On Constitutive Models for Limited Elastic, Molecular Based Materials

The response function for a general class of elastic molecular based materials characterized by their limiting molecular chain extensibility and depending on only the first principal invariant of the Cauchy–Green deformation tensor together with a certain molecular based limiting extensibility parameter is introduced. The constitutive response function for the Gent material is then derived inversely as the [0/1] Padé approximant of this class, a result that leads naturally to an infinite geometric series representation of its response function. Truncation of this series function characterizes a familiar class of quadratic materials now having physically relevant material constants. It is shown that the [0/2] approximant of the response function for the general class of restricted elastic materials leads inversely to a new constitutive model and its series representation. Of course, many familiar limited elastic material models are members of the general class. The Padé approximants for some response functions are not, and empirical modifications that admit these as members of the general class are described. Examples of two limited elastic models in the class that are not Padé approximants are noted. The strain energy functions for a few of the restricted elastic models described are presented

On Constitutive Models for Limited Elastic, Molecular Based Materials

The response function for a general class of elastic molecular based materials characterized by their limiting molecular chain extensibility and depending on only the first principal invariant of the Cauchy–Green deformation tensor together with a certain molecular based limiting extensibility parameter is introduced. The constitutive response function for the Gent material is then derived inversely as the [0/1] Padé approximant of this class, a result that leads naturally to an infinite geometric series representation of its response function. Truncation of this series function characterizes a familiar class of quadratic materials now having physically relevant material constants. It is shown that the [0/2] approximant of the response function for the general class of restricted elastic materials leads inversely to a new constitutive model and its series representation. Of course, many familiar limited elastic material models are members of the general class. The Padé approximants for some response functions are not, and empirical modifications that admit these as members of the general class are described. Examples of two limited elastic models in the class that are not Padé approximants are noted. The strain energy functions for a few of the restricted elastic models described are presented

Pathogenic mycobacteria achieve cellular persistence by inhibiting the Niemann-Pick Type C disease cellular pathway

Background. Tuberculosis remains a major global health concern. The ability to prevent phagosome-lysosome fusion is a key mechanism by which intracellular mycobacteria, including Mycobacterium tuberculosis, achieve long-term persistence within host cells. The mechanisms underpinning this key intracellular pro-survival strategy remain incompletely understood. Host macrophages infected with intracellular mycobacteria share phenotypic similarities with cells taken from patients suffering from Niemann-Pick Disease Type C (NPC), a rare lysosomal storage disease in which endocytic trafficking defects and lipid accumulation within the lysosome lead to cell dysfunction and cell death. We investigated whether these shared phenotypes reflected an underlying mechanistic connection between mycobacterial intracellular persistence and the host cell pathway dysfunctional in NPC.  Methods. The induction of NPC phenotypes in macrophages from wild-type mice or obtained from healthy human donors was assessed via infection with mycobacteria and subsequent measurement of lipid levels and intracellular calcium homeostasis. The effect of NPC therapeutics on intracellular mycobacterial load was also assessed.  Results. Macrophages infected with intracellular mycobacteria phenocopied NPC cells, exhibiting accumulation of multiple lipid types, reduced lysosomal Ca 2+ levels, and defects in intracellular trafficking. These NPC phenotypes could also be induced using only lipids/glycomycolates from the mycobacterial cell wall. These data suggest that intracellular mycobacteria inhibit the NPC pathway, likely via inhibition of the NPC1 protein, and subsequently induce altered acidic store Ca 2+ homeostasis. Reduced lysosomal calcium levels may provide a mechanistic explanation for the reduced levels of phagosome-lysosome fusion in mycobacterial infection. Treatments capable of correcting defects in NPC mutant cells via modulation of host cell calcium were of benefit in promoting clearance of mycobacteria from infected host cells.  Conclusion. These findings provide a novel mechanistic explanation for mycobacterial intracellular persistence, and suggest that targeting interactions between the mycobacteria and host cell pathways may provide a novel avenue for development of anti-TB therapies