Evaluating geodesic active contours in microcalcifications segmentation on mammograms.

Breast cancer is the most commonly occurring type of cancer among women, and it is the major cause of female cancer-related deaths worldwide. Its incidence is increasing in developed as well as developing countries. Efficient strategies to reduce the high death rates due to breast cancer include early detection and tumor removal in the initial stages of the disease. Clinical and mammographic examinations are considered the best methods for detecting the early signs of breast cancer; however, these techniques are highly dependent on breast characteristics, equipment quality, and physician experience. Computer-aided diagnosis (CADx) systems have been developed to improve the accuracy of mammographic diagnosis; usually such systems may involve three steps: (i) segmentation; (ii) parameter extraction and selection of the segmented lesions and (iii) lesions classification. Literature considers the first step as the most important of them, as it has a direct impact on the lesions characteristics that will be used in the further steps. In this study, the original contribution is a microcalcification segmentation method based on the geodesic active contours (GAC) technique associated with anisotropic texture filtering as well as the radiologists' knowledge. Radiologists actively participate on the final step of the method, selecting the final segmentation that allows elaborating an adequate diagnosis hypothesis with the segmented microcalcifications presented in a region of interest (ROI). The proposed method was assessed by employing 1000 ROIs extracted from images of the Digital Database for Screening Mammography (DDSM). For the selected ROIs, the rate of adequately segmented microcalcifications to establish a diagnosis hypothesis was at least 86.9%, according to the radiologists. The quantitative test, based on the area overlap measure (AOM), yielded a mean of 0.52±0.20 for the segmented images, when all 2136 segmented microcalcifications were considered. Moreover, a statistical difference was observed between the AOM values for large and small microcalcifications. The proposed method had better or similar performance as compared to literature for microcalcifications with maximum diameters larger than 460µm. For smaller microcalcifications the performance was limited.

Palytoxin and the sodium/potassium pump--phosphorylation and potassium interaction.

We proposed a reaction model for investigating interactions between K+ and the palytoxin-sodium-potassium (PTX-Na+/K+) pump complex under conditions where enzyme phosphorylation may occur. The model is composed of (i) the Albers-Post model for Na+/K+-ATPase, describing Na+ and K+ pumping; (ii) the reaction model proposed for Na+/K+-ATPase interactions with its ligands (Na+, K+, ATP, ADP and P) and with PTX. A mathematical model derived for representing the reactions was used to simulate experimental studies of the PTX-induced current, in different concentrations for the pump ligands. The simulations allow interpretation of the simultaneous action of Na+/K+-ATPase phosphorylation and K+ on the PTX-induced channels. The results suggest that(i) phosphorylation increases the PTX toxic effect, increasing its affinity and reducing the K+occlusion rate, and (ii) K+ causes channel blockage, increases the toxin dissociation rate and impedes the induced channel phosphorylation, implying reduction of the PTX toxic effect.

Investigating the potassium interactions with the palytoxin induced channels in Na+/K+ pump.

K(+) has been appointed as the main physiological inhibitor of the palytoxin (PTX) effect on the Na(+)/K(+) pump. This toxin acts opening monovalent cationic channels through the Na(+)/K(+) pump. We investigate, by means of computational modeling, the kinetic mechanisms related with K(+) interacting with the complex PTX-Na(+)/K(+) pump. First, a reaction model, with structure similar to Albers-Post model, describing the functional cycle of the pump, was proposed for describing K(+) interference on the complex PTX-Na(+)/K(+) pump in the presence of intracellular ATP. A mathematic model was derived from the reaction model and it was possible to solve numerically the associated differential equations and to simulate experimental maneuvers about the PTX induced currents in the presence of K(+) in the intra- and extracellular space as well as ATP in the intracellular. After the model adjusting to the experimental data, a Monte Carlo method for sensitivity analysis was used to analyze how each reaction parameter acts during each experimental maneuver involving PTX. For ATP and K(+) concentrations conditions, the simulations suggest that the enzyme substate with ATP bound to its high-affinity sites is the main substate for the PTX binding. The activation rate of the induced current is limited by the K(+) deocclusion from the PTX-Na(+)/K(+) pump complex. The K(+) occlusion in the PTX induced channels in the enzymes with ATP bound to its low-affinity sites is the main mechanism responsible for the reduction of the enzyme affinity to PTX.

Effect of palytoxin on the sodium-potassium pump: model and simulation.

We propose a reaction model for the palytoxin-sodium-potassium (PTX-Na(+)/K(+)) pump complex. The model, which is similar to the Albers-Post model for Na(+)/K(+)-ATPase, is used to elucidate the effect of PTX on Na(+)/K(+)-ATPase during the enzyme interactions with Na(+) and/or K(+) ions. Conformational substates and reactions for the pump are incorporated into the Albers-Post model to represent enzymes with or without bound PTX. A mathematical model based on the reaction scheme is used in simulations modeling experimental studies of PTX-induced ionic currents. Our simulations suggest that (i) extracellular Na(+) as well as K(+) promotes PTX-induced channel blockage; (ii) extracellular K(+) accelerates PTX unbinding; and (iii) K(+) occlusion in the PTX-pump complex is essential for describing the PTX-induced current dynamics.

Identifying essential conditions for refractoriness of Leão's spreading depression-computational modeling.

A mathematical description of the restoring ionic mechanisms in a compartmentalized electrochemical model of neuronal tissues was developed aiming at studying the essential conditions for refractoriness of Leão's spreading depression (SD). The model comprehends the representation of a plexiform layer, composed by synaptic terminals and glial process immersed in an extracellular space where the space-temporal variations of the ionic concentrations were described by electrodiffusion equations. The synaptic transmission was described by differential equations representing the corresponding chemical reactions associated with the neurotransmitter release, diffusion, binding to its receptor in the postsynaptic membrane and the uptake by the presynaptic terminals. The effect of the neurotransmitter binding to the receptor induces changes in the permeability of the postsynaptic membrane and the corresponding transmembrane fluxes were calculated. The fluxes promote changes in the external ionic concentrations, changing the ionic electrodiffusion through the extracellular space. The description of these mechanisms provides the reaction-diffusion structure of the model and allows simulating the wave propagation. The simulations of experimental maneuvers of application of two consecutive stimuli for inducing SD suggest: (i) the extracellular space acts coupling the postsynaptic terminals and glial cells recovery mechanisms in such a way that the extracellular ionic concentrations change only during the wave front; (ii) the potassium removed from the extracellular by the glial cells, originated from the depolarization of the synaptic terminals returns slowly limited by the glial release, contributing for the refractoriness of the tissue; (iii) critical points for sodium and potassium transmembrane fluxes could be identified, allowing proposing specific conditions for the interplay between channels and pumps fluxes for determining the absolute and relative refractory periods.

Model and simulation of Na+/K+ pump phosphorylation in the presence of palytoxin.

The ATP hydrolysis reactions responsible for the Na(+)/K(+)-ATPase phosphorylation, according to recent experimental evidences, also occur for the PTX-Na(+)/K(+) pump complex. Moreover, it has been demonstrated that PTX interferes with the enzymes phosphorylation status. However, the reactions involved in the PTX-Na(+)/K(+) pump complex phosphorylation are not very well established yet. This work aims at proposing a reaction model for PTX-Na(+)/K(+) pump complex, with similar structure to the Albers-Post model, to contribute to elucidate the PTX effect over Na(+)/K(+)-ATPase phosphorylation and dephosphorylation. Computational simulations with the proposed model support several hypotheses and also suggest: (i) phosphorylation promotes an increase of the open probability of induced channels; (ii) PTX reduces the Na(+)/K(+) pump phosphorylation rate; (iii) PTX may cause conformational changes to substates where the Na(+)/K(+)-ATPase may not be phosphorylated; (iv) PTX can bind to substates of the two principal states E1 and E2, with highest affinity to phosphorylated enzymes and with ATP bound to its low-affinity sites. The proposed model also allows previewing the behavior of the PTX-pump complex substates for different levels of intracellular ATP concentrations.

Evaluating the entrainment of the alpha rhythm during stroboscopic flash stimulation by means of coherence analysis.

Two major conflicting hypotheses propose that alpha rhythm activity should be either the output of a linear filter having a white noise as input or reflect the output of a nonlinear oscillator. External stimulation can be employed to test for nonlinearity in alpha genesis, since an entrainment of such rhythmic activity (shift in the alpha peak) could only be explained by nonlinear relationships. Flash photic stimulation has been used to investigate such entrainment. Nevertheless, only entrainments due to the second harmonic of the stimulation could be suitably measured. Aiming at overcoming this limitation, a coherence-based technique is proposed for evaluating the strength of responses due to rhythmic stimulation. It was applied to the occipital EEG derivations of 12 normal subjects during stroboscopic stimulation. Entrainment of alpha rhythm by the second harmonic of the stimulation occurred in 75% of the subjects, whilst no spectral shifts were observed for the remained that exhibited broadband alpha peak at rest. However, stimulating with fundamental frequency close to that peak led to entrainment in all subjects. These differences in the degree of synchronization due to stimulation at the first and second harmonics should reflect complex nonlinear mechanisms in alpha genesis.

Estimaçäo de ordem para modelagem auto-regressiva no EEG neonatal / Estimation of the for auto-regressive modelling in neonatal EEG

A estimação espectral auto-regressiva tem se mostrado uma ferramenta útil na análise do sinal EEG, contudo, é necessário calcular-se a ordem do modelo. Neste trabalho, critérios objetivos para seleção da ordem foram aplicados ao EEG neonatal em diferentes estados do ciclo sono-vigília. A ordem ótima mediana encontra-se geralmente na faixa entre 5 e 8 (freqüência de amostragem de 128 Hz e trechos EEG de 1 s), e média próxima de 7 para os três padrões de sono-vigília.