosis of neuropathy (NDS >3) defined an NFD of <27.8/mm2 with a sensitivity of 0.82 (95% CI 0.68–0.92) and specificity of 0.52 (0.40–0.64) and for detecting patients at risk of foot ulceration (NDS >6) defined a NFD cutoff of <20.8/mm2 with a sensitivity of 0.71 (0.42–0.92) and specificity of 0.64 (0.54–0.74). ---------- CONCLUSIONS: CCM is a noninvasive clinical technique that may be used to detect early nerve damage and stratify diabetic patients with increasing neuropathic severity. Established diabetic neuropathy leads to pain and foot ulceration. Detecting neuropathy early may allow intervention with treatments to slow or reverse this condition (1). Recent studies suggested that small unmyelinated C-fibers are damaged early in diabetic neuropathy (2–4) but can only be detected using invasive procedures such as sural nerve biopsy (4,5) or skin-punch biopsy (6–8). Our studies have shown that corneal confocal microscopy (CCM) can identify early small nerve fiber damage and accurately quantify the severity of diabetic neuropathy (9–11). We have also shown that CCM relates to intraepidermal nerve fiber loss (12) and a reduction in corneal sensitivity (13) and detects early nerve fiber regeneration after pancreas transplantation (14). Recently we have also shown that CCM detects nerve fiber damage in patients with Fabry disease (15) and idiopathic small fiber neuropathy (16) when results of electrophysiology tests and quantitative sensory testing (QST) are normal. In this study we assessed corneal sensitivity and corneal nerve morphology using CCM in diabetic patients stratified for the severity of diabetic neuropathy using neurological evaluation, electrophysiology tests, and QST. This enabled us to compare CCM and corneal esthesiometry with established tests of diabetic neuropathy and define their sensitivity and specificity to detect diabetic patients with early neuropathy and those at risk of foot ulceration.

Destination positioning opportunities elicited through the repertory test with laddering analysis

While in many travel situations consumers have an almost limitless range of destinations to choose from, their actual decision set will usually only comprise between two and six destinations. One of the greatest challenges facing destination marketers is positioning their destination, against the myriad of competing places that offer similar features, into consumer decision sets. Since positioning requires a narrow focus, marketing communications must present a succinct and meaningful proposition, the selection of which is often problematic for destination marketing organisations (DMO), which deal with a diverse and often eclectic range of attributes in addition to numerous self-interested and demanding stakeholders. This paper reports the application of two qualitative techniques used to explore the range of cognitive attributes, consequences and personal values that represent potential positioning opportunities in the context of short break holidays. The Repertory Test is an effective technique for understanding the salient attributes used by a traveller to differentiate destinations, while Laddering Analysis enables the researcher to explore the smaller set of personal values guiding such decision making. A key finding of the research was that while individuals might vary in their repertoire of salient attributes, there was a commonality of shared consequences and values.

A measurement instrument for process modeling research : development, test and procedural model

Process modeling is an emergent area of Information Systems research that is characterized through an abundance of conceptual work with little empirical research. To fill this gap, this paper reports on the development and validation of an instrument to measure user acceptance of process modeling grammars. We advance an extended model for a multi-stage measurement instrument development procedure, which incorporates feedback from both expert and user panels. We identify two main contributions: First, we provide a validated measurement instrument for the study of user acceptance of process modeling grammars, which can be used to assist in further empirical studies that investigate phenomena associated with the business process modeling domain. Second, in doing so, we describe in detail a procedural model for developing measurement instruments that ensures high levels of reliability and validity, which may assist fellow scholars in executing their empirical research.

A test of podcasting effectiveness for lecture revision

It is important to understand how student performance when higher education is delivered by via new technology. Podcasting is a relatively recent new technology gaining widespread use across the world. We present the results of a quasi-experimental research project that finds when podcasts are used as a revision tool, student performance in Accounting improves. We highlight that aligning podcast use with pedagological design is important and discuss constraints on and barriers to the use of podcasting in higher education.

A virtual test assessment tool for second year signal processing students

The development and use of a virtual assessment tool for a signal processing unit is described. It allows students to take a test from anywhere using a web browser to connect to the university server that hosts the test. While student responses are of the multiple choice type, they have to work out problems to arrive at the answer to be entered. CGI programming is used to verify student identification information and record their scores as well as provide immediate feedback after the test is complete. The tool has been used at QUT for the past 3 years and student feedback is discussed. The virtual assessment tool is an efficient alternative to marking written assignment reports that can often take more hours than actual lecture hall contact from a lecturer or tutor. It is especially attractive for very large classes that are now the norm at many universities in the first two years.

A controlled rapid approach to curriculum change : addressing the pressures of increased test-based accountability on schools

Increasingly, large amounts of public and private money are being invested in education and as a result, schools are becoming more accountable to stakeholders for this financial input. In terms of the curriculum, governments worldwide are frequently tying school funding to students‟ and schools‟ academic performances, which are monitored through high-stakes testing programs. To accommodate the resultant pressures from these testing initiatives, many principals are re-focussing their school‟s curriculum on the testing requirements. Such a re-focussing, which was examined critically in this thesis, constituted an externally facilitated rapid approach to curriculum change. In line with previously enacted change theories and recommendations from these, curriculum change in schools has tended to be a fairly slow, considered, collaborative process that is facilitated internally by a deputy-principal (curriculum). However, theoretically based research has shown that such a process has often proved to be difficult and very rarely successful. The present study reports and theorises the experiences of an externally facilitated process that emerged from a practitioner model of change. This case study of the development of the controlled rapid approach to curriculum change began by establishing the reasons three principals initiated curriculum change and why they then engaged an outsider to facilitate the process. It also examined this particular change process from the perspectives of the research participants. The investigation led to the revision of the practitioner model as used in the three schools and challenged the current thinking about the process of school curriculum change. The thesis aims to offer principals and the wider education community an alternative model for consideration when undertaking curriculum change. Finally, the thesis warns that, in the longer term, the application of study‟s revised model (the Controlled Rapid Approach to Curriculum Change [CRACC] Model) may have less then desirable educational consequences.

A test of the job demands : resources model with HIV/AIDS volunteers

Burnout has been identified as a significant factor in HIV/AIDS volunteering. It has been associated with depression, anxiety and the loss of volunteers from the health care delivery system. The aim of this study was to test the independence of the health and motivational processes hypothesized within the Job Demands – Resources model of burnout in HIV/AIDS volunteers. Participants were 307 HIV/AIDS volunteers from state AIDS Councils throughout Australia who completed self-report measures pertaining to role ambiguity and role conflict, social support, burnout, intrinsic and organizational satisfaction, and depression. Findings suggested that the independence of the dual processes hypothesized by the model was only partially supported. These findings provide a model for burnout which gives a framework for interventions at both the individual and organizational level which would contribute to the prevention of burnout, depression, and job dissatisfaction in HIV/AIDS volunteers.

Insulin-like growth factor-i : vitronectin complex-induced changes in gene expression effect breast cell survival and migration

Recent studies have demonstrated that IGF-I associates with VN through IGF-binding proteins (IGFBP) which in turn modulate IGF-stimulated biological functions such as cell proliferation, attachment and migration. Since IGFs play important roles in transformation and progression of breast tumours, we aimed to describe the effects of IGF-I:IGFBP:VN complexes on breast cell function and to dissect mechanisms underlying these responses. In this study we demonstrate that substrate-bound IGF-I:IGFBP:VN complexes are potent stimulators of MCF-7 breast cell survival, which is mediated by a transient activation of ERK/MAPK and sustained activation of PI3-K/AKT pathways. Furthermore, use of pharmacological inhibitors of the MAPK and PI3-K pathways confirms that both pathways are involved in IGF-I:IGFBP:VN complex-mediated increased cell survival. Microarray analysis of cells stimulated to migrate in response to IGF-I:IGFBP:VN complexes identified differential expression of genes with previously reported roles in migration, invasion and survival (Ephrin-B2, Sharp-2, Tissue-factor, Stratifin, PAI-1, IRS-1). These changes were not detected when the IGF-I analogue (\[L24]\[A31]-IGF-I), which fails to bind to the IGF-I receptor, was substituted; confirming the IGF-I-dependent differential expression of genes associated with enhanced cell migration. Taken together, these studies have established that IGF-I:IGFBP:VN complexes enhance breast cell migration and survival, processes central to facilitating metastasis. This study highlights the interdependence of ECM and growth factor interactions in biological functions critical for metastasis and identifies potential novel therapeutic targets directed at preventing breast cancer progression.