Gene Expression Complex Networks: Synthesis, Identification, and Analysis

Thanks to recent advances in molecular biology, allied to an ever increasing amount of experimental data, the functional state of thousands of genes can now be extracted simultaneously by using methods such as cDNA microarrays and RNA-Seq. Particularly important related investigations are the modeling and identification of gene regulatory networks from expression data sets. Such a knowledge is fundamental for many applications, such as disease treatment, therapeutic intervention strategies and drugs design, as well as for planning high-throughput new experiments. Methods have been developed for gene networks modeling and identification from expression profiles. However, an important open problem regards how to validate such approaches and its results. This work presents an objective approach for validation of gene network modeling and identification which comprises the following three main aspects: (1) Artificial Gene Networks (AGNs) model generation through theoretical models of complex networks, which is used to simulate temporal expression data; (2) a computational method for gene network identification from the simulated data, which is founded on a feature selection approach where a target gene is fixed and the expression profile is observed for all other genes in order to identify a relevant subset of predictors; and (3) validation of the identified AGN-based network through comparison with the original network. The proposed framework allows several types of AGNs to be generated and used in order to simulate temporal expression data. The results of the network identification method can then be compared to the original network in order to estimate its properties and accuracy. Some of the most important theoretical models of complex networks have been assessed: the uniformly-random Erdos-Renyi (ER), the small-world Watts-Strogatz (WS), the scale-free Barabasi-Albert (BA), and geographical networks (GG). The experimental results indicate that the inference method was sensitive to average degree k variation, decreasing its network recovery rate with the increase of k. The signal size was important for the inference method to get better accuracy in the network identification rate, presenting very good results with small expression profiles. However, the adopted inference method was not sensible to recognize distinct structures of interaction among genes, presenting a similar behavior when applied to different network topologies. In summary, the proposed framework, though simple, was adequate for the validation of the inferred networks by identifying some properties of the evaluated method, which can be extended to other inference methods.

Functional microarray analysis suggests repressed cell-cell signaling and cell survival-related modules inhibit progression of head and neck squamous cell carcinoma

Background: Cancer shows a great diversity in its clinical behavior which cannot be easily predicted using the currently available clinical or pathological markers. The identification of pathways associated with lymph node metastasis (N+) and recurrent head and neck squamous cell carcinoma (HNSCC) may increase our understanding of the complex biology of this disease. Methods: Tumor samples were obtained from untreated HNSCC patients undergoing surgery. Patients were classified according to pathologic lymph node status (positive or negative) or tumor recurrence (recurrent or non-recurrent tumor) after treatment (surgery with neck dissection followed by radiotherapy). Using microarray gene expression, we screened tumor samples according to modules comprised by genes in the same pathway or functional category. Results: The most frequent alterations were the repression of modules in negative lymph node (N0) and in non-recurrent tumors rather than induction of modules in N+ or in recurrent tumors. N0 tumors showed repression of modules that contain cell survival genes and in non-recurrent tumors cell-cell signaling and extracellular region modules were repressed. Conclusions: The repression of modules that contain cell survival genes in N0 tumors reinforces the important role that apoptosis plays in the regulation of metastasis. In addition, because tumor samples used here were not microdissected, tumor gene expression data are represented together with the stroma, which may reveal signaling between the microenvironment and tumor cells. For instance, in non-recurrent tumors, extracellular region module was repressed, indicating that the stroma and tumor cells may have fewer interactions, which disable metastasis development. Finally, the genes highlighted in our analysis can be implicated in more than one pathway or characteristic, suggesting that therapeutic approaches to prevent tumor progression should target more than one gene or pathway, specially apoptosis and interactions between tumor cells and the stroma.

Spectroscopic, structural, and functional characterization of the alternative low-spin state of horse heart cytochrome c

The alternative low-spin states of Fe3+ and Fe2+ cytochrome c induced by SDS or AOT/hexane reverse micelles exhibited the heme group in a less rhombic symmetry and were characterized by electron paramagnetic resonance, UV-visible, CD, magnetic CD, fluorescence, and Raman resonance. Consistent with the replacement of Met 80 by another strong field ligand at the sixth heme iron coordination position, Fe3+ ALSScytc exhibited 1-nm Soret band blue shift and e enhancement accompanied by disappearance of the 695-nm charge transfer band. The Raman resonance, CD, and magnetic CD spectra of Fe3+ and Fe2+ ALSScytc exhibited significant changes suggestive of alterations in the heme iron microenvironment and conformation and should not be assigned to unfold because the Trp(59) fluorescence remained quenched by the neighboring heme group. ALSScytc was obtained with His(33) and His(26) carboxyethoxylated horse cytochrome c and with tuna cytochrome c (His(33) replaced by Asn) pointing out Lys(79) as the probable heme iron ligand. Fe3+ ALSScytc retained the capacity to cleave tert-butylhydroperoxide and to be reduced by dithiothreitol and diphenylacetaldehyde but not by ascorbate. Compatible with a more open heme crevice, ALSScytc exhibited a redox potential similar to 200 mV lower than the wild-type protein (1220 mV) and was more susceptible to the attack of free radicals.

Bulk structures of PtO and PtO(2) from density functional calculations

Platinum plays an important role in catalysis and electrochemistry, and it is known that the direct interaction of oxygen with Pt surfaces can lead to the formation of platinum oxides (PtO(x)), which can affect the reactivity. To contribute to the atomistic understanding of the atomic structure of PtO(x), we report a density functional theory study of the atomic structure of bulk PtO(x) (1 <= x <= 2). From our calculations, we identified a lowest-energy structure (GeS type, space group Pnma) for PtO, which is 0.181 eV lower in energy than the structure suggested by W. J. Moore and L. Pauling [J. Am. Chem. Soc. 63, 1392 (1941)] (PtS type). Furthermore, two atomic structures were identified for PtO(2), which are almost degenerate in energy with the lowest-energy structure reported so far for PtO(2) (CaCl(2) type). Based on our results and analysis, we suggest that Pt and O atoms tend to form octahedron motifs in PtO(x) even at lower O composition by the formation of Pt-Pt bonds.

Functional specialization of Eucalyptus fine roots: contrasting potential uptake rates for nitrogen, potassium and calcium tracers at varying soil depths

1. Little is known about the role of deep roots in the nutrition of forest trees and their ability to provide a safety-net service taking up nutrients leached from the topsoil. 2. To address this issue, we studied the potential uptake of N, K and Ca by Eucalyptus grandis trees (6 years of age - 25 m mean height), in Brazil, as a function of soil depth, texture and water content. We injected NO(3)(-)- (15)N, Rb(+) (analogue of K(+)) and Sr(2+) (analogue of Ca(2+)) tracers simultaneously in a solution through plastic tubes at 10, 50, 150 and 300 cm in depth in a sandy and a clayey Ferralsol soil. A complete randomized design was set up with three replicates of paired trees per injection depth and soil type. Recently expanded leaves were sampled at various times after tracer injection in the summer, and the experiment was repeated in the winter. Soil water contents were continuously monitored at the different depths in the two soils. 3. Determination of foliar Rb and Sr concentrations and (15)N atom % made it possible to estimate the relative uptake potential (RUP) of tracer injections from the four soil depths and the specific RUP (SRUP), defined as RUP, per unit of fine root length density in the corresponding soil layer. 4. The highest tracer uptake rates were found in the topsoil, but contrasting RUP distributions were observed for the three tracers. Whilst the RUP was higher for NO(3)(-)- (15)N than for Rb(+) and Sr(2+) in the upper 50 cm of soil, the highest SRUP values for Sr(2+) and Rb(+) were found at a depth of 300 cm in the sandy soil, as well as in the clayey soil when gravitational solutions reached that depth. 5. Our results suggest that the fine roots of E. grandis trees exhibit contrasting potential uptake rates with depth depending on the nutrient. This functional specialization of roots might contribute to the high growth rates of E. grandis trees, efficiently providing the large amounts of nutrients required throughout the development of these fast-growing plantations.

Building a Open Source Framework for Virtual Medical Training

This paper presents a framework to build medical training applications by using virtual reality and a tool that helps the class instantiation of this framework. The main purpose is to make easier the building of virtual reality applications in the medical training area, considering systems to simulate biopsy exams and make available deformation, collision detection, and stereoscopy functionalities. The instantiation of the classes allows quick implementation of the tools for such a purpose, thus reducing errors and offering low cost due to the use of open source tools. Using the instantiation tool, the process of building applications is fast and easy. Therefore, computer programmers can obtain an initial application and adapt it to their needs. This tool allows the user to include, delete, and edit parameters in the functionalities chosen as well as storing these parameters for future use. In order to verify the efficiency of the framework, some case studies are presented.

Cardiac and peripheral adjustments induced by early exercise training intervention were associated with autonomic improvement in infarcted rats: role in functional capacity and mortality

Aims To test the effects of early exercise training (ET) on left ventricular (LV) and autonomic functions, haemodynamics, tissues blood flows (BFs), maximal oxygen consumption (VO(2) max), and mortality after myocardial infarction (MI) in rats. Methods and results Male Wistar rats were divided into: control (C), sedentary-infarcted (SI), and trained-infarcted (TI). One week after MI, TI group underwent an ET protocol (90 days, 50-70% VO2 max). Left ventricular function was evaluated noninvasively and invasively. Baroreflex sensitivity, heart rate variability, and pulse interval were measured. Cardiac output (CO) and regional BFs were determined using coloured microspheres. Infarcted area was reduced in TI (19 +/- 6%) compared with SI (34 +/- 5%) after ET. Exercise training improved the LV and autonomic functions, the CO and regional BF changes induced by MI, as well as increased SERCA2 expression and mRNA vascular endothelial growth factor levels. These changes brought about by ET resulted in mortality rate reduction in the TI (13%) group compared with the SI (54%) group. Conclusion Early aerobic ET reduced cardiac and peripheral dysfunctions and preserved cardiovascular autonomic control after MI in trained rats. Consequently, these ET-induced changes resulted in improved functional capacity and survival after MI.

On the functional integration between postural and supra-postural tasks on the basis of contextual cues and task constraint

In order to evaluate the effects of uncertainty about direction of mechanical perturbation and supra-postural task constraint on postural control young adults had their upright stance perturbed while holding a tray in a horizontal position Stance was perturbed by moving forward or backward a supporting platform contrasting situations of certainty versus uncertainty of direction of displacement Increased constraint on postural stability was Imposed by a supra-postural task of equilibrating a cylinder on the tray Performance was assessed through EMG of anterior leg muscles angular displacement of the main Joints involved in the postural reactions and displacement of the tray Results showed that both certainty on the direction of perturbation and Increased supra-postural task constraint led to decreased angular displacement of the knee and the hip Furthermore combination of certainty and high supra-postural task constraint produced shorter latency of muscular activation Such postural responses were paralleled by decreased displacement of the tray Thesi results suggest a functional integration between the tasks with central set priming reactive postural responses from contextual cues and Increased stability demand (C) 2010 Elsevier B V All rights reserved

Pseudomonas fluorescens lipase immobilization on polysiloxane-polyvinyl alcohol composite chemically modified with epichlorohydrin

The technique based on sol-gel approach was used to generate silica matrices derivatives by hydrolysis of silane compounds. The present work evaluates a hybrid matrix obtained with tetraethoxysilane (TEOS) and polyvinyl alcohol (PVA) on the immobilization yield of lipase from Pseudomonas fluorescens. The resulting polysiloxane-polyvinyl alcohol (POS-PVA) matrix combines the property of PVA as a suitable polymer to retain proteins with an excellent optical, thermal and chemical stability of the host silicon oxide matrix. Aiming to render adequate functional groups to the covalent binding with the enzyme the POS-PVA matrix was chemically modified using epichlorohydrin. The results were compared with immobilized derivative on POS-PVA activated with glutaraldehyde. Immobilization yield based on the recovered lipase activity depended on the activating agent and the highest efficiency (32%) was attained when lipase was immobilized on POS-PVA activated with epichlorohydrin, which, probably, provided more linkage points for the covalent bind of the enzyme on the support. This was confirmed by determining the morphological properties using different techniques as X-ray diffraction and scanning electron microscopy (SEM). Comparative studies were carried out to attain optimal activities for free lipase and immobilized systems. For this purpose, a central composite experimental design with different combinations of pH and temperature was performed. Enzymatic hydrolysis with the immobilized enzyme in the framework of the Michaelis-Menten mechanism was also reported. Under optimum conditions, the immobilized derivative on POS-PVA activated with epichlorohydrin showed to have more affinity for the substrate in the hydrolysis of olive oil, with a Michaelis-Menten constant value (K-m) of 293 mM, compared to the value of 401 mM obtained for the immobilized lipase on support activated with glutaraldehyde. Data generated by DSC showed that both immobilized derivatives have similar thermal stabilities. (C) 2007 Elsevier B.V. All rights reserved.

Upper limb assessment in tetraplegia: clinical, functional and kinematic correlations

The aim of this study was to correlate clinical and functional evaluations with kinematic variables of upper limp reach-to-grasp movement in patients with tetraplegia. Twenty chronic patients were selected to perform reach-to-grasp kinematic assessment using a target placed at a distance equal to the arm`s length. Kinematic variables (hand peak velocity, movement time, percent time-to-maximal velocity, index of curvature, number of peaks, and joint range of motion) were correlated to clinical (Standard Neurological Classification of Spinal Cord Injury-American Spinal Injury Association) and functional [Functional Independence Measure (FIM) and Spinal Cord Independence Measure II (SCIM II)) evaluation scores. Twenty control participants were also selected to obtain normal reference parameters. There was a positive correlation between total motor index and FIM (r=0.6089; P=0.0044) and SCIM II (r=0.5229; P=0.018). Both functional scores showed positive correlation with each other (r=0.8283; P<0.0001). A correlation was also observed between the right and left motor indices, the motor AM, and the SCIM II in most of the reach-to-grasp kinematic variables studied (hand peak velocity, movement time, index of curvature, and number of peaks). In contrast, for the joint range of motion (shoulder, elbow, and wrist), only the wrist in the horizontal plane showed correlation with clinical variables. This study shows that muscle strength assessed by the American Spinal Injury Association motor index influences the reach-to-grasp kinematic variables of patients with tetraplegia. However, the functional assessments did not present the same influence.

Robust STATCOM control for the stabilisation of fixed-speed wind turbines during low voltages

This paper presents a robust voltage control scheme for fixed-speed wind generators using a static synchronous compensator (STATCOM) controller. To enable a linear and robust control framework with structured uncertainty, the overall system is represented by a linear part plus a nonlinear part that covers an operating range of interest required to ensure stability during severe low voltages. The proposed methodology is flexible and readily applicable to larger wind farms of different configurations. The performance of the control strategy is demonstrated on a two area test system. Large disturbance simulations demonstrate that the proposed controller enhances voltage stability as well as transient stability of induction generators during low voltage ride through (LVRT) transients and thus enhances the LVRT capability. (C) 2011 Elsevier Ltd. All rights reserved.

Support Tool to the Validation Process of Functional Requirements

The activity of validating identified requirements for an information system helps to improve the quality of a requirements specification document and, consequently, the success of a project. Although various different support tools to requirements engineering exist in the market, there is still a lack of automated support for validation activity. In this context, the purpose of this paper is to make up for that deficiency, with the use of an automated tool, to provide the resources for the execution of an adequate validation activity. The contribution of this study is to enable an agile and effective follow-up of the scope established for the requirements, so as to lead the development to a solution which would satisfy the real necessities of the users, as well as to supply project managers with relevant information about the maturity of the analysts involved in requirements specification.

Process oriented framework to support PLM implementation

Product lifecycle management (PLM) innovates as it defines both the product as a central element to aggregate enterprise information and the lifecycle as a new time dimension for information integration and analysis. Because of its potential benefits to shorten innovation lead-times and to reduce costs, PLM has attracted a lot of attention at industry and at research. However, the current PLM implementation stage at most organisations still does not apply the lifecycle management concepts thoroughly. In order to close the existing realisation gap, this article presents a process oriented framework to support effective PLM implementation. The framework central point consists of a set of lifecycle oriented business process reference models which links the necessary fundamental concepts, enterprise knowledge and software solutions to effectively deploy PLM. (c) 2007 Elsevier B.V. All rights reserved.

Integrating technology roadmapping and portfolio management at the front-end of new product development

Many authors point out that the front-end of new product development (NPD) is a critical success factor in the NPD process and that numerous companies face difficulties in carrying it out appropriately. Therefore, it is important to develop new theories and proposals that support the effective implementation of this earliest phase of NPD. This paper presents a new method to support the development of front-end activities based on integrating technology roadmapping (TRM) and project portfolio management (PPM). This new method, called the ITP Method, was implemented at a small Brazilian high-tech company in the nanotechnology industry to explore the integration proposal. The case study demonstrated that the ITP Method provides a systematic procedure for the fuzzy front-end and integrates innovation perspectives into a single roadmap, which allows for a better alignment of business efforts and communication of product innovation goals. Furthermore, the results indicated that the method may also improve quality, functional integration and strategy alignment. (C) 2010 Elsevier Inc. All rights reserved.

Contributions of HRM throughout the stages of environmental management: methodological triangulation applied to companies in Brazil

The purpose of this research is to analyze the contribution of human resources management throughout the evolutionary stages of environmental management in Brazilian companies. A theoretical framework concerning environmental management and its evolution and the `greening` of the functional and competitive dimensions of human resource management were developed. A methodological triangulation was developed in two complimentary phases. In the first phase, data were collected from 94 Brazilian companies with ISO 14001 certification. The data collected were analyzed and processed using statistical techniques. The conclusions of the first phase supported the second phase of this empirical research. The second phase consisted of a study of multiple cases in four Brazilian companies. The results show evidence of the first known empirical study of contributions of human resource dimensions throughout the stages of environmental management in Brazilian manufacturing companies.