In vivo knockdown of the androgen receptor results in growth inhibition and regression of well-established, castration-resistant prostate tumours

Purpose: Progression to the castration-resistant state is the incurable and lethal end stage of prostate cancer, and there is strong evidence that androgen receptor (AR) still plays a central role in this process. We hypothesize that knocking down AR will have a major effect on inhibiting growth of castration-resistant tumors. Experimental Design: Castration-resistant C4-2 human prostate cancer cells stably expressing a tetracycline-inducible AR-targeted short hairpin RNA (shRNA) were generated to directly test the effects of AR knockdown in C4-2 human prostate cancer cells and tumors. Results:In vitro expression of AR shRNA resulted in decreased levels of AR mRNA and protein, decreased expression of prostate-specific antigen (PSA), reduced activation of the PSA-luciferase reporter, and growth inhibition of C4-2 cells. Gene microarray analyses revealed that AR knockdown under hormone-deprived conditions resulted in activation of genes involved in apoptosis, cell cycle regulation, protein synthesis, and tumorigenesis. To ensure that tumors were truly castration-resistant in vivo, inducible AR shRNA expressing C4-2 tumors were grown in castrated mice to an average volume of 450 mm3. In all of the animals, serum PSA decreased, and in 50% of them, there was complete tumor regression and disappearance of serum PSA. Conclusions: Whereas castration is ineffective in castration-resistant prostate tumors, knockdown of AR can decrease serum PSA, inhibit tumor growth, and frequently cause tumor regression. This study is the first direct evidence that knockdown of AR is a viable therapeutic strategy for treatment of prostate tumors that have already progressed to the castration-resistant state.

Positive relationships among collaboration for innovation, past innovation abandonment and future product introduction in manufacturing SMEs

The importance of collaboration for firm level innovation has been well established but much of the research focuses on large firms, with little research on small and medium enterprises. This paper investigates the links between product innovation and external collaboration and between future product innovation and past abandonment in small and medium sized firms, analysing data from 449 manufacturing firms, collected through the Australian Business Longitudinal Database. Our findings indicate firms that sought ideas or solutions from external network such as suppliers, or business partners reported higher level of new product introduction than firms that did not have any external collaboration. Further, firms with past abandonment experiences reported higher levels of new product introduction than firms that did not have such experience. Additionally, the findings indicated that firms with external collaboration were more likely to introduce new products even if they had previously experienced abandonment of a product innovation than firms without external collaboration. Implications, limitations and future research are outlined.

Examining the covert nature of product placement : implications for public policy

As consumers become better educated and more skeptical of traditional advertising, alternate forms of marketing communication have emerged that aim to influence audiences unobtrusively. One such example is product placement. Product placement has attracted ongoing debate as to whether it is covert, unethical, and influences consumption. The current article examines the nature and practice of product placement in this light. This taxonomy of product placement attributes is based on current marketing practice and examines whether this is, indeed, a covert marketing strategy. Further, it presents a conceptualization of the influence of product placement on consumer welfare. We highlight that the many forms of product placement necessitate independent evaluation to determine ethical and regulatory standards. Operational solutions for developing public policy are offered.

Boosting your product's country of origin

This article offers managerial implications for improving consumer perceptions of a product’s country of origin.

How do consumers react to physically larger models? Effects of model body size, weight control beliefs and product type on evaluations and body perceptions

The purpose of this article is to examine how a consumer’s weight control beliefs (WCB), a female advertising model’s body size (slim or large) and product type influence consumer evaluations and consumer body perceptions. The study uses an experiment of 371 consumers. The design of the experiment was a 2 (weight control belief: internal, external) X 2 (model size: larger sized, slim) X 2 (product type: weight controlling, non-weight controlling) between-participants factorial design. Results reveal two key contributions. First, larger sized models result in consumers feeling less pressure from society to be thin, viewing their actual shape as slimmer relative to viewing a slim model and wanting a thinner ideal body shape. Slim models result in the opposite effects. Second this research reveals a boundary condition for the extent to which endorser–product congruency theory can be generalized to endorsers of a larger body size. Results indicate that consumer WCB may be a useful variable to consider when marketers consider the use of larger models in advertising.

Assessing the leanness in product design : a model for planned design reuse

Shrinking product lifecycles, tough international competition, swiftly changing technologies, ever increasing customer quality expectation and demanding high variety options are some of the forces that drive next generation of development processes. To overcome these challenges, design cost and development time of product has to be reduced as well as quality to be improved. Design reuse is considered one of the lean strategies to win the race in this competitive environment. design reuse can reduce the product development time, product development cost as well as number of defects which will ultimately influence the product performance in cost, time and quality. However, it has been found that no or little work has been carried out for quantifying the effectiveness of design reuse in product development performance such as design cost, development time and quality. Therefore, in this study we propose a systematic design reuse based product design framework and developed a design leanness index (DLI) as a measure of effectiveness of design reuse. The DLI is a representative measure of reuse effectiveness in cost, development time and quality. Through this index, a clear relationship between reuse measure and product development performance metrics has been established. Finally, a cost based model has been developed to maximise the design leanness index for a product within the given set of constraints achieving leanness in design process.

An intelligent data mining technique for product quality improvement

Advances in data mining have provided techniques for automatically discovering underlying knowledge and extracting useful information from large volumes of data. Data mining offers tools for quick discovery of relationships, patterns and knowledge in large complex databases. Application of data mining to manufacturing is relatively limited mainly because of complexity of manufacturing data. Growing self organizing map (GSOM) algorithm has been proven to be an efficient algorithm to analyze unsupervised DNA data. However, it produced unsatisfactory clustering when used on some large manufacturing data. In this paper a data mining methodology has been proposed using a GSOM tool which was developed using a modified GSOM algorithm. The proposed method is used to generate clusters for good and faulty products from a manufacturing dataset. The clustering quality (CQ) measure proposed in the paper is used to evaluate the performance of the cluster maps. The paper also proposed an automatic identification of variables to find the most probable causative factor(s) that discriminate between good and faulty product by quickly examining the historical manufacturing data. The proposed method offers the manufacturers to smoothen the production flow and improve the quality of the products. Simulation results on small and large manufacturing data show the effectiveness of the proposed method.

Distinguishing forced versus discretionary replacements in new product diffusion models

In many product categories of durable goods such as TV, PC, and DVD player, the largest component of sales is generated by consumers replacing existing units. Aggregate sales models proposed by diffusion of innovation researchers for the replacement component of sales have incorporated several different replacement distributions such as Rayleigh, Weibull, Truncated Normal and Gamma. Although these alternative replacement distributions have been tested using both time series sales data and individual-level actuarial “life-tables” of replacement ages, there is no census on which distributions are more appropriate to model replacement behaviour. In the current study we are motivated to develop a new “modified gamma” distribution by two reasons. First we recognise that replacements have two fundamentally different drivers – those forced by failure and early, discretionary replacements. The replacement distribution for each of these drivers is expected to be quite different. Second, we observed a poor fit of other distributions to out empirical data. We conducted a survey of 8,077 households to empirically examine models of replacement sales for six electronic consumer durables – TVs, VCRs, DVD players, digital cameras, personal and notebook computers. This data allows us to construct individual-level “life-tables” for replacement ages. We demonstrate the new modified gamma model fits the empirical data better than existing models for all six products using both a primary and a hold-out sample.

Service enhanced manufacturing in the building and construction product system

This report examines the involvement of manufacturers in value-adding through service-enhancement of product offerings. This focus has been prompted by:  emphasis in the knowledge-economy literature on the increasing role played by services in economic growth; and  recent analysis which suggests that the most dynamic sector of many economies is an integrated manufacturing-services sector (see Part One of this report). The report initially describes the emergence of an integrated manufacturing-services sector in the context of increasingly knowledge-based economic systems. Part Two reports on the results of a survey of manufacturers in the building and construction product system, investigating their involvement in service provision. Parts Three and Four present two case studies of exemplary manufacturers involved in adding value to their manufacturing operations through services offered on building and construction projects. The report examines manufacturers of materials, products, equipment and machinery used on building and construction projects. The two case study sections of the report, in part, focus on a major project undertaken by each of the manufacturers. This project element of activity is focussed on (as opposed to wholesale or retail supply), because this area of activity involves a broader array of service-enhancement mechanisms and more complex bundling of products and services.

The building and construction product system : the emergence of new innovative businesses

This report examines the conditions surrounding the emergence and growth of innovative new firms in the building and construction product system. The focus on innovative new firms was prompted by diverse literatures which highlight the pivotal roles of innovation and new business activity in driving economic growth. 9 The literature concludes that the founders of new firms are likely to be innovative and that new firms are likely to promote industry innovation and efficiency. New businesses have also been found to have positive employment impacts and to grow faster than established firms.

Mapping the building and construction product system : preliminary report

This Preliminary Report has been prepared by researchers at The Australian Expert Group in Industry Studies (AEGIS) for the Commonwealth Department of Industry, Science and Resources. It is intended to provide a preliminary 'product system map' of the building and construction industries which defines the system, identifies the major segments, describes key industry players and institutions and provides the basis for exploring relationships, innovation and information flows within the industries. This Preliminary Report is the first of a series of five which will explore the building and construction product system in some depth. This first report does not present original research, although it does include some new interview data and analysis of a variety of written sources. This report is rather a reformulation of existing statistical and analytical material from a product system-based perspective. It is intended to provide the basis for subsequent studies by putting what is already known into an alternative framework and allowing us to see it through a new lens.

The dynamics and performance of the building and construction product system

During 1999 the Department of Industry, Science and Resources (ISR) published 4 research reports it had commissioned from the Australian Expert Group in Industry Studies (AEGIS), a research centre of the University of Western Sydney, Macarthur. ISR will shortly publish the fifth and final report in this series. The five reports were commissioned by the Department, as part of the Building and Construction Action Agenda process, to investigate the dynamics and performance of the sector, particularly in relation its innovative capacity. Professor Jane Marceau, PVCR at the University of Western Sydney and Director of AEGIS, led the research team. Dr Karen Manley was the researcher and joint author on three of the five reports. This paper outlines the approach and key findings of each of the five reports. The reports examined 5 key elements of the ‘building and construction product system’. The term ‘product system’ reflects the very broad range of industries and players we consider to contribute to the performance of the building and construction industries. The term ‘product system’ also highlights our focus on the systemic qualities of the building and construction industries. We were most interested in the inter-relationships between key segments and players and how these impacted on the innovation potential of the product system. The ‘building and construction product system’ is hereafter referred to as ‘the industry’ for ease of presentation. All the reports are based, at least in part, on an interviewing or survey research phase which involved gathering data from public and private sector players nationally. The first report ‘maps’ the industry to identify and describe its key elements and the inter-relationships between them. The second report focuses specifically on the linkages between public-sector research organisations and firms in the industry. The third report examines the conditions surrounding the emergence of new businesses in the industry. The fourth report examines how manufacturing businesses are responding to customer demands for ‘total solutions’ to their building and construction needs, by providing various services to clients. The fifth report investigates the capacity of the industry to encourage and undertake energy efficient building design and construction.

Inhibition of integrative cartilage repair by proteoglycan 4 in synovial fluid

To determine the effects of the articular cartilage surface, as well as synovial fluid (SF) and its components, specifically proteoglycan 4 (PRG4) and hyaluronic acid (HA), on integrative cartilage repair in vitro. Methods. Blocks of calf articular cartilage were harvested, some with the articular surface intact and others without. Some of the latter types of blocks were pretreated with trypsin, and then with bovine serum albumin, SF, PRG4, or HA. Immunolocalization of PRG4 on cartilage surfaces was performed after treatment. Pairs of similarly treated cartilage blocks were incubated in partial apposition for 2 weeks in medium supplemented with serum and 3 H-proline. Following culture, mechanical integration between apposed cartilage blocks was assessed by measuring adhesive strength, and protein biosynthesis and deposition were determined by incorporated 3 H-proline. Results. Samples with articular surfaces in apposition exhibited little integrative repair compared with samples with cut surfaces in apposition. PRG4 was immunolocalized at the articular cartilage surface, but not in deeper, cut surfaces (without treatment). Cartilage samples treated with trypsin and then with SF or PRG4 exhibited an inhibition of integrative repair and positive immunostaining for PRG4 at treated surfaces compared with normal cut cartilage samples, while samples treated with HA exhibited neither inhibited integrative repair nor PRG4 at the tissue surfaces. Deposition of newly synthesized protein was relatively similar under conditions in which integration differed significantly. Conclusion. These results support the concept that PRG4 in SF, which normally contributes to cartilage lubrication, can inhibit integrative cartilage repair. This has the desirable effect of preventing fusion of apposing surfaces of articulating cartilage, but has the undesirable effect of inhibiting integrative repair.

Data and process requirements for product recall coordination

When an organisation becomes aware that one of its products may pose a safety risk to customers, it must take appropriate action as soon as possible or it can be held liable. The ability to automatically trace potentially dangerous goods through the supply chain would thus help organisations fulfill their legal obligations in a timely and effective manner. Furthermore, product recall legislation requires manufacturers to separately notify various government agencies, the health department and the public about recall incidents. This duplication of effort and paperwork can introduce errors and data inconsistencies. In this paper, we examine traceability and notification requirements in the product recall domain from two perspectives: the activities carried out during the manufacturing and recall processes and the data collected during the enactment of these processes. We then propose a workflow-based coordination framework to support these data and process requirements.