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This project investigates furniture design, focussing especially upon that for serial production. This necessitates a balance between aesthetics and manufacturing imperatives where the need for economical production has to be reconciled with the need for the pieces to be well able to endure sustained use. As a consequence, the designs have to be predicated upon soundengineering principles. To achieve the ideal of an art and physics synthesis, this body of research inquires into the models and concepts that are offered to us from natural solutions and the subsequent engineering solutions they suggest. In chapter one, I discuss significant background influences, being a preoccupation with music and the seemingly remote activity of sailing. I argue that both these activities are physical and that in fact they are quite sympathetic. Their influence is formative and automatic. Also discussed in the first chapter are a number of significant earlier designs. The works offered in my submission are described in chapter two. While all the objects are related, they are categorised in several groups where, by logic, they form a part of a closer family. The design rationale for each work is discussed and one in particular, the Dechaineux Theatre Lectern, is singled out to explain the process of design and construction for that work but it is indicative of the kind of process that all the pieces have undergone. Further, there is a brief description of significant related works that are not central to the project. Chapter three focuses upon three areas of inquiry. Unlike, the automatic or subconscious background influences described in chapter one, these are at the forefront of my mind. I describe my interest in the universal ideals of proportion, ratio, number and also music. The second area is that of the engineer, how structures are made and the principles that make them a success while the third area deals with the issue of sustainable design. In chapter four, I explain how the three areas of inquiry find expression in my work. In doing so I place this project within an 'ideas' context rather than a stylistic context. The conclusion documents outcomes and the progress of a number of the designs from my submission that are either being manufactured or are planned for manufacture. The potential influence that this project is having with furniture manufacturing in Tasmania is discussed as well as indications for future directions.

This project investigates furniture design, focussing especially upon that for serial production. This necessitates a balance between aesthetics and manufacturing imperatives where the need for economical production has to be reconciled with the need for the pieces to be well able to endure sustained use. As a consequence, the designs have to be predicated upon soundengineering principles. To achieve the ideal of an art and physics synthesis, this body of research inquires into the models and concepts that are offered to us from natural solutions and the subsequent engineering solutions they suggest. In chapter one, I discuss significant background influences, being a preoccupation with music and the seemingly remote activity of sailing. I argue that both these activities are physical and that in fact they are quite sympathetic. Their influence is formative and automatic. Also discussed in the first chapter are a number of significant earlier designs. The works offered in my submission are described in chapter two. While all the objects are related, they are categorised in several groups where, by logic, they form a part of a closer family. The design rationale for each work is discussed and one in particular, the Dechaineux Theatre Lectern, is singled out to explain the process of design and construction for that work but it is indicative of the kind of process that all the pieces have undergone. Further, there is a brief description of significant related works that are not central to the project. Chapter three focuses upon three areas of inquiry. Unlike, the automatic or subconscious background influences described in chapter one, these are at the forefront of my mind. I describe my interest in the universal ideals of proportion, ratio, number and also music. The second area is that of the engineer, how structures are made and the principles that make them a success while the third area deals with the issue of sustainable design. In chapter four, I explain how the three areas of inquiry find expression in my work. In doing so I place this project within an 'ideas' context rather than a stylistic context. The conclusion documents outcomes and the progress of a number of the designs from my submission that are either being manufactured or are planned for manufacture. The potential influence that this project is having with furniture manufacturing in Tasmania is discussed as well as indications for future directions.

Loss of functional adenomatous polyposis coli (APC) protein results in the stabilization of cytosolic beta-catenin and activation of genes that are responsive to Lef/Tcf family transcription factors. We have recently shown that an independent cell adhesion and integrin linked kinase (ILK)-dependent pathway can also activate beta-catenin/LEF mediated gene transcription and downregulate E-cadherin expression. In addition, ILK activity and expression are elevated in adenomatous polyposis and colon carcinomas. To examine the role of this pathway in the background of APC mutations we inhibited ILK activity in APC-/- human colon carcinoma cell lines. In all cases, inhibition of ILK resulted in substantial inhibition of TCF mediated gene transcription and inhibition of transcription and expression of the TCF regulated gene, cyclin D1. Inhibition of ILK resulted in decreased nuclear beta-catenin expression, and in the inhibition of phosphorylation of GSK-3 and stimulation of its activity, leading to accelerated degradation of beta-catenin. In addition, inhibition of ILK suppressed cell growth in culture as well as growth of human colon carcinoma cells in SCID mice. Strikingly, inhibition of ILK also resulted in the transcriptional stimulation of E-cadherin expression and correlated with the inhibition of gene transcription of snail, a repressor of E-cadherin gene expression. Overexpression of ILK caused a stimulation of expression of snail, but snail expression was found not to be regulated by beta-catenin/Tcf. These data demonstrate that ILK can regulate beta-catenin/TCF and snail transcription factors by distinct pathways. We propose that inhibition of ILK may be a useful strategy in the control of progression of colon as well as other carcinomas. Oncogene (2001) 20, 133 - 140.

Background: Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international consortium of 62 centres in 20 countries evaluating the use of targeted PCa screening in men with BRCA1/2 mutations. Objective: To report the first year's screening results for all men at enrolment in the study. Design, setting and participants: We recruited men aged 40-69 yr with germline BRCA1/2 mutations and a control group of men who have tested negative for a pathogenic BRCA1 or BRCA2 mutation known to be present in their families. All men underwent prostate-specific antigen (PSA) testing at enrolment, and those men with PSA > 3 ng/ml were offered prostate biopsy. Outcome measurements and statistical analysis: PSA levels, PCa incidence, and tumour characteristics were evaluated. The Fisher exact test was used to compare the number of PCa cases among groups and the differences among disease types. Results and limitations: We recruited 2481 men (791 BRCA1 carriers, 531 BRCA1 controls; 731 BRCA2 carriers, 428 BRCA2 controls). A total of 199 men (8%) presented with PSA > 3.0 ng/ml, 162 biopsies were performed, and 59 PCas were diagnosed (18 BRCA1 carriers, 10 BRCA1 controls; 24 BRCA2 carriers, 7 BRCA2 controls); 66% of the tumours were classified as intermediate-or high-risk disease. The positive predictive value (PPV) for biopsy using a PSA threshold of 3.0 ng/ml in BRCA2 mutation carriers was 48%-double the PPV reported in population screening studies. A significant difference in detecting intermediate-or high-risk disease was observed in BRCA2 carriers. Ninety-five percent of the men were white, thus the results cannot be generalised to all ethnic groups. Conclusions: The IMPACT screening network will be useful for targeted PCa screening studies in men with germline genetic risk variants as they are discovered. These preliminary results support the use of targeted PSA screening based on BRCA genotype and show that this screening yields a high proportion of aggressive disease. Patient summary: In this report, we demonstrate that germline genetic markers can be used to identify men at higher risk of prostate cancer. Targeting screening at these men resulted in the identification of tumours that were more likely to require treatment. (C) 2014 European Association of Urology. Published by Elsevier B. V. All rights reserved.

To characterize the synovial fluid (SF) derived T cell populations in psoriatic arthritis (PsA) and compare with similar populations from rheumatoid arthritis (RA).Paired peripheral blood (PB) and SF samples were analyzed by 3 color flow cytometry using monoclonal antibodies to CD3, CD4, CD8, HLA-DR, CD25, CD45RA, and CD45RO.There was a significantly increased CD8+ T cell population in PsA SF compared to RA: PsA mean 61% (range 35-93), RA mean 46% (range 6-72) (p0.005). This resulted in a reversal of the CD4:CD8 ratio in PsA SF compared to RA SF (p0.001). Patients with oligoarticular PsA had the most pronounced differences in SF derived T cell populations compared to RA (p0.0005) but these results were not significantly different from PsA patients with a polyarticular disease pattern. PB PsA T cell populations were not different from controls, in contrast to RA, where the CD4+ T cell population was increased (p0.0026), giving an exaggerated PB CD4:CD8 ratio. The majority of PsA SF CD8+ T cells expressed CD45RO, mean 73% (range 58-95), and HLA-DR antigen: mean 72% (range 38-94). Low levels of CD25 were detectable in this population, indicating a nonclassical activation pattern: mean 2% (range 0.3-4.4).In PsA, activated (HLA-DR+) and mature (CD45RO+) CD8+ T cells predominate in SE Analysis of this population may uncover clues to pathogenesis in this HLA class I mediated disease.