Impact of extracellular matrix derived from osteoarthritis subchondral bone osteoblasts on osteocytes : role of integrinβ1 and focal adhesion kinase signaling cues

INTRODUCTION: Our recent study indicated that subchondral bone pathogenesis in osteoarthritis (OA) is associated with osteocyte morphology and phenotypic abnormalities. However, the mechanism underlying this abnormality needs to be identified. In this study we investigated the effect of extracellular matrix (ECM) produced from normal and OA bone on osteocytic cells function. METHODS: De-cellularized matrices, resembling the bone provisional ECM secreted from primary human subchondral bone osteoblasts (SBOs) of normal and OA patients were used as a model to study the effect on osteocytic cells. Osteocytic cells (MLOY4 osteocyte cell line) cultured on normal and OA derived ECMs were analyzed by confocal microscopy, scanning electron microscopy (SEM), cell attachment assays, zymography, apoptosis assays, qRT-PCR and western blotting. The role of integrinβ1 and focal adhesion kinase (FAK) signaling pathways during these interactions were monitored using appropriate blocking antibodies. RESULTS: The ECM produced by OA SBOs contained less mineral content, showed altered organization of matrix proteins and matrix structure compared with the matrices produced by normal SBOs. Culture of osteocytic cells on these defective OA ECM resulted in a decrease of integrinβ1 expression and the de-activation of FAK cell signaling pathway, which subsequently affected the initial osteocytic cell's attachment and functions including morphological abnormalities of cytoskeletal structures, focal adhesions, increased apoptosis, altered osteocyte specific gene expression and increased Matrix metalloproteinases (MMP-2) and -9 expression. CONCLUSION: This study provides new insights in understanding how altered OA bone matrix can lead to the abnormal osteocyte phenotypic changes, which is typical in OA pathogenesis.

Applying the Haddon Matrix in the context of work-related road safety

The Haddon Matrix was developed in the 1960s road safety arena, and has since been used in many public health settings. The literature and two specific case studies are reviewed to describe the background to the Haddon Matrix, identify how it has been critiqued and developed over time and practical applications in the work-related road safety context. Haddon’s original focus on the road, vehicle and driver has been extended and applied to include organisational safety culture, journey management and wider issues in society that affect occupational drivers and the communities in which they work. The paper shows that the Haddon Matrix has been applied in many projects and contexts. Practical work-related road safety applications include providing a comprehensive systems-based safety management framework to inform strategy. It has also been used to structure the review or gap analysis of current programs and processes, identify and develop prevention measures and as a tool for effective post-event investigations.

Density-matrix renormalization-group studies of the spin-1/2 Heisenberg system with dimerization and frustration

Using the density-matrix renormalization-group technique, we study the ground-state phase diagram and other low-energy properties of an isotropic antiferromagnetic spin-1/2 chain with both dimerization and frustration, i.e., an alternation delta of the nearest-neighbor exchanges and a next-nearest-neighbor exchange J(2). For delta = 0, the system is gapless for J(2) < J(2c) and has a gap for J(2) > J(2c) where J(2c) is about 0.241. For J(2) = J(2c) the gap above the ground state grows as delta to the power 0.667 +/- 0.001. In the J(2)-delta plane, there is a disorder line 2J(2) + delta = 1. To the left of this line, the peak in the static structure factor S(q) is at q(max) = pi (Neel phase), while to the right of the line, q(max) decreases from pi to pi/2 as J(2) is increased to large values (spiral phase). For delta = 1, the system is equivalent to two coupled chains as on a ladder and it is gapped for all values of the interchain coupling.

Nonlocal continuum mechanics based ultrasonic flexural wave dispersion characteristics of a monolayer graphene embedded in polymer matrix

Wave propagation in graphene sheet embedded in elastic medium (polymer matrix) has been a topic of great interest in nanomechanics of graphene sheets, where the equivalent continuum models are widely used. In this manuscript, we examined this issue by incorporating the nonlocal theory into the classical plate model. The influence of the nonlocal scale effects has been investigated in detail. The results are qualitatively different from those obtained based on the local/classical plate theory and thus, are important for the development of monolayer graphene-based nanodevices. In the present work, the graphene sheet is modeled as an isotropic plate of one-atom thick. The chemical bonds are assumed to be formed between the graphene sheet and the elastic medium. The polymer matrix is described by a Pasternak foundation model, which accounts for both normal pressure and the transverse shear deformation of the surrounding elastic medium. When the shear effects are neglected, the model reduces to Winkler foundation model. The normal pressure or Winkler elastic foundation parameter is approximated as a series of closely spaced, mutually independent, vertical linear elastic springs where the foundation modulus is assumed equivalent to stiffness of the springs. For this model, the nonlocal governing differential equations of motion are derived from the minimization of the total potential energy of the entire system. An ultrasonic type of flexural wave propagation model is also derived and the results of the wave dispersion analysis are shown for both local and nonlocal elasticity calculations. From this analysis we show that the elastic matrix highly affects the flexural wave mode and it rapidly increases the frequency band gap of flexural mode. The flexural wavenumbers obtained from nonlocal elasticity calculations are higher than the local elasticity calculations. The corresponding wave group speeds are smaller in nonlocal calculation as compared to local elasticity calculation. The effect of y-directional wavenumber (eta(q)) on the spectrum and dispersion relations of the graphene embedded in polymer matrix is also observed. We also show that the cut-off frequencies of flexural wave mode depends not only on the y-direction wavenumber but also on nonlocal scaling parameter (e(0)a). The effect of eta(q) and e(0)a on the cut-off frequency variation is also captured for the cases of with and without elastic matrix effect. For a given nanostructure, nonlocal small scale coefficient can be obtained by matching the results from molecular dynamics (MD) simulations and the nonlocal elasticity calculations. At that value of the nonlocal scale coefficient, the waves will propagate in the nanostructure at that cut-off frequency. In the present paper, different values of e(0)a are used. One can get the exact e(0)a for a given graphene sheet by matching the MD simulation results of graphene with the results presented in this article. (c) 2012 Elsevier Ltd. All rights reserved.

On the distribution of the signs of the conjugates of the cyclotomic units in the maximal real subfield of the qth cyclotomic field, q A prime

Let F = Ǫ(ζ + ζ ^–1) be the maximal real subfield of the cyclotomic field Ǫ(ζ) where ζ is a primitive qth root of unity and q is an odd rational prime. The numbers u₁=-1, u_k=(ζ^k-ζ^-k)/(ζ-ζ^-1), k=2,…,p, p=(q-1)/2, are units in F and are called the cyclotomic units. In this thesis the sign distribution of the conjugates in F of the cyclotomic units is studied.

Let G(F/Ǫ) denote the Galoi's group of F over Ǫ, and let V denote the units in F. For each σϵ G(F/Ǫ) and μϵV define a mapping sgn_σ: V→GF(2) by sgn_σ(μ) = 1 iff σ(μ) ˂ 0 and sgn_σ(μ) = 0 iff σ(μ) ˃ 0. Let {σ₁, ... , σ_p} be a fixed ordering of G(F/Ǫ). The matrix M_q=(sgn_σj(v_i) ) , i, j = 1, ... , p is called the matrix of cyclotomic signatures. The rank of this matrix determines the sign distribution of the conjugates of the cyclotomic units. The matrix of cyclotomic signatures is associated with an ideal in the ring GF(2) [x] / (x^p+ 1) in such a way that the rank of the matrix equals the GF(2)-dimension of the ideal. It is shown that if p = (q-1)/ 2 is a prime and if 2 is a primitive root mod p, then M_q is non-singular. Also let p be arbitrary, let ℓ be a primitive root mod q and let L = {i | 0 ≤ i ≤ p-1, the least positive residue of defined by ℓⁱ mod q is greater than p}. Let H_q(x) ϵ GF(2)[x] be defined by H_q(x) = g. c. d. ((Σ xⁱ/I ϵ L) (x+1) + 1, x^p + 1). It is shown that the rank of M_q equals the difference p - degree H_q(x).

Further results are obtained by using the reciprocity theorem of class field theory. The reciprocity maps for a certain abelian extension of F and for the infinite primes in F are associated with the signs of conjugates. The product formula for the reciprocity maps is used to associate the signs of conjugates with the reciprocity maps at the primes which lie above (2). The case when (2) is a prime in F is studied in detail. Let T denote the group of totally positive units in F. Let U be the group generated by the cyclotomic units. Assume that (2) is a prime in F and that p is odd. Let F₍₂₎ denote the completion of F at (2) and let V₍₂₎ denote the units in F₍₂₎. The following statements are shown to be equivalent. 1) The matrix of cyclotomic signatures is non-singular. 2) U∩T = U². 3) U∩F²₍₂₎ = U². 4) V₍₂₎/ V₍₂₎² = ˂v₁ V₍₂₎²˃ ʘ…ʘ˂v_p V₍₂₎²˃ ʘ ˂3V₍₂₎²˃.

The rank of M_q was computed for 5≤q≤929 and the results appear in tables. On the basis of these results and additional calculations the following conjecture is made: If q and p = (q -1)/ 2 are both primes, then M_q is non-singular.

Formation of ferromagnetic clusters in GaAs matrix and GaAs/AlGaAs superlattice through Mn ion implantation at two different temperatures

Different submicron ferromagnets are fabricated into GaAs and GaAs/AlGaAs superlattice through ion implantation at two different temperatures followed by thermal annealing. The structural and magnetic properties of the granular film are studied by an atomic force microscope, X-ray diffraction and alternating gradient magnetometer. By analyzing the saturation magnetization M-s, remanence M-r, coercivity H-c and remanence ratio S-q, it is confirmed that both MnGa and MnAs clusters are formed in the 350degreesC-implanted samples whereas only MnAs clusters are formed in the room-temperature implanted samples. (C) 2004 Elsevier B.V. All rights reserved.