Human breast tumor slices as an alternative approach to cell lines to individualize research for each patient

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Lack of influence of the Schneiderian membrane in forming new bone apical to implants simultaneously installed with sinus floor elevation: an experimental study in monkeys

Aim: To describe the early healing processes around the implants installed after elevation of the sinus mucosa applying the lateral access technique without the use of grafting material.Material and methods: Immediately after the elevation of the maxillary sinus Schneiderian membrane by the lateral approach in eight monkeys, implants were installed without the use of grafting material. The healing of the tissue around the implants was evaluated after 4, 10, 20 and 30 days. Ground sections were prepared and analyzed histologically.Results: After 4 days of healing, the formation of coagulum and provisional matrix was documented within the elevated area. At 10-day interval, sprouts of woven bone were in continuity with the parent bone, and partly in contact with the implant surface at the base of the augmented area. While bone-to-implant contact increased after 20 and 30 days, the area underneath the Schneiderian membrane appeared reduced in volume and condensed toward the apex of the implants. The sinus mucosa was to some extent collapsed onto the implant surface and on the newly formed bone.Conclusions: The void initially occupied by the coagulum after sinus membrane elevation shrank substantially during the observation period. A lack of influence of the Schneiderian membrane in bone formation apical to implants was documented in the early phase of healing.

Use of a titanium device in lateral sinus floor elevation: an experimental study in monkeys

Aim: To evaluate the effect of a space-maintaining device fixed to the lateral wall of the maxillary sinus after the elevation of the sinus mucosa on bone filling of the sinus cavity. Material and methods: Immediately after the elevation of the maxillary sinus Schneiderian membrane accomplished through lateral antrostomy in four monkeys, a titanium device was affixed to the lateral sinus wall protruding into the sinus cavity to maintain the mucosa elevated without the use of grafting material. The healing of the tissue around the implants was evaluated after 3 and 6 months. Ground sections were prepared and analyzed histologically. Results: The void under the elevated sinus membrane, originally filled with the blood clot, was reduced after 3 as well as after 6 months of healing of about 56% and 40.5%, respectively. In seven out of eight cases, the devices had perforated the sinus mucosa. The formation of mineralized bone and bone marrow amounted to about 42% and 69% after 3 and 6 months, respectively. The connective tissue represented about 53% and 23% of the newly formed tissue after 3 and 6 months, respectively. Conclusions: New bone formation was found below the devices. However, shrinkage of the newly formed tissue was observed both after 3 and 6 months of healing. Hence, the space-maintaining function of the devices used in the present study has to be questioned.

Protective effects of Tacrolimus, a calcineurin inhibitor, in experimental periodontitis in rats

Objective: Periodontitis is a well-appreciated example of leukocyte-mediated bone loss and inflammation with pathogenic features similar to those observed in other inflammatory diseases, such as arthritis. Since Tacrolimus, is an immunomodulatory drug used for the treatment of some cases of arthritis, we hypothesized that it may modulate periodontal disease.Design: Using a murine model of ligature-induced periodontal disease, we assessed the effects of daily administrations of Tacrolimus (1 mg/kg body weight) on bone loss, enzymatic (myeloperoxidase) analysis, differential white blood cells counts, airpouch exudate and cytokine expression for 5-30 days.Results: Radiographic, enzymatic (myeloperoxidase) and histological analysis revealed that Tacrolimus reduced the severity of periodontitis. More specifically, Tacrolimus suppressed the expression of serum interleukin (IL-1 beta), tumour necrosis factor (TNF-alpha), IL-6, airpouch exudate PGE(2) and leukocytosis usually observed after the induction of periodontitis. Tacrolimus treatment in periodontitis-induced rats conferred protection against the inflammation-induced tissue and bone loss associated with periodontitis, through a mechanism involving IL-1 beta, TNF-alpha and IL-6.Conclusions: the effects of Tacrolimus on periodontal disease pathogenesis may provide clues to a novel approach to host modulation therapy in destructive periodontal disease. (C) 2007 Elsevier Ltd. All rights reserved.

A machine learning approach for genome-wide prediction of morbid and druggable human genes based on systems-level data

Background: The genome-wide identification of both morbid genes, i.e., those genes whose mutations cause hereditary human diseases, and druggable genes, i.e., genes coding for proteins whose modulation by small molecules elicits phenotypic effects, requires experimental approaches that are time-consuming and laborious. Thus, a computational approach which could accurately predict such genes on a genome-wide scale would be invaluable for accelerating the pace of discovery of causal relationships between genes and diseases as well as the determination of druggability of gene products.Results: In this paper we propose a machine learning-based computational approach to predict morbid and druggable genes on a genome-wide scale. For this purpose, we constructed a decision tree-based meta-classifier and trained it on datasets containing, for each morbid and druggable gene, network topological features, tissue expression profile and subcellular localization data as learning attributes. This meta-classifier correctly recovered 65% of known morbid genes with a precision of 66% and correctly recovered 78% of known druggable genes with a precision of 75%. It was than used to assign morbidity and druggability scores to genes not known to be morbid and druggable and we showed a good match between these scores and literature data. Finally, we generated decision trees by training the J48 algorithm on the morbidity and druggability datasets to discover cellular rules for morbidity and druggability and, among the rules, we found that the number of regulating transcription factors and plasma membrane localization are the most important factors to morbidity and druggability, respectively.Conclusions: We were able to demonstrate that network topological features along with tissue expression profile and subcellular localization can reliably predict human morbid and druggable genes on a genome-wide scale. Moreover, by constructing decision trees based on these data, we could discover cellular rules governing morbidity and druggability.

Artificial neural networks: A novel approach to analysing the nutritional ecology of a blowfly species, Chrysomya megacephala

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

pK determination. A mean field, Poisson-Boltzmann approach

A model describing dissociation of monoprotonic acid and a method for the determination of its pK value are presented. The model is based on a mean field approximation. The Poisson-Boltzmann equation, adopting spherical symmetry, is numerically solved, and the solution of its linearized form is written. By use of the pH values of a dilution experiment of galacturonic acid as the entry data, the proposed method allowed estimation of the value of pK = 3.25 at a temperature of 25 degrees C. Values for the complex dimensions and dissociation degree are calculated using experimental pH values for solution concentration values ranging from 0.1 to 60 mM. The present analysis leads to the conclusion that the Poisson-Boltzmann equation or its linear form is equally suited for the description of such systems.

Nucleon-nucleon scattering within a multiple subtractive renormalization approach

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Bound states of the barium atom by the hyperspherical approach

We present a nonadiabatic hyperspherical calculation of the highly excited and low lying doubly excited states of the barium atom using effective potentials for the two optically active electrons' interactions. Within the hyperspherical adiabatic approach the investigation of the spectra is performed with potential curves and nonadiabatic couplings of a unique radial variable, which allows clear identification of the states. The convergence of energy is obtained within well established bound limits, and the precision is comparable to accurate configuration interaction calculations. A very good agreement with experimental results is obtained with only few nonadiabatic couplings. (C) 2004 American Institute of Physics.

A new approach for determining stability constants of metal ion complexes in aquatic systems based on flow injection-ion exchange-flame atomic absorption spectrometry coupling

A method based an ion exchange(IE)-atomic absorption spectrometry(AAS) coupled by flow techniques, allowing the determination of formation constants of, at least, the first species of complex systems, in aqueous solution, was developed.The IE-AAS coupling reduces significantly the number of experimental steps in comparison with IE batch methods, resulting in an important increase in analytical rate. The method is simple both from experimental and computational points of view, making possible its utilization by workers without special expertise in the field of complex equilibria in solution. on the other hand, taking into account mainly the amount of hollow cathode lamps available to date, the developed procedure may be applied, within certain limitations, to the study of many systems whose features prevent the use of traditional approaches.

Modeling thermal conductivity, specific heat, and density of milk: A neural network approach

The accurate determination of thermophysical properties of milk is very important for design, simulation, optimization, and control of food processing such as evaporation, heat exchanging, spray drying, and so forth. Generally, polynomial methods are used for prediction of these properties based on empirical correlation to experimental data. Artificial neural networks are better Suited for processing noisy and extensive knowledge indexing. This article proposed the application of neural networks for prediction of specific heat, thermal conductivity, and density of milk with temperature ranged from 2.0 to 71.0degreesC, 72.0 to 92.0% of water content (w/w), and 1.350 to 7.822% of fat content (w/w). Artificial neural networks presented a better prediction capability of specific heat, thermal conductivity, and density of milk than polynomial modeling. It showed a reasonable alternative to empirical modeling for thermophysical properties of foods.

Heat transfer in fixed bed: a model non-linearity approach

Studies have been carried out on the heat transfer in a packed bed of glass beads percolated by air at moderate flow rates. Rigorous statistic analysis of the experimental data was carried out and the traditional two parameter model was used to represent them. The parameters estimated were the effective radial thermal conductivity, k, and the wall coefficient, h, through the least squares method. The results were evaluated as to the boundary bed inlet temperature, T-o, number of terms of the solution series and number of experimental points used in the estimate. Results indicated that a small difference in T-o was sufficient to promote great modifications in the estimated parameters and in the statistical properties of the model. The use of replicas at points of high parametric information of the model improved the results, although analysis of the residuals has resulted in the rejection of this alternative. In order to evaluate cion-linearity of the model, Bates and Watts (1988) curvature measurements and the Box (1971) biases of the coefficients were calculated. The intrinsic curvatures of the model (IN) tend to be concentrated at low bed heights and those due to parameter effects (PE) are spread all over the bed. The Box biases indicated both parameters as responsible for the curvatures PE, h being somewhat more problematic. (C) 2000 Elsevier B.V. Ltd. All rights reserved.

Ghost poles in the nucleon propagator in the linear sigma model approach and its role in pi N low-energy theorems

Complex mass poles, or ghost poles, are present in the Hartree-Fock solution of the Schwinger-Dyson equation for the nucleon propagator in renormalizable models with Yukawa-type meson-nucleon couplings, as shown many years ago by Brown, Puff and Wilets (BPW), These ghosts violate basic theorems of quantum field theory and their origin is related to the ultraviolet behavior of the model interactions, Recently, Krein et.al, proved that the ghosts disappear when vertex corrections are included in a self-consistent way, softening the interaction sufficiently in the ultraviolet region. In previous studies of pi N scattering using ''dressed'' nucleon propagator and bare vertices, did by Nutt and Wilets in the 70's (NW), it was found that if these poles are explicitly included, the value of the isospin-even amplitude A((+)) is satisfied within 20% at threshold. The absence of a theoretical explanation for the ghosts and the lack of chiral symmetry in these previous studies led us to re-investigate the subject using the approach of the linear sigma-model and study the interplay of low-energy theorems for pi N scattering and ghost poles. For bare interaction vertices we find that ghosts are present in this model as well and that the A((+)) value is badly described, As a first approach to remove these complex poles, we dress the vertices with phenomenological form factors and a reasonable agreement with experiment is achieved, In order to fix the two cutoff parameters, we use the A((+)) value for the chiral limit (m(pi) --> 0) and the experimental value of the isoscalar scattering length, Finally, we test our model by calculating the phase shifts for the S waves and we find a good agreement at threshold. (C) 1997 Elsevier B.V. B.V.

Jahn-Teller effect on the structure of the Sm-doped PbTiO3: A theoretical approach

Samarium doped PbTiO3 (PT:Sm) and pure PbTiO3 (PT) powders were obtained by polymeric precursor method. These powders were characterized by X-ray diffraction (XRD) and theoretical calculations using the CRYSTAL98 program. The effect of the samarium atom is taken into account only indirectly. The experimental models were compared with the cubic (ideal) and tetragonal theoretical models. The structure deformations existent in the experimental compounds were analyzed from the tiny structural differences that lead to perturbations in the crystal orbital splittings. This paper proposes an efficient alternative methodology for defining structural distortions. (c) 2007 Elsevier B.V. All rights reserved.

Use of homeopathic preparations in experimental studies with healthy plants

Background. The last comprehensive review of experimental research on effects of homeopathic treatments on plants was published in 1984, and lacked formal predefined criteria to assess study quality. Since then several new studies with more advanced methods have been published.Objectives: To compile a review of the literature on basic research in homeopathy with healthy plants with particular reference to studies investigating specific effects of homeopathic remedies.Methods: The literature search included English, French, German, Italian, Portuguese and Spanish publications from 1920 to April 2009, using predefined selection criteria. We included experiments with healthy whole plants, seeds, plant parts and cells. The outcomes had to be measured by established procedures and statistically evaluated. We developed a Manuscript Information Score (MIS) and included only publications which provided enough information for proper interpretation (MIS >= 5). A formallised Study Methods Evaluation Procedure (SMEP) was used to evaluate these studies, and the subgroup of studies with adequate controls to identify specific effects.Results: A total of 86 studies in 79 publications was identified, 43 studies included statistics, 29 had MIS >= 5, and 15 studies investigated the specificity of homeopathic preparations. Specific effects of decimal, centesimal and fifty millesimal potencies were found including dilution levels far beyond the Avogadro number. In consecutive series of potencies only some of the tested potencies showed effects. There were many individual studies with diverse methods and very few reproduction trials.Conclusions: Healthy plant models seem an useful approach to investigate basic research questions about the specificity of homeopathic preparations. More investigations with more advanced methods are recommended, especially in the sectors of potentisation techniques, effective potency levels and conditions for reproducibility. Systematic negative control experiments should become a routine procedure to control the stability of the experimental systems. Homeopathy (2009) 98, 228-243.