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[Modelling of intraperitoneal chemohyperthermia: experimental study and identification of certain thermal aspects].

Intraperitoneal chemohyperthermia is more and more considered as an interesting therapeutic option in cases of some abdominal cancers, particularly of digestive origin. However, many technical aspects of this treatment remain far from being mastered, particularly the homogeneous dispatch of temperatures within the abdomen cavity. This work consists, first of all, in an experimental study, which is being carried out on a physical "prototype" of the abdomen, on which different hot fluid flows and injection conditions (configurations) are investigated. The results of this experimental study are prospected in two ways. First, an a priori thermal model is proposed, based on physical equations (heat transfer, etc.). Then a "black box" model is identified from the measured temperatures evolutions, so as to obtain a model of the "system" behaviour. Finally, the two modelling approaches are being compared, and the results converge to a simple expression of a few parameters, either physical or identified. These modelling results have helped to optimize the injection circuit and its running parameters while applied to the human treatment.

Algorithms↗

Building on the WLF/free volume framework: utilization of the coupling model in the relaxation dynamics of the gelatin/cosolute system.

The onset of softening in the glass transition dispersion of the gelatin/cosolute system at 78% solids was examined using the stress relaxation modulus and dynamic oscillatory data on shear. Measurements were made between 5 and -70 degrees C, and isothermal runs were reduced to a master curve covering 21 orders of magnitude in the time domain. The sharpness with which the mechanical properties of our system changed with temperature was reflected in the shift factor a(T) used to pinpoint the glass transition temperature (T(g)). The prevalent analytical framework traditionally employed to follow the transition from the rubbery to glasslike consistency in biomaterials is that of the free volume theory in conjunction with the WLF equation. Increasingly, the combined WLF/free volume approach is challenged by the coupling model, which is able to provide additional insights into the physics of intermolecular interactions in synthetic materials at the vicinity of T(g). The model in the form of the Kohlrausch-Williams-Watts function described well the spectral shape of the local segmental motions of gelatin/cosolute at T(g). The analysis provided the intermolecular interaction constant and apparent relaxation time, parameters which depend on chemical structure. Results appear to be encouraging for further explorations of the dynamics of densely packed biomaterials at the glass transition region.

Animals↗

Quantitating effector and regulatory T lymphocytes in immune responses by limiting dilution analysis modeling.

Although there is currently no doubt that regulatory lymphocytes represent a master player in the immune system, a major unresolved problem is the accurate quantitation of these cells among unfractionated cell populations. This difficulty mainly arises because there are no specific immunophenotypic markers that can reliably discriminate between effector and regulatory lymphocytes. To face this problem, we have developed computational models of limiting dilution analyses addressing the question of the accurate estimation of the frequencies of effector and regulatory cells functionally engaged in an immune response. A set of generic equations were provided to form a framework for modeling limiting dilution data, enabling discrimination between qualitatively different models of suppression. These models include either one or two subpopulations of regulatory cells, featured by either low or potent regulatory activity. The potential of this modeling approach was illustrated by the accurate determination of the frequencies of effector and regulatory T lymphocytes in one real limiting dilution experiment of CD4+ CD25+ T lymphocytes performed in the context of an allogeneic response in the human system. The crucial advantage of the limiting dilution method over the "static, phenotype-based" method is the dynamic evaluation of effector and regulatory T cell biology through their actual functional activity.

Animals↗

Rules for reinvestment.

In response to further validation of the Reinvestment Scale by Chell, Graydon, Crowley, and Child, a structural equation model was formulated to clarify the relationship between the predisposition for conscious control of an otherwise automatic motor skill (reinvestment), verbal knowledge, and performance degradation under pressure. The model implies that the more task-relevant movement knowledge the performer holds, the stronger the propensity to reinvest.

Automatism↗

Analysis of Apparent Noncompetitive Responses to Competitive H(1)-Histamine Receptor Antagonists in Fluorescent Imaging Plate Reader-Based Calcium Assays.

We have examined the utility of high throughput fluorescent imaging plate reader (FLIPR)-based calcium assays for pharmacological characterization of G-protein coupled receptors (GPCRs) using recombinant and native human H1-histamine receptors (H(1)-HR), expressed in HEK293 and HeLa S3 cells, respectively, as model systems. For stably transfected HEK293 cell lines, the potency of histamine for elevating intracellular calcium increased (pD(2), 7.13 and 7.86) with increased H(1)-HR density (about 0.8 and 14 pmol/mg protein, respectively), though histamine binding affinities were similar. The classic H(1)-HR competitive antagonists diphenhydramine and chlorpheniramine appeared noncompetitive by causing depressions of the maximal histamine responses along with rightward shifts of histamine concentration-response curves, thus precluding Schild analysis. Applying the generalized Cheng-Prusoff equation to antagonist concentration-response curves for inhibition of fixed histamine concentrations yielded apparent pK(b) values that were consistent among recombinant and native receptors at different expression levels. These pK(b) values for diphenhydramine and chlorpheniramine (e.g., 7.83 and 8.77, respectively) were in good agreement with binding pK(i) values (e.g., 7.98 and 8.52, respectively). Apparent antagonist affinities determined from FLIPR calcium and competition binding assays were also consistent for the competitive antagonists mepyramine, tripelennamine, and promethazine. In phosphoinositide hydrolysis assays, chlorpheniramine exhibited insurmountable inhibition of histamine calcium responses, although to a lesser extent than that observed in calcium assays; pK(b) values were similar. These results demonstrate that competitive antagonist potencies can be attained from FLIPR-derived data by application of the generalized Cheng-Prusoff equation, despite apparent noncompetitive antagonism under these assay conditions. Apparent noncompetitive antagonist effects may in part be attributable to a lack of equilibrium of histamine and antagonists with H(1)-HR within the short duration of rapid transient effects of histamine on intracellular calcium.

Journal Article↗

Speech dysfunction of obstructive sleep apnea. A discriminant analysis of its descriptors.

We have previously demonstrated a relationship between abnormal speech and obstructive sleep apnea in a small subject sample. The present study was designed to replicate the previous one with a much larger population, analyze the perceptual characteristics of the speech quality, and determine the degree to which each of three descriptors of speech abnormality contributed to the perception of speech abnormality. Ten graduate students in speech pathology listened in two 1.5 hour sessions to 252 random speech samples presented on a master tape. There were 81 subjects comprised of 27 sleep apnea patients, 27 matched chronic obstructive pulmonary disease control patients, and 27 matched normal control subjects. Rating the speech along an equally-appearing interval scale from 1 to 7, the judges heard abnormal resonance, articulation or phonation in 74 percent of the sleep apnea subjects, 53 percent of the COPD subjects, and 7 percent of the normal subjects (significant difference by chi 2 test at the .01 level of confidence). Discriminant function equations based on these speech descriptors correctly identified 96.3 percent of the normal subjects and 63.0 percent of the sleep apnea subjects. Analysis of abnormal speech resonance, articulation and phonation may identify obstructive sleep apnea or may provide insight into its pathology.

Adult↗

Strategies to achieve fit in implant prosthodontics: a review of the literature.

PURPOSE: This paper reviews the literature on advanced strategies that attempt to improve fit in implant prosthodontics with reference to the concept of the "distortion equation." MATERIALS AND METHODS: The majority of the articles reviewed were either clinical or technique articles that advocated strategies to improve fit in implant prosthodontics. A limited number of retrospective and prospective clinical trial studies were included as they related to the topic. Reviewed articles were limited to those that addressed advanced strategies to improve fit. All of the scientific studies included in this review used an in vitro experimental design. The advanced strategies were categorized into methods that address intraoral indexing and methods that use the implant master cast. RESULTS: Relatively few methods have been scientifically proven to improve fit in implant prosthodontics. Most of the tested strategies still resulted in a slight misfit of the frameworks to the implant abutments/analogues. CONCLUSION: Multiple factors preclude that the concept of "passive fit" can be achieved in implant prosthodontics, even with the use of advanced strategies. The use of meticulous, accurate implant prosthodontic procedures and the appropriate use of advanced strategies continue to be the recommended means of achieving precise fit of the implant prosthesis to the intraoral abutments.

Animals↗

On growth and dispersal of population.

In his unpublished Master's thesis of 1921, the young Hotelling invented an ingenious model of population growth and diffusion. The contribution remained widely unknown until Waldo Tobler and Alan Wilson edited it as an article in 1978. Not even then did it trigger any outburst of contributions. Meanwhile, in 1951, Skellam invented the same model for non-human populations. Unlike in economics, it was a great success in ecology. In a recent contribution, Skellam is named Father of Ecological Diffusion and more than 1000 articles on the subject are listed. There were many attempts at solving the equation, but none were quite successful. The Hotelling and Skellam models both assumed a given saturation population that nature could support. In 1985 the present author suggested that an explicit production function be introduced in the Hotelling model, as a man produces his own means of subsistence. Moreover, it was proposed that diffusion be related to spatial differences in per capita productivity, rather than to those in population density. The present contribution is a rejoinder. It is shown that the stationary solutions to the original Hotelling model are periodic and dip into negative populations, whereas this is avoided by the modified model suggested. It can thus be used to show how agglomerative structures may evolve.

Demography↗

A review of drainage and spontaneous rupture in free standing thin films with tangentially immobile interfaces.

A review of spontaneous rupture in thin films with tangentially immobile interfaces is presented that emphasizes the theoretical developments of film drainage and corrugation growth through the linearization of lubrication theory in a cylindrical geometry. Spontaneous rupture occurs when corrugations from adjacent interfaces become unstable and grow to a critical thickness. A corrugated interface is composed of a number of waveforms and each waveform becomes unstable at a unique transition thickness. The onset of instability occurs at the maximum transition thickness, and it is shown that only upper and lower bounds of this thickness can be predicted from linear stability analysis. The upper bound is equivalent to the Frenkel criterion and is obtained from the zeroth order approximation of the H3 term in the evolution equation. This criterion is determined solely by the film radius, interfacial tension and Hamaker constant. The lower bound is obtained from the first order approximation of the H3 term in the evolution equation and is dependent on the film thinning velocity. A semi-empirical equation, referred to as the MTR equation, is obtained by combining the drainage theory of Manev et al. [J. Dispersion Sci. Technol., 18 (1997) 769] and the experimental measurements of Radoev et al. [J. Colloid Interface Sci. 95 (1983) 254] and is shown to provide accurate predictions of film thinning velocity near the critical thickness of rupture. The MTR equation permits the prediction of the lower bound of the maximum transition thickness based entirely on film radius, Plateau border radius, interfacial tension, temperature and Hamaker constant. The MTR equation extrapolates to Reynolds equation under conditions when the Plateau border pressure is small, which provides a lower bound for the maximum transition thickness that is equivalent to the criterion of Gumerman and Homsy [Chem. Eng. Commun. 2 (1975) 27]. The relative accuracy of either bound is thought to be dependent on the amplitude of the hydrodynamic corrugations, and a semi-empirical correlation is also obtained that permits the amplitude to be calculated as a function of the upper and lower bound of the maximum transition thickness. The relationship between the evolving theoretical developments is demonstrated by three film thickness master curves, which reduce to simple analytical expressions under limiting conditions when the drainage pressure drop is controlled by either the Plateau border capillary pressure or the van der Waals disjoining pressure. The master curves simplify solution of the various theoretical predictions enormously over the entire range of the linear approximation. Finally, it is shown that when the Frenkel criterion is used to assess film stability, recent studies reach conclusions that are contrary to the relevance of spontaneous rupture as a cell-opening mechanism in foams.

Journal Article↗

Combined body plethysmographic, spirometric and flow volume reference values for male and female children aged 6 to 16 years obtained from "hospital normals".

UNLABELLED: Vital capacity (VC) and its subdivisions (IC and ERV), total lung capacity (TLC), residual volume (RV), peak expiratory flow (PEF), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), maximum flow volume curve (MEF75, MEF50, MEF25, MMEF, FEF75-85), airway resistance (Rtot, Reff) and the thoracic gas volume at resting expiratory position (FRC) were measured in 187 girls and 213 boys (hospital normals) aged 6 to 16 years. The measurements were carried out consecutively on the same subjects in the morning using a volume-constant plethysmograph (Master-Lab, E. Jaeger; programs: body plethysmography, spirometry and flow volume). Using multiple regression analysis the best fitting curves for the prediction of normal values for boys and girls were selected. Analyses of covariance were performed to compare the adjusted means of the spirometric and body plethysmographic variables of the male and female subjects. As expected, we found higher static and dynamic (FVC, FEV1, PEF) lung volumes in boys than in girls relating to height. The flows (MMEF, MEF50, MEF25, FEF75-85) were significantly lower in the male than in the female subjects of the same age justifying separate prediction equations, but the same equation for both genders may be used for the resistance variables Rtot and Reff. Our results are compared with those of previous studies. CONCLUSION: Lung volumes and flows differ significantly between girls and boys calling for separate reference values for female and male subjects of the same age.

Adolescent↗

Scaling analysis of a divergent prefactor in the metastable lifetime of a square-lattice Ising ferromagnet at low temperatures.

We examine a square-lattice nearest-neighbor Ising quantum ferromagnet coupled to d-dimensional phonon baths. Using the density-matrix equation, we calculate the transition rates between configurations, which determines the specific dynamic. Applying the calculated stochastic dynamic in Monte Carlo simulations, we measure the lifetimes of the metastable state. As the magnetic field approaches [H]/J=2 at low temperatures, the lifetime prefactor diverges because the transition rates between certain configurations approach zero under these conditions. Near [H]/J=2 and zero temperature, the divergent prefactor shows scaling behavior as a function of the field, temperature, and the dimension of the phonon baths. With proper scaling, the simulation data at different temperatures and for different dimensions of the baths collapse well onto two master curves, one for [H]/J>2 and one for [H]/J<2.

Journal Article↗

Prediction of activity for nonnucleoside inhibitors with HIV-1 reverse transcriptase based on Monte Carlo simulations.

Results of Monte Carlo (MC) simulations for more than 200 nonnucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs) representing eight diverse chemotypes have been correlated with their anti-HIV activities in an effort to establish simulation protocols and methods that can be used in the development of more effective drugs. Each inhibitor was modeled in a complex with the protein and by itself in water, and potentially useful descriptors of binding affinity were collected during the MC simulations. A viable regression equation was obtained for each data set using an extended linear response approach, which yielded r(2) values between 0.54 and 0.85 and an average unsigned error of only 0.50 kcal/mol. The most common descriptors confirm that a good geometrical match between the inhibitor and the protein is important and that the net loss of hydrogen bonds with the inhibitor upon binding is unfavorable. Other physically reasonable descriptors of binding are needed on a chemotype case-by-case basis. By including descriptors in common from the individual fits, combination regressions that include multiple data sets were also developed. This procedure led to a refined "master" regression for 210 NNRTIs with an r(2) of 0.60 and a cross-validated q(2) of 0.55. The computed activities show an rms error of 0.86 kcal/mol in comparison with experiment and an average unsigned error of 0.69 kcal/mol. Encouraging results were obtained for the predictions of 27 NNRTIs, representing a new chemotype not included in the development of the regression model. Predictions for this test set using the master regression yielded a q(2) value of 0.51 and an average unsigned error of 0.67 kcal/mol. Finally, additional regression analysis reveals that use of ligand-only descriptors leads to models with much diminished predictive ability.

Alkynes↗

Further insights into the universality of colloidal aggregation.

Dynamic light scattering (DLS) performed at various scattering wave vectors provides detailed information about the aggregation kinetics and the cluster mass distribution (CMD) in colloidal dispersions. Detailed modeling of the aggregation kinetics with population balance equations requires a quantitative connection between the CMD and measurable quantities such as the angle dependent hydrodynamic radii obtained by DLS. For this purpose we evaluate and compare various models for the structure factor of fractal aggregates. Additionally, we introduce a simple scattering model that accounts for the contribution of internal cluster dynamics of fractal clusters to the first cumulant of the dynamic structure factor. We show that this contribution allows to quantitatively describe previously measured experimental data on the scattering wave vector dependence of the hydrodynamic radius in diffusion limited cluster-cluster aggregation (DLCA), which was shown to exhibit some kind of universality behavior (master curve). Using the same scattering model, we analyze a similar set of experimental data but in reaction limited cluster-cluster aggregation (RLCA). We find that in this case the crossover from RLCA to DLCA and gravitational settling both have a significant influence on the CMD and consequently on the scattering wave vector dependent DLS data. Only when accounting for both these effects they temporarily compensate each other and a satisfactory representation of the aggregation master curve is possible for the RLCA data at longer times. Indeed, we find that either crossover from RLCA to DLCA or gravitational settling, when present individually, causes the loss of a master curve for aggregation.

Biophysics↗

Regulation of c-maf gene expression by Pax6 in cultured cells.

c-Maf is a bZip transcription factor expressed in developmental and cellular differentiation processes. Recently, a c-maf knockout mouse model, showing abnormal lens development, has been reported. In order to study the regulation mechanisms of c-maf gene expression during the differentiation process we have cloned and functionally characterized the rat c-maf (maf-2) gene. The rat c-maf gene is an intronless gene, covering a length of 3.5 kb. Transient transfection analysis of the 5'-flanking region of the c-maf gene using luciferase as the reporter gene shows that Pax6, a master transcription factor for lens development, strongly activates the c-maf promoter construct. Endogenous c-maf is also activated by the Pax6 expression vector. Electrophoresis mobility shift assay and DNase I footprinting analysis show that at least three Pax6-binding sites are located in the 5'-flanking and 5'-non-coding regions of the rat c-maf gene. The c-maf gene was also markedly activated by its own product, c-Maf, through the MARE (Maf recognition element), suggesting that a positive autoregulatory mechanism controls this gene. In situ hybridization histochemical detection of Pax6 and c-Maf in the E14 lens showed that both mRNAs are expressed in the lens equator where lens epithelial cells are differentiating to lens fiber cells. These results suggest that a Pax6/c-Maf transcription factor cascade is working in lens development.

Animals↗

Structure of molecular liquids: cavity and bridge functions of the hard spheroid fluid.

We present methodologies for calculating the direct correlation function c(1,2), the cavity function y(1,2), and the bridge function b(1,2), for molecular liquids, from Monte Carlo simulations. As an example we present results for the isotropic hard spheroid fluid with elongation e = 3. The simulation data are compared with the results from integral equation theory. In particular, we solve the Percus-Yevick and hypernetted chain equations. In addition, we calculate the first two terms in the virial expansion of the bridge function and incorporate this into the closure. At low densities, the bridge functions calculated by theory and from simulation are in good agreement, lending support to the correctness of our numerical procedures. At higher densities, the hypernetted chain results are brought into closer agreement with simulation by incorporating the approximate bridge function, but significant discrepancies remain.

Journal Article↗

Acid-base properties of brown seaweed biomass considered as a Donnan gel. A model reflecting electrostatic effects and chemical heterogeneity.

Brown seaweeds are interesting materials to be used as biosorbents for heavy metals due to their high binding ability and low cost. The study of the passive biosorption of protons on this kind of materials and its dependency on pH, ionic strength, and medium composition is essential for the practical application of brown algae in wastewater treatment. This work reports the results of the study of the proton binding equilibria of dead biomass from the seaweeds Sargassum muticum, Cystoseira baccata, and Saccorhiza polyschides by potentiometric titration with a glass electrode in the pH range between 2 and 8. Two different salts, NaCl and KNO3, in concentrations ranging from 0.05 to 2 mol x L(-1), were used as background electrolytes. The influence of the ionic strength was accounted for by means of the Donnan model in combination with the master curve approach. Different empirical expressions to describe the swelling behavior of the biosorbent were tested. On the basis of the intrinsic affinity distribution analysis a unimodal Langmuir-Freundlich isotherm was selected to describe the proton binding properties. The results show very little influence of the type of salt. The ionic strength dependency of the proton binding is very similar for the three species, and average empirical expressions of the Donnan volume are proposed. The maximum proton binding capacities obtained ranged between 2.4 and 2.9 mol x kg(-1), with average intrinsic proton affinity constants between 3.1 and 3.3, and heterogeneity parameters of ca. 0.5 for S. muticum and C. baccata, and slightly higher (ca. 0.7) for S. polyschides. The combined Langmuir-Freundlich equation and Donnan model allowed a good description of the experimental charge vs pH curves obtained.

Adsorption↗

Assessment of the diagnosis and prevalence of asthma in Australian indigenous children.

BACKGROUND AND OBJECTIVE: Although the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire has been used in many countries and has been validated previously, it has not been used in Australian Indigenous communities. We endeavoured to assess its performance when administered in Aboriginal and Torres Strait Islander communities. METHODS: In a cross-sectional study, we assessed the ISAAC's questionnaire when administered face-to-face in Indigenous communities in the Torres Strait region, Australia. RESULTS: Comparing responses to the questionnaire with clinical assessment of 260 Indigenous children by a pediatric respiratory physician, sensitivity (87%) was high, but specificity (51%) and positive predictive value (33%) were low. Using a logistic regression model, we determined which questions were most useful in predicting a clinical diagnosis of asthma. Using a predictive equation, asthma was detected with 79% sensitivity and 77% specificity, and the calculated weighted estimate of asthma prevalence in the region was 16.3%. CONCLUSION: Our findings reveal that although the ISAAC questionnaire is a reasonably sensitive tool for both epidemiologic and clinical studies of asthma in Indigenous communities, its value is enhanced when used in conjunction with a predictive model. We have also shown that asthma is prevalent in the Torres Strait region.

Adolescent↗

Development of spatial memory and spatial orientation in preschoolers and primary school children.

The present study addresses the question of what kind of information children use when orientating in new environments, if given proximal and distal landmarks, and how spatial memory develops in the investigated age groups. Ten 5-year-old, ten 7-year-old and ten 10-year-old children were presented with the 'Kiel Locomotor Maze', containing features of the Radial Arm Maze and the Morris Water Maze, in order to assess spatial memory and orientation. Children had to learn to approach baited locations only. Task difficulty was equated with respect to the children's age. Training was given until the children reached criterion. During testing, the maze configuration and response requirements were systematically altered, including response rotation, cue rotation, cue deletion and response rotation with cue deletion in order to assess the spatial strategies used by the children. During training and testing, working-memory errors (WM), reference-memory errors (RM) and working-reference memory errors (WR) were recorded. As expected, no difference between age groups appeared during training, thus confirming comparable task difficulty across age groups. During testing, age groups differed significantly with regard to the orientation strategy used. The 5-year-olds were bound to a cue strategy, orientating towards local, proximal cues. The 10-year-olds mastered all tasks, thus displaying a place strategy, being able to use distal cues for orientation, and were even able to do so after being rotated 180 degrees. The 7-year-olds proved to be at an age of transition: five of them were bound to a cue strategy, five children were able to adopt a place strategy. The differences in the orientation strategies used by children of different age groups was reflected by the sum of errors they made, also by RM. WM were found to be rare, especially in older children. We conclude that preschoolers use a cue strategy, that the development of place strategies occurs during primary school age and seems to be complete by the age of 10 years.

Age Factors↗