p53 prevents progression of nevi to melanoma predominantly through cell cycle regulation

p53 is the central member of a critical tumor suppressor pathway in virtually all tumor types, where it is silenced mainly by missense mutations. In melanoma, p53 predominantly remains wild type, thus its role has been neglected. To study the effect of p53 on melanocyte function and melanomagenesis, we crossed the 'high-p53'Mdm4+/- mouse to the well-established TP-ras0/+ murine melanoma progression model. After treatment with the carcinogen dimethylbenzanthracene (DMBA), TP-ras0/+ mice on the Mdm4+/- background developed fewer tumors with a delay in the age of onset of melanomas compared to TP-ras0/+ mice. Furthermore, we observed a dramatic decrease in tumor growth, lack of metastasis with increased survival of TP-ras0/+: Mdm4+/- mice. Thus, p53 effectively prevented the conversion of small benign tumors to malignant and metastatic melanoma. p53 activation in cultured primary melanocyte and melanoma cell lines using Nutlin-3, a specific Mdm2 antagonist, supported these findings. Moreover, global gene expression and network analysis of Nutlin-3-treated primary human melanocytes indicated that cell cycle regulation through the p21WAF1/CIP1 signaling network may be the key anti-melanomagenic activity of p53.

The life-cycle of the fashion garment and the role of Australian mass market designers

This paper uses the lens of life-cycle thinking to discuss recent developments in the Australian mass market fashion industry, and to explore the opportunities and barriers to implementing lifecycle thinking within mass market design processes. Life-cycle analysis is a quantitative tool used to assess the environmental impact of a material or product. However the underlying thinking of life-cycle analysis can also be employed more generally, enabling a designer to assess their processes and design decisions for sustainability. A fashion designer employing life cycle thinking would consider every stage in the life of a garment from fibre and textiles through to consumer use, to eventual disposal and beyond disposal to reuse and later disassembly for fibre recycling. Although life-cycle thinking is rarely considered in the design processes of the fast-paced, price-driven mass market, this paper explores its potential and suggests ways in which it could be implemented.

Public participation in infrastructure and construction projects in China: From an EIA-based to a whole-cycle process

Many governments world-wide are increasingly encouraging the involvement of interested individuals, groups and organisations in their publicinfrastructure and construction (PIC) projects as a means of improving the openness, transparency and accountability of the decision-making process and help improve the projects’ long-term viability and benefits to the community. In China, however, the current participatory mechanism at the project level exists only as part of the environmental impact assessment (EIA) process. With an increasing demand for PIC projects and social equality in China, this suggests a need to bring the participatory process into line with international practice. The aim of this paper, therefore, is to identify the weaknesses of EIA-basedpublicparticipation in China and the means by which it may be improved for the whole lifecycle of PIC schemes. To do this, the results of a series of interviews with a diverse group of experts is reported which analyse the nature and extent of existing problems of publicparticipation in EIA and suggestions for improvement. These indicate that the current level of participation in PIC projects is quite limited, particularly in the crucial earlier stages, primarily due to traditional culture and values, uneven progress in the adoption of participatory mechanisms, the risk of not meeting targets and lack of confidence in public competence. Finally, aprocess flowchart is proposed to guide construction practitioners and the community in general.

Spectrum sensing using two-stage detection to compensate for reduced primary user duty cycle

Spectrum sensing is considered to be one of the most important tasks in cognitive radio. One of the common assumption among current spectrum sensing detectors is the full presence or complete absence of the primary user within the sensing period. In reality, there are many situations where the primary user signal only occupies a portion of the observed signal and the assumption of primary user duty cycle not necessarily fulfilled. In this paper we show that the true detection performance can degrade from the assumed achievable values when the observed primary user exhibits a certain duty cycle. Therefore, a two-stage detection method incorporating primary user duty cycle that enhances the detection performance is proposed. The proposed detector can improve the probability of detection under low duty cycle at the expense of a small decrease in performance at high duty cycle.

The pomegranate cycle : reconfiguring opera through performance, technology & composition

The Pomegranate Cycle is a practice-led enquiry consisting of a creative work and an exegesis. This project investigates the potential of self-directed, technologically mediated composition as a means of reconfiguring gender stereotypes within the operatic tradition. This practice confronts two primary stereotypes: the positioning of female performing bodies within narratives of violence and the absence of women from authorial roles that construct and regulate the operatic tradition. The Pomegranate Cycle redresses these stereotypes by presenting a new narrative trajectory of healing for its central character, and by placing the singer inside the role of composer and producer. During the twentieth and early twenty-first century, operatic and classical music institutions have resisted incorporating works of living composers into their repertory. Consequently, the canon’s historic representations of gender remain unchallenged. Historically and contemporarily, men have almost exclusively occupied the roles of composer, conductor, director and critic, and therefore men have regulated the pedagogy, performance practices, repertoire and organisations that sustain classical music. In this landscape, women are singers, and few have the means to challenge the constructions of gender they are asked to reproduce. The Pomegranate Cycle uses recording technologies as the means of driving change because these technologies have already challenged the regulation of the classical tradition by changing people’s modes of accessing, creating and interacting with music. Building on the work of artists including Phillips and van Veen, Robert Ashley and Diamanda Galas, The Pomegranate Cycle seeks to broaden the definition of what opera can be. This work examines the ways in which the operatic tradition can be hybridised with contemporary musical forms such as ambient electronica, glitch, spoken word and concrete sounds as a way of bringing the form into dialogue with contemporary music cultures. The ultilisation of other sound cultures within the context of opera enables women’s voices and stories to be presented in new ways, while also providing a point of friction with opera’s traditional storytelling devices. The Pomegranate Cycle simulates aesthetics associated with Western art music genres by drawing on contemporary recording techniques, virtual instruments and sound-processing plug-ins. Through such simulations, the work disrupts the way virtuosic human craft has been used to generate authenticity and regulate access to the institutions that protect and produce Western art music. The DIY approach to production, recording, composition and performance of The Pomegranate Cycle demonstrates that an opera can be realised by a single person. Access to the broader institutions which regulate the tradition are not necessary. In short, The Pomegranate Cycle establishes that a singer can be more than a voice and a performing body. She can be her own multimedia storyteller. Her audience can be anywhere.

Sustainability in road transport : an integrated life cycle analysis for estimating emissions

Despite of a significant contribution of transport sector in the global economy and society, it is one of the largest sources of global energy consumption, green house gas emissions and environmental pollutions. A complete look onto the whole life cycle environmental inventory of this sector will be helpful to generate a holistic understanding of contributory factors causing emissions. Previous studies were mainly based on segmental views which mostly compare environmental impacts of different modes of transport, but very few consider impacts other than the operational phase. Ignoring the impacts of non-operational phases, e.g., manufacture, construction, maintenance, may not accurately reflect total contributions on emissions. Moreover an integrated study for all motorized modes of road transport is also needed to achieve a holistic estimation. The objective of this study is to develop a component based life cycle inventory model which considers impacts of both operational and non-operational phases of the whole life as well as different transport modes. In particular, the whole life cycle of road transport has been segmented into vehicle, infrastructure, fuel and operational components and inventories have been conducted on each component. The inventory model has been demonstrated using the road transport of Singapore. Results show that total life cycle green house gas emissions from the road transport sector of Singapore is 7.8 million tons per year, among which operational phase and non-operational phases contribute about 55% and about 45%, respectively. Total amount of criteria air pollutants are 46, 8.5, 33.6, 13.6 and 2.6 thousand tons per year for CO, SO2, NOx, VOC and PM10, respectively. From the findings, it can be deduced that stringent government policies on emission control measures have a significant impact on reducing environmental pollutions. In combating global warming and environmental pollutions the promotion of public transport over private modes is an effective sustainable policy.

Simple rules to contain an invasive species with a complex life cycle and high dispersal capacity

Designing practical rules for controlling invasive species is a challenging task for managers, particularly when species are long-lived, have complex life cycles and high dispersal capacities. Previous findings derived from plant matrix population analyses suggest that effective control of long-lived invaders may be achieved by focusing on killing adult plants. However, the cost-effectiveness of managing different life stages has not been evaluated. We illustrate the benefits of integrating matrix population models with decision theory to undertake this evaluation, using empirical data from the largest infestation of mesquite (Leguminosae: Prosopis spp) within Australia. We include in our model the mesquite life cycle, different dispersal rates and control actions that target individuals at different life stages with varying costs, depending on the intensity of control effort. We then use stochastic dynamic programming to derive cost-effective control strategies that minimize the cost of controlling the core infestation locally below a density threshold and the future cost of control arising from infestation of adjacent areas via seed dispersal. Through sensitivity analysis, we show that four robust management rules guide the allocation of resources between mesquite life stages for this infestation: (i) When there is no seed dispersal, no action is required until density of adults exceeds the control threshold and then only control of adults is needed; (ii) when there is seed dispersal, control strategy is dependent on knowledge of the density of adults and large juveniles (LJ) and broad categories of dispersal rates only; (iii) if density of adults is higher than density of LJ, controlling adults is most cost-effective; (iv) alternatively, if density of LJ is equal or higher than density of adults, management efforts should be spread between adults, large and to a lesser extent small juveniles, but never saplings. Synthesis and applications.In this study, we show that simple rules can be found for managing invasive plants with complex life cycles and high dispersal rates when population models are combined with decision theory. In the case of our mesquite population, focussing effort on controlling adults is not always the most cost-effective way to meet our management objective.

A framework for life cycle cost estimation of a product family at the early stage of product development

A cost estimation method is required to estimate the life cycle cost of a product family at the early stage of product development in order to evaluate the product family design. There are difficulties with existing cost estimation techniques in estimating the life cycle cost for a product family at the early stage of product development. This paper proposes a framework that combines a knowledge based system and an activity based costing techniques in estimating the life cycle cost of a product family at the early stage of product development. The inputs of the framework are the product family structure and its sub function. The output of the framework is the life cycle cost of a product family that consists of all costs at each product family level and the costs of each product life cycle stage. The proposed framework provides a life cycle cost estimation tool for a product family at the early stage of product development using high level information as its input. The framework makes it possible to estimate the life cycle cost of various product family that use any types of product structure. It provides detailed information related to the activity and resource costs of both parts and products that can assist the designer in analyzing the cost of the product family design. In addition, it can reduce the required amount of information and time to construct the cost estimation system.

Cytokine synthesis by intestinal intraepithelial lymphocytes. Both gamma/delta T cell receptor-positive and alpha/beta T cell receptor-positive T cells in the G1 phase of cell cycle produce IFN-gamma and IL-5

Murine intestinal intraepithelial lymphocytes (IEL) have been shown to contain subsets of alpha/beta TCR+ and gamma/delta TCR+ T cells that spontaneously produce cytokines such as IFN-gamma and IL-5. We have now determined the nature and cell cycle stage of these cytokine-producing T lymphocytes in EIL by using IFN-gamma- and IL-5-specific ELISPOT assay, cytokine-specific mRNA-cDNA dot-blot hybridization and polymerase chain reaction, and flow cytometry (FACS) for DNA analysis. When CD3+ T cells from IEL of normal C3H/HeN mice were separated into low and high density fractions by discontinuous Percoll gradients, IFN-gamma and IL-5 spot-forming cells were only found in the former population. Analysis of mRNA for these cytokines by both IFN-gamma- and IL-5-specific dot-blot hybridization and polymerase chain reaction revealed that higher levels of message for IFN-gamma and IL-5 were also seen in the low density fraction. However, cell cycle analysis of these two fractions by FACS using propidium iodide showed a similar pattern of cell cycle stages in both low and high density populations (G0 + G1 approximately 96 to 98% and S/G2 + M approximately 2 to 4%). Finally, mRNA from gamma/delta TCR+ and alpha/beta TCR+ T cells in both low and high density fractions of IEL were analyzed for IFN-gamma and IL-5 message by polymerase chain reaction. After 35 cycles of amplification, both gamma/delta TCR+ and alpha/beta TCR+ T cells in the low density fraction expressed higher levels of message for these two cytokines when compared with the high density population. These results have now shown that both gamma/delta and alpha/beta TCR+ IEL can be separated into low and high density subsets and both fractions possess a similar stage of cell cycle. However, only the low density cells (in G1 phase) of both gamma/delta and alpha/beta TCR types possess increased cytokine-specific mRNA and produce the cytokines IFN-gamma and IL-5. Our results suggest that alpha/beta TCR+ and gamma/delta TCR+ IEL can produce cytokines without cell proliferation.

Life cycle of the eel

Poem

Whole life cycle costing for Malaysia high-rise residential building : a needs?

The continuous growth of high-rise residential properties indicates that there is a need for an effective property management system to provide a sustainable high-rise residential property development. As intensive as these studies are, they do not attempt to investigate the correlation between property management systems with the trends of Malaysia high-rise residential property development. By examining the trends and scenario of Malaysia high-rise residential property development, this paper aims to gain an understanding of impacts from the effectiveness of property management in this scope area. Findings from this scoping paper will assist in providing a greater understanding and possible solutions for the current Malaysian property management systems for the expanding high-rise residential unit market.

An exploratory review of whole life cycle costing for Malaysia property development

The demand of implementing Whole Life Cycle Costing (WLCC) towards property development has increased since the launch of Value Management Circular 3/2009 by the Economic Planning Unit Malaysia. The circular made compulsory for all public construction projects and programme including property development estimated more than RM 50 Million to conduct WLCC. However, a knowledge gap on WLCC approach still exists and become a barrier among the practitioner in Malaysia particularly in property development industry. The main focus of this paper is to discuss the WLCC approach and introduce the indicator that need to be considered in Malaysia property development.

Ironmongeries life cycle costing and quality satisfaction

Most commonly, residents are always arguing about the satisfaction of sustainability and quality of their high rise residential property. This paper aim is to maintain the best quality satisfaction of the door hardware by introducing the whole life cycle costing approach to the property manager of the public housing in Johor. This paper looks into the current situation of ironmongeries (door hardware) of 2 public housings in Johor, Malaysia and testing the whole life cycle costing approach towards them. The calculation and the literature review are conducted. The questionnaire surveys of 2 public housings were conducted to make clear the occupants’ evaluation about the actual quality conditions of the ironmongeries in their house. As a result, the quality of door hardware based on the whole life cycle costing approach is one of the best among their previous decision making tool that have been applied. Practitioners can benefit from this paper as it provides information on calculating the whole life costing and making the decisions about ironmongeries selection of their properties.

Whole life cycle costing and quality satisfaction : public housing floor material

Most commonly, residents are always arguing about the satisfaction of sustainability and quality of their high rise residential property. This paper aim is to maintain the best quality satisfaction of the floor materials by introducing the whole life cycle costing approach to the property manager of the public housing in Johor. This paper looks into the current situation of floor material of two public housings in Johor, Malaysia and testing the whole life cycle costing approach towards them. The cost figures may be implemented to justify higher investments, for examples, in the quality or flexibility of building solutions through a long-term cost reduction. The calculation and the literature review are conducted. The questionnaire surveys of two public housings were conducted to make clear the occupants’ evaluation about the actual quality conditions of the floor material in their house. As a result, the quality of floor material based on the whole life cycle costing approach is one of the best among their previous decision making tool that was applied. Practitioners can benefit from this paper as it provides information on calculating the whole life costing and making the decisions for floor material selection for their properties.