Influence of the Degree of Deacetylation of Chitosan and BMP-2 Concentration on Biocompatibility and Osteogenic Properties of BMP-2/PLA Granule-Loaded Chitosan/β-Glycerophosphate Hydrogels

Compositions based on chitosan/β-glycerophosphate hydrogels with highly porous polylactide granules can be used to obtain moldable bone graft materials that have osteoinductive and osteoconductive properties. To eliminate the influence of such characteristics as chain length, degree of purification, and molecular weight on a designed material, the one-stock chitosan sample was reacetylated to degrees of deacetylation (DD%) of 19.5, 39, 49, 55, and 56. A study of the chitosan/β-glycerophosphate hydrogel with chitosan of a reduced DD% showed that a low degree of deacetylation increased the MSCs (multipotent stromal cells) viability rate in vitro and reduced the leukocyte infiltration in subcutaneous implantation to Wistar rats in vivo. The addition of 12 wt% polylactide granules resulted in optimal composite mechanical and moldable properties, and increased the modulus of elasticity of the hydrogel-based material by approximately 100 times. Excessive filling of the material with PLA (polylactide) granules (more than 20%) led to material destruction at a ~10% strain. Osteoinductive and osteoconductive properties of the chitosan hydrogel-based material with reacetylated chitosan (39 DD%) and highly porous polylactide granules impregnated with BMP-2 (bone morphogenetic protein-2) have been demonstrated in models of orthotopic and ectopic bone formation. When implanted into a critical-size calvarial defect in rats, the optimal concentration of BMP-2 was 10 μg/mL: bone tissue areas filled the entire material’s thickness. Implantation of the material with 50 μg/mL BMP-2 was accompanied with excessive growth of bone tissue and material displacement beyond the defect. Significant osteoinductive and osteoconductive properties of the material with 10 μg/mL of BMP-2 were also shown in subcutaneous implantation.     

Adaptive local grid refinement algorithms for finite-element collocation

An adaptive grid refinement procedure allows accurate solutions to advection-dominated, time-dependent flows using finite-element collocation. The technique relies on a data structure that is readily amenable to parallel computing. The paper discusses computational aspects of the method.     

A Generally Covariant Wave Equation for Grand Unified Field Theory

A generally covariant wave equation is derived geometrically for grand unified field theory. The equation states most generally that the covariant d'Alembertian acting on the vielbein vanishes for the four fields which are thought to exist in nature: gravitation, electromagnetism, weak field and strong field. The various known field equations are derived from the wave equation when the vielbein is the eigenfunction. When the wave equation is applied to gravitation the wave equation is the eigenequation of wave mechanics corresponding to Einstein's field equation in classical mechanics, the vielbein eigenfunction playing the role of the quantized gravitational field. The three Newton laws, Newton's law of universal gravitation, and the Poisson equation are recovered in the classical and nonrelativistic, weak-field limits of the quantized gravitational field. The single particle wave-equation and Klein-Gordon equations are recovered in the relativistic, weak-field limit of the wave equation when scalar components are considered of the vielbein eigenfunction of the quantized gravitational field. The Schrödinger equation is recovered in the non-relativistec, weak-field limit of the Klein-Gordon equation). The Dirac equation is recovered in this weak-field limit of the quantized gravitational field (the nonrelativistic limit of the relativistic, quantezed gravitational field when the vielbein plays the role of the spinor. The wave and field equations of O(3) electrodynamics are recovered when the vielbein becomes the relativistic dreibein (triad) eigenfunction whose three orthonormal space indices become identified with the three complex circular indices (1), (2), (3), and whose four spacetime indices are the indices of non-Euclidean spacetime (the base manifold). This dreibein is the potential dreibein of the O(3) electromagnetic field (an electromagnetic potential four-vector for each index (1), (2), (3)). The wave equation of the parity violating weak field is recovered when the orthonormal space indices of the relativistic dreibein eigenfunction are identified with the indices of the three massive weak field bosons. The wave equation of the strong field is recovered when the orthonormal space indices of the relativistic vielbein eigenfunction become the eight indices defined by the group generators of the SU (3) group.     

A modified method of characteristics incorporating streamline diffusion

A hybrid finite-element method, combining ideas from a modified method of characteristics and the streamline diffusion method, delivers accurate solutions to the advection–diffusion equation. An error analysis for the case of tensorial diffusion shows that the lowest-order version of the scheme, which allows one to use a symmetric linear solvers at each time step, possesses first-order accuracy in time and space. Numerical experiments demonstrate the scheme's ability to model advection-dominated transport of solute plumes without distorting sharp fronts. © 1995 John Wiley & Sons, Inc.     

Dynamic supercoiling bifurcations of growing elastic filaments

Certain bacteria form filamentous colonies when the cells fail to separate after dividing. In Bacillus subtilis, Bacillus thermus, and Cyanobacteria, the filaments can wrap into complex supercoiled structures as the cells grow. The structures may be solenoids or plectonemes, with or without branches in the latter case. Any microscopic theory of these morphological instabilities must address the nature of pattern selection in the presence of growth, for growth renders the problem nonautonomous and the bifurcations dynamic. To gain insight into these phenomena, we formulate a general theory for growing elastic filaments with bending and twisting resistance in a viscous medium, and study an illustrative model problem: a growing filament with preferred twist, closed into a loop. Growth depletes the twist, inducing a twist strain. The closure of the loop prevents the filament from unwinding back to the preferred twist; instead, twist relaxation is accomplished by the formation of supercoils. Growth also produces viscous stresses on the filament which even in the absence of twist produce buckling instabilities. Our linear stability analysis and numerical studies reveal two dynamic regimes. For small intrinsic twist the instability is akin to Euler buckling, leading to solenoidal structures, while for large twist it is like the classic writhing of a twisted filament, producing plectonemic windings. This model may apply to situations in which supercoils form only, or more readily, when axial rotation of filaments is blocked. Applications to specific biological systems are proposed.     

Information and asymptotic efficiency of the case-cohort sampling design in Cox's regression model

Efficiencies of the maximum pseudolikelihood estimator and a number of related estimators for the case-cohort sampling design in the proportional hazards regression model are studied. The asymptotic information and lower bound for estimating the parametric regression parameter are calculated based on the effective score, which is obtained by determining the component of the parametric score orthogonal to the space generated by the infinite-dimensional nuisance parameter. The asymptotic distributions of the maximum pseudolikelihood and related estimators in an i.i.d. setting show that these estimators do not achieve the computed asymptotic lower bound. Simple guidelines are provided to determine in which instances such estimators are close enough to efficient for practical purposes.