Extracting directed information flow networks: an application to genetics and semantics.

We introduce a general method to infer the directional information flow between populations whose elements are described by n-dimensional vectors of symbolic attributes. The method is based on the Jensen-Shannon divergence and on the Shannon entropy and has a wide range of application. We show here the results of two applications: first we extract the network of genetic flow between meadows of the seagrass Poseidonia oceanica, where the meadow elements are specified by sets of microsatellite markers, and then we extract the semantic flow network from a set of Wikipedia pages, showing the semantic channels between different areas of knowledge.

A heterogeneous tube model of intestinal drug absorption based on probabilistic concepts.

PURPOSE: To develop an approach based on computer simulations for the study of intestinal drug absorption. METHODS: The drug flow in the gastrointestinal tract was simulated with a biased random walk model in the heterogeneous tube model (Pharm. Res. 16, 87-91, 1999), while probability concepts were used to describe the dissolution and absorption processes. An amount of drug was placed into the input end of the tube and allowed to flow, dissolve and absorb along the tube. Various drugs with a diversity in dissolution and permeability characteristics were considered. The fraction of dose absorbed (Fabs) was monitored as a function of time measured in Monte Carlo steps (MCS). The absorption number An was calculated from the mean intestinal transit time and the absorption rate constant adhering to each of the drugs examined. RESULTS: A correspondence between the probability factor used to simulate drug absorption and the conventional absorption rate constant derived from the analysis of data was established. For freely soluble drugs, the estimates for Fabs derived from simulations using as an intestinal transit time 24500 MCS (equivalent to 4.5 h) were in accord with the corresponding data obtained from literature. For sparingly soluble drugs, a comparison of the normalized concentration profiles in the tube derived from the heterogeneous tube model and the classical macroscopic mass balance approach enabled the estimation of the dissolution probability factor for five drugs examined. The prediction of Fabs can be accomplished using estimates for the absorption and the dissolution probability factors. CONCLUSIONS: A fully computerized approach which describes the flow, dissolution and absorption of drug in the gastrointestinal tract in terms of probability concepts was developed. This approach can be used to predict Fabs for drugs with various solubility and permeability characteristics provided that probability factors for dissolution and absorption are available.

Heterogeneous tube model for the study of small intestinal transit flow.

PURPOSE: A Monte-Carlo computer simulation technique was employed to study the details of the small intestinal transit flow in the gastrointestinal (GI) tract. METHODS: A heterogeneous tube model was constructed using a numerical computer simulation technique. The model was built from first principles and included several heterogeneous characteristics of the GI tract structure. We used a random, dendritic-type internal structure representing the villi of the GI tract. The small intestinal transit flow was simulated using two diffusion models, namely, the blind ant and the myopic ant models, which are different models to account the elapse of time, and which are both based on statistical properties of random walks. For each one of the models we utilize two types of biased random walk, placing different emphasis in the motion towards the output of the tube. We monitored the flow of the drug in terms of Monte-Carlo time steps (MCS) through the tube walls and dendritic villi present. RESULTS: The frequency of the transit times was dependent on the structure of the dendritic villi and on the type of biased random walk. The small intestinal flow profile of literature data for a large number of drugs was well characterized by the heterogeneous model using, as parameters, a certain number of villi per unit length of the tube and specific characteristics for both types of the biased random walk. A correspondence between the MCS and real time units was achieved. CONCLUSIONS: The transit process of the oral dosage forms in the GI tract can be reproduced with the heterogeneous model developed. This model can be used to study GI absorption phenomena.