508,092 research outputs found

    Effective and efficient algorithm for multiobjective optimization of hydrologic models

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    Practical experience with the calibration of hydrologic models suggests that any single-objective function, no matter how carefully chosen, is often inadequate to properly measure all of the characteristics of the observed data deemed to be important. One strategy to circumvent this problem is to define several optimization criteria (objective functions) that measure different (complementary) aspects of the system behavior and to use multicriteria optimization to identify the set of nondominated, efficient, or Pareto optimal solutions. In this paper, we present an efficient and effective Markov Chain Monte Carlo sampler, entitled the Multiobjective Shuffled Complex Evolution Metropolis (MOSCEM) algorithm, which is capable of solving the multiobjective optimization problem for hydrologic models. MOSCEM is an improvement over the Shuffled Complex Evolution Metropolis (SCEM-UA) global optimization algorithm, using the concept of Pareto dominance (rather than direct single-objective function evaluation) to evolve the initial population of points toward a set of solutions stemming from a stable distribution (Pareto set). The efficacy of the MOSCEM-UA algorithm is compared with the original MOCOM-UA algorithm for three hydrologic modeling case studies of increasing complexity

    Development and Validation of a Modified Multiple Errands Test for Adults with Intellectual Disabilities

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    Background: The aims of the current study were to adapt a version of the MET for people with intellectual disabilities (IDs) and assess its ecological and construct validity. Material and Methods: Using a correlational design, 40 participants with IDs were invited to complete a battery of neuropsychological assessments and the modified Multiple Errands Test for Intellectual Disabilities (mMET-IDs). Results: The ability to successfully complete tasks on the mMET-IDs correlated significantly with measures of the Supervisory Attentional System, namely, the Tower of London Test and the Six Parts Test. However, performance on the mMET-IDs and the Six Parts Test could be accounted for by Verbal IQ and receptive vocabulary. The mMET-IDs failed to correlate with the DEX-IR. Conclusions: The mMET-IDs can be successfully used to assess some aspects of the Supervisory Attentional System in people with IDs. Further development is needed, however, to improve the ecological validity of the mMET-IDs

    Strong negative self regulation of Prokaryotic transcription factors increases the intrinsic noise of protein expression

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    Background Many prokaryotic transcription factors repress their own transcription. It is often asserted that such regulation enables a cell to homeostatically maintain protein abundance. We explore the role of negative self regulation of transcription in regulating the variability of protein abundance using a variety of stochastic modeling techniques. Results We undertake a novel analysis of a classic model for negative self regulation. We demonstrate that, with standard approximations, protein variance relative to its mean should be independent of repressor strength in a physiological range. Consequently, in that range, the coefficient of variation would increase with repressor strength. However, stochastic computer simulations demonstrate that there is a greater increase in noise associated with strong repressors than predicted by theory. The discrepancies between the mathematical analysis and computer simulations arise because with strong repressors the approximation that leads to Michaelis-Menten-like hyperbolic repression terms ceases to be valid. Because we observe that strong negative feedback increases variability and so is unlikely to be a mechanism for noise control, we suggest instead that negative feedback is evolutionarily favoured because it allows the cell to minimize mRNA usage. To test this, we used in silico evolution to demonstrate that while negative feedback can achieve only a modest improvement in protein noise reduction compared with the unregulated system, it can achieve good improvement in protein response times and very substantial improvement in reducing mRNA levels. Conclusions Strong negative self regulation of transcription may not always be a mechanism for homeostatic control of protein abundance, but instead might be evolutionarily favoured as a mechanism to limit the use of mRNA. The use of hyperbolic terms derived from quasi-steady-state approximation should also be avoided in the analysis of stochastic models with strong repressors

    Feature Extraction in Signal Regression: A Boosting Technique for Functional Data Regression

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    Main objectives of feature extraction in signal regression are the improvement of accuracy of prediction on future data and identification of relevant parts of the signal. A feature extraction procedure is proposed that uses boosting techniques to select the relevant parts of the signal. The proposed blockwise boosting procedure simultaneously selects intervals in the signal’s domain and estimates the effect on the response. The blocks that are defined explicitly use the underlying metric of the signal. It is demonstrated in simulation studies and for real-world data that the proposed approach competes well with procedures like PLS, P-spline signal regression and functional data regression. The paper is a preprint of an article published in the Journal of Computational and Graphical Statistics. Please use the journal version for citation

    Gene autoregulation via intronic microRNAs and its functions

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    Background: MicroRNAs, post-transcriptional repressors of gene expression, play a pivotal role in gene regulatory networks. They are involved in core cellular processes and their dysregulation is associated to a broad range of human diseases. This paper focus on a minimal microRNA-mediated regulatory circuit, in which a protein-coding gene (host gene) is targeted by a microRNA located inside one of its introns. Results: Autoregulation via intronic microRNAs is widespread in the human regulatory network, as confirmed by our bioinformatic analysis, and can perform several regulatory tasks despite its simple topology. Our analysis, based on analytical calculations and simulations, indicates that this circuitry alters the dynamics of the host gene expression, can induce complex responses implementing adaptation and Weber's law, and efficiently filters fluctuations propagating from the upstream network to the host gene. A fine-tuning of the circuit parameters can optimize each of these functions. Interestingly, they are all related to gene expression homeostasis, in agreement with the increasing evidence suggesting a role of microRNA regulation in conferring robustness to biological processes. In addition to model analysis, we present a list of bioinformatically predicted candidate circuits in human for future experimental tests. Conclusions: The results presented here suggest a potentially relevant functional role for negative self-regulation via intronic microRNAs, in particular as a homeostatic control mechanism of gene expression. Moreover, the map of circuit functions in terms of experimentally measurable parameters, resulting from our analysis, can be a useful guideline for possible applications in synthetic biology.Comment: 29 pages and 7 figures in the main text, 18 pages of Supporting Informatio

    Optimal measurement of visual motion across spatial and temporal scales

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    Sensory systems use limited resources to mediate the perception of a great variety of objects and events. Here a normative framework is presented for exploring how the problem of efficient allocation of resources can be solved in visual perception. Starting with a basic property of every measurement, captured by Gabor's uncertainty relation about the location and frequency content of signals, prescriptions are developed for optimal allocation of sensors for reliable perception of visual motion. This study reveals that a large-scale characteristic of human vision (the spatiotemporal contrast sensitivity function) is similar to the optimal prescription, and it suggests that some previously puzzling phenomena of visual sensitivity, adaptation, and perceptual organization have simple principled explanations.Comment: 28 pages, 10 figures, 2 appendices; in press in Favorskaya MN and Jain LC (Eds), Computer Vision in Advanced Control Systems using Conventional and Intelligent Paradigms, Intelligent Systems Reference Library, Springer-Verlag, Berli
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