84 research outputs found

    Parameter Estimation for Gene Regulatory Networks from Microarray Data: Cold Shock Response in Saccharomyces cerevisiae

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    We investigated the dynamics of a gene regulatory network controlling the cold shock response in budding yeast, Saccharomyces cerevisiae. The medium-scale network, derived from published genome-wide location data, consists of 21 transcription factors that regulate one another through 31 directed edges. The expression levels of the individual transcription factors were modeled using mass balance ordinary differential equations with a sigmoidal production function. Each equation includes a production rate, a degradation rate, weights that denote the magnitude and type of influence of the connected transcription factors (activation or repression), and a threshold of expression. The inverse problem of determining model parameters from observed data is our primary interest. We fit the differential equation model to published microarray data using a penalized nonlinear least squares approach. Model predictions fit the experimental data well, within the 95 % confidence interval. Tests of the model using randomized initial guesses and model-generated data also lend confidence to the fit. The results have revealed activation and repression relationships between the transcription factors. Sensitivity analysis indicates that the model is most sensitive to changes in the production rate parameters, weights, and thresholds of Yap1, Rox1, and Yap6, which form a densely connected core in the network. The modeling results newly suggest that Rap1, Fhl1, Msn4, Rph1, and Hsf1 play an important role in regulating the early response to cold shock in yeast. Our results demonstrate that estimation for a large number of parameters can be successfully performed for nonlinear dynamic gene regulatory networks using sparse, noisy microarray data

    Influence of organic molecules on the aggregation of TiO2 nanoparticles in acidic conditions

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    Engineered nanoparticles released into the environment may interact with natural organic matter (NOM). Surface complexation affects the surface potential, which in turn may lead to aggregation of the particles. Aggregation of synthetic TiO2 (anatase) nanoparticles in aqueous suspension was investigated at pH 2.8 as a function of time in the presence of various organic molecules and Suwannee River fulvic acid (SRFA), using dynamic light scattering (DLS) and high-resolution transmission electron microscopy (TEM). Results showed that the average hydrodynamic diameter and ?-potential were dependent on both concentration and molecular structure of the organic molecule. Results were also compared with those of quantitative batch adsorption experiments. Further, a time study of the aggregation of TiO2 nanoparticles in the presence of 2,3-dihydroxybenzoic acid (2,3-DHBA) and SRFA, respectively, was performed in order to observe changes in ?-potential and particle size over a time period of 9 months. In the 2,3-DHBA-TiO2 system, ?-potentials decreased with time resulting in charge neutralization and/or inversion depending on ligand concentration. Aggregate sizes increased initially to the micrometer size range, followed by disaggregation after several months. No or very little interaction between SRFA and TiO2 occurred at the lowest concentrations tested. However, at the higher concentrations of SRFA, there was an increase in both aggregate size and the amount of SRFA adsorbed to the TiO2 surface. This was in correlation with the ?-potential that decreased with increased SRFA concentration, leading to destabilization of the system. These results stress the importance of performing studies over both short and long time periods to better understand and predict the long-term effects of nanoparticles in the environment

    Staging Relationships With History: The Cultural, Natural, and Eternal Ruins of Bears Ears National Monument

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    How can we, as designers of the built environment, use history as a means of transforming the future, here and now? Rooted deeply within the canyons and mesas of the 1.3-million-acre monument in southeastern Utah, the endangered ruins of Bears Ears hold ancient stories of human interconnectivity with the environment ? narratives central to Native American spirituality that unfold the earth as a living, breathing entity with an eternal pulse. In reinterpreting and transforming these stories, can modern visitors reimagine a different place in nature that might even inform the survival of humankind into the future? In response to the current treatment of history as something in the past, this project aims to create a threshold between the distant past and the untold future by framing present experiences with additions to the Bears Ears National Monument. Standing as an architectural repository of many mythologies and narratives about the world, this interpretive center and corresponding observation platforms aim to direct us back to the core narratives and structures of feeling in the universe. The central intention focuses on the visitors? participation with the history that carries us forward in ways that may benefit us all

    Pulmonary Arterial Blood Volume and Tissue Volume in Man and Dog

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    After the injection of an ethyl ether-alcohol solution above the pulmonic valve, the pulmonary arterial circulation time was determined in conscious man by an established body plethysmographic technique and in anesthetized man by a newly developed pneumotachographic method. In the anesthetized dog, estimates of pulmonary arterial circulation time determined by this new method were compared with those simultaneously determined by the plethysmographic method; agreement was good. The usefulness of applying corrective factors for the right-to-left intrapulmonary shunt and the uptake of ether gas from the alveoli into the blood while the ether gas is being evolved from the initial injection was evaluated from the dog experiments. In five humans with normal pulmonary arterial pressures, pulmonary arterial blood volume estimated by these methods was 172 ± 22 (sd) ml. Estimates of pulmonary tissue volume in both dogs and man were much larger than previously reported values determined from the tritiated water space of the lungs but more in keeping with previously published estimates of the total water content of the lungs determined at postmortem examination.</jats:p
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