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.     

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.     

Self-diffusion in a non-uniform one dimensional system of point particles with collisions

Summary We generalize the results of Spitzer, Jepsen and others [1–4] on the motion of a tagged particle in a uniform one dimensional system of point particles undergoing elastic collisions to the case where there is also an external potential U(x). When U(x) is periodic or random (bounded and statistically translation invariant) then the scaled trajectory of a tagged particle converges, as A , to a Brownian motion W _D (t) with diffusion constant , where is the average density, is the mean absolute velocity and ^–1 the temperature of the system. When U(x) is itself changing on a macroscopic scale, i.e. , then the limiting process is a spatially dependent diffusion. The stochastic differential equation describing this process is now non-linear, and is particularly simple in Stratonovich form. This lends weight to the belief that heuristics are best done in that form.Dedicated to Frank Spitzer on the occasion of his 60th birthdayWork supported in part by NSF Grants No. PHY 8201708 and No. DMR 81-14726Heisenberg-fellowAlso Department of Physics     

Forward reactions and the exploration of particle dynamics

Since the polarization structure of reactions in the collinear directions is greatly simplified, since reactions at very high energies tend to be predominantly close to collinear, and since the one-particle exchange mechanisms are more pronounced in the forward direction, tests of one-particle-exchange (OPE) mechanisms are formulated for collinear reactions. The number of amplitudes are derived for a reaction with arbitrary spins, and examples for the practically occurring cases are given. The results are applied to the reaction 1/2+1/21+1 and in particular ton+pd+ (or to its inverse). A detailed procedure is outlined for a step-by-step testing of the various OPE processes in this reaction through a series of polarization experiments. In particular, the tests can separate out theJ=0 andJ=1/2 OPE processes.     

On the Nature of the 7-Norbornadienyllithiums. Preliminary Communication

Lithium reductions of 7-chloronorbornadiene and of bis(7-norbornadienyl)mercury both provide (C₇H₇)₂Li₂ ( 5a ). This product is accompanied by C₇H₇Li₂Cl ( 5c ) in the first case, and by C₇H₇Li ( 5b ) in the second. The theoretically anticipated properties of all three organolithiums are apparent in the consistent C_s symmetry of their hydrocarbon ligands, their protolytic destruction by 12-crown-4, and their significant J(C(7), Li) ( 5a , 7.6; 5b , 16.0; 5c 8.9 Hz).