Hierarchical modelling of acclimatory processesstar, open

The term acclimation has been used with several connotations in the field of acclimatory physiology. An attempt has been made, in this paper, to define precisely the term “acclimation” for effective modelling of acclimatory processes. Acclimation is defined with respect to a specific variable, as cumulative experience gained by the organism when subjected to a step change in the environment. Experimental observations on a large number of variables in animals exposed to sustained stress, show that after initial deviation from the basal value (defined as “growth”), the variables tend to return to basal levels (defined as “decay”). This forms the basis for modelling biological responses in terms of their growth and decay. Hierarchical systems theory as presented by Mesarovic, Macko & Takahara (1970) facilitates modelling of complex and partially characterized systems. This theory, in conjunction with “growth-decay” analysis of biological variables, is used to model temperature regulating system in animals exposed to cold. This approach appears to be applicable at all levels of biological organization. Regulation of hormonal activity which forms a part of the temperature regulating system, and the relationship of the latter with the “energy” system of the animal of which it forms a part, are also effectively modelled by this approach. It is believed that this systematic approach would eliminate much of the current circular thinking in the area of acclimatory physiology.

Three-dimensional structure of heat shock protein 90 from Plasmodium falciparum: molecular modelling approach to rational drug design against malaria

We have recently implicated heat shock protein 90 from Plasmodium falciparum (PfHsp90) as a potential drug target against malaria. Using inhibitors specific to the nucleotide binding domain of Hsp90, we have shown potent growth inhibitory effects on development of malarial parasite in human erythrocytes. To gain better understanding of the vital role played by PfHsp90 in parasite growth, we have modeled its three dimensional structure using recently described full length structure of yeast Hsp90. Sequence similarity found between PfHsp90 and yeast Hsp90 allowed us to model the core structure with high confidence. The superimposition of the predicted structure with that of the template yeast Hsp90 structure reveals an RMSD of 3.31 angstrom. The N-terminal and middle domains showed the least RMSD (1.76 angstrom) while the more divergent C-terminus showed a greater RMSD (2.84 angstrom) with respect to the template. The structure shows overall conservation of domains involved in nucleotide binding, ATPase activity, co-chaperone binding as well as inter-subunit interactions. Important co-chaperones known to modulate Hsp90 function in other eukaryotes are conserved in malarial parasite as well. An acidic stretch of amino acids found in the linker region, which is uniquely extended in PfHsp90 could not be modeled in this structure suggesting a flexible conformation. Our results provide a basis to compare the overall structure and functional pathways dependent on PfHsp90 in malarial parasite. Further analysis of differences found between human and parasite Hsp90 may make it possible to design inhibitors targeted specifically against malaria.

Modelling of a patch repair to a thin cracked sheet

Integrity enhancement of damaged or design deficient structures through repairs is attracting considerable engineering attention. Bonded composite patch repairs to cracked metallic sheets offer various advantages over riveted doubler type, particularly for airframe applications. This paper first reviews the R&D activity in the area of structural repairs. It then approaches the problem of a composite patch repair to a cracked aluminium sheet with different finite element modelling strategies and compares their outcome. The efficient finite element modelling approach thus established is used to study the effect of patch material, patch size, patch symmetry and adhesive thickness on repair performance as the crack grows in the repair configuration. (C) 1999 Elsevier Science Ltd. All rights reserved.