536 research outputs found

    Application of a sustainability index for integrated urban water management in Southern African cities: Case study comparison – Maputo and Hermanus

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    Poor service provision in developing countries, and particularly the provision of water-related services, present serious challenges to urban development. It is estimated that 300 m. people in Africa do not have access to safe drinking water and 313 m. have limited access to adequate sanitation. The critical situation in the water sector continues to undermine strategies for poverty eradication and retards development. It is possible that the failure in service provision can in part be attributed to an inability by policy makers to address urban water management in a holistic  manner. In this study, a systems approach has been adopted to develop a composite index that could be used to assess the potential of a town or city to be sustainable. This index, the Sustainability Index for Integrated Urban Water Management (SIUWM) is composed of 5 components which disaggregate into 20 indicators and ultimately into 64 variables. Two Southern African urban centres, Hermanus and Maputo, were selected as initial case studies to test the applicability and validity of the index and to compare their sustainability index scores. Results of the SIUWM  application demonstrate that the index could highlight areas for  improvement and ultimately guide appropriate action and policy-making towards better service delivery and improved resource management

    Determination of composition and structure of spongy bone tissue in human head of femur by Raman spectral mapping

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    Biomechanical properties of bone depend on the composition and organization of collagen fibers. In this study, Raman microspectroscopy was employed to determine the content of mineral and organic constituents and orientation of collagen fibers in spongy bone in the human head of femur at the microstructural level. Changes in composition and structure of trabecula were illustrated using Raman spectral mapping. The polarized Raman spectra permit separate analysis of local variations in orientation and composition. The ratios of ν2PO43−/Amide III, ν4PO43−/Amide III and ν1CO32−/ν2PO43− are used to describe relative amounts of spongy bone components. The ν1PO43−/Amide I ratio is quite susceptible to orientation effect and brings information on collagen fibers orientation. The results presented illustrate the versatility of the Raman method in the study of bone tissue. The study permits better understanding of bone physiology and evaluation of the biomechanical properties of bone

    Glutamate Slows Axonal Transport of Neurofilaments in Transfected Neurons

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    Neurofilaments are transported through axons by slow axonal transport. Abnormal accumulations of neurofilaments are seen in several neurodegenerative diseases, and this suggests that neurofilament transport is defective. Excitotoxic mechanisms involving glutamate are believed to be part of the pathogenic process in some neurodegenerative diseases, but there is currently little evidence to link glutamate with neurofilament transport. We have used a novel technique involving transfection of the green fluorescent protein–tagged neurofilament middle chain to measure neurofilament transport in cultured neurons. Treatment of the cells with glutamate induces a slowing of neurofilament transport. Phosphorylation of the side-arm domains of neurofilaments has been associated with a slowing of neurofilament transport, and we show that glutamate causes increased phosphorylation of these domains in cell bodies. We also show that glutamate activates members of the mitogen-activated protein kinase family, and that these kinases will phosphorylate neurofilament side-arm domains. These results provide a molecular framework to link glutamate excitotoxicity with neurofilament accumulation seen in some neurodegenerative diseases

    Characterization of ERG, AR and PTEN gene status in circulating tumor cells from patients with castration-resistant prostate cancer

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    Hormone-driven expression of the ERG oncogene after fusion with TMPRSS2 occurs in 30% to 70% of therapy-naive prostate cancers. Its relevance in castration-resistant prostate cancer (CRPC) remains controversial as ERG is not expressed in some TMPRSS2-ERG androgen-independent xenograft models. However, unlike these models, CRPC patients have an increasing prostate-specific antigen, indicating active androgen receptor signaling. Here, we collected blood every month from 89 patients (54 chemotherapy-naive patients and 35 docetaxel-treated patients) treated in phase I/phase II clinical trials of an orally available, highly specific CYP17 inhibitor, abiraterone acetate, that ablates the synthesis of androgens and estrogens that drive TMPRSS2-ERG fusions. We isolated circulating tumor cells (CTC) by anti-epithelial cell adhesion molecule immunomagnetic selection followed by cytokeratin and CD45 immunofluorescence and 4',6diamidino-2-phenylindole staining. We used multicolor fluorescence in situ hybridization to show that CRPC CTCs, metastases, and prostate tissue invariably had the same ERG gene status as therapy-naive tumors (n = 31). We then used quantitative reverse transcription-PCR to show that ERG expression was maintained in CRPC. We also observed homogeneity in ERG gene rearrangement status in CTCs (n = 48) in contrast to significant heterogeneity of AR copy number gain and PTEN loss, suggesting that rearrangement of ERG may be an earlier event in prostate carcinogenesis. We finally report a significant association between ERG rearrangements in therapy-naive tumors, CRPCs, and CTCs and magnitude of prostate-specific antigen decline (P = 0.007) in CRPC patients treated with abiraterone acetate. These data confirm that CTCs are malignant in origin and indicate that hormone-regulated expressio

    Controlling the Thermal Stability and Volatility of Organogold(I) Compounds for Vapor Deposition with Complementary Ligand Design

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    Submitted versionAtomic layer deposition (ALD) of gold is being studied by multiple research groups, but to date no process using non-energetic co-reactants has been demonstrated. In order to access milder co-reactants, precursors with higher thermal stability are required. We set out to uncover how structure and bonding affect the stability and volatility of a family of twelve organogold(I) compounds using a combination of techniques: X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and density functional theory (DFT). Small, unsubstituted phosphonium ylide ligands bind more strongly to Au(I) than their silyl-substituted analogues, but the utility of both these ligands suffers due to their poor volatility and substantial thermal decomposition. Pentafluorophenyl (C6F5) is introduced as a new, very electronegative ligand for gold vapor deposition precursors, and it was found that the disadvantage to volatility due to π-stacking and other intermolecular interactions in the solid state was overshadowed by dramatic improvements to kinetic and thermodynamic stability. We introduce a new figure of merit to compare and rank the suitability of these and other complexes as precursors for vapor deposition. Finally, DFT calculations on four compounds that have high figures of merit show a linear correlation between the gold-coordinative ligand bond dissociation energies and the observed decomposition temperatures, highlighting and justifying this design strategy

    African Dreams: Locating Urban Infrastructure in the 2030 Sustainable Developmental Agenda

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    This paper examines African urban infrastructure and service delivery as an entry point for connecting African aspirations with the harsh developmental imperatives of urban management, creating a dialogue between scholarly knowledge and sustainable development policy aspirations. We note a shift to multi-nodal urban governance and highlight the significance of the synthesis of social, economic and ecological values in a normative vision of what an African metropolis might aspire to by 2030. The sustainable development vision provides a useful stimulus for Africa’s urban poly-crisis, demanding fresh interdisciplinary and normatively explicit thinking, grounded in a practical and realistic understanding of Africa’s infrastructure and governance challenges

    Making science of influencing: assessing the impact of development research

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    The impact and influence of development research is an agenda that has been gathering momentum over the last few years. This agenda is a coming together of two divergent concerns. The first, from the funders of research, draws on results based management and is concerned with getting value-for-money from research spending or with ‘more bang for the buck’. The second, more typical of those in the development studies research community, is concerned with whether research in the area is ‘making a difference’. Among development researchers there is also often a political or normative basis – addressing global poverty and inequality – and catalysing change. The meanings of the terms’ impact and influence are multiple, multi-layered and complex to track. They may refer to use (i.e. consideration) or actual outcome(s) of social change. They can be visible or invisible; progressive or regressive. Impacts and influence can be intended or unintended and immediate or long-term. The processes of impact and influence are acknowledged to be non-linear, iterative and complex. This paper considers the impact and influence of development research from a plurality of perspectives. Interest in the impact/influence of research projects aggregates upwards to support the overall case for (often public) funding of development research (in areas that are likely to play a major role in the next few years in changing the climate for public expenditure in light of the global financial crisis)

    A retrospective analysis of clinical outcome of patients with chemo-refractory metastatic breast cancer treated in a single institution phase I unit

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    BACKGROUND AND METHODS: Novel approaches to treat chemo-refractory metastatic breast cancer (MBC) are currently under investigation. This retrospective series reviews the outcome of 70 MBC patients who have participated in 30 phase I trials at the Royal Marsden Hospital from 2002 to 2009. RESULTS: The median treatment lines before phase I trial entry for MBC was 5 (range: 1-12 lines). The overall response rate was 11.4% (95% CI: 4.0-18.9%) and the clinical benefit rate at 4 months was 20% (95% CI: 10.6-29.3). The median time to progression was 7.0 weeks (95% CI: 6.4-7.5) and median overall survival was 8.7 months (95% CI: 7.6-9.8) from start of first phase I treatment. No patients discontinued trial because of treatment-related toxicities. Abnormal lactate dehydrogenase, serum albumin <35 mg per 100 ml, >or=5 previous treatment lines, liver metastases and Eastern Cooperative Group performance status >or=2 at study entry were significantly associated with poor overall survival in multivariate analysis. CONCLUSION: This retrospective analysis provides evidence that patients with MBC tolerate phase I clinical trials and a significant proportion of patients with chemo-refractory disease, particularly those with triple-negative or Her2-positive breast cancer, may benefit from treatment

    Damage signature of fatigued fabric reinforced plastics in the pulsed ultrasonic polar scan

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    This study investigates the use of both the amplitude and time-of-flight based pulsed ultrasonic polar scan (P-UPS) for the nondestructive detection and evaluation of fatigue damage in fiber reinforced composites. Several thermoplastic carbon fabric reinforced PPS specimens (CETEX), loaded under various fatigue conditions, have been scanned at multiple material spots according to the P-UPS technique in order to extract material degradation in a quantitative way. The P-UPS results indicate that shear dominated fatigued carbon/PPS goes with a reduction of shear properties combined with large fiber distortions. The P-UPS results of the tension-tension fatigued carbon/PPS samples on the other hand reveal a directional degradation of the stiffness properties, reaching a maximum reduction of -12.8% along the loading direction. The P-UPS extracted damage characteristics are fully supported by simulations, conventional destructive tests as well as visual inspection. The results demonstrate the excellent capability of the P-UPS method for nondestructively assessing and quantifying both shear-dominated and tension-tension fatigue damage in fabric reinforced plastics
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