Structured modeling of recombinant protein production in batch and fed-batch culture of baculovirus-infected insect cells

The infection of insect cells with baculovirus was described in a mathematical model as a part of the structured dynamic model describing whole animal cell metabolism. The model presented here is capable of simulating cell population dynamics, the concentrations of extracellular and intracellular viral components, and the heterologous product titers. The model describes the whole processes of viral infection and the effect of the infection on the host cell metabolism. Dynamic simulation of the model in batch and fed-batch mode gave good agreement between model predictions and experimental data. Optimum conditions for insect cell culture and viral infection in batch and fed-batch culture were studied using the model.

Shared and unique environmental factors determine the ecology of methanogens in humans and rats

OBJECTIVE: This study ascertains the relative contributions of genetics and environment in determining methane emission in humans and rats. There is considerable interest in the factors determining the microbial species that inhabit the colon. Methanogens, which are archaebacteria, are an easily detected colonic luminal bacteria because they respire methane. They are present in some but not all human colons and lower animal hindguts. Opinion varies on the nature of the factors influencing this ecology with some studies proposing the existence of host genetic influences. METHODS: Methane emission was measured in human twin pairs by gas chromatography, and structural equation modeling was used to determine the proportion of genetic and environmental determinants. The importance of the timing of environmental effects and rat strain on the trait of methane emission were ascertained by experiments with cohabiting methanogenic and nonmethanogenic rats. RESULTS: Analysis of breath samples from 274 adolescent twin pairs and their families indicated that the major influences on the trait of methane emission are the result of shared (53%, 95% confidence interval 39-61) and unique environmental (47%, 95% confidence interval 38-56) effects. No significant autosomal genetic effects were detected, but as observed in other studies, men (37%) were less likely to excrete methane in their breath than women (63%). Investigation of methane emission in rats indicated that environmental effects in this animal are most potent during the weaning period, with stable gut microbial ecology thereafter for some but not all rat strains. CONCLUSIONS: These results are consistent with shared and unique environmental factors being the main determinants of the ecology of this colonic microbe. (Am J Gastroenterol 2000;95:2872-2879. (C) 2000 by Am. Coll. of Gastroenterology).

An update on genetic, structural and functional studies of arylamine N-acetyltransferases in eucaryotes and procaryotes

Arylamine N-acetyltransferase (NAT) was first identified as the inactivator of the anti-tubercular drug isoniazid, The enzyme was shown to catalyse the transfer of an acetyl group from acetyl-CoA to the terminal nitrogen of the hydrazine drug. The rate of inactivation of isoniazid was polymorphically distributed in the population and was one of the first examples of pharmacogenetic variation, NAT was identified recently in Mycobacterium tuberculosis and is a candidate for; modulating the response to isoniazid, Genome sequences have revealed many homologous members of this unique family of enzymes. The first three-dimensional structure of a member of the NAT family identifies a catalytic triad consisting of aspartate, histidine and cysteine proposed to form the activation mechanism. So far, all procaryotic NATs resemble the human enzyme which acetylates isoniazid (NAT2), Human NAT2 is characteristic of drug-metabolizing enzymes: it is found in liver and intestine, In humans and other mammals, there are up to three different isoenzymes. If only one isoenzyme is present, it is like human NAT1. Human NAT1 and its murine equivalent specifically acetylate the folate catabolite p-amino-benzoylglutamate. NAT1 and its murine homologue each have a ubiquitous tissue distribution and are expressed early in development at the blastocyst stage, During murine embryonic development, NAT is expressed in the developing neural tube. The proposed endogenous role of NAT in folate metabolism, and its multi-allelic nature, indicate that its role in development should be assessed further.

A novel genetic locus for low renin hypertension: familial hyperaldosteronism type II maps to chromosome 7 (7p22)

Familial hyperaldosteronism type II (FH-II) is caused by adrenocortical hyperplasia or aldosteronoma or both and is frequently transmitted in an autosomal dominant fashion. Unlike FH type I (FI-I-I), which results from fusion of the CYP11B1 and CYP11B2 genes, hyperaldosteronism in FH-II is not glucocorticoid remediable. A large family with FH-II was used for a genome wide search and its members were evaluated by measuring the aldosterone:renin ratio. In those with an increased ratio, FH-II was confirmed by fludrocortisone suppression testing. After excluding most of the genome, genetic linkage was identified with a maximum two point lod score of 3.26 at theta =0, between FH-II in this family and the polymorphic markers D7S511, D7S517, and GATA24F03 on chromosome 7,a region that corresponds to cytogenetic band 7p22. This is the first identified locus for FH-II; its molecular elucidation may provide further insight into the aetiology of primary aldosteronism.

Finite element modeling of fluid-rock interaction problems in pore-fluid saturated hydrothermal/sedimentary basins

In order to use the finite element method for solving fluid-rock interaction problems in pore-fluid saturated hydrothermal/sedimentary basins effectively and efficiently, we have presented, in this paper, the new concept and numerical algorithms to deal with the fundamental issues associated with the fluid-rock interaction problems. These fundamental issues are often overlooked by some purely numerical modelers. (1) Since the fluid-rock interaction problem involves heterogeneous chemical reactions between reactive aqueous chemical species in the pore-fluid and solid minerals in the rock masses, it is necessary to develop the new concept of the generalized concentration of a solid mineral, so that two types of reactive mass transport equations, namely, the conventional mass transport equation for the aqueous chemical species in the pore-fluid and the degenerated mass transport equation for the solid minerals in the rock mass, can be solved simultaneously in computation. (2) Since the reaction area between the pore-fluid and mineral surfaces is basically a function of the generalized concentration of the solid mineral, there is a definite need to appropriately consider the dependence of the dissolution rate of a dissolving mineral on its generalized concentration in the numerical analysis. (3) Considering the direct consequence of the porosity evolution with time in the transient analysis of fluid-rock interaction problems; we have proposed the term splitting algorithm and the concept of the equivalent source/sink terms in mass transport equations so that the problem of variable mesh Peclet number and Courant number has been successfully converted into the problem of constant mesh Peclet and Courant numbers. The numerical results from an application example have demonstrated the usefulness of the proposed concepts and the robustness of the proposed numerical algorithms in dealing with fluid-rock interaction problems in pore-fluid saturated hydrothermal/sedimentary basins. (C) 2001 Elsevier Science B.V. All rights reserved.

Minimum-order stable recursive filter design via the genetic algorithm approach

In this paper, the minimum-order stable recursive filter design problem is proposed and investigated. This problem is playing an important role in pipeline implementation sin signal processing. Here, the existence of a high-order stable recursive filter is proved theoretically, in which the upper bound for the highest order of stable filters is given. Then the minimum-order stable linear predictor is obtained via solving an optimization problem. In this paper, the popular genetic algorithm approach is adopted since it is a heuristic probabilistic optimization technique and has been widely used in engineering designs. Finally, an illustrative example is sued to show the effectiveness of the proposed algorithm.

An L-system-based plant modeling language

Cpfg is a program for simulating and visualizing plant development, based on the theory of L-systems. A special-purpose programming language, used to specify plant models, is an essential feature of cpfg. We review postulates of L-system theory that have influenced the design of this language. We then present the main constructs of this language, and evaluate it from a user's perspective.

L-studio/cpfg: A software system for modeling plants

L-studio/cpfg is a plant modeling software system designed for Windows 95/98/NT platforms. Its key components are the L-system-based plant simulator cpfg and the modeling environment called L-studio. We overview version 1.0 of this system from the user's perspective.

Modeling of heat transfer in fluidized-bed coating of cylinders

A numerical model of heat transfer in fluidized-bed coating of solid cylinders is presented. By defining suitable dimensionless parameters, the governing equations and its associated initial and boundary conditions are discretized using the method of orthogonal collocation and the resulting ordinary differential equations simultaneously solved for the dimensionless coating thickness and wall temperatures. Parametric Studies showed that the dimensionless coating thickness and wall temperature depend on the relative heat capacities of the polymer powder and object, the latent heat of fusion and the size of the cylinder. Model predictions for the coating thickness and wall temperature compare reasonably well with numerical predictions and experimental coating data in the literature and with our own coating experiments using copper cylinders immersed in nylon-11 and polyethylene powders. (C) 2001 Elsevier Science Ltd. All rights reserved.

Social structures, genetic structures and dispersal strategies in Australian rabbit (Oryctolagus cuniculus) populations

In this study, the pattern of movement of young male and female rabbits and the genetic structures present in adult male and female populations in four habitats was examined. The level of philopatry in young animals was found to vary between 18-90% for males and 32-95% for females in different populations. It was skewed, with more males dispersing than females in some but not all populations. Analysis of allozyme data using spatial autocorrelation showed that adult females from the same social group, unlike males, were significantly related in four of the five populations studied. Changes in genetic structure and rate of dispersal were measured before and during the recovery of a population that was artificially reduced in size. There were changes in the rate and distance of dispersal with density and sex. Subadults of both sexes moved further in the first year post crash (low density) than in the following years. While the level of dispersal for females was lower than that of the males for the first 3 years, thereafter (high density) both sexes showed similar, low levels of dispersal (20%). The density at which young animals switch behaviour between dispersal and philopatry differed for males and females. The level of genetic structuring in adult females was high in the precrash population, reduced in the first year post crash and undetectable in the second year. Dispersal behaviour of rabbits both affects the genetic structure of the population and changes with conditions. Over a wide range of levels of philopatry, genetic structuring is present in the adult female, but not the male population. Consequently, though genetic structuring is present, it does not lead to inbreeding. More long-distance movements are found in low-density populations, even though vacant warrens are available near birth warrens. The distances moved decreased as density increased. Calculation of the effective population size (N-e) shows that changes in dispersal distance offset changes in density, so that N-e remains constant.