2,355 research outputs found

    Estimating the furrow infiltration characteristic from a single advance point

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    Management and control of surface irrigation, in particular furrow irrigation, is limited by spatio-temporal soil infiltration variability as well as the high cost and time associated with collecting intensive field data for estimation of the infiltration characteristics. Recent work has proposed scaling the commonly used infiltration function by using a model infiltration curve and a single advance point for every other furrow in an irrigation event. Scaling factors were calculated for a series of furrows at two sites and at four points down the length of the field (0.25 L, 0.5 L, 0.75 L and L). Differences in the value of the scaling factor with distance were found to be a function of the shape of the advance curves. It is concluded that use of points early in the advance results in a substantial loss of accuracy and should be avoided. The scaling factor was also strongly correlated with the furrow-wetted perimeter suggesting that the scaling is an appropriate way of both predicting and accommodating the effect of the hydraulic variability

    Carbon storage and DNA absorption in allophanic soils and paleosols

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    Andisols and andic paleosols dominated by the nanocrystalline mineral allophane sequester large amounts of carbon (C), attributable mainly to its chemical bonding with charged hydroxyl groups on the surface of allophane together with its physical protection in nanopores within and between allophane nanoaggregates. C near-edge X-ray absorption fine structure (NEXAFS) spectra for a New Zealand Andisol (Tirau series) showed that the organic matter (OM) mainly comprises quinonic, aromatic, aliphatic, and carboxylic C. In different buried horizons from several other Andisols, C contents varied but the C species were similar, attributable to pedogenic processes operating during developmental upbuilding, downward leaching, or both. The presence of OM in natural allophanic soils weakened the adsorption of DNA on clay; an adsorption isotherm experiment involving humic acid (HA) showed that HA-free synthetic allophane adsorbed seven times more DNA than HA-rich synthetic allophane. Phosphorus X-ray absorption near-edge structure (XANES) spectra for salmonsperm DNA and DNA-clay complexes indicated that DNA was bound to the allophane clay through the phosphate group, but it is not clear if DNA was chemically bound to the surface of the allophane or to OM, or both. We plan more experiments to investigate interactions among DNA, allophane (natural and synthetic), and OM. Because DNA shows a high affinity to allophane, we are studying the potential to reconstruct late Quaternary palaeoenvironments by attempting to extract and characterise ancient DNA from allophanic paleosol

    Dynamic Modelling under Uncertainty: The Case of Trypanosoma brucei Energy Metabolism

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    Kinetic models of metabolism require detailed knowledge of kinetic parameters. However, due to measurement errors or lack of data this knowledge is often uncertain. The model of glycolysis in the parasitic protozoan Trypanosoma brucei is a particularly well analysed example of a quantitative metabolic model, but so far it has been studied with a fixed set of parameters only. Here we evaluate the effect of parameter uncertainty. In order to define probability distributions for each parameter, information about the experimental sources and confidence intervals for all parameters were collected. We created a wiki-based website dedicated to the detailed documentation of this information: the SilicoTryp wiki (http://silicotryp.ibls.gla.ac.uk/wiki/Glycolysis). Using information collected in the wiki, we then assigned probability distributions to all parameters of the model. This allowed us to sample sets of alternative models, accurately representing our degree of uncertainty. Some properties of the model, such as the repartition of the glycolytic flux between the glycerol and pyruvate producing branches, are robust to these uncertainties. However, our analysis also allowed us to identify fragilities of the model leading to the accumulation of 3-phosphoglycerate and/or pyruvate. The analysis of the control coefficients revealed the importance of taking into account the uncertainties about the parameters, as the ranking of the reactions can be greatly affected. This work will now form the basis for a comprehensive Bayesian analysis and extension of the model considering alternative topologies

    Treatment of developmental dyslexia: A review

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    Remarkably few research articles on the treatment of developmental dyslexia were published during the last 25 years. Some treatment research arose from the temporal processing theory, some from the phonological deficit hypothesis and some more from the balance model of learning to read and dyslexia. Within the framework of that model, this article reviews the aetiology of dyslexia sub-types, the neuropsychological rationale for treatment, the treatment techniques and the outcomes of treatment research. The possible mechanisms underlying the effects of treatment are discussed. © 2005 Informa UK Ltd All rights reserved

    LC–MS-based absolute metabolite quantification:Application to metabolic flux measurement in trypanosomes

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    Human African trypanosomiasis is a neglected tropical disease caused by the protozoan parasite, Trypanosoma brucei. In the mammalian bloodstream, the trypanosome’s metabolism differs significantly from that of its host. For example, the parasite relies exclusively on glycolysis for energy source. Recently, computational and mathematical models of trypanosome metabolism have been generated to assist in understanding the parasite metabolism with the aim of facilitating drug development. Optimisation of these models requires quantitative information, including metabolite concentrations and/or metabolic fluxes that have been hitherto unavailable on a large scale. Here, we have implemented an LC–MS-based method that allows large scale quantification of metabolite levels by using U-13C-labelled E. coli extracts as internal standards. Known amounts of labelled E. coli extract were added into the parasite samples, as well as calibration standards, and used to obtain calibration curves enabling us to convert intensities into concentrations. This method allowed us to reliably quantify the changes of 43 intracellular metabolites and 32 extracellular metabolites in the medium over time. Based on the absolute quantification, we were able to compute consumption and production fluxes. These quantitative data can now be used to optimise computational models of parasite metabolism

    An orbital fistula complicating anaerobic frontal sinusitis and osteomyelitis

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    A patient is described with an orbital fistula complicating frontal sinusitis and osteomyelitis of the frontal bone. The fistula was excised, but a fortnight later an acute exacerbation occurred. From the discharging pus a Staphylococcus aureus was cultured and from mucosa obtained during surgery a microaerophilic Streptococcus. These findings led to the diagnosis: synergistic bacterial inflammation of the frontal sinus, with osteomyelitis and orbital cellulitis

    Metabolic compartmentalization in the human cortex and hippocampus: evidence for a cell- and region-specific localization of lactate dehydrogenase 5 and pyruvate dehydrogenase

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    BACKGROUND: For a long time now, glucose has been thought to be the main, if not the sole substrate for brain energy metabolism. Recent data nevertheless suggest that other molecules, such as monocarboxylates (lactate and pyruvate mainly) could be suitable substrates. Although monocarboxylates poorly cross the blood brain barrier (BBB), such substrates could replace glucose if produced locally.The two key enzymatiques systems required for the production of these monocarboxylates are lactate dehydrogenase (LDH; EC1.1.1.27) that catalyses the interconversion of lactate and pyruvate and the pyruvate dehydrogenase complex that irreversibly funnels pyruvate towards the mitochondrial TCA and oxydative phosphorylation. RESULTS: In this article, we show, with monoclonal antibodies applied to post-mortem human brain tissues, that the typically glycolytic isoenzyme of lactate dehydrogenase (LDH-5; also called LDHA or LDHM) is selectively present in astrocytes, and not in neurons, whereas pyruvate dehydrogenase (PDH) is mainly detected in neurons and barely in astrocytes. At the regional level, the distribution of the LDH-5 immunoreactive astrocytes is laminar and corresponds to regions of maximal 2-deoxyglucose uptake in the occipital cortex and hippocampus. In hippocampus, we observed that the distribution of the oxidative enzyme PDH was enriched in the neurons of the stratum pyramidale and stratum granulosum of CA1 through CA4, whereas the glycolytic enzyme LDH-5 was enriched in astrocytes of the stratum moleculare, the alveus and the white matter, revealing not only cellular, but also regional, selective distributions. The fact that LDH-5 immunoreactivity was high in astrocytes and occurred in regions where the highest uptake of 2-deoxyglucose was observed suggests that glucose uptake followed by lactate production may principally occur in these regions. CONCLUSION: These observations reveal a metabolic segregation, not only at the cellular but also at the regional level, that support the notion of metabolic compartmentalization between astrocytes and neurons, whereby lactate produced by astrocytes could be oxidized by neurons

    Unmappable ventricular tachycardia after an old myocardial infarction. Long-term results of substrate modification in patients with an implantable cardioverter defibrillator

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    Purpose The frequent occurrence of ventricular tachycardia can create a serious problem in patients with an implantable cardioverter defibrillator. We assessed the long-term efficacy of catheter-based substrate modification using the voltage mapping technique of infarct-related ventricular tachycardia and recurrent device therapy. Methods The study population consisted of 27 consecutive patients (age 68 +/- 8 years, 25 men, mean left ventricular ejection fraction 31 +/- 9%) with an old myocardial infarction and multiple and/or hemodynamically not tolerated ventricular tachycardia necessitating repeated device therapy. A total of 31 substrate modification procedures were performed using the three-dimensional electroanatomical mapping system. Patients were followed up for a median of 23.5 (interquartile range 6.5-53.2) months before and 37.8 (interquartile range 11.7-71.8) months after ablation. Antiarrhythmic drugs were not changed after the procedure, and were stopped 6 to 9 months after the procedure in patients who did not show ventricular tachycardia recurrence. Results Median ventricular tachycardias were 1.6 (interquartile range 0.7-6.7) per month before and 0.2 (interquartile range 0.00-1.3) per month after ablation (P = 0.006). Nine ventricular fibrillation episodes were registered in seven patients before and two after ablation (P = 0.025). Median antitachycardia pacing decreased from 1.6 (interquartile range 0.01-5.5) per month before to 0.18 (interquartile range 0.00-1.6) per month after ablation (P = 0.069). Median number of shocks decreased from 0.19 (interquartile range 0.04-0.81) per month before to 0.00 (interquartile range 0.00-0.09) per month after ablation (P = 0.001). One patient had a transient ischemic attack during the procedure, and another developed pericarditis. Nine patients died during follow-up, eight patients due to heart failure and one patient during valve surgery. Conclusion Catheter-based substrate modification using voltage mapping results in a long-lasting reduction of cardioverter defibrillator therapy in patients with multiple and/or hemodynamically not tolerated infarct-related ventricular tachyarrhythmia

    Kinetic modeling of tricarboxylic acid cycle and glyoxylate bypass in Mycobacterium tuberculosis, and its application to assessment of drug targets

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    BACKGROUND: Targeting persistent tubercule bacilli has become an important challenge in the development of anti-tuberculous drugs. As the glyoxylate bypass is essential for persistent bacilli, interference with it holds the potential for designing new antibacterial drugs. We have developed kinetic models of the tricarboxylic acid cycle and glyoxylate bypass in Escherichia coli and Mycobacterium tuberculosis, and studied the effects of inhibition of various enzymes in the M. tuberculosis model. RESULTS: We used E. coli to validate the pathway-modeling protocol and showed that changes in metabolic flux can be estimated from gene expression data. The M. tuberculosis model reproduced the observation that deletion of one of the two isocitrate lyase genes has little effect on bacterial growth in macrophages, but deletion of both genes leads to the elimination of the bacilli from the lungs. It also substantiated the inhibition of isocitrate lyases by 3-nitropropionate. On the basis of our simulation studies, we propose that: (i) fractional inactivation of both isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2 is required for a flux through the glyoxylate bypass in persistent mycobacteria; and (ii) increasing the amount of active isocitrate dehydrogenases can stop the flux through the glyoxylate bypass, so the kinase that inactivates isocitrate dehydrogenase 1 and/or the proposed inactivator of isocitrate dehydrogenase 2 is a potential target for drugs against persistent mycobacteria. In addition, competitive inhibition of isocitrate lyases along with a reduction in the inactivation of isocitrate dehydrogenases appears to be a feasible strategy for targeting persistent mycobacteria. CONCLUSION: We used kinetic modeling of biochemical pathways to assess various potential anti-tuberculous drug targets that interfere with the glyoxylate bypass flux, and indicated the type of inhibition needed to eliminate the pathogen. The advantage of such an approach to the assessment of drug targets is that it facilitates the study of systemic effect(s) of the modulation of the target enzyme(s) in the cellular environment
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