Coupled swelling and large strain model for hydrogels: application to the nucleus pulposus of the intervertebral disc

The main constituents of the nucleus puposus , the centrl gelatinous part of the intervertebral disc, are water and a solid extracellular matrix of macromolecules. Based on this observation, the nucleus pulposus can be seen as a gel-like material in wich swelling - due to the diffusion of the fluid molecules into the macromolecular network - and large strain elasticity, induced by the macromollecular chains, occur. In recent literature, many autors have been interested in describing such a coupled deformation-diffusion problem for gels. Most of the tim, these works where formulated with respect to the dry configuration of the material. Howevver, for the nucleus pulposus, the dru configuration does not exist. Thus, the formulation of the deformation-diffusion problem should be modified in order to consider a reference configuration, wich is undeformed and unconstrained (but already swollen). The theoretical aspects of the derivation of this coupled deformation-diffusion model is proposed. Then, this model is numerically implemented in the finite element commercial software ABAQUS. The state of equilibrium are investigated on simple homogeneous examples. Finally, the himan nucleus pulposus of the intervertebral disc is chosen as a representative complex crample of application for this approach. The associated annulus fibrosus is modelled using an anisotropic hyperelastic material law

High Mutability of the Tumor Suppressor Genes RASSF1 and RBSP3 (CTDSPL) in Cancer

BACKGROUND:Many different genetic alterations are observed in cancer cells. Individual cancer genes display point mutations such as base changes, insertions and deletions that initiate and promote cancer growth and spread. Somatic hypermutation is a powerful mechanism for generation of different mutations. It was shown previously that somatic hypermutability of proto-oncogenes can induce development of lymphomas. METHODOLOGY/PRINCIPAL FINDINGS:We found an exceptionally high incidence of single-base mutations in the tumor suppressor genes RASSF1 and RBSP3 (CTDSPL) both located in 3p21.3 regions, LUCA and AP20 respectively. These regions contain clusters of tumor suppressor genes involved in multiple cancer types such as lung, kidney, breast, cervical, head and neck, nasopharyngeal, prostate and other carcinomas. Altogether in 144 sequenced RASSF1A clones (exons 1-2), 129 mutations were detected (mutation frequency, MF = 0.23 per 100 bp) and in 98 clones of exons 3-5 we found 146 mutations (MF = 0.29). In 85 sequenced RBSP3 clones, 89 mutations were found (MF = 0.10). The mutations were not cytidine-specific, as would be expected from alterations generated by AID/APOBEC family enzymes, and appeared de novo during cell proliferation. They diminished the ability of corresponding transgenes to suppress cell and tumor growth implying a loss of function. These high levels of somatic mutations were found both in cancer biopsies and cancer cell lines. CONCLUSIONS/SIGNIFICANCE:This is the first report of high frequencies of somatic mutations in RASSF1 and RBSP3 in different cancers suggesting it may underlay the mutator phenotype of cancer. Somatic hypermutations in tumor suppressor genes involved in major human malignancies offer a novel insight in cancer development, progression and spread

Coupled swelling and large strain model for hydrogels: application to the nucleus pulposus of the intervertebral disc

The main constituents of the nucleus puposus , the centrl gelatinous part of the intervertebral disc, are water and a solid extracellular matrix of macromolecules. Based on this observation, the nucleus pulposus can be seen as a gel-like material in wich swelling - due to the diffusion of the fluid molecules into the macromolecular network - and large strain elasticity, induced by the macromollecular chains, occur. In recent literature, many autors have been interested in describing such a coupled deformation-diffusion problem for gels. Most of the tim, these works where formulated with respect to the dry configuration of the material. Howevver, for the nucleus pulposus, the dru configuration does not exist. Thus, the formulation of the deformation-diffusion problem should be modified in order to consider a reference configuration, wich is undeformed and unconstrained (but already swollen). The theoretical aspects of the derivation of this coupled deformation-diffusion model is proposed. Then, this model is numerically implemented in the finite element commercial software ABAQUS. The state of equilibrium are investigated on simple homogeneous examples. Finally, the himan nucleus pulposus of the intervertebral disc is chosen as a representative complex crample of application for this approach. The associated annulus fibrosus is modelled using an anisotropic hyperelastic material law

Systems biology of cancer: entropy, disorder, and selection-driven evolution to independence, invasion and "swarm intelligence"

Our knowledge of the biology of solid cancer has greatly progressed during the last few years, and many excellent reviews dealing with the various aspects of this biology have appeared. In the present review, we attempt to bring together these subjects in a general systems biology narrative. It starts from the roles of what we term entropy of signaling and noise in the initial oncogenic events, to the first major transition of tumorigenesis: the independence of the tumor cell and the switch in its physiology, i.e. from subservience to the organism to its own independent Darwinian evolution. The development after independence involves a constant dynamic reprogramming of the cells and the emergence of a sort of collective intelligence leading to invasion and metastasis and seldom to the ultimate acquisition of immortality through inter-individual infection. At each step, the probability of success is minimal to infinitesimal, but the number of cells possibly involved and the time scale account for the relatively high occurrence of tumorigenesis and metastasis in multicellular organisms.JOURNAL ARTICLESCOPUS: ar.jinfo:eu-repo/semantics/publishe