PDGF is a potent initiator of bone formation in a tissue engineered model of pathological ossification

Heterotopic ossification (HO) is a debilitating condition defined by the rapid formation of bone in soft tissues. What makes HO fascinating is firstly the rate at which bone is deposited, and secondly the fact that this bone is structurally and compositionally similar to that of a healthy adult. If the mechanisms governing HO are understood, they have the potential to be exploited for the development of potent osteoinductive therapies. With this aim, we utilised a tissue engineered skeletal muscle model to better understand the role of inflammation on this debilitating phenomenon. We showed myoblasts could be divided into two distinct populations, myogenic cells and undifferentiated "reserve" cells. Gene expression analysis of myogenic and osteo-regulatory markers confirmed that "reserve" cells were primed for osteogenic differentiation, but had a reduced capacity for myogenesis. Osteogenic differentiation was significantly enhanced in the presence of PDGF-BB and BMP2, and correlated with conversion to a Sca-1(+) /CD73(+) phenotype. Alizarin red staining showed that PDGF-BB promoted significantly more mineral deposition than BMP2. Finally, we showed that PDGF-induced mineralisation was blocked in the presence of the pro-inflammatory cytokines TNFα and IL1. In conclusion, the present study identified that PDGF-BB is a potent osteoinductive factor in a model of tissue engineered skeletal muscle, and that the osteogenic capacity of this protein was modulated in the presence of pro-inflammatory cytokines. These findings reveal a possible mechanism by which HO develops following trauma. Importantly, these findings have implications for the induction and control of bone formation for regenerative medicine

Identifying the cellular mechanisms leading to heterotopic ossification

Heterotopic ossification (HO) is a debilitating condition defined by the de novo development of bone within non-osseous soft tissues, and can be either hereditary or acquired. The hereditary condition, fibrodysplasia ossificans progressiva is rare but life threatening. Acquired HO is more common and results from a severe trauma that produces an environment conducive for the formation of ectopic endochondral bone. Despite continued efforts to identify the cellular and molecular events that lead to HO, the mechanisms of pathogenesis remain elusive. It has been proposed that the formation of ectopic bone requires an osteochondrogenic cell type, the presence of inductive agent(s) and a permissive local environment. To date several lineage-tracing studies have identified potential contributory populations. However, difficulties identifying cells in vivo based on the limitations of phenotypic markers, along with the absence of established in vitro HO models have made the results difficult to interpret. The purpose of this review is to critically evaluate current literature within the field in an attempt identify the cellular mechanisms required for ectopic bone formation. The major aim is to collate all current data on cell populations that have been shown to possess an osteochondrogenic potential and identify environmental conditions that may contribute to a permissive local environment. This review outlines the pathology of endochondral ossification, which is important for the development of potential HO therapies and to further our understanding of the mechanisms governing bone formation

Quantum computing with four-particle decoherence-free states in ion trap

Quantum computing gates are proposed to apply on trapped ions in decoherence-free states. As phase changes due to time evolution of components with different eigenenergies of quantum superposition are completely frozen, quantum computing based on this model would be perfect. Possible application of our scheme in future ion-trap quantum computer is discussed.Comment: 10 pages, no figures. Comments are welcom

Defining the balance between regeneration and pathological ossification in skeletal muscle

Heterotopic ossification (HO) is characterised by the formation of bone at atypical sites. This type of ectopic bone formation is most prominent in skeletal muscle, most frequently resulting as a consequence of physical trauma and associated with aberrant tissue regeneration. The condition is debilitating, reducing a patient’s range of motion and potentially causing severe pathologies resulting from nerve and vascular compression. Despite efforts to understand the pathological processes governing HO, there remains a lack of consensus regarding the micro-environmental conditions conducive to its formation, and attempting to define the balance between muscle regeneration and pathological ossification remains complex. The development of HO is thought to be related to a complex interplay between factors released both locally and systemically in response to trauma. It develops as skeletal muscle undergoes significant repair and regeneration, and is likely to result from the misdirected differentiation of endogenous or systemically derived progenitors in response to biochemical and/or environmental cues. The process can be sequentially delineated by the presence of inflammation, tissue breakdown, adipogenesis, hypoxia, neo-vasculogenesis, chondrogenesis and ossification. However, exactly how each of these stages contributes to the formation of HO is at present not well understood. Our previous review examined the cellular contribution to HO. Therefore, the principal aim of this review will be to comprehensively outline changes in the local tissue micro-environment following trauma, and identify how these changes can alter the balance between skeletal muscle regeneration and ectopic ossification. An understanding of the mechanisms governing this condition is required for the development and advancement of HO prophylaxis and treatment, and may even hold the key to unlocking novel methods for engineering hard tissues

Defining the balance between regeneration and pathological ossification in skeletal muscle

Heterotopic ossification (HO) is characterised by the formation of bone at atypical sites. This type of ectopic bone formation is most prominent in skeletal muscle, most frequently resulting as a consequence of physical trauma and associated with aberrant tissue regeneration. The condition is debilitating, reducing a patient’s range of motion and potentially causing severe pathologies resulting from nerve and vascular compression. Despite efforts to understand the pathological processes governing HO, there remains a lack of consensus regarding the micro-environmental conditions conducive to its formation, and attempting to define the balance between muscle regeneration and pathological ossification remains complex. The development of HO is thought to be related to a complex interplay between factors released both locally and systemically in response to trauma. It develops as skeletal muscle undergoes significant repair and regeneration, and is likely to result from the misdirected differentiation of endogenous or systemically derived progenitors in response to biochemical and/or environmental cues. The process can be sequentially delineated by the presence of inflammation, tissue breakdown, adipogenesis, hypoxia, neo-vasculogenesis, chondrogenesis and ossification. However, exactly how each of these stages contributes to the formation of HO is at present not well understood. Our previous review examined the cellular contribution to HO. Therefore, the principal aim of this review will be to comprehensively outline changes in the local tissue micro-environment following trauma, and identify how these changes can alter the balance between skeletal muscle regeneration and ectopic ossification. An understanding of the mechanisms governing this condition is required for the development and advancement of HO prophylaxis and treatment, and may even hold the key to unlocking novel methods for engineering hard tissues

Annexin-enriched osteoblast-derived vesicles act as an extracellular site of mineral nucleation within developing stem cell cultures

The application of extracellular vesicles (EVs) as natural delivery vehicles capable of enhancing tissue regeneration could represent an exciting new phase in medicine. We sought to define the capacity of EVs derived from mineralising osteoblasts (MO-EVs) to induce mineralisation in mesenchymal stem cell (MSC) cultures and delineate the underlying biochemical mechanisms involved. Strikingly, we show that the addition of MO-EVs to MSC cultures significantly (P < 0.05) enhanced the expression of alkaline phosphatase, as well as the rate and volume of mineralisation beyond the current gold-standard, BMP-2. Intriguingly, these effects were only observed in the presence of an exogenous phosphate source. EVs derived from non-mineralising osteoblasts (NMO-EVs) were not found to enhance mineralisation beyond the control. Comparative label-free LC-MS/MS profiling of EVs indicated that enhanced mineralisation could be attributed to the delivery of bridging collagens, primarily associated with osteoblast communication, and other non-collagenous proteins to the developing extracellular matrix. In particular, EV-associated annexin calcium channelling proteins, which form a nucleational core with the phospholipid-rich membrane and support the formation of a pre-apatitic mineral phase, which was identified using infrared spectroscopy. These findings support the role of EVs as early sites of mineral nucleation and demonstrate their value for promoting hard tissue regeneration

Decoherence of electron spin qubits in Si-based quantum computers

Direct phonon spin-lattice relaxation of an electron qubit bound by a donor impurity or quantum dot in SiGe heterostructures is investigated. The aim is to evaluate the importance of decoherence from this mechanism in several important solid-state quantum computer designs operating at low temperatures. We calculate the relaxation rate $1/T_1$ as a function of [100] uniaxial strain, temperature, magnetic field, and silicon/germanium content for Si:P bound electrons. The quantum dot potential is much smoother, leading to smaller splittings of the valley degeneracies. We have estimated these splittings in order to obtain upper bounds for the relaxation rate. In general, we find that the relaxation rate is strongly decreased by uniaxial compressive strain in a SiGe-Si-SiGe quantum well, making this strain an important positive design feature. Ge in high concentrations (particularly over 85%) increases the rate, making Si-rich materials preferable. We conclude that SiGe bound electron qubits must meet certain conditions to minimize decoherence but that spin-phonon relaxation does not rule out the solid-state implementation of error-tolerant quantum computing.Comment: 8 figures. To appear in PRB-July 2002. Revisions include: some references added/corrected, several typos fixed, a few things clarified. Nothing dramati

Physical structuring of injectable polymeric systems to controllably deliver nanosized extracellular vesicles

Extracellular vesicles (EVs) are emerging as a promising alternative approach to cell‐therapies. However, to realize the potential of these nanoparticles as new regenerative tools, healthcare materials that address the current limitations of systemic administration need to be developed. Here, two technologies for controlling the structure of alginate based microgel suspensions are used to develop sustained local release of EVs, in vitro. Microparticles formed using a shearing technique are compared to those manufactured using vibrational technology, resulting in either anisotropic sheet‐like or spheroid particles, respectively. EVs harvested from preosteoblasts are isolated using differential ultracentrifugation and successfully loaded into the two systems, while maintaining their structures. Promisingly, in addition to exhibiting even EV distribution and high stability, controlled release of vesicles from both structures is exhibited, in vitro, over the 12 days studied. Interestingly, a significantly greater number of EVs are released from the suspensions formed by shearing (69.9 ± 10.5%), compared to the spheroids (35.1 ± 7.6%). Ultimately, alterations to the hydrogel physical structures have shown to tailor nanoparticle release while simultaneously providing ideal material characteristics for clinical injection. Thus, the sustained release mechanisms achieved through manipulating the formation of such biomaterials provide a key to unlocking the therapeutic potential held within EVs

Generation of atom-photon entangled states in atomic Bose-Einstein condensate via electromagnetically induced transparency

In this paper, we present a method to generate continuous-variable-type entangled states between photons and atoms in atomic Bose-Einstein condensate (BEC). The proposed method involves an atomic BEC with three internal states, a weak quantized probe laser and a strong classical coupling laser, which form a three-level Lambda-shaped BEC system. We consider a situation where the BEC is in electromagnetically induced transparency (EIT) with the coupling laser being much stronger than the probe laser. In this case, the upper and intermediate levels are unpopulated, so that their adiabatic elimination enables an effective two-mode model involving only the atomic field at the lowest internal level and the quantized probe laser field. Atom-photon quantum entanglement is created through laser-atom and inter-atomic interactions, and two-photon detuning. We show how to generate atom-photon entangled coherent states and entangled states between photon (atom) coherent states and atom-(photon-) macroscopic quantum superposition (MQS) states, and between photon-MQS and atom-MQS states.Comment: 9 pages, 1 figur

A framework for the analysis of the potential performance of Chief Information Officers

Information Systems Function is an organisational area of major importance in the context of the competitive development of organisations. At the centre of the Information Systems Function we find the Chief Information Officer (CIO), who is the main responsible for the organisation and leadership of this function. Given the nature of the duties assigned to the CIO, her/his work directly influences the development of an organisation, so it has become important to assess her/his potential performance before s/he finds herself/him in charge of the information systems function. This article proposes the CIO Performance Square - a framework for analysing the potential performance of CIOs based on their education and experience.- (undefined