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.

Assimilating cell sheets and hybrid scaffolds for dermal tissue engineering

Cell sheets can be used to produce neo-tissue with mature extracellular matrix. However, extensive contraction of cell sheets remains a problem. We devised a technique to overcome this problem and applied it to tissue engineer a dermal construct. Human dermal fibroblasts were cultured with poly(lactic-co-glycolic acid)-collagen meshes and collagen-hyaluronic acid foams. Resulting cell sheets were folded over the scaffolds to form dermal constructs. Human keratinocytes were cultured on these dermal constructs to assess their ability to support bilayered skin regeneration. Dermal constructs produced with collagen-hyaluronic acid foams showed minimal contraction, while those with poly(lactic-co-glycolic acid)-collagen meshes curled up. Cell proliferation and metabolic activity profiles were characterized with PicoGreen and AlamarBlue assays, respectively. Fluorescent labeling showed high cell viability and F-actin expression within the constructs. Collagen deposition was detected by immunocytochemistry and electron microscopy. Transforming Growth Factor-alpha and beta1, Keratinocyte Growth Factor and Vascular Endothelial Growth Factor were produced at various stages of culture, measured by RT-PCR and ELISA. These results indicated that assimilating cell sheets with mechanically stable scaffolds could produce viable dermal-like constructs that do not contract. Repeated enzymatic treatment cycles for cell expansion is unnecessary, while the issue of poor cell seeding efficiency in scaffolds is eliminated.

Identification of acoustic emission wave modes for accurate source location in plate-like structures

Acoustic emission (AE) technique is a popular tool used for structural health monitoring of civil, mechanical and aerospace structures. It is a non-destructive method based on rapid release of energy within a material by crack initiation or growth in the form of stress waves. Recording of these waves by means of sensors and subsequent analysis of the recorded signals convey information about the nature of the source. Ability to locate the source of stress waves is an important advantage of AE technique; but as AE waves travel in various modes and may undergo mode conversions, understanding of the modes (‘modal analysis’) is often necessary in order to determine source location accurately. This paper presents results of experiments aimed at finding locations of artificial AE sources on a thin plate and identifying wave modes in the recorded signal waveforms. Different source locating techniques will be investigated and importance of wave mode identification will be explored.

Shoot growth dynamics and photosynthetic response to increased nitrogen availability in the alpine willow salix-glauca

Plants subjected to increases in the supply of resource(s) limiting growth may allocate more of those resources to existing leaves, increasing photosynthetic capacity, and/or to production of more leaves, increasing whole-plant photosynthesis. The responses of three populations of the alpine willow, Salix glauca, growing along an alpine topographic sequence representing a gradient in soil moisture and organic matter, and thus potential N supply, to N amendments, were measured over two growing seasons, to elucidate patterns of leaf versus shoot photosynthetic responses. Leaf-(foliar N, photosynthesis rates, photosynthetic N-use efficiency) and shoot-(leaf area per shoot, number of leaves per shoot, stem weight, N resorption efficiency) level measurements were made to examine the spatial and temporal variation in these potential responses to increased N availability. The predominant response of the willows to N fertilization was at the shoot-level, by production of greater leaf area per shoot. Greater leaf area occurred due to production of larger leaves in both years of the experiment and to production of more leaves during the second year of fertilization treatment. Significant leaf-level photosynthetic response occurred only during the first year of treatment, and only in the dry meadow population. Variation in photosynthesis rates was related more to variation in stomatal conductance than to foliar N concentration. Stomatal conductance in turn was significantly related to N fertilization. Differences among the populations in photosynthesis, foliar N, leaf production, and responses to N fertilization indicate N availability may be lowest in the dry meadow population, and highest in the ridge population. This result is contrary to the hypothesis that a gradient of plant available N corresponds with a snowpack/topographic gradient.

An alginate-based hybrid system for growth factor delivery in the functional repair of large bone defects

The treatment of challenging fractures and large osseous defects presents a formidable problem for orthopaedic surgeons. Tissue engineering/regenerative medicine approaches seek to solve this problem by delivering osteogenic signals within scaffolding biomaterials. In this study, we introduce a hybrid growth factor delivery system that consists of an electrospun nanofiber mesh tube for guiding bone regeneration combined with peptide-modified alginate hydrogel injected inside the tube for sustained growth factor release. We tested the ability of this system to deliver recombinant bone morphogenetic protein-2 (rhBMP-2) for the repair of critically-sized segmental bone defects in a rat model. Longitudinal [mu]-CT analysis and torsional testing provided quantitative assessment of bone regeneration. Our results indicate that the hybrid delivery system resulted in consistent bony bridging of the challenging bone defects. However, in the absence of rhBMP-2, the use of nanofiber mesh tube and alginate did not result in substantial bone formation. Perforations in the nanofiber mesh accelerated the rhBMP-2 mediated bone repair, and resulted in functional restoration of the regenerated bone. [mu]-CT based angiography indicated that perforations did not significantly affect the revascularization of defects, suggesting that some other interaction with the tissue surrounding the defect such as improved infiltration of osteoprogenitor cells contributed to the observed differences in repair. Overall, our results indicate that the hybrid alginate/nanofiber mesh system is a promising growth factor delivery strategy for the repair of challenging bone injuries.

Urban growth monitoring techniques for sustainable development

This paper discusses the role of advance techniques for monitoring urban growth and change for sustainable development of urban environment. It also presents results of a case study involving satellite data for land use/land cover classification of Lucknow city using IRS-1C multi-spectral features. Two classification algorithms have been used in the study. Experiments were conducted to see the level of improvement in digital classification of urban environment using Artificial Neural Network (ANN) technique.

Embedding 'philosophy in the classroom' in pre-service teacher education

The holistic conception of the troika, as described in the first chapter, centres on the relationship between the implicit and explicit teaching of values the nurturing of the specific dimensions of quality teaching and the opportunity to ‘walk the talk’ of the values education program through aspects such as practical citizenship (Lovat, Toomey, Clement, Crotty & Nielsen, 2009). It is proposed in this chapter that the conception can be realized through the embedding of Philosophy in the Classroom within pre-service teaching programs. The troika, a Russian sleigh with three horses, only function well when there is complete synergy and balance between all Classroom is a scaffold for ensuring that all three elements of the troika, namely, quality teaching, values education and service learning in the form of education for citizenship, exist within the classroom to achieve an optimal learning, growth and wellbeing for all students. For this to be more widely accomplished Philosophy in the Classroom and discusses how it constitutes a successful synergy and balance of the troika for effective teaching. It then proposes how it might be embedded into pre-service teacher education.

Vitrification as a prospect for cryopreservation of tissue-engineered constructs

Cryopreservation plays a significant function in tissue banking and will presume yet larger value when more and more tissue-engineered products will routinely enter the clinical arena. The most common concept underlying tissue engineering is to combine a scaffold (cellular solids) or matrix (hydrogels) with living cells to form a tissue-engineered construct (TEC) to promote the repair and regeneration of tissues. The scaffold and matrix are expected to support cell colonization, migration, growth and differentiation, and to guide the development of the required tissue. The promises of tissue engineering, however, depend on the ability to physically distribute the products to patients in need. For this reason, the ability to cryogenically preserve not only cells, but also TECs, and one day even whole laboratory-produced organs, may be indispensable. Cryopreservation can be achieved by conventional freezing and vitrification (ice-free cryopreservation). In this publication we try to define the needs versus the desires of vitrifying TECs, with particular emphasis on the cryoprotectant properties, suitable materials and morphology. It is concluded that the formation of ice, through both direct and indirect effects, is probably fundamental to these difficulties, and this is why vitrification seems to be the most promising modality of cryopreservation

Examination of relationships between urban form, household activities, and time allocation in the Atlanta Metropolitan Region

A substantial body of research is focused on understanding the relationships between socio-demographics, land-use characteristics, and mode specific attributes on travel mode choice and time-use patterns. Residential and commercial densities, inter-mixing of land uses, and route directness in conjunction with transportation performance characteristics interact to influence accessibility to destinations as well as time spent traveling and engaging in activities. This study uniquely examines the activity durations undertaken for out-of-home subsistence; maintenance, and discretionary activities. Also examined are total tour durations (summing all activity categories within a tour). Cross-sectional activities are obtained from household activity travel survey data from the Atlanta Metropolitan Region. Time durations allocated to weekdays and weekends are compared. The censoring and endogeneity between activity categories and within individuals are captured using multiple equations Tobit models. The analysis and modeling reveal that land-use characteristics such as net residential density and the number of commercial parcels within a kilometer of a residence are associated with differences in weekday and weekend time-use allocations. Household type and structure are significant predictors across the three activity categories, but not for overall travel times. Tour characteristics such as time-of-day and primary travel mode of the tours also affect traveler's out-of-home activity-tour time-use patterns.

Innovation in construction : a case study of the Australian context

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).

Integrated sustainable urban infrastructure management: the Brisbane urban growth model

Sustainable urban development and the liveability of a city are increasingly important issues in the context of land use planning and infrastructure management. In recent years, the promotion of sustainable urban development in Australia and overseas is facing various physical, socio-economic and environmental challenges. These challenges and problems arise from the lack of capability of local governments to accommodate the needs of the population and economy in a relatively short timeframe. The planning of economic growth and development is often dealt with separately and not included in the conventional land use planning process. There is also a sharp rise in the responsibilities and roles of local government for infrastructure planning and management. This increase in responsibilities means that local elected officials and urban planners have less time to prepare background information and make decisions. The Brisbane Urban Growth Model has proven initially successful in providing a dynamic platform to ensure timely and coordinated delivery of urban infrastructure. Most importantly, this model is the first step for local governments in moving toward a systematic approach to pursuing sustainable and effective urban infrastructure management.

The role of sulphates and organic vapours in growth of newly formed particles in a eucalypt forest

The influence of biogenic particle formation on climate is a well recognised phenomenon. To understand the mechanisms underlying the biogenic particle formation, determining the chemical composition of the new particles and therefore the species that drive the particle production is of utmost importance. Due to the very small amount of mass involved, indirect approaches are frequently used to infer the composition. We present here the results of such an indirect approach by simultaneously measuring volatile and hygroscopic properties of newly formed particles in a forest environment. It is shown that the particles are composed of both sulphates and organics, with the amount of sulphate component strongly depending on the available gas-phase sulphuric acid, and the organic components having the same volatility and hygroscopicity as photooxidation products of a monoterpene such as α-pinene. Our findings agree with a two-step process through nucleation and cluster formation followed by simultaneous growth by condensation of sulphates and organics that take the particles to climatically relevant sizes.

Sustainable water provision : challenges, alternative strategies and sources in the era of climate change

As a result of rapid urbanisation, population growth, changes in lifestyle, pollution and the impacts of climate change, water provision has become a critical challenge for planners and policy-makers. In the wake of increasingly difficult water provision and drought, the notion that freshwater is a finite and vulnerable resource is increasingly being realised. Many city administrations around the world are struggling to provide water security for their residents to maintain lifestyle and economic growth. This chapter reviews the global challenge of providing freshwater to sustain lifestyles and economic growth, and the contributing challenges of climate change, urbanisation, population growth and problems in rainfall distribution. The chapter proceeds to evaluate major alternatives to current water sources such as conservation, recycling and reclamation, and desalination. Integrated water resource management is briefly looked at to explore its role in complementing water provision. A comparative study on alternative resources is undertaken to evaluate their strengths, weaknesses, opportunities and constraints, and the results are discussed.

Sustainable urban infrastructure development in south east Asia : evidence from Hong Kong, Kuala Lumpur and Singapore

Many South East Asian cities have experienced substantial physical, economic and social transformations during the past several decades. The rapid pace of globalisation and economic restructuring has resulted in these cities receiving the full impact of urbanisation pressures. In an attempt to ease these pressures, cities such as Singapore, Hong Kong and Kuala Lumpur have advocated growth management approaches focussing especially on urban infrastructure sustainability. These approaches aim to achieve triple bottom line sustainability by balancing economic and social development, and environmental protection. This chapter evaluates three Asia-Pacific city cases, Singapore, Hong Kong and Kuala Lumpur, and assesses their experiences in managing their urban forms and infrastructure whilst promoting sustainable patterns of urban development.

Brisbane urban growth model : an integrated infrastructure management framework for Brisbane, Australia

In recent years, local government infrastructure management practices have evolved from conventional land use planning to more wide ranging and integrated urban growth and infrastructure management approaches. The roles and responsibilities of local government are no longer simply to manage daily operational functions of a city and provide basic infrastructure. Local governments are now required to undertake economic planning, manage urban growth; be involved in major infrastructure planning; and even engage in achieving sustainable development objectives. The Brisbane Urban Growth model has proven initially successful to ensure timely and coordinated delivery of urban infrastructure. This model may be the first step for many local governments to move toward an integrated, sustainable and effective infrastructure management.