Osteocyte dysfunction promotes osteoarthritis through MMP13-dependent suppression of subchondral bone homeostasis.

Osteoarthritis (OA), long considered a primary disorder of articular cartilage, is commonly associated with subchondral bone sclerosis. However, the cellular mechanisms responsible for changes to subchondral bone in OA, and the extent to which these changes are drivers of or a secondary reaction to cartilage degeneration, remain unclear. In knee joints from human patients with end-stage OA, we found evidence of profound defects in osteocyte function. Suppression of osteocyte perilacunar/canalicular remodeling (PLR) was most severe in the medial compartment of OA subchondral bone, with lower protease expression, diminished canalicular networks, and disorganized and hypermineralized extracellular matrix. As a step toward evaluating the causality of PLR suppression in OA, we ablated the PLR enzyme MMP13 in osteocytes while leaving chondrocytic MMP13 intact, using Cre recombinase driven by the 9.6-kb DMP1 promoter. Not only did osteocytic MMP13 deficiency suppress PLR in cortical and subchondral bone, but it also compromised cartilage. Even in the absence of injury, osteocytic MMP13 deficiency was sufficient to reduce cartilage proteoglycan content, change chondrocyte production of collagen II, aggrecan, and MMP13, and increase the incidence of cartilage lesions, consistent with early OA. Thus, in humans and mice, defects in PLR coincide with cartilage defects. Osteocyte-derived MMP13 emerges as a critical regulator of cartilage homeostasis, likely via its effects on PLR. Together, these findings implicate osteocytes in bone-cartilage crosstalk in the joint and suggest a causal role for suppressed perilacunar/canalicular remodeling in osteoarthritis

Photoluminescence and photoluminescence excitation studies of lateral size effects in Zn_{1-x}Mn_xSe/ZnSe quantum disc samples of different radii

Quantum disc structures (with diameters of 200 nm and 100 nm) were prepared from a Zn_{0.72}Mn_{0.28}Se/ZnSe single quantum well structure by electron beam lithography followed by an etching procedure which combined dry and wet etching techniques. The quantum disc structures and the parent structure were studied by photoluminescence and photoluminescence excitation spectroscopy. For the light-hole excitons in the quantum well region, shifts of the energy positions are observed following fabrication of the discs, confirming that strain relaxation occurs in the pillars. The light-hole exciton lines also sharpen following disc fabrication: this is due to an interplay between strain effects (related to dislocations) and the lateral size of the discs. A further consequence of the small lateral sizes of the discs is that the intensity of the donor-bound exciton emission from the disc is found to decrease with the disc radius. These size-related effects occur before the disc radius is reduced to dimensions necessary for lateral quantum confinement to occur but will remain important when the discs are made small enough to be considered as quantum dots.Comment: LaTeX2e, 13 pages, 6 figures (epsfig

Evolutionary multi-stage financial scenario tree generation

Multi-stage financial decision optimization under uncertainty depends on a careful numerical approximation of the underlying stochastic process, which describes the future returns of the selected assets or asset categories. Various approaches towards an optimal generation of discrete-time, discrete-state approximations (represented as scenario trees) have been suggested in the literature. In this paper, a new evolutionary algorithm to create scenario trees for multi-stage financial optimization models will be presented. Numerical results and implementation details conclude the paper

The hyperon mean free paths in the relativistic mean field

The $\Lambda$- and $\Xi^-$-hyperon mean free paths in nuclei are firstly calculated in the relativistic mean field (RMF) theory. The real parts of the optical potential are derived from the RMF approach, while the imaginary parts are obtained from those of nucleons with the relations: $U^{\mathrm{IY}}_{\mathrm{S}} = \alpha_{\sigma \mathrm{Y}}\cdot U_{\mathrm{S}}^{\mathrm{IN}}$ and $U^{\mathrm{IY}}_{\mathrm{V}} = \alpha_{\omega \mathrm{Y}}\cdot U_{\mathrm{V}}^{\mathrm{IN}}$ . With the assumption, the depth of the imaginary potential for $\Xi^-$ is $W_{\Xi}\simeq-$ 3.5 MeV, and for $\Lambda$ is $W_{\Lambda}\simeq-$ 7 MeV at low incident energy. We find that, the hyperon mean free path decreases with the increase of the hyperon incident energies, from 200 MeV to 800 MeV; and in the interior of the nuclei, the mean free path is about $2\sim 3$ fm for $\Lambda$, and about $4\sim 8$ fm for $\Xi^-$, depending on the hyperon incident energy.Comment: 5 figures, 6 page

Foundations of self-consistent particle-rotor models and of self-consistent cranking models

The Kerman-Klein formulation of the equations of motion for a nuclear shell model and its associated variational principle are reviewed briefly. It is then applied to the derivation of the self-consistent particle-rotor model and of the self-consistent cranking model, for both axially symmetric and triaxial nuclei. Two derivations of the particle-rotor model are given. One of these is of a form that lends itself to an expansion of the result in powers of the ratio of single-particle angular momentum to collective angular momentum, that is essentual to reach the cranking limit. The derivation also requires a distinct, angular-momentum violating, step. The structure of the result implies the possibility of tilted-axis cranking for the axial case and full three-dimensional cranking for the triaxial one. The final equations remain number conserving. In an appendix, the Kerman-Klein method is developed in more detail, and the outlines of several algorithms for obtaining solutions of the associated non-linear formalism are suggested.Comment: 29 page

Small damping approach in Fermi-liquid theory

The validity of small damping approximation (SDA) for the quasi-classical description of the averaged properties of nuclei at high temperatures is studied within the framework of collisional kinetic theory. The isoscalar collective quadrupole vibrations in hot nuclei are considered. We show that the extension of the SDA, by accounting for the damping of the distribution function $\delta f$ in the collision integral reduces the rate of variation with temperature of the Fermi surface distortion effects. The damping of the $\delta f$ in the collision integral increases significantly the collisional width of the giant quadrupole resonance (GQR) for small enough values of the relaxation time. The temperature dependence of the eigenenergy of the GQR becomes much more weaker than in the corresponding SDA case.Comment: 11 pages, 3 figure

A Bogomol`nyi equation for intersecting domain walls

We argue that the Wess-Zumino model with quartic superpotential admits static solutions in which three domain walls intersect at a junction. We derive an energy bound for such junctions and show that configurations saturating it preserve 1/4 supersymmetry.Comment: 4 pages revtex. No figures. Revised version to appear in Physical Review Letters includes discussion of the supersymmetry algebr

On the existence of supersolid helium-4 monolayer films

Extensive Monte Carlo simulations of helium-4 monolayer films adsorbed on weak substrates have been carried out, aimed at ascertaining the possible occurrence of a quasi-two-dimensional supersolid phase. Only crystalline films not registered with underlying substrates are considered. Numerical results yield strong evidence that helium-4 will not form a supersolid film on {any} substrate strong enough to stabilize a crystalline layer. On weaker substrates, continuous growth of a liquid film takes place