Depth distribution of the velvet belly, Etmopterus spinax, in relation to growth and reproductive cycle: The case study of a deep-water lantern shark with a wide-ranging critical habitat

The velvet belly lantern shark, Etmopterus spinax (Squaliformes: Etmopteridae), is a small-sized squalid shark commonly found in deep waters off the Portuguese coast, mainly on soft bottoms. In this study, 67 research cruise bottom trawl tows (with 1-hour duration) were carried out at depths that ranged from 84 to 786 m. A total of 396 specimens (192 males and 204 females) were caught, with total lengths and ages ranging, respectively, from 10.2 to 32.9 cm and 0 to 7 years for males and from 9.8 to 41.1 cm and 0 to 10 years for females. Size, age, sex and maturity stages were found to be correlated with depth, with the larger, older and mostly mature specimens occurring predominantly at greater depths. There seems to be a depth-related migration, where the pregnant females migrate from deeper mating grounds to shallower nursery grounds. The sex ratios were relatively similar in the shallower strata, but females dominated at more than 600 m and were exclusive at more than 700 m. Fishing-related mortality may have complex and significant repercussions on this species, given that commercial fisheries are impacting different segments of this population differently.

Life cycle modelling and design knowledge development in 3D virtual environments : final report

Experience plays an important role in building management. “How often will this asset need repair?” or “How much time is this repair going to take?” are types of questions that project and facility managers face daily in planning activities. Failure or success in developing good schedules, budgets and other project management tasks depend on the project manager's ability to obtain reliable information to be able to answer these types of questions. Young practitioners tend to rely on information that is based on regional averages and provided by publishing companies. This is in contrast to experienced project managers who tend to rely heavily on personal experience. Another aspect of building management is that many practitioners are seeking to improve available scheduling algorithms, estimating spreadsheets and other project management tools. Such “micro-scale” levels of research are important in providing the required tools for the project manager's tasks. However, even with such tools, low quality input information will produce inaccurate schedules and budgets as output. Thus, it is also important to have a broad approach to research at a more “macro-scale.” Recent trends show that the Architectural, Engineering, Construction (AEC) industry is experiencing explosive growth in its capabilities to generate and collect data. There is a great deal of valuable knowledge that can be obtained from the appropriate use of this data and therefore the need has arisen to analyse this increasing amount of available data. Data Mining can be applied as a powerful tool to extract relevant and useful information from this sea of data. Knowledge Discovery in Databases (KDD) and Data Mining (DM) are tools that allow identification of valid, useful, and previously unknown patterns so large amounts of project data may be analysed. These technologies combine techniques from machine learning, artificial intelligence, pattern recognition, statistics, databases, and visualization to automatically extract concepts, interrelationships, and patterns of interest from large databases. The project involves the development of a prototype tool to support facility managers, building owners and designers. This final report presents the AIMMTM prototype system and documents how and what data mining techniques can be applied, the results of their application and the benefits gained from the system. The AIMMTM system is capable of searching for useful patterns of knowledge and correlations within the existing building maintenance data to support decision making about future maintenance operations. The application of the AIMMTM prototype system on building models and their maintenance data (supplied by industry partners) utilises various data mining algorithms and the maintenance data is analysed using interactive visual tools. The application of the AIMMTM prototype system to help in improving maintenance management and building life cycle includes: (i) data preparation and cleaning, (ii) integrating meaningful domain attributes, (iii) performing extensive data mining experiments in which visual analysis (using stacked histograms), classification and clustering techniques, associative rule mining algorithm such as “Apriori” and (iv) filtering and refining data mining results, including the potential implications of these results for improving maintenance management. Maintenance data of a variety of asset types were selected for demonstration with the aim of discovering meaningful patterns to assist facility managers in strategic planning and provide a knowledge base to help shape future requirements and design briefing. Utilising the prototype system developed here, positive and interesting results regarding patterns and structures of data have been obtained.

Life Cycle Modelling and Design Knowledge Development in 3D Virtual Environments

Experience plays an important role in building management. “How often will this asset need repair?” or “How much time is this repair going to take?” are types of questions that project and facility managers face daily in planning activities. Failure or success in developing good schedules, budgets and other project management tasks depend on the project manager's ability to obtain reliable information to be able to answer these types of questions. Young practitioners tend to rely on information that is based on regional averages and provided by publishing companies. This is in contrast to experienced project managers who tend to rely heavily on personal experience. Another aspect of building management is that many practitioners are seeking to improve available scheduling algorithms, estimating spreadsheets and other project management tools. Such “micro-scale” levels of research are important in providing the required tools for the project manager's tasks. However, even with such tools, low quality input information will produce inaccurate schedules and budgets as output. Thus, it is also important to have a broad approach to research at a more “macro-scale.” Recent trends show that the Architectural, Engineering, Construction (AEC) industry is experiencing explosive growth in its capabilities to generate and collect data. There is a great deal of valuable knowledge that can be obtained from the appropriate use of this data and therefore the need has arisen to analyse this increasing amount of available data. Data Mining can be applied as a powerful tool to extract relevant and useful information from this sea of data. Knowledge Discovery in Databases (KDD) and Data Mining (DM) are tools that allow identification of valid, useful, and previously unknown patterns so large amounts of project data may be analysed. These technologies combine techniques from machine learning, artificial intelligence, pattern recognition, statistics, databases, and visualization to automatically extract concepts, interrelationships, and patterns of interest from large databases. The project involves the development of a prototype tool to support facility managers, building owners and designers. This Industry focused report presents the AIMMTM prototype system and documents how and what data mining techniques can be applied, the results of their application and the benefits gained from the system. The AIMMTM system is capable of searching for useful patterns of knowledge and correlations within the existing building maintenance data to support decision making about future maintenance operations. The application of the AIMMTM prototype system on building models and their maintenance data (supplied by industry partners) utilises various data mining algorithms and the maintenance data is analysed using interactive visual tools. The application of the AIMMTM prototype system to help in improving maintenance management and building life cycle includes: (i) data preparation and cleaning, (ii) integrating meaningful domain attributes, (iii) performing extensive data mining experiments in which visual analysis (using stacked histograms), classification and clustering techniques, associative rule mining algorithm such as “Apriori” and (iv) filtering and refining data mining results, including the potential implications of these results for improving maintenance management. Maintenance data of a variety of asset types were selected for demonstration with the aim of discovering meaningful patterns to assist facility managers in strategic planning and provide a knowledge base to help shape future requirements and design briefing. Utilising the prototype system developed here, positive and interesting results regarding patterns and structures of data have been obtained.

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.

The urban water cycle : towards integrated resource management and more sustainable water management systems

The increasing scarcity of water in the world, along with rapid population increase in urban areas, gives reason for concern and highlights the need for integrating water and wastewater management practices. The uncontrolled growth in urban areas has made planning, management and expansion of water and wastewater infrastructure systems very difficult and expensive. In order to achieve sustainable wastewater treatment and promote the conservation of water and nutrient resources, this chapter advocates the need for a closed-loop treatment system approach, and the transformation of the traditional linear treatment systems into integrated cyclical treatment systems. The recent increased understanding of integrated resource management and a shift towards sustainable management and planning of water and wastewater infrastructure are also discussed.

Whole life cycle costing for Malaysia residential property development : the cultural environment

As knowledge of the residential development costing impact on resource and budgeting use increase, developers are moving towards more sustainable solution by implementing whole life cycle costing. Property management requires an understanding of infrastructure management, service life planning and quality management. Today, people are beginning to realize that effective property management in high-rise residential property can sustain the property value and maintain high returns on their investment. 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. For such reasons, this paper attempts to study the culture that have been applied due the residential property development in Malaysia as to improve to the best and sustainable practice in providing the best cost effectiveness management system in residential property development.

Inhibition of activated fibroblast growth factor receptor 2 in endometrial cancer cells induces cell death despite PTEN abrogation

KRAS activation and PTEN inactivation are frequent events in endometrial tumorigenesis, occurring in 10% to 30% and 26% to 80% of endometrial cancers, respectively. Because we have recently shown activating mutations in fibroblast growth factor receptor 2 (FGFR2) in 16% of endometrioid endometrial cancers, we sought to determine the genetic context in which FGFR2 mutations occur. Analysis of 116 primary endometrioid endometrial cancers revealed that FGFR2 and KRAS mutations were mutually exclusive, whereas FGFR2 mutations were seen concomitantly with PTEN mutations. Here, we show that shRNA knockdown of FGFR2 or treatment with a pan-FGFR inhibitor, PD173074, resulted in cell cycle arrest and induction of cell death in endometrial cancer cells with activating mutations in FGFR2. This cell death in response to FGFR2 inhibition occurred within the context of loss-of-function mutations in PTEN and constitutive AKT phosphorylation, and was associated with a marked reduction in extracellular signal-regulated kinase 1/2 activation. Together, these data suggest that inhibition of FGFR2 may be a viable therapeutic option in endometrial tumors possessing activating mutations in FGFR2, despite the frequent abrogation of PTEN in this cancer type.

Brivanib alaninate, a dual inhibitor of vascular endothelial growth factor receptor and fibroblast growth factor receptor tyrosine kinases, induces growth inhibition in mouse models of human hepatocellular carcinoma

PURPOSE: Hreceptor (VEGFR) and FGF receptor (FGFR) signaling pathways. EXPERIMENTAL DESIGN: Six different s.c. patient-derived HCC xenografts were implanted into mice. Tumor growth was evaluated in mice treated with brivanib compared with control. The effects of brivanib on apoptosis and cell proliferation were evaluated by immunohistochemistry. The SK-HEP1 and HepG2 cells were used to investigate the effects of brivanib on the VEGFR-2 and FGFR-1 signaling pathways in vitro. Western blotting was used to determine changes in proteins in these xenografts and cell lines. RESULTS: Brivanib significantly suppressed tumor growth in five of six xenograft lines. Furthermore, brivanib-induced growth inhibition was associated with a decrease in phosphorylated VEGFR-2 at Tyr(1054/1059), increased apoptosis, reduced microvessel density, inhibition of cell proliferation, and down-regulation of cell cycle regulators. The levels of FGFR-1 and FGFR-2 expression in these xenograft lines were positively correlated with its sensitivity to brivanib-induced growth inhibition. In VEGF-stimulated and basic FGF stimulated SK-HEP1 cells, brivanib significantly inhibited VEGFR-2, FGFR-1, extracellular signal-regulated kinase 1/2, and Akt phosphorylation. CONCLUSION: This study provides a strong rationale for clinical investigation of brivanib in patients with HCC.

Business cycle dynamics with duration dependence and leading indicators

Durland and McCurdy [Durland, J.M., McCurdy, T.H., 1994. Duration-dependent transitions in a Markov model of US GNP growth. Journal of Business and Economic Statistics 12, 279–288] investigated the issue of duration dependence in US business cycle phases using a Markov regime-switching approach, introduced by Hamilton [Hamilton, J., 1989. A new approach to the analysis of time series and the business cycle. Econometrica 57, 357–384] and extended to the case of variable transition parameters by Filardo [Filardo, A.J., 1994. Business cycle phases and their transitional dynamics. Journal of Business and Economic Statistics 12, 299–308]. In Durland and McCurdy’s model duration alone was used as an explanatory variable of the transition probabilities. They found that recessions were duration dependent whilst expansions were not. In this paper, we explicitly incorporate the widely-accepted US business cycle phase change dates as determined by the NBER, and use a state-dependent multinomial Logit modelling framework. The model incorporates both duration and movements in two leading indexes – one designed to have a short lead (SLI) and the other designed to have a longer lead (LLI) – as potential explanatory variables. We find that doing so suggests that current duration is not only a significant determinant of transition out of recessions, but that there is some evidence that it is also weakly significant in the case of expansions. Furthermore, we find that SLI has more informational content for the termination of recessions whilst LLI does so for expansions.

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.

Fatigue crack growth and fatigue life evaluation for welded steel bridge members with initial crack

Initial crack widely exists in the welded members of steel bridge induced by the welding procedure or by the fatigue damage crack initiation. The behavior of crack growth with a view to fatigue damage accumulation on the tip of cracks is discussed. Fatigue life of welded components with initial crack in bridges under traffic loading is investigated. Based on existing fatigue experiment results of welded members with initial crack and the fatigue experiment results of welded bridge members under constant stress cycles, the crack would keep semi-elliptical shape with variable ratio of a/c during the crack propagation. Based on the concept of continuum damage accumulated on the tip of fatigue cracks,the fatigue damage law suitable for steel bridge members under traffic loading is modified to consider the crack growth.The virtual crack growth method and the semi-elliptical crack shape assumption are proposed in this paper to deduce a new model of fatigue crack growth rate for welded bridge members under traffic loading. And the calculated method of the stress intensity factor necessary for evaluation of the fatigue life of welded bridge members with cracks is discussed.The proposed fatigue crack growth model is then applied to calculate the crack growth and the fatigue life of existing welded members with fatigue experimental results. The fatigue crack propagation computation results show that the ratio of crack depth to the half crack surface length a/c is variable during crack propagation process and the stress cycle increases with the increase of a0/c0 with certain a0/t0 .The calculated and measured fatigue lives are generally in good agreement,at some initial conditions of cracking, for welded members widely used in steel bridges.