114 research outputs found

    Reduced tubulin tyrosination as an early marker of mercury toxicity in differentiating N2a cells

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    The aims of this work were to compare the effects of methyl mercury chloride and Thimerosal on neurite/process outgrowth and microtubule proteins in differentiating mouse N2a neuroblastoma and rat C6 glioma cells. Exposure for 4 h to sublethal concentrations of both compounds inhibited neurite outgrowth to a similar extent in both cells lines compared to controls. In the case of N2a cells, this inhibitory effect by both compounds was associated with a fall in the reactivity of western blots of cell extracts with monoclonal antibody T1A2, which recognises C-terminally tyrosinated α-tubulin. By contrast, reactivity with monoclonal antibody B512 (which recognises total α-tubulin) was unaffected at the same time point. These findings suggest that decreased tubulin tyrosination represents a neuron-specific early marker of mercury toxicity associated with impaired neurite outgrowth

    The toxicity of chlorpyrifos towards differentiating mouse N2a neuroblastoma cells

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    The aim of this work was to study the effects of chlorpyrifos (CPF) on the outgrowth of axons by differentiating mouse N2a neuroblastoma cells. This was achieved by morphological, Western blotting and enzymatic analyses of cells induced to differentiate in the presence and absence of CPF added either at the same time (co-differentiation) or 16 h after (post-differentiation) the induction of cell differentiation. The outgrowth of axon-like processes was impaired following 4 or 8 h exposure to CPF in both co- and post-differentiation experiments. Western blotting analysis revealed reduced levels of neurofilament heavy chain (NF-H) following 8 h of exposure but no significant effect at 4 h under both co- and post-differentiation conditions. By contrast, levels of the heat shock protein HSP-70 were raised at both time points, but only in co-differentiation experiments. Neuropathy target esterase (NTE) activity was lower than controls following 4 or 8 h of exposure under co-differentiation conditions, but not under any post-differentiation conditions. The results suggest that the inhibition of axon production and maintenance by CPF in differentiating N2a cells may involve multiple targets, which are different under co- and post-differentiation conditions

    Intermittency on Simultaneous Observations of Riometer at Several Antarctic Locations

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    It is well known that auroral radio wave absorption, as measured by riometers, consists of periods of relative quiescence which are interrupted by short bursts of activity. Such patterns in activity are observed in systems ranging from the stock market to turbulence, i.e. they exhibit intermittency. In the case of the auroral absorption it has also been found that intermittency strongly depends on the magnetic local time, being largest in the night-time sector. This can be interpreted as indicating that the precipitating particles responsible of the absorption exhibit intermittency, especially near the substorm eye, where the level of turbulence increases. Here, we analyse simultaneous observations of riometer absorption at seven Antarctic locations, to determine whether they exhibit intermittency. We determine the Probability Distribution Functions of the fluctuations of riometer absorption for absorption events larger than 0.1 dB, as well as those for the time-intervals between absorption events. Observations are for locations within the austral auroral absorption zone and on the polar cap. It is found that the parameters of a power law used to describe the calculated PDFs are consistent with the formation of coherent structures being more frequent within the auroral zone, as a manifestation of intermittency

    Design and Optimisation of a Microwave Reactor for Kilo-Scale Polymer Synthesis

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    Current industrial production of polymer resins is generally undertaken in large multi-tonne stirred tank reactors. These are characterised by relatively slow heating and cooling cycles, resulting in long vessel cycle times and extended production campaigns. In this work we present a design for a hybrid microwave/oil jacket proof of concept system capable of producing up to 4.1 kg of polymer resin per batch. By exploiting rapid volumetric heating effects of microwave energy at 2.45GHz, we have optimised the synthetic regime, such that a 3.7 kg batch of polyester resin pre-polymer can be made in only 8 hours 20 minutes, with higher molecular weight (Mn 2,100) compared to the conventional process taking 22 hours 15 minutes (Mn 1,200), yielding an increase in synthesis rate of at least 265. The increase in polymer molecular weight also suggests a higher conversion was achieved over a shorter time scale

    Design and optimisation of a microwave reactor for kilo-scale polymer synthesis

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    Current industrial production of polymer resins is generally undertaken in large multi-tonne stirred tank reactors. These are characterised by relatively slow heating and cooling cycles, resulting in long vessel cycle times and extended production campaigns. In this work we present a design for a hybrid microwave/oil jacket proof of concept system capable of producing up to 4.1?kg of polymer resin per batch. By exploiting rapid volumetric heating effects of microwave energy at 2.45?GHz, we have optimised the synthetic regime, such that a 3.7?kg batch of polyester resin pre-polymer can be made in only 8?h 20?min, with higher molecular weight (Mn 2100) compared to the conventional process taking 22?h 15?min (Mn 1200), yielding an increase in synthesis rate of at least 265%. The increase in polymer molecular weight also suggests a higher conversion was achieved over a shorter time scale

    Coupling climate and economic models in a cost-benefit framework: a convex optimization approach

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    In this paper we present a general method, based on a convex optimisation technique, that facilitates the coupling of climate and economic models in a cost-benefit framework. As a demonstration of the method, we couple an economic growth model Ă  la Ramsey adapted from DICE-99 with an efficient intermediate complexity climate model, C-GOLDSTEIN, which has highly simplified physics, but fully 3-D ocean dynamics. As in DICE-99 we assume that an economic cost is associated with global temperature change: this change is obtained from the climate model which is driven by the GHG concentrations computed from the economic growth path. The work extends a previous paper in which these models were coupled in cost-effectiveness mode. Here we consider the more intricate cost-benefit coupling in which the climate impact is not fixed a priori. We implement the coupled model using an oracle-based optimisation technique. Each model is contained in an oracle which supplies model output and information on its sensitivity to a master program. The algorithm Proximal-ACCPM guarantees the convergence of the procedure under sufficient convexity assumptions. Our results demonstrate the possibility of a consistent, cost-benefit, climate-damage optimisation analysis with a 3-D climate model

    Using the past to constrain the future: how the palaeorecord can improve estimates of global warming

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    Climate sensitivity is defined as the change in global mean equilibrium temperature after a doubling of atmospheric CO2 concentration and provides a simple measure of global warming. An early estimate of climate sensitivity, 1.5-4.5{\deg}C, has changed little subsequently, including the latest assessment by the Intergovernmental Panel on Climate Change. The persistence of such large uncertainties in this simple measure casts doubt on our understanding of the mechanisms of climate change and our ability to predict the response of the climate system to future perturbations. This has motivated continued attempts to constrain the range with climate data, alone or in conjunction with models. The majority of studies use data from the instrumental period (post-1850) but recent work has made use of information about the large climate changes experienced in the geological past. In this review, we first outline approaches that estimate climate sensitivity using instrumental climate observations and then summarise attempts to use the record of climate change on geological timescales. We examine the limitations of these studies and suggest ways in which the power of the palaeoclimate record could be better used to reduce uncertainties in our predictions of climate sensitivity.Comment: The final, definitive version of this paper has been published in Progress in Physical Geography, 31(5), 2007 by SAGE Publications Ltd, All rights reserved. \c{opyright} 2007 Edwards, Crucifix and Harriso

    Oracle-based optimization applied to climate model calibration

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    In this paper, we show how oracle-based optimization can be effectively used for the calibration of an intermediate complexity climate model. In a fully developed example, we estimate the 12 principal parameters of the C-GOLDSTEIN climate model by using an oracle- based optimization tool, Proximal-ACCPM. The oracle is a procedure that finds, for each query point, a value for the goodness-of-fit function and an evaluation of its gradient. The difficulty in the model calibration problem stems from the need to undertake costly calculations for each simulation and also from the fact that the error function used to assess the goodness-of-fit is not convex. The method converges to a Fbest fit_ estimate over 10 times faster than a comparable test using the ensemble Kalman filter. The approach is simple to implement and potentially useful in calibrating computationally demanding models based on temporal integration (simulation), for which functional derivative information is not readily available

    Scale issues in soil moisture modelling: problems and prospects

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    Soil moisture storage is an important component of the hydrological cycle and plays a key role in land-surface-atmosphere interaction. The soil-moisture storage equation in this study considers precipitation as an input and soil moisture as a residual term for runoff and evapotranspiration. A number of models have been developed to estimate soil moisture storage and the components of the soil-moisture storage equation. A detailed discussion of the impli cation of the scale of application of these models reports that it is not possible to extrapolate processes and their estimates from the small to the large scale. It is also noted that physically based models for small-scale applications are sufficiently detailed to reproduce land-surface- atmosphere interactions. On the other hand, models for large-scale applications oversimplify the processes. Recently developed physically based models for large-scale applications can only be applied to limited uses because of data restrictions and the problems associated with land surface characterization. It is reported that remote sensing can play an important role in over coming the problems related to the unavailability of data and the land surface characterization of large-scale applications of these physically based models when estimating soil moisture storage.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

    The Effects of Sugars Intake and Frequency of Ingestion on Dental Caries Increment in a Three-year Longitudinal Study

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    A three-year longitudinal study was carried out with a group of children, initially aged 11-15, residing in non-fluoridated rural communities in south-central Michigan. This report analyzes the relation between caries increment and consumption of sugars from all sources to see if accepted relationships have changed with the caries decline in the United States. There were 499 children who provided three or more 24-hour dietary recall interviews, and who received dental examinations at baseline and after three years. Caries increment averaged 2.91 DMFS over the three years, with 81 % of new lesions on pit-and-fissure surfaces. Consumption of sugars from all sources averaged 156 g per day for males and 127 g per day for females, an average of 52 kg per person per year. Sugars constituted one-quarter of total caloric intake for both boys and girls, and the average number of eating occasions per day was 4.3. Children who consumed a higher proportion of their total energy intake as sugars had a higher increment of approximal caries, though there was little relation to pit-and-fissure caries. The average number of daily eating occasions was not related to caries increment, nor was the average number of sugary snacks (defined as foods with 15% or more of sugars) consumed between meals, but the average consumption of between-meal sugars was related to the approximal caries increment. When children were categorized by high caries increment compared with no caries increment, a tendency toward more frequent snacks was seen in the high-caries children. In an age of generally declining caries, it was concluded that higher average daily consumption of sugars, and higher between-meal consumption of sugars, was still a risk factor for children susceptible to approximal caries. Overall frequency of eating and frequency of ingestion of sugary foods between meals, however, were both poorly related to approximal caries increment. Pit-and-fissure caries could not be related to any aspect of sugars consumption.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67206/2/10.1177_00220345880670111201.pd
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