576 research outputs found

    Cell-Type-Specific Cytokinin Distribution within the Arabidopsis Primary Root Apex

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    Cytokinins (CKs) play a crucial role in many physiological and developmental processes at the levels of individual plant components (cells, tissues, and organs) and by coordinating activities across these parts. High-resolution measurements of intracellular CKs in different plant tissues can therefore provide insights into their metabolism and mode of action. Here, we applied fluorescence-activated cell sorting of green fluorescent protein (GFP)-marked cell types, combined with solid-phase microextraction and an ultra-high-sensitivity mass spectrometry (MS) method for analysis of CK biosynthesis and homeostasis at cellular resolution. This method was validated by series of control experiments, establishing that protoplast isolation and cell sorting procedures did not greatly alter endogenous CK levels. The MS-based method facilitated the quantification of all the well known CK isoprenoid metabolites in four different transgenic Arabidopsis thaliana lines expressing GFP in specific cell populations within the primary root apex. Our results revealed the presence of a CK gradient within the Arabidopsis root tip, with a concentration maximum in the lateral root cap, columella, columella initials, and quiescent center cells. This distribution, when compared with previously published auxin gradients, implies that the well known antagonistic interactions between the two hormone groups are cell type specific

    PGI8 ECONOMIC EVALUATION OF ADACOLUMN® APHERESIS FOR THE TREATMENT OF PATIENTS WITH MODERATE TO SEVERE CROHN'S DISEASE (CD)/ULCERATIVE COLITIS (UC)

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    Registers of the Swedish total population and their use in medical research

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    The primary aim of the Swedish national population registration system is to obtain data that (1) reflect the composition, relationship and identities of the Swedish population and (2) can be used as the basis for correct decisions and measures by government and other regulatory authorities. For this purpose, Sweden has established two population registers: (1) The Population Register, maintained by the Swedish National Tax Agency ("Folkbokforingsregistret"); and (2) The Total Population Register (TPR) maintained by the government agency Statistics Sweden ("Registret over totalbefolkningen"). The registers contain data on life events including birth, death, name change, marital status, family relationships and migration within Sweden as well as to and from other countries. Updates are transmitted daily from the Tax Agency to the TPR. In this paper we describe the two population registers and analyse their strengths and weaknesses. Virtually 100 % of births and deaths, 95 % of immigrations and 91 % of emigrations are reported to the Population Registers within 30 days and with a higher proportion over time. The over-coverage of the TPR, which is primarily due to underreported emigration data, has been estimated at up to 0.5 % of the Swedish population. Through the personal identity number, assigned to all residents staying at least 1 year in Sweden, data from the TPR can be used for medical research purposes, including family design studies since each individual can be linked to his or her parents, siblings and offspring. The TPR also allows for identification of general population controls, participants in cohort studies, as well as calculation of follow-up time.NonePublishe

    Global parameter identification of stochastic reaction networks from single trajectories

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    We consider the problem of inferring the unknown parameters of a stochastic biochemical network model from a single measured time-course of the concentration of some of the involved species. Such measurements are available, e.g., from live-cell fluorescence microscopy in image-based systems biology. In addition, fluctuation time-courses from, e.g., fluorescence correlation spectroscopy provide additional information about the system dynamics that can be used to more robustly infer parameters than when considering only mean concentrations. Estimating model parameters from a single experimental trajectory enables single-cell measurements and quantification of cell--cell variability. We propose a novel combination of an adaptive Monte Carlo sampler, called Gaussian Adaptation, and efficient exact stochastic simulation algorithms that allows parameter identification from single stochastic trajectories. We benchmark the proposed method on a linear and a non-linear reaction network at steady state and during transient phases. In addition, we demonstrate that the present method also provides an ellipsoidal volume estimate of the viable part of parameter space and is able to estimate the physical volume of the compartment in which the observed reactions take place.Comment: Article in print as a book chapter in Springer's "Advances in Systems Biology

    Aperture synthesis for gravitational-wave data analysis: Deterministic Sources

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    Gravitational wave detectors now under construction are sensitive to the phase of the incident gravitational waves. Correspondingly, the signals from the different detectors can be combined, in the analysis, to simulate a single detector of greater amplitude and directional sensitivity: in short, aperture synthesis. Here we consider the problem of aperture synthesis in the special case of a search for a source whose waveform is known in detail: \textit{e.g.,} compact binary inspiral. We derive the likelihood function for joint output of several detectors as a function of the parameters that describe the signal and find the optimal matched filter for the detection of the known signal. Our results allow for the presence of noise that is correlated between the several detectors. While their derivation is specialized to the case of Gaussian noise we show that the results obtained are, in fact, appropriate in a well-defined, information-theoretic sense even when the noise is non-Gaussian in character. The analysis described here stands in distinction to ``coincidence analyses'', wherein the data from each of several detectors is studied in isolation to produce a list of candidate events, which are then compared to search for coincidences that might indicate common origin in a gravitational wave signal. We compare these two analyses --- optimal filtering and coincidence --- in a series of numerical examples, showing that the optimal filtering analysis always yields a greater detection efficiency for given false alarm rate, even when the detector noise is strongly non-Gaussian.Comment: 39 pages, 4 figures, submitted to Phys. Rev.

    Mathematical modelling of polyamine metabolism in bloodstream-form trypanosoma brucei: An application to drug target identification

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    © 2013 Gu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThis article has been made available through the Brunel Open Access Publishing Fund.We present the first computational kinetic model of polyamine metabolism in bloodstream-form Trypanosoma brucei, the causative agent of human African trypanosomiasis. We systematically extracted the polyamine pathway from the complete metabolic network while still maintaining the predictive capability of the pathway. The kinetic model is constructed on the basis of information gleaned from the experimental biology literature and defined as a set of ordinary differential equations. We applied Michaelis-Menten kinetics featuring regulatory factors to describe enzymatic activities that are well defined. Uncharacterised enzyme kinetics were approximated and justified with available physiological properties of the system. Optimisation-based dynamic simulations were performed to train the model with experimental data and inconsistent predictions prompted an iterative procedure of model refinement. Good agreement between simulation results and measured data reported in various experimental conditions shows that the model has good applicability in spite of there being gaps in the required data. With this kinetic model, the relative importance of the individual pathway enzymes was assessed. We observed that, at low-to-moderate levels of inhibition, enzymes catalysing reactions of de novo AdoMet (MAT) and ornithine production (OrnPt) have more efficient inhibitory effect on total trypanothione content in comparison to other enzymes in the pathway. In our model, prozyme and TSHSyn (the production catalyst of total trypanothione) were also found to exhibit potent control on total trypanothione content but only when they were strongly inhibited. Different chemotherapeutic strategies against T. brucei were investigated using this model and interruption of polyamine synthesis via joint inhibition of MAT or OrnPt together with other polyamine enzymes was identified as an optimal therapeutic strategy.The work was carried out under a PhD programme partly funded by Prof. Ray Welland, School of Computing Science, University of Glasgo

    Tracking tracer motion in a 4-D electrical resistivity tomography experiment

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    A new framework for automatically tracking subsurface tracers in electrical resistivity tomography (ERT) monitoring images is presented. Using computer vision and Bayesian inference techniques, in the form of a Kalman filter, the trajectory of a subsurface tracer is monitored by predicting and updating a state model representing its movements. Observations for the Kalman filter are gathered using the maximally stable volumes algorithm, which is used to dynamically threshold local regions of an ERT image sequence to detect the tracer at each time step. The application of the framework to the results of 2-D and 3-D tracer monitoring experiments show that the proposed method is effective for detecting and tracking tracer plumes in ERT images in the presence of noise, without intermediate manual intervention

    HD 65949: Rosetta Stone or Red Herring

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    HD 65949 is a late B star with exceptionally strong Hg II at 3984[A], but it is not a typical HgMn star. The Re II spectrum is of extraordinary strength. Abundances, or upper limits are derived here for 58 elements based on a model with Teff = 13100K, and log(g) = 4.0. Even-Z elements through nickel show minor deviations from solar abundances. Anomalies among the odd-Z elements through copper are mostly small. Beyond the iron peak, a huge scatter is found. The abundance pattern of the heaviest elements resembles the N=126 r-process peak of solar material, though not in detail. We find a significant correlation of the abundance excesses with second ionization potentials for elements with Z > 30. This indicates the relevance of photospheric or near-photospheric processes. We explore a model with mass accretion of exotic material followed by the more commonly accepted differentiation by diffusion. That model leads to a number of predictions which challenge future work. Likely primary and secondary masses are near 3.3 and 1.6 M(solar), with a separation of ca. 0.25 AU. New atomic structure calculations are presented in two appendices.Comment: Accepted by MNRAS: 16 pages, 5 figure

    Quantitative predictions on auxin-induced polar distribution of PIN proteins during vein formation in leaves

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    The dynamic patterning of the plant hormone auxin and its efflux facilitator the PIN protein are the key regulator for the spatial and temporal organization of plant development. In particular auxin induces the polar localization of its own efflux facilitator. Due to this positive feedback auxin flow is directed and patterns of auxin and PIN arise. During the earliest stage of vein initiation in leaves auxin accumulates in a single cell in a rim of epidermal cells from which it flows into the ground meristem tissue of the leaf blade. There the localized auxin supply yields the successive polarization of PIN distribution along a strand of cells. We model the auxin and PIN dynamics within cells with a minimal canalization model. Solving the model analytically we uncover an excitable polarization front that triggers a polar distribution of PIN proteins in cells. As polarization fronts may extend to opposing directions from their initiation site we suggest a possible resolution to the puzzling occurrence of bipolar cells, such we offer an explanation for the development of closed, looped veins. Employing non-linear analysis we identify the role of the contributing microscopic processes during polarization. Furthermore, we deduce quantitative predictions on polarization fronts establishing a route to determine the up to now largely unknown kinetic rates of auxin and PIN dynamics.Comment: 9 pages, 4 figures, supplemental information included, accepted for publication in Eur. Phys. J.

    INPUT SELECTION BY EPR-MOGA

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    The growing availability of field data, from information and communication technologies (ICTs) in "smart'' urban infrastructures, allows data modeling to understand complex phenomena and to support management decisions. Among the analyzed phenomena, those related to storm water quality modeling have recently been gaining interest in the scientific literature. Nonetheless, the large amount of available data poses the problem of selecting relevant variables to describe a phenomenon and enable robust data modeling. This paper presents a procedure for the selection of relevant input variables using the multi-objective evolutionary polynomial regression (EPR-MOGA) paradigm. The procedure is based on scrutinizing the explanatory variables that appear inside the set of EPR-MOGA symbolic model expressions of increasing complexity and goodness of fit to target output. The strategy also enables the selection to be validated by engineering judgement. In such context, the multiple case study extension of EPR-MOGA, called MCS-EPR-MOGA, is adopted. The application of the proposed procedure to modeling storm water quality parameters in two French catchments shows that it was able to significantly reduce the number of explanatory variables for successive analyses. Finally, the EPR-MOGA models obtained after the input selection are compared with those obtained by using the same technique without benefitting from input selection and with those obtained in previous works where other data-modeling techniques were used on the same data. The comparison highlights the effectiveness of both EPR-MOGA and the input selection procedure
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