Search PubMed⌕ Search

Biomedical subjects

M Filoche

Publications and source records attributed to M Filoche.

14 recordsLinked to original sources
PubMed2006

Mathematical basis for a general theory of Laplacian transport towards irregular interfaces.

The theory of Laplacian transport towards and across irregular surfaces is reformulated in terms of the Dirichlet-to-Neumann operator and its spectral characteristics. This permits us to obtain an exact equivalent circuit for the impedance of a working interface of arbitrary shape. The important result is that only very few eigenmodes of this operator do govern the entire response of a macroscopic system. This property drastically simplifies the understanding of irregular or prefractal interfaces. The results can be applied in electrochemistry, physiology and chemical engineering, fields where exchange processes across surfaces with complex geometry are ubiquitous.

Journal Article↗
PubMed2005

Multifractal properties of the harmonic measure on Koch boundaries in two and three dimensions.

The multifractal properties of the harmonic measure on quadratic and cubic Koch boundaries are studied with the help of a new fast random walk algorithm adapted to these fractal geometries. The conjectural logarithmic development of local multifractal exponents is guessed for regular fractals and checked by extensive numerical simulations. This development allows one to compute the multifractal exponents of the harmonic measure with high accuracy, even with the first generations of the fractal. In particular, the information dimension in the case of the concave cubic Koch surface embedded in three dimensions is found to be slightly higher than its value D1 =2 for a smooth boundary.

Journal Article↗
PubMed2005

Diffusional screening in real 3D human acini--a theoretical study.

Gas exchange at the acinar level involves several physico-chemical phenomena within a complex geometry. A gas transport model, which takes into account both the diffusion into the acinus and the diffusion across the alveolar membrane, is used to understand gas mixing in realistic systems. It is first shown that the behaviour of the system, computed on model geometries in 3D, only depends on the topological structure of the acinus. Taking advantage of this property, a new efficient method based on random walks on a lattice is used to compute gas diffusion in structures taken from real morphological data. This approach shows that, at rest, the human acinus efficiency is only 30-40%. These results provide a new evidence of the existence of diffusional screening at the acinar level. This implies permanent spatial inhomogeneity of oxygen and carbon dioxide partial pressure. The notion of an "alveolar gas" is reinterpreted as a spatial average of the gas distribution. This model casts new light on the respiratory properties of other gas mixtures, such as helium-oxygen.

Cell Membrane Permeability↗
PubMed2005

Diffusion-reaction in branched structures: theory and application to the lung acinus.

An exact "branch by branch" calculation of the diffusional flux is proposed for partially absorbed random walks on arbitrary tree structures. In the particular case of symmetric trees, an explicit analytical expression is found which is valid whatever the size of the tree. Its application to the respiratory phenomena in pulmonary acini gives an analytical description of the crossover regime governing the human lung efficiency.

Animals↗
PubMed2004

An optimal bronchial tree may be dangerous.

The geometry and dimensions of branched structures such as blood vessels or airways are important factors in determining the efficiency of physiological processes. It has been shown that fractal trees can be space filling and can ensure minimal dissipation. The bronchial tree of most mammalian lungs is a good example of an efficient distribution system with an approximate fractal structure. Here we present a study of the compatibility between physical optimization and physiological robustness in the design of the human bronchial tree. We show that this physical optimization is critical in the sense that small variations in the geometry can induce very large variations in the net air flux. Maximum physical efficiency therefore cannot be a sufficient criterion for the physiological design of bronchial trees. Rather, the design of bronchial trees must be provided with a safety factor and the capacity for regulating airway calibre. Paradoxically, our results suggest that bronchial malfunction related to asthma is a necessary consequence of the optimized efficiency of the tree structure.

Asthma↗
PubMed2004

Renormalized random walk study of oxygen absorption in the human lung.

The possibility to renormalize random walks is used to study numerically the oxygen diffusion and permeation in the acinus, the diffusion cell terminating the mammalian airway tree. This is done in a 3D tree structure which can be studied from its topology only. The method is applied to the human acinus real morphology as studied by Haefeli-Bleuer and Weibel in order to compute the respiratory efficiency of the human lung. It provides the first quantitative evidence of the role of diffusion screening in real 3D mammalian respiration. The net result of this study is that, at rest, the efficiency of the human acinus is only of order 33%. Application of these results to CO2 clearance provides for the first time a theoretical support to the empirical relation between the O2 and CO2 partial pressures in blood.

Bronchi↗
PubMed2004

Cancer death statistics: analogy between epidemiology and critical systems in physics.

The determination of risk factors in carcinogenesis is said to be an essential step towards the understanding of this disease. Most mathematical models describing the evolution of mortality figures use the concept of death probability (or "force of mortality" or "hazard of death"). When summarizing the death statistics through this unique parameter, one implicitly makes the assumption that the death events are independent from one individual to another. In this paper, we show that this hypothesis has profound consequences as it implies a "gaussian" behavior of the death statistics fluctuations. In order to verify the validity of this assumption, French cancer death statistics between the years 1978-1996 are examined. Their fluctuations, for every age bracket, are computed and then compared to the expected gaussian fluctuations that should emerge from a model of death probability. We show that the observed fluctuations are in close agreement with a gaussian model up to 35-40 years. After 40 years, the fluctuations are much higher and cannot be explained by a model where every individual would have a given "probability of death". These observations may produce a new insight into old-age cancer mortality. It suggests that there could exist a major difference between cancers in young or older organisms: cancer developed in young organisms are the consequence of a specific attack against an organ (essentially originated from a single cause, like a virus or a genetic deficiency). On the other hand, older organism are closer to a "critical state" and, as such, the outcome of a cancer in a given organ could be the consequence of a chain of "malfunctions" (analogous to an avalanche in physical systems) in the entire organism.

Adolescent↗
PubMed2003

Interplay between geometry and flow distribution in an airway tree.

Uniform flow distribution in a symmetric volume can be realized through a symmetric branched tree. It is shown here, however, by 3D numerical simulation of the Navier-Stokes equations, that the flow partitioning can be highly sensitive to deviations from exact symmetry if inertial effects are present. The flow asymmetry is quantified and found to depend on the Reynolds number. Moreover, for a given Reynolds number, we show that the flow distribution depends on the aspect ratio of the branching elements as well as their angular arrangement. Our results indicate that physiological variability should be severely restricted in order to ensure adequate fluid distribution through a tree.

Animals↗
PubMed2003

Diffusional screening in the human pulmonary acinus.

In the mammalian lung acini, O(2) diffuses into quasi-static air toward the alveolar membrane, where the gas exchange with blood takes place. The O(2) flux is then influenced by the O(2) diffusivity, the membrane permeability, and the acinus geometric complexity. This phenomenon has been recently studied in an abstract geometric model of the acinus, the Hilbert acinus (Sapoval B, Filoche M, and Weibel ER, Proc Natl Acad Sci USA 99: 10411, 2002). This is extended here to a more realistic geometry originated from the morphological model of Kitaoka et al. (Kitaoka K, Tamura S, and Takaki R, J Appl Physiol 88: 2260-2268, 2000). Two-dimensional numerical simulations of the steady-state diffusion equation with mixed boundary conditions are used to quantify the process. The alveolar O(2) concentration, or partial pressure, and the O(2) flux are computed and show that diffusional screening exists at rest. These results confirm that smaller acini are more efficient, as suggested for the Hilbert acini.

Algorithms↗
PubMed2002

Smaller is better--but not too small: a physical scale for the design of the mammalian pulmonary acinus.

The transfer of oxygen from air to blood in the lung involves three processes: ventilation through the airways, diffusion of oxygen in the air phase to the alveolar surface, and finally diffusion through tissue into the capillary blood. The latter two steps occur in the acinus, where the alveolar gas-exchange surface is arranged along the last few generations of airway branching. For the acinus to work efficiently, oxygen must reach the last branches of acinar airways, even though some of it is absorbed along the way. This "screening effect" is governed by the relative values of physical factors like diffusivity and permeability as well as size and design of the acinus. Physics predicts that efficient acini should be space-filling surfaces and should not be too large. It is shown that the mammalian acini fulfill these requirements, small mammals being more efficient than large ones both at rest and in exercise.

Animals↗
PubMed2000

Diffusion-reorganized aggregates: attractors in diffusion processes?

A process based on particle evaporation, diffusion, and redeposition is applied iteratively to a two-dimensional object of arbitrary shape. The evolution spontaneously transforms the object morphology, converging to branched structures. Independently of initial geometry, the structures found after a long time present fractal geometry with a fractal dimension around 1.75. The final morphology, which constantly evolves in time, can be considered as the dynamic attractor of this evaporation-diffusion-redeposition operator. The ensemble of these fractal shapes can be considered to be the dynamical equilibrium geometry of a diffusion-controlled self-transformation process.

Journal Article↗
PubMed2000

Transfer across random versus deterministic fractal interfaces.

A numerical study of the transfer across random fractal surfaces shows that their responses are very close to the response of deterministic model geometries with the same fractal dimension. The simulations of several interfaces with prefractal geometries show that, within very good approximation, the flux depends only on a few characteristic features of the interface geometry: the lower and higher cutoffs and the fractal dimension. Although the active zones are different for different geometries, the electrode responses are very nearly the same. In that sense, the fractal dimension is the essential "universal" exponent which determines the net transfer.

Journal Article↗
PubMed2000

A unified theory of the B-Z transition of DNA in high and low concentrations of multivalent ions.

We showed recently that the high-salt transition of poly[d(G-C)]. poly[d(G-C)] between B-DNA and Z-DNA (at [NaCl] = 2.25 M or [MgCl(2)] = 0.7 M) can be ascribed to the lesser electrostatic free energy of the B form, due to better immersion of the phosphates in the solution. This property was incorporated in cylindrical DNA models that were analyzed by Poisson-Boltzmann theory. The results are insensitive to details of the models, and in fair agreement with experiment. In contrast, the Z form of the poly[d(G-m5C)] duplex is stabilized by very small concentrations of magnesium. We now show that this striking difference is accommodated quantitatively by the same electrostatic theory, without any adjustable parameter. The different responses to magnesium of the methylated and nonmethylated polymers do not come from stereospecific cation-DNA interactions: they stem from an experimentally derived, modest difference in the nonelectrostatic component of the free energy difference (or NFED) between the Z and B forms. The NFED is derived from circular DNA measurements. The differences between alkaline earth and transition metal ions are explained by weak coordination of the latter. The theory also explains the induction of the transition by micromolar concentrations of cobalt hexammine, again without specific binding or adjustable parameters. Hence, in the case of the B-Z transition as in others (e.g., the folding of tRNA and of ribozymes), the effect of multivalent cations on nucleic acid structure is mediated primarily by nonspecific ion-polyelectrolyte interactions. We propose this as a general rule for which convincing counter-examples are lacking.

Circular Dichroism↗