Oncology research and clinical decisions based on immunohistochemistry: the importance of the technical aspects that support a complex method

Immunohistochemistry (IHC) is the group of techniques that use antibodies as specific reagents to identify and demonstrate several cell and tissue components that are antigens. This linking allows locating and identifying the in situ presence of various substances by means of color that is associated with the formed antigen-antibody complexes. The practical value of this biotechnology area, widely used in Pathology and Oncology, in diagnostic, prognostic, theranostic and research context, results from the possibility of combining a colour marker with an antibody without causing any damage to specific binding established between antibody and antigen. This provides the microscopic observation of the target locations where the antibody and hence the antigen are present. IHC is presented as a powerful means for identification of several cellular and tissue structures that can be associated with pathologies, and of the consequences, at functional and morphological level, of these same elements action.

A new post-metallocene-ti catalyst with maltolate bidentade ligand: an investigation in heterogeneous polymerization reactions in different mesoporous supports

A new titanium catalyst easily synthesized from ethylmaltol bidentate chelator ligand was studied in homogeneous and heterogeneous ethylene polymerization. The dichlorobis(3-hydroxy-2-ethyl-4-pyrone)titanium(IV) complex was characterized by 1H and 13C NMR (nuclear magnetic resonance), UV-Vis and elemental analysis. Theoretical study by density functional theory (DFT) showed that the complex chlorines exhibit cis configuration, which is important for the activity in olefin polymerization. The complex was supported by two methods, direct impregnation or methylaluminoxane (MAO) pre-treatment, in five mesoporous supports: MCM-41 (micro and nano), SBA-15 and also the corresponding modified Al species. All the catalytic systems were active in ethylene polymerization and the catalytic activity was strongly influenced by the method of immobilization of the catalyst and the type of support.

Graded Meshes In Bio-thermal Problems With Transmission-line Modeling Method.

In this study, the transmission-line modeling (TLM) applied to bio-thermal problems was improved by incorporating several novel computational techniques, which include application of graded meshes which resulted in 9 times faster in computational time and uses only a fraction (16%) of the computational resources used by regular meshes in analyzing heat flow through heterogeneous media. Graded meshes, unlike regular meshes, allow heat sources to be modeled in all segments of the mesh. A new boundary condition that considers thermal properties and thus resulting in a more realistic modeling of complex problems is introduced. Also, a new way of calculating an error parameter is introduced. The calculated temperatures between nodes were compared against the results obtained from the literature and agreed within less than 1% difference. It is reasonable, therefore, to conclude that the improved TLM model described herein has great potential in heat transfer of biological systems.

Flow injection green method for the quantitative analysis of ketoconazole in pharmaceutical preparations

A flow injection method for the quantitative analysis of ketoconazole in tablets, based on the reaction with iron (III) ions, is presented. Ketoconazole forms a red complex with iron ions in an acid medium, with maximum absorbance at 495 nm. The detection limit was estimated to be 1×10--4 mol L-1; the quantitation limit is about 3×10--4 mol L-1 and approximately 30 determinations can be performed in an hour. The results were compared with those obtained with a reference HPLC method. Statistical comparisons were done using the Student's t procedure and the F test. Complete agreement was found at the 0.95 significance level between the proposed flow injection and the HPLC procedures. The two methods present similar precision, i.e., for HPLC the mean relative standard deviation was ca. 1.2% and for FIA ca. 1.6%.

An Eulerian Immersed Boundary Method for flow simulations over stationary and moving rigid bodies

The fluid flow over bodies with complex geometry has been the subject of research of many scientists and widely explored experimentally and numerically. The present study proposes an Eulerian Immersed Boundary Method for flows simulations over stationary or moving rigid bodies. The proposed method allows the use of Cartesians Meshes. Here, two-dimensional simulations of fluid flow over stationary and oscillating circular cylinders were used for verification and validation. Four different cases were explored: the flow over a stationary cylinder, the flow over a cylinder oscillating in the flow direction, the flow over a cylinder oscillating in the normal flow direction, and a cylinder with angular oscillation. The time integration was carried out by a classical 4th order Runge-Kutta scheme, with a time step of the same order of distance between two consecutive points in x direction. High-order compact finite difference schemes were used to calculate spatial derivatives. The drag and lift coefficients, the lock-in phenomenon and vorticity contour plots were used for the verification and validation of the proposed method. The extension of the current method allowing the study of a body with different geometry and three-dimensional simulations is straightforward. The results obtained show a good agreement with both numerical and experimental results, encouraging the use of the proposed method.

A simplified minimal residual disease polymerase chain reaction method at early treatment points can stratify children with acute lymphoblastic leukemia into good and poor outcome groups

Background Minimal residual disease is an important independent prognostic factor in childhood acute lymphoblastic leukemia. The classical detection methods such as multiparameter flow cytometry and real-time quantitative polymerase chain reaction analysis are expensive, time-consuming and complex, and require considerable technical expertise. Design and Methods We analyzed 229 consecutive children with acute lymphoblastic leukemia treated according to the GBTLI-99 protocol at three different Brazilian centers. Minimal residual disease was analyzed in bone marrow samples at diagnosis and on days 14 and 28 by conventional homo/heteroduplex polymerase chain reaction using a simplified approach with consensus primers for IG and TCR gene rearrangements. Results At least one marker was detected by polymerase chain reaction in 96.4%, of the patients. By combining the minimal residual disease results obtained on days 14 and 28, three different prognostic groups were identified: minimal residual disease negative on days 14 and 28, positive on day 14/negative on day 28, and positive on both. Five-year event-free survival rates were 85%, 75.6%,, and 27.8%, respectively (p<0.0001). The same pattern of stratification held true for the group of intensively treated children. When analyzed in other subgroups of patients such as those at standard and high risk at diagnosis, those with positive B-derived CD10, patients positive for the TEL/AML1 transcript, and patients in morphological remission on a day 28 marrow, the event-free survival rate was found to be significantly lower in patients with positive minimal residual disease on day 28. Multivariate analysis demonstrated that the detection of minimal residual disease on day 28 is the most significant prognostic factor. Conclusions This simplified strategy for detection of minimal residual disease was feasible, reproducible, cheaper and simpler when compared with other methods, and allowed powerful discrimination between children with acute lymphoblastic leukemia with a good and poor outcome.

Study of the influence of indium segregation on the optical properties of InGaAs/GaAs quantum wells via split-operator method

In the case of quantum wells, the indium segregation leads to complex potential profiles that are hardly considered in the majority of the theoretical models. The authors demonstrated that the split-operator method is useful tool for obtaining the electronic properties in these cases. Particularly, they studied the influence of the indium surface segregation in optical properties of InGaAs/GaAs quantum wells. Photoluminescence measurements were carried out for a set of InGaAs/GaAs quantum wells and compared to the results obtained theoretically via split-operator method, showing a good agreement.

Electron collisions with the CH(2)O-H(2)O complex

We report cross sections for elastic collisions of low-energy electrons with the CH(2)O-H(2)O complex. We employed the Schwinger multichannel method with pseudopotentials in the static-exchange and in the static-exchange-polarization approximations for energies from 0.1 to 20 eV. We considered four different hydrogen-bonded structures for the complex that were generated by classical Monte Carlo simulations. Our aim is to investigate the effect of the water molecule on the pi* shape resonance of formaldehyde. Previous studies reported a pi* shape resonance for CH(2)O at around 1 eV. The resonance positions of the complexes appear at lower energies in all cases due to the mutual polarization between the two molecules. This indicates that the presence of water may favor dissociation by electron impact and may lead to an important effect on strand breaking in wet DNA by electron impact.

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.

Digital frequency relaying based on the modified least mean square method

This research presents a method for frequency estimation in power systems using an adaptive filter based on the Least Mean Square Algorithm (LMS). In order to analyze a power system, three-phase voltages were converted into a complex signal applying the alpha beta-transform and the results were used in an adaptive filtering algorithm. Although the use of the complex LMS algorithm is described in the literature, this paper deals with some practical aspects of the algorithm implementation. In order to reduce computing time, a coefficient generator was implemented. For the algorithm validation, a computing simulation of a power system was carried Out using the ATP software. Many different situations were Simulated for the performance analysis of the proposed methodology. The results were compared to a commercial relay for validation, showing the advantages of the new method. (C) 2009 Elsevier Ltd. All rights reserved.

Automatic tuning method for the design of supplementary damping controllers for flexible alternating current transmission system devices

The design of supplementary damping controllers to mitigate the effects of electromechanical oscillations in power systems is a highly complex and time-consuming process, which requires a significant amount of knowledge from the part of the designer. In this study, the authors propose an automatic technique that takes the burden of tuning the controller parameters away from the power engineer and places it on the computer. Unlike other approaches that do the same based on robust control theories or evolutionary computing techniques, our proposed procedure uses an optimisation algorithm that works over a formulation of the classical tuning problem in terms of bilinear matrix inequalities. Using this formulation, it is possible to apply linear matrix inequality solvers to find a solution to the tuning problem via an iterative process, with the advantage that these solvers are widely available and have well-known convergence properties. The proposed algorithm is applied to tune the parameters of supplementary controllers for thyristor controlled series capacitors placed in the New England/New York benchmark test system, aiming at the improvement of the damping factor of inter-area modes, under several different operating conditions. The results of the linear analysis are validated by non-linear simulation and demonstrate the effectiveness of the proposed procedure.

A simple method for non-linear analysis of steel fiber reinforced concrete

This paper proposes a physical non-linear formulation to deal with steel fiber reinforced concrete by the finite element method. The proposed formulation allows the consideration of short or long fibers placed arbitrarily inside a continuum domain (matrix). The most important feature of the formulation is that no additional degree of freedom is introduced in the pre-existent finite element numerical system to consider any distribution or quantity of fiber inclusions. In other words, the size of the system of equations used to solve a non-reinforced medium is the same as the one used to solve the reinforced counterpart. Another important characteristic of the formulation is the reduced work required by the user to introduce reinforcements, avoiding ""rebar"" elements, node by node geometrical definitions or even complex mesh generation. Bounded connection between long fibers and continuum is considered, for short fibers a simplified approach is proposed to consider splitting. Non-associative plasticity is adopted for the continuum and one dimensional plasticity is adopted to model fibers. Examples are presented in order to show the capabilities of the formulation.

An EFG method for the nonlinear analysis of plates undergoing arbitrarily large deformations

The applicability of a meshfree approximation method, namely the EFG method, on fully geometrically exact analysis of plates is investigated. Based on a unified nonlinear theory of plates, which allows for arbitrarily large rotations and displacements, a Galerkin approximation via MLS functions is settled. A hybrid method of analysis is proposed, where the solution is obtained by the independent approximation of the generalized internal displacement fields and the generalized boundary tractions. A consistent linearization procedure is performed, resulting in a semi-definite generalized tangent stiffness matrix which, for hyperelastic materials and conservative loadings, is always symmetric (even for configurations far from the generalized equilibrium trajectory). Besides the total Lagrangian formulation, an updated version is also presented, which enables the treatment of rotations beyond the parameterization limit. An extension of the arc-length method that includes the generalized domain displacement fields, the generalized boundary tractions and the load parameter in the constraint equation of the hyper-ellipsis is proposed to solve the resulting nonlinear problem. Extending the hybrid-displacement formulation, a multi-region decomposition is proposed to handle complex geometries. A criterium for the classification of the equilibrium`s stability, based on the Bordered-Hessian matrix analysis, is suggested. Several numerical examples are presented, illustrating the effectiveness of the method. Differently from the standard finite element methods (FEM), the resulting solutions are (arbitrary) smooth generalized displacement and stress fields. (c) 2007 Elsevier Ltd. All rights reserved.

Exergy-based method for analyzing the composition of the electricity cost generated in gas-fired combined cycle plants

The proposed method to analyze the composition of the cost of electricity is based on the energy conversion processes and the destruction of the exergy through the several thermodynamic processes that comprise a combined cycle power plant. The method uses thermoeconomics to evaluate and allocate the cost of exergy throughout the processes, considering costs related to inputs and investment in equipment. Although the concept may be applied to any combined cycle or cogeneration plant, this work develops only the mathematical modeling for three-pressure heat recovery steam generator (HRSG) configurations and total condensation of the produced steam. It is possible to study any n x 1 plant configuration (n sets of gas turbine and HRSGs associated to one steam turbine generator and condenser) with the developed model, assuming that every train operates identically and in steady state. The presented model was conceived from a complex configuration of a real power plant, over which variations may be applied in order to adapt it to a defined configuration under study [Borelli SJS. Method for the analysis of the composition of electricity costs in combined cycle thermoelectric power plants. Master in Energy Dissertation, Interdisciplinary Program of Energy, Institute of Eletro-technical and Energy, University of Sao Paulo, Sao Paulo, Brazil, 2005 (in Portuguese)]. The variations and adaptations include, for instance, use of reheat, supplementary firing and partial load operation. It is also possible to undertake sensitivity analysis on geometrical equipment parameters. (C) 2007 Elsevier Ltd. All rights reserved.

Computational Method to Determine Reflected Ultrasonic Signals From Arbitrary-Geometry Targets

A computational method based on the impulse response and on the discrete representation computational concept is proposed for the determination of the echo responses from arbitrary-geometry targets. It is supposed that each point of the transducer aperture can be considered as a source radiating hemispherical waves to the reflector. The local interaction with each of the hemispherical waves at the reflector surface can be modeled as a plane wave impinging on a planar surface, using the respective reflection coefficient. The method is valid for all field regions and can be performed for any excitation waveform radiated from an arbitrary acoustic aperture. The effects of target geometry, position, and material on both the amplitude and the shape of the echo response are studied. The model is compared with experimental results obtained using broadband transducers together with plane and cylindrical concave rectangular reflectors (aluminum, brass, and acrylic), as well as a circular cavity placed on a plane surface, in a water medium. The method can predict the measured echoes accurately. This paper shows an improved approach of the method, considering the reflection coefficient for all incident hemispherical waves arriving at each point of the target surface.