143 research outputs found

    Unexpected Caisson Problems, Soil Structure Interaction Predictions and Required Ground Modification

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    Recent advances in strain measurement using optical fibers provide new opportunities for monitoring the performance of geotechnical structures during and after construction. Brillouin optical time-domain reflectometry (BOTDR) is an innovative technique that allows measurement of full strain profiles using standard optical fibers. In this paper, two case studies illustrating the application of the distributed optical fiber strain sensors are presented. One is monitoring of an old masonry tunnel when a new tunnel was constructed nearby and the other is monitoring the behavior of secant piled walls for basement construction. Both sites are located in London. The advantages and limitations of this new sensor technology for monitoring geotechnical structures are discussed. The paper describes the caisson construction problems encountered and the required modification necessary for a 55-story residential high-rise in Chicago’s near north side. Belled caissons were planned on a very thin hardpan bearing layer which was underlain by water bearing dense silt that extended to dolomite bedrock. Three filtered dewatering wells extending into the fractured rock surface were planned to reduce the hydrostatic pressure head within the silt to permit the belled construction. A complete collapse of the dense silt layer during the installation of the first dewatering well undermined the planned belled caisson foundation system. An additional subsurface investigation, a compaction grouting program and further in-situ pressuremeter testing was then performed. Subsequent modified performance predictions required the addition of selective micropile underpinning after completion of the planned system of grade beams and belled caisson installation. Settlement monitoring during building construction confirmed settlements within or less than the predicted settlement range

    Replication Fork Polarity Gradients Revealed by Megabase-Sized U-Shaped Replication Timing Domains in Human Cell Lines

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    In higher eukaryotes, replication program specification in different cell types remains to be fully understood. We show for seven human cell lines that about half of the genome is divided in domains that display a characteristic U-shaped replication timing profile with early initiation zones at borders and late replication at centers. Significant overlap is observed between U-domains of different cell lines and also with germline replication domains exhibiting a N-shaped nucleotide compositional skew. From the demonstration that the average fork polarity is directly reflected by both the compositional skew and the derivative of the replication timing profile, we argue that the fact that this derivative displays a N-shape in U-domains sustains the existence of large-scale gradients of replication fork polarity in somatic and germline cells. Analysis of chromatin interaction (Hi-C) and chromatin marker data reveals that U-domains correspond to high-order chromatin structural units. We discuss possible models for replication origin activation within U/N-domains. The compartmentalization of the genome into replication U/N-domains provides new insights on the organization of the replication program in the human genome

    Transcription Initiation Activity Sets Replication Origin Efficiency in Mammalian Cells

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    Genomic mapping of DNA replication origins (ORIs) in mammals provides a powerful means for understanding the regulatory complexity of our genome. Here we combine a genome-wide approach to identify preferential sites of DNA replication initiation at 0.4% of the mouse genome with detailed molecular analysis at distinct classes of ORIs according to their location relative to the genes. Our study reveals that 85% of the replication initiation sites in mouse embryonic stem (ES) cells are associated with transcriptional units. Nearly half of the identified ORIs map at promoter regions and, interestingly, ORI density strongly correlates with promoter density, reflecting the coordinated organisation of replication and transcription in the mouse genome. Detailed analysis of ORI activity showed that CpG island promoter-ORIs are the most efficient ORIs in ES cells and both ORI specification and firing efficiency are maintained across cell types. Remarkably, the distribution of replication initiation sites at promoter-ORIs exactly parallels that of transcription start sites (TSS), suggesting a co-evolution of the regulatory regions driving replication and transcription. Moreover, we found that promoter-ORIs are significantly enriched in CAGE tags derived from early embryos relative to all promoters. This association implies that transcription initiation early in development sets the probability of ORI activation, unveiling a new hallmark in ORI efficiency regulation in mammalian cells

    Microbial sulfate reduction and metal attenuation in pH 4 acid mine water

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    Sediments recovered from the flooded mine workings of the Penn Mine, a Cu-Zn mine abandoned since the early 1960s, were cultured for anaerobic bacteria over a range of pH (4.0 to 7.5). The molecular biology of sediments and cultures was studied to determine whether sulfate-reducing bacteria (SRB) were active in moderately acidic conditions present in the underground mine workings. Here we document multiple, independent analyses and show evidence that sulfate reduction and associated metal attenuation are occurring in the pH-4 mine environment. Water-chemistry analyses of the mine water reveal: (1) preferential complexation and precipitation by H2S of Cu and Cd, relative to Zn; (2) stable isotope ratios of 34S/32S and 18O/16O in dissolved SO4 that are 2–3 ‰ heavier in the mine water, relative to those in surface waters; (3) reduction/oxidation conditions and dissolved gas concentrations consistent with conditions to support anaerobic processes such as sulfate reduction. Scanning electron microscope (SEM) analyses of sediment show 1.5-micrometer, spherical ZnS precipitates. Phospholipid fatty acid (PLFA) and denaturing gradient gel electrophoresis (DGGE) analyses of Penn Mine sediment show a high biomass level with a moderately diverse community structure composed primarily of iron- and sulfate-reducing bacteria. Cultures of sediment from the mine produced dissolved sulfide at pH values near 7 and near 4, forming precipitates of either iron sulfide or elemental sulfur. DGGE coupled with sequence and phylogenetic analysis of 16S rDNA gene segments showed populations of Desulfosporosinus and Desulfitobacterium in Penn Mine sediment and laboratory cultures

    Health system outcomes and determinants amenable to public health in industrialized countries: a pooled, cross-sectional time series analysis

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    BACKGROUND: Few studies have tried to assess the combined cross-sectional and temporal contributions of a more comprehensive set of amenable factors to population health outcomes for wealthy countries during the last 30 years of the 20(th )century. We assessed the overall ecological associations between mortality and factors amenable to public health. These amenable factors included addictive and nutritional lifestyle, air quality, public health spending, healthcare coverage, and immunizations. METHODS: We used a pooled cross-sectional, time series analysis with corrected fixed effects regression models in an ecological design involving eighteen member countries of the Organisation for Economic Cooperation and Development during the period 1970 to 1999. RESULTS: Alcohol, tobacco, and fat consumption, and sometimes, air pollution were significantly associated with higher all-cause mortality and premature death. Immunizations, health care coverage, fruit/vegetable and protein consumption, and collective health expenditure had negative effects on mortality and premature death, even after controlling for the elderly, density of practicing physicians, doctor visits and per capita GDP. However, tobacco, air pollution, and fruit/vegetable intake were sometimes sensitive to adjustments. CONCLUSION: Mortality and premature deaths could be improved by focusing on factors that are amenable to public health policies. Tackling these issues should be reflected in the ongoing assessments of health system performance

    Identification of Brain Nuclei Implicated in Cocaine-Primed Reinstatement of Conditioned Place Preference: A Behaviour Dissociable from Sensitization

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    Relapse prevention represents the primary therapeutic challenge in the treatment of drug addiction. As with humans, drug-seeking behaviour can be precipitated in laboratory animals by exposure to a small dose of the drug (prime). The aim of this study was to identify brain nuclei implicated in the cocaine-primed reinstatement of a conditioned place preference (CPP). Thus, a group of mice were conditioned to cocaine, had this place preference extinguished and were then tested for primed reinstatement of the original place preference. There was no correlation between the extent of drug-seeking upon reinstatement and the extent of behavioural sensitization, the extent of original CPP or the extinction profile of mice, suggesting a dissociation of these components of addictive behaviour with a drug-primed reinstatement. Expression of the protein product of the neuronal activity marker c-fos was assessed in a number of brain regions of mice that exhibited reinstatement (R mice) versus those which did not (NR mice). Reinstatement generally conferred greater Fos expression in cortical and limbic structures previously implicated in drug-seeking behaviour, though a number of regions not typically associated with drug-seeking were also activated. In addition, positive correlations were found between neural activation of a number of brain regions and reinstatement behaviour. The most significant result was the activation of the lateral habenula and its positive correlation with reinstatement behaviour. The findings of this study question the relationship between primed reinstatement of a previously extinguished place preference for cocaine and behavioural sensitization. They also implicate activation patterns of discrete brain nuclei as differentiators between reinstating and non-reinstating mice

    Deontic Justice and Organizational Neuroscience

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