The impact of measurement errors in the identification of regulatory networks

Background: There are several studies in the literature depicting measurement error in gene expression data and also, several others about regulatory network models. However, only a little fraction describes a combination of measurement error in mathematical regulatory networks and shows how to identify these networks under different rates of noise. Results: This article investigates the effects of measurement error on the estimation of the parameters in regulatory networks. Simulation studies indicate that, in both time series (dependent) and non-time series (independent) data, the measurement error strongly affects the estimated parameters of the regulatory network models, biasing them as predicted by the theory. Moreover, when testing the parameters of the regulatory network models, p-values computed by ignoring the measurement error are not reliable, since the rate of false positives are not controlled under the null hypothesis. In order to overcome these problems, we present an improved version of the Ordinary Least Square estimator in independent (regression models) and dependent (autoregressive models) data when the variables are subject to noises. Moreover, measurement error estimation procedures for microarrays are also described. Simulation results also show that both corrected methods perform better than the standard ones (i.e., ignoring measurement error). The proposed methodologies are illustrated using microarray data from lung cancer patients and mouse liver time series data. Conclusions: Measurement error dangerously affects the identification of regulatory network models, thus, they must be reduced or taken into account in order to avoid erroneous conclusions. This could be one of the reasons for high biological false positive rates identified in actual regulatory network models.

Eddy Formation in the Tropical Atlantic Induced by Abrupt Changes in the Meridional Overturning Circulation

The variability of the meridional overturning circulation (MOC) in the upper tropical Atlantic basin is investigated using a reduced-gravity model in a simplified domain. Four sets of idealized numerical experiments are performed: (i) switch-on of the MOC until a fixed value when a constant northward flow is applied along the western boundary; (ii) MOC with a variable flow; (iii) MOC in a quasi-steady flow; and (iv) shutdown of the MOC in the Northern Hemisphere. Results from experiments (i) show that eddies are generated at the equatorial region by shear instability and detached northward; eddies are responsible for an enhancement of the mean flow and the variability of the MOC. Results from experiments (ii) show a transitional behavior of the MOC related to the eddy generation in interannual-decadal time scales as the Reynolds number varies due to the variations in the MOC. In experiments (iii), a critical Reynolds number Re(c) around 30 is found, above which eddies are generated. Experiments (iv) demonstrate that even after the collapse of MOC in the Northern Hemisphere, eddies can still be generated and carry energy across the equator into the Northern Hemisphere; these eddies act to attenuate the impact of the MOC shutdown on short time scales. The results described here may be particularly pertinent to ocean general circulation models in which the Reynolds number lies close to the bifurcation point separating the laminar and turbulent regimes.

Forest-related partnerships in Brazilian Amazonia: There is more to sustainable forest management than reduced impact logging

There is more to sustainable forest management than reduced impact logging. Partnerships between multiple actors are needed in order to create the institutional context for good forest governance and sustainable forest management and stimulate the necessary local community involvement. The idea behind this is that the parties would be able to achieve more jointly than on their own by combining assets, knowledge, skills and political power of actors at different levels of scale. This article aims to demonstrate by example the nature and variety of forest-related partnerships in Brazilian Amazonia. Based on the lessons learned from these cases and the authors` experience, the principal characteristics of successful partnerships are described, with a focus on political and socioeconomic aspects. These characteristics include fairly negotiated partnership objectives, the active involvement of the public sector as well as impartial brokers, equitable and cost-effective institutional arrangements, sufficient and equitably shared benefits for all the parties involved, addressing socioeconomic drawbacks, and taking measures to maintain sustainable exploitation levels. The authors argue that, in addition to product-oriented partnerships which focus on sustainable forest management, there is also a need for politically oriented partnerships based on civil society coalitions. The watchdog function of these politically oriented partnerships, their awareness-raising campaigns regarding detrimental policies and practices, and advocacy for good forest governance are essential for the creation of the appropriate legal and political framework for sustainable forest management. (C) 2008 Elsevier B.V. All rights reserved.

Bayesian updating rules in continuous opinion dynamics models

Here, I investigate the use of Bayesian updating rules applied to modeling how social agents change their minds in the case of continuous opinion models. Given another agent statement about the continuous value of a variable, we will see that interesting dynamics emerge when an agent assigns a likelihood to that value that is a mixture of a Gaussian and a uniform distribution. This represents the idea that the other agent might have no idea about what is being talked about. The effect of updating only the first moments of the distribution will be studied, and we will see that this generates results similar to those of the bounded confidence models. On also updating the second moment, several different opinions always survive in the long run, as agents become more stubborn with time. However, depending on the probability of error and initial uncertainty, those opinions might be clustered around a central value.

Improvements on ICA mixture models for image pre-processing and segmentation

Today several different unsupervised classification algorithms are commonly used to cluster similar patterns in a data set based only on its statistical properties. Specially in image data applications, self-organizing methods for unsupervised classification have been successfully applied for clustering pixels or group of pixels in order to perform segmentation tasks. The first important contribution of this paper refers to the development of a self-organizing method for data classification, named Enhanced Independent Component Analysis Mixture Model (EICAMM), which was built by proposing some modifications in the Independent Component Analysis Mixture Model (ICAMM). Such improvements were proposed by considering some of the model limitations as well as by analyzing how it should be improved in order to become more efficient. Moreover, a pre-processing methodology was also proposed, which is based on combining the Sparse Code Shrinkage (SCS) for image denoising and the Sobel edge detector. In the experiments of this work, the EICAMM and other self-organizing models were applied for segmenting images in their original and pre-processed versions. A comparative analysis showed satisfactory and competitive image segmentation results obtained by the proposals presented herein. (C) 2008 Published by Elsevier B.V.

Treatment of Obese Adolescents: The Influence of Periodization Models and ACE Genotype

The aims of the present study were to compare the effects of two periodization models on metabolic syndrome risk factors in obese adolescents and verify whether the angiotensin-converting enzyme (ACE) genotype is important in establishing these effects. A total of 32 postpuberty obese adolescents were submitted to aerobic training (AT) and resistance training (RT) for 14 weeks. The subjects were divided into linear periodization (LP, n = 16) or daily undulating periodization (DUP, n = 16). Body composition, visceral and subcutaneous fat, glycemia, insulinemia, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profiles, blood pressure, maximal oxygen consumption (VO(2max)), resting metabolic rate (RMR), muscular endurance were analyzed at baseline and after intervention. Both groups demonstrated a significant reduction in body mass, BMI, body fat, visceral and subcutaneous fat, total and low-density lipoprotein cholesterol, blood pressure and an increase in fat-free mass, VO(2max), and muscular endurance. However, only DUP promoted a reduction in insulin concentrations and HOMA-IR. It is important to emphasize that there was no statics difference between LP and DUP groups; however, it appears that there may be bigger changes in the DUP than LP group in some of the metabolic syndrome risk factors in obese adolescents with regard to the effect size (ES). Both periodization models presented a large effect on muscular endurance. Despite the limitation of sample size, our results suggested that the ACE genotype may influence the functional and metabolic characteristics of obese adolescents and may be considered in the future strategies for massive obesity control.

Coconut coir as biosorbent for Cr(VI) removal from laboratory wastewater

A high cost-effective treatment of sulphochromic waste is proposed employing a raw coconut coir as biosorbent for Cr(VI) removal. The ideal pH and sorption kinetic, sorption capacities, and sorption sites were the studied biosorbent parameters. After testing five different isotherm models with standard solutions, Redlich-Peterson and Toth best fitted the experimental data, obtaining a theoretical Cr(VI) sorption capacity (SC) of 6.3 mg g(-1). Acid-base potentiometric titration indicated around of 73% of sorption sites were from phenolic compounds, probably lignin. Differences between sorption sites in the coconut coir before and after Cr adsorption identified from Fourier transform infrared spectra suggested a modification of sorption sites after sulphochromic waste treatment, indicating that the sorption mechanism involves organic matter oxidation and chromium uptake. For sulphocromic waste treatment, the SC was improved to 26.8 +/- 0.2 mg g(-1), and no adsorbed Cr(VI) was reduced, remaining only Cr(III) in the final solution. The adsorbed material was calcinated to obtain Cr2O3, with a reduction of more than 60% of the original mass. (c) 2008 Elsevier B.V. All rights reserved.

Dysautonomia due to reduced cholinergic neurotransmission causes cardiac remodeling and heart failure

Overwhelming evidence supports the importance of the sympathetic nervous system in heart failure. In contrast, much less is known about the role of failing cholinergic neurotransmission in cardiac disease. By using a unique genetically modified mouse line with reduced expression of the vesicular acetylcholine transporter (VAChT) and consequently decreased release of acetylcholine, we investigated the consequences of altered cholinergic tone for cardiac function. M-mode echocardiography, hemodynamic experiments, analysis of isolated perfused hearts, and measurements of cardiomyocyte contraction indicated that VAChT mutant mice have decreased left ventricle function associated with altered calcium handling. Gene expression was analyzed by quantitative reverse transcriptase PCR and Western blotting, and the results indicated that VAChT mutant mice have profound cardiac remodeling and reactivation of the fetal gene program. This phenotype was attributable to reduced cholinergic tone, since administration of the cholinesterase inhibitor pyridostigmine for 2 weeks reversed the cardiac phenotype in mutant mice. Our findings provide direct evidence that decreased cholinergic neurotransmission and underlying autonomic imbalance cause plastic alterations that contribute to heart dysfunction.

Acute high-intensity exercise with low energy expenditure reduced LDL-c and total cholesterol in men

A reduction in LDL cholesterol and an increase in HDL cholesterol levels are clinically relevant parameters for the treatment of dyslipidaemia, and exercise is often recommended as an intervention. This study aimed to examine the effects of acute, high-intensity exercise (similar to 90% VO(2max)) and varying carbohydrate levels (control, low and high) on the blood lipid profile. Six male subjects were distributed randomly into exercise groups, based on the carbohydrate diets (control, low and high) to which the subjects were restricted before each exercise session. The lipid profile (triglycerides, VLDL, HDL cholesterol, LDL cholesterol and total cholesterol) was determined at rest, and immediately and 1 h after exercise bouts. There were no changes in the time exhaustion (8.00 +/- A 1.83; 7.82 +/- A 2.66; and 9.09 +/- A 3.51 min) and energy expenditure (496.0 +/- A 224.8; 411.5 +/- A 223.1; and 592.1 +/- A 369.9 kJ) parameters with the three varying carbohydrate intake (control, low and high). Glucose and insulin levels did not show time-dependent changes under the different conditions (P > 0.05). Total cholesterol and LDL cholesterol were reduced after the exhaustion and 1 h recovery periods when compared with rest periods only in the control carbohydrate intake group (P < 0.05), although this relation failed when the diet was manipulated. These results indicate that acute, high-intensity exercise with low energy expenditure induces changes in the cholesterol profile, and that influences of carbohydrate level corresponding to these modifications fail when carbohydrate (low and high) intake is manipulated.

Antinociceptive effect of stimulating the occipital or retrosplenial cortex in rats

A role for the occipital or retrosplenial cortex in nociceptive processing has not been demonstrated yet, but connections from these cortices to brain structures involved in descending pain-inhibitory mechanisms were already demonstrated. This study demonstrated that the electrical stimulation of the occipital or retrosplenial cortex produces antinociception in the rat tail-flick and formalin tests. Bilateral lesions of the dorsolateral funiculus abolished the effect of cortical stimulation in the tail-flick test. Injection of glutamate into the same targets was also antinociceptive in the tail-flick test. No rats stimulated in the occipital or retrosplenial cortex showed any change in motor performance on the Rota-rod test, or had epileptiform changes in the EEG recording during or up to 3 hours after stimulation. The antinociception induced by occipital cortex stimulation persisted after neural block of the retrosplenial cortex. The effect of retrosplenial cortex stimulation also persisted after neural block of the occipital cortex. We conclude that stimulation of the occipital or retrosplenial cortex in rats leads to antinociception activating distinct descending pain-inhibitory mechanisms, and this is unlikely to result from a reduced motor performance or a postictal phenomenon. Perspective: This study presents evidence that stimulation of the retrosplenial or occipital cortex produces antinociception in rat models of acute pain. These findings enhance our understanding of the role of the cerebral cortex in control of pain. (C) 2010 by the American Pain Society

Enzymatic Hydrolysis of Chemithermomechanically Pretreated Sugarcane Bagasse and Samples with Reduced Initial Lignin Content

Chemithermomechanical (CTM) processing was used to pretreat sugarcane bagasse with the aim of increasing cell wall accessibility to hydrolytic enzymes. Yields of the pretreated samples were in the range of 75-94%. Disk refining and alkaline-CTM and alkaline/sulfite-CTM pretreatments yielded pretreated materials with 21.7, 17.8, and 15.3% of lignin, respectively. Hemicellulose content was also decreased to some extent. Fibers of the pretreated materials presented some external fibrillation, fiber curling, increased swelling, and high water retention capacity. Cellulose conversion of the alkaline-CTM- and alkaline/sulfite-CTM-pretreated samples reached 50 and 85%, respectively, after 96 h of enzymatic hydrolysis. Two samples with low initial lignin content were also evaluated after the mildest alkaline-CTM pretreatment. One sample was a partially delignified mill-processed bagasse. The other was a sugarcane hybrid selected in a breeding program. Samples with lower initial lignin content were hydrolyzed considerably faster in the first 24 h of enzymatic digestion. For example, enzymatic hydrolysis of the sample with the lowest initial lignin content (14.2%) reached 64% cellulose conversion after only 24 h of hydrolysis when compared with the 30% observed for the mill-processed bagasse containing an initial lignin content of 24.4%. (C) 2011 American Institute of Chemical Engineers Biotechnol. Prog., 27: 395-401, 2011

Aerodynamic study of three-dimensional larynx models using finite element methods

The airflow velocities and pressures are calculated from a three-dimensional model of the human larynx by using the finite element method. The laryngeal airflow is assumed to be incompressible, isothermal, steady, and created by fixed pressure drops. The influence of different laryngeal profiles (convergent, parallel, and divergent), glottal area, and dimensions of false vocal folds in the airflow are investigated. The results indicate that vertical and horizontal phase differences in the laryngeal tissue movements are influenced by the nonlinear pressure distribution across the glottal channel, and the glottal entrance shape influences the air pressure distribution inside the glottis. Additionally, the false vocal folds increase the glottal duct pressure drop by creating a new constricted channel in the larynx, and alter the airflow vortexes formed after the true vocal folds. (C) 2007 Elsevier Ltd. All rights reserved.

Integrating structural and input design of a 2-DOF high-speed parallel manipulator: A flexible model-based approach

This paper discusses the integrated design of parallel manipulators, which exhibit varying dynamics. This characteristic affects the machine stability and performance. The design methodology consists of four main steps: (i) the system modeling using flexible multibody technique, (ii) the synthesis of reduced-order models suitable for control design, (iii) the systematic flexible model-based input signal design, and (iv) the evaluation of some possible machine designs. The novelty in this methodology is to take structural flexibilities into consideration during the input signal design; therefore, enhancing the standard design process which mainly considers rigid bodies dynamics. The potential of the proposed strategy is exploited for the design evaluation of a two degree-of-freedom high-speed parallel manipulator. The results are experimentally validated. (C) 2010 Elsevier Ltd. All rights reserved.

Simplified models for cross-section stress demands on C-section purlins in uplift

The objective of this paper is to provide and verify simplified models that predict the longitudinal stresses that develop in C-section purlins in uplift. The paper begins with the simple case of flexural stress: where the force has to be applied at the shear center, or the section braced in both flanges. Restrictions on load application point and restraint of the flanges are removed until arriving at the more complex problem of bending when movement of the tension flange alone is restricted, as commonly found in purlin-sheeting systems. Winter`s model for predicting the longitudinal stresses developed due to direct torsion is reviewed, verified, and then extended to cover the case of a bending member with tension flange restraint. The developed longitudinal stresses from flexure and restrained torsion are used to assess the elastic stability behavior of typical purlin-sheeting systems. Finally, strength predictions of typical C-section purlins are provided for existing AISI methods and a newly proposed extension to the direct strength method that employs the predicted longitudinal stress distributions within the strength prediction. (C) 2009 Elsevier Ltd. All rights reserved.

Failure Mechanisms in Sand over a Deep Active Trapdoor

An experimental testing program was undertaken to investigate failure mechanisms induced by the active movement of a deep rectangular trapdoor underlying a granular soil. Reduced-scale models were tested under normal gravity as well as under an increased gravitational field using a centrifuge facility. Some models were used to evaluate the performance of both flexible and rigid pipes undergoing a localized loss of support. Failure mechanisms in the longitudinal direction of the models were characterized by a single, well-defined failure surface that developed within the limits of the trapdoor. However, failure mechanisms in the transverse direction of the models were characterized by multiple failure surfaces extending outside the limits of the trapdoor. Significant dilation of the soil located immediately above the trapdoor was identified in the failure of the models. The pattern of the failure mechanisms was found to be affected by the stress level and backfill density. Higher stress levels were found to lead to well-developed failure zones. The influence of backfill density was found to be more relevant in models involving flexible pipes. Pipes embedded within loose backfill were severely damaged after loss of support, while pipes embedded in dense backfill experienced negligible deformations. These results indicate that damage to pipelines caused by ground loss of support can be significantly minimized by controlling the compaction of the fill.