Key Points• Rigidity of an opsonized red cell that contacts a macrophage is found to hyperactivate myosin-II and thus overpowers CD47's self-signaling. • Red cell shape modulates CD47's signaling of self and highlights biophysical contributions to phagocytosis.A macrophage engulfs another cell or foreign particle in an adhesive process that often activates myosin-II, unless the macrophage also engages "marker of self" CD47 that inhibits myosin. For many cell types, adhesion-induced activation of myosin-II is maximized by adhesion to a rigid rather than a flexible substrate. Here we demonstrate that rigidity of a phagocytosed cell also hyperactivates myosin-II, which locally overwhelms selfsignaling at a phagocytic synapse. Cell stiffness is one among many factors including shape that changes in erythropoiesis, in senescence and in diseases ranging from inherited anemias and malaria to cancer. Controlled stiffening of normal human red blood cells (RBCs) in different shapes does not compromise CD47's interaction with the macrophage self-recognition receptor signal regulatory protein alpha (SIRPA). Uptake of antibodyopsonized RBCs is always fastest with rigid RBC discocytes, which also show that maximal active myosin-II at the synapse can dominate self-signaling by CD47. Rigid but rounded RBC stomatocytes signal self better than rigid RBC discocytes, highlighting the effects of shape on CD47 inhibition. Physical properties of phagocytic targets thus regulate self signaling, as is relevant to erythropoiesis, to clearance of rigid RBCs after blood storage, clearance of rigid pathological cells such as thalassemic or sickle cells, and even to interactions of soft/stiff cancer cells with macrophages. (Blood. 2015;125(3):542-552)

Scarring is a long-lasting problem in higher animals, and reductionist approaches could aid in developing treatments. Here, we show that co-polymerization of collagen-I with polyacrylamide produces minimal matrix models of scars (MMMS), in which fractal-fiber bundles segregate heterogeneously to the hydrogel subsurface. Matrix stiffens locally – as in scars – while allowing separate control over adhesive-ligand density. The MMMS elicits scar-like phenotypes from mesenchymal stem cells (MSCs): cells spread and polarize quickly, increasing nucleoskeletal lamin-A yet expressing the ‘scar marker’, smooth muscle actin (SMA) more slowly. Surprisingly, expression responses to MMMS exhibit less cell-to-cell noise than homogeneously stiff gels. Such differences from bulk-average responses arise because a strong SMA repressor, NKX2.5, slowly exits the nucleus on rigid matrices. NKX2.5 overexpression overrides rigid phenotypes, inhibiting SMA and cell spreading, while cytoplasm-localized NKX2.5 mutants degrade in well-spread cells. MSCs thus form a ‘mechanical memory’ of rigidity by progressively suppressing NKX2.5, thereby elevating SMA in a scar-like state.

Osteoarthritis (OA) is a common cause of pain and disability and is often associated with the degeneration of articular cartilage. Lesions to the articular surface, which are thought to progress to OA, have the potential to be repaired using tissue engineering strategies; however, it remains challenging to instruct cell differentiation within a scaffold to produce tissue with appropriate structural, chemical and mechanical properties. We aimed to address this by driving progenitor cells to adopt a chondrogenic phenotype through the tailoring of scaffold composition and physical properties. Monomeric type-I and type-II collagen scaffolds, which avoid potential immunogenicity associated with fibrillar collagens, were fabricated with and without chondroitin sulfate (CS) and their ability to stimulate the chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells was assessed. Immunohistochemical analyses showed that cells produced abundant collagen type-II on type-II scaffolds and collagen type-I on type-I scaffolds. Gene expression analyses indicated that the addition of CS – which was released from scaffolds quickly – significantly upregulated expression of type II collagen, compared to type-I and pure type-II scaffolds. We conclude that collagen type-II and CS can be used to promote a more chondrogenic phenotype in the absence of growth factors, potentially providing an eventual therapy to prevent OA.

The rare earth metals have been identified by the European Union and the United States as being at greatest supply risk of all the materials for clean energy technologies. Of particular concern are neodymium and dysprosium, both of which are employed in neodymium-iron-boron based magnets. Recycling of magnets based on these materials and contained within obsolete electronic equipment, could provide an additional and secure supply. In the present work, hydrogen has been employed as a processing agent to decrepitate sintered neodymium-iron-boron based magnets contained within hard disk drives into a demagnetised, hydrogenated powder. This powder was then extracted mechanically from the devices with an extraction efficiency of 90 ±5 % and processed further using a combination of sieves and ball bearings, to produce a powder containing <330 parts per million of nickel contamination. It is then possible for the extracted powder to be re-processed in a number of ways, namely, directly by blending and re-sintering to form fully dense magnets, by Hydrogenation, Disproportionation, Desorption, Recombination processing to produce an anisotropic coercive powder suitable for bonded magnets, by re-melting; or by chemical extraction of the rare earth elements from the alloy. For example, it was shown that, by the re-sintering route, it was possible to recover >90% of the magnetic properties of the starting material with significantly less energy than that employed in primary magnet production. The particular route used will depend upon the magnetic properties required, the level of contamination of the extracted material and the compositional variation of the feedstock. The various possibilities have been summarised in a flow diagram. INTRODUCTION:Rare earth magnets based upon neodymium-iron-boron (NdFeB) are employed in many clean energy and high tech applications, including hard disk drives (HDDs), motors in electric vehicles and electric generators in wind turbines. In recent years, the supply of rare earth metals has come under considerable strain. China currently provides over 85% of rare earth metals to the world market but, in recent years, began to impose export quotas. This resulted in dramatic price fluctuations for the rare earth metals, in particular, neodymium, praseodymium and dysprosium, the rare earth constituents of NdFeB magnets. According to the EU Critical Materials list (2010, 2014) and the US Department of Energy's energy critical element list (2010), the rare earth metals are classified as at greatest risk of supply shortages compared to those of all other materials used for clean energy technologies. There are several ways in which these material shortages could be addressed including: (a) opening rare earth mines in countries outside of China, (b) using alternative technologies which do not contain rare earths (c) reducing the amount of rare earth metal used in particular

The bio-corrosion behaviour of Mg-3Zn-0.3Ca (wt.%) alloy in simulated body fluid (SBF) at 37°C has been investigated using immersion testing and electrochemical measurements. Heat treatment has been used to alter the grain size and secondary phase volume fraction; the effects of these on the bio-corrosion behaviour of the alloy were then determined. The as-cast sample has the highest bio-corrosion rate due to micro-galvanic corrosion between the eutectic product (Mg+Ca2Mg6Zn3) and the surrounding magnesium matrix. The bio-corrosion resistance of the alloy can be improved by heat treatment. The volume fraction of secondary phases and grain size are both key factors controlling the bio-corrosion rate of the alloy. The bio-corrosion rate increases with volume fraction of secondary phase. When this is lower than 0.8%, the dependence of bio-corrosion rate becomes noticeable: large grains corrode more quickly.