Methionine down-regulates TLR4/MyD88/NF-kappa B signalling in osteoclast precursors to reduce bone loss during osteoporosis

Background and PurposeStudies have demonstrated that a moderate intake of amino acids is associated with development of bone health. Methionine, a sulphur-containing essential amino acid, has been largely implicated for improving cartilage formation, however its physiological significance on bone integrity and functionality have not been elucidated. We investigated whether methionine can prevent osteoporotic bone loss. Experimental ApproachThe anti-resorptive effect of methionine, (250mgkg(-1) body wt administered in drinking water for 10 weeks), was evaluated in ovariectomized (OVX) rats by monitoring changes in bone turnover, formation of osteoclasts from blood-derived mononuclear cells and changes in the synthesis of pro-osteoclastogenic cytokines. Key resultsMethionine improved bone density and significantly decreased the degree of osteoclast development from blood mononuclear cells in OVX rats, as indicated by decreased production of osteoclast markers tartarate resistant acid phosphatase b (TRAP5b) and MIP-1. siRNA-mediated knockdown of myeloid differentiation primary response 88 MyD88], a signalling molecule in the toll-like receptor (TLR) signalling cascade, abolished the synthesis of both TRAP5b and MIP-1 in developing osteoclasts. Methionine supplementation disrupted osteoclast development by inhibiting TLR-4/MyD88/NF-B pathway. Conclusions and ImplicationsTLR-4/MyD88/NF-B signalling pathway is integral for osteoclast development and this is down-regulated in osteoporotic system on methionine treatment. Methionine treatment could be beneficial for the treatment of postmenopausal osteoporosis.

Multifunctional Properties of Multistage Spark Plasma Sintered HA-BaTiO3-Based Piezobiocomposites for Bone Replacement Applications

This work reports the processing-microstructure-property correlation of novel HA-BaTiO3-based piezobiocomposites, which demonstrated the bone-mimicking functional properties. A series of composites of hydroxyapatite (HA) with varying amounts of piezoelectric BaTiO3 (BT) were optimally processed using uniquely designed multistage spark plasma sintering (SPS) route. Transmission electron microscopy imaging during in situ heating provides complementary information on the real-time observation of sintering behavior. Ultrafine grains (0.50m) of HA and BT phases were predominantly retained in the SPSed samples. The experimental results revealed that dielectric constant, AC conductivity, piezoelectric strain coefficient, compressive strength, and modulus values of HA-40wt% BT closely resembles with that of the natural bone. The addition of 40wt% BT enhances the long-crack fracture toughness, compressive strength, and modulus by 132%, 200%, and 165%, respectively, with respect to HA. The above-mentioned exceptional combination of functional properties potentially establishes HA-40wt% BT piezocomposite as a new-generation composite for orthopedic implant applications.

Minimum switching loss pulse width modulation for reduced power conversion loss in reactive power compensators

Advanced bus-clamping switching sequences, which employ an active vector twice in a subcycle, are used to reduce line current distortion and switching loss in a space vector modulated voltage source converter. This study evaluates minimum switching loss pulse width modulation (MSLPWM), which is a combination of such sequences, for static reactive power compensator (STATCOM) application. It is shown that MSLPWM results in a significant reduction in device loss over conventional space vector pulse width modulation. Experimental verification is presented at different power levels of up to 150 kVA.

Ontology analysis of global gene expression differences of human bone marrow stromal cells cultured on 3D scaffolds or 2D films

Differences in gene expression of human bone marrow stromal cells (hBMSCs) during culture in three-dimensional (3D) nanofiber scaffolds or on two-dimensional (2D) films were investigated via pathway analysis of microarray mRNA expression profiles. Previous work has shown that hBMSC culture in nanofiber scaffolds can induce osteogenic differentiation in the absence of osteogenic supplements (OS). Analysis using ontology databases revealed that nanofibers and OS regulated similar pathways and that both were enriched for TGF-beta and cell-adhesion/ECM-receptor pathways. The most notable difference between the two was that nanofibers had stronger enrichment for cell-adhesion/ECM-receptor pathways. Comparison of nanofibers scaffolds with flat films yielded stronger differences in gene expression than comparison of nanofibers made from different polymers, suggesting that substrate structure had stronger effects on cell function than substrate polymer composition. These results demonstrate that physical (nanofibers) and biochemical (OS) signals regulate similar ontological pathways, suggesting that these cues use similar molecular mechanisms to control hBMSC differentiation. Published by Elsevier Ltd.

Perovskite ceramic nanoparticles in polymer composites for augmenting bone tissue regeneration

There is increasing interest in the use of nanoparticles as fillers in polymer matrices to develop biomaterials which mimic the mechanical, chemical and electrical properties of bone tissue for orthopaedic applications. The objective of this study was to prepare poly(epsilon-caprolactone) (PCL) nanocomposites incorporating three different perovskite ceramic nanoparticles, namely, calcium titanate (CT), strontium titanate (ST) and barium titanate (BT). The tensile strength and modulus of the composites increased with the addition of nanoparticles. Scanning electron microscopy indicated that dispersion of the nanoparticles scaled with the density of the ceramics, which in turn played an important role in determining the enhancement in mechanical properties of the composite. Dielectric spectroscopy revealed improved permittivity and reduced losses in the composites when compared to neat PCL. Nanofibrous scaffolds were fabricated via electrospinning. Induction coupled plasma-optical emission spectroscopy indicated the release of small quantities of Ca+2, Sr+2, Ba+2 ions from the scaffolds. Piezo-force microscopy revealed that BT nanoparticles imparted piezoelectric properties to the scaffolds. In vitro studies revealed that all composites support osteoblast proliferation. Expression of osteogenic genes was enhanced on the nanocomposites in the following order: PCL/CT>PCL/ST>PCL/BT>PCL. This study demonstrates that the use of perovskite nanoparticles could be a promising technique to engineer better polymeric scaffolds for bone tissue engineering.

Analytical evaluation of harmonic distortion factor corresponding to generalised advanced bus-clamping pulse width modulation

A few advanced bus-clamping pulse width modulation (ABCPWM) methods have been proposed recently for a three-phase inverter. With these methods, each phase is clamped, switched at nominal frequency, and switched at twice the nominal frequency in different regions of the fundamental cycle. This study proposes a generalised ABCPWM scheme, encompassing the few ABCPWM schemes that have been proposed and many more ABCPWM schemes that have not been reported yet. Furthermore, analytical closed-form expression is derived for the harmonic distortion factor corresponding to the generalised ABCPWM. This factor is independent of load parameters. The analytical expression derived here brings out the dependence of root-mean-square (RMS) current ripple on modulation index, and can be used to evaluate the RMS current ripple corresponding to any ABCPWM scheme. The analytical closed-form expression is validated experimentally in terms of measured weighted total harmonic distortion (THD) in line voltage (V-WTHD) and measured THD in line current (I-THD) on a 6 kW induction motor drive.

Hydroxyapatite-titanium bulk composites for bone tissue engineering applications

The research work on bulk hydroxyapatite (HA)-based composites are driven by the need to develop biomaterials with better mechanical properties without compromising its bioactivity and biocompatibility properties. Despite several years of research, the mechanical properties of the HA-based composites still need to be enhanced to match the properties of natural cortical bone. In this regard, the scope of this review on the HA-based bulk biomaterials is limited to the processing and the mechanical as well as biocompatibility properties for bone tissue engineering applications of a model system that is hydroxyapatite-titanium (HA-Ti) bulk composites. It will be discussed in this review how HA-Ti based bulk composites can be processed to have better fracture toughness and strength without compromising biocompatibility. The advantages of the functionally gradient materials to integrate the mechanical and biocompatibility properties is a promising approach in hard tissue engineering and has been emphasized here in reference to the limited literature reports. On the biomaterials fabrication aspect, the recent results are discussed to demonstrate that advanced manufacturing techniques, like spark plasma sintering can be adopted as a processing route to restrict the sintering reactions, while enhancing the mechanical properties. Various toughening mechanisms related to careful tailoring of microstructure are discussed. The in vitro cytocompatibilty, cell fate processes as well as in vivo biocompatibility results are also reviewed and the use of flow cytometry to quantify in vitro cell fate processes is being emphasized. (C) 2014 Wiley Periodicals, Inc.

Optimal Pulse Width Modulation of Voltage-Source Inverter fed Motor Drives with Relaxation of Quarter Wave Symmetry Condition

Optimal switching angles for minimization of total harmonic distortion of line current (I-THD) in a voltage source inverter are determined traditionally by imposing half-wave symmetry (HWS) and quarter-wave symmetry (QWS) conditions on the pulse width modulated waveform. This paper investigates optimal switching angles with QWS relaxed. Relaxing QWS expands the solution space and presents the possibility of improved solutions. The optimal solutions without QWS are shown here to outperform the optimal solutions with QWS over a range of modulation index (M) between 0.82 and 0.94 for a switching frequency to fundamental frequency ratio of 5. Theoretical and experimental results are presented on a 2.3kW induction motor drive.

Low-frequency dc bus ripple cancellation in single phase pulse-width modulation inverters

This study presents a topology for a single-phase pulse-width modulation (PWM) converter which achieves low-frequency ripple reduction in the dc bus even when there are grid frequency variations. A hybrid filter is introduced to absorb the low-frequency current ripple in the dc bus. The control strategy for the proposed filter does not require the measurement of the dc bus ripple current. The design criteria for selecting the filter components are also presented in this study. The effectiveness of the proposed circuit has been tested and validated experimentally. A smaller dc-link capacitor is sufficient to keep the low-frequency bus ripple to an acceptable range in the proposed topology.

Adaptive Pulse Width Control and Sampling for Low Power Pulse Oximetry

Remote sensing of physiological parameters could be a cost effective approach to improving health care, and low-power sensors are essential for remote sensing because these sensors are often energy constrained. This paper presents a power optimized photoplethysmographic sensor interface to sense arterial oxygen saturation, a technique to dynamically trade off SNR for power during sensor operation, and a simple algorithm to choose when to acquire samples in photoplethysmography. A prototype of the proposed pulse oximeter built using commercial-off-the-shelf (COTS) components is tested on 10 adults. The dynamic adaptation techniques described reduce power consumption considerably compared to our reference implementation, and our approach is competitive to state-of-the-art implementations. The techniques presented in this paper may be applied to low-power sensor interface designs where acquiring samples is expensive in terms of power as epitomized by pulse oximetry.

Investigations on Optimal Pulse-Width Modulation to Minimize Total Harmonic Distortion in the Line Current

PWM waveforms with positive voltage transition at the positive zero crossing of the fundamental voltage (type-A) are generally considered for PWM waveform with even number of switching angles per quarter whereas, waveforms with negative voltage transition at the positive zero crossing (type-B) are considered for odd number of switching angles per quarter. Optimal PWM, for minimization of total harmonic distortion of line to line (VWTHD), is generally solved with the aforementioned criteria. This paper establishes that a combination of both types of waveforms gives better performance than any individual type in terms of minimum VWTHD for complete range of modulation index (M). Optimal PWM for minimum VWTHD is solved for PWM waveforms with pulse numbers (P) of 5 and 7. Both type-A and type-B waveforms are found to be better in different ranges of M. The theoretical findings are confirmed through simulation and experimental results on a 3.7 kW squirrel cage induction motor in an open-loop V/f drive. Further, the optimal PWM is analysed from a space vector point of view.

A new approach to depict bone surfaces in finger imaging using photoacoustic tomography

Imaging the vasculature close around the finger joints is of interest in the field of rheumatology. Locally increased vasculature in the synovial membrane of these joints can be a marker for rheumatoid arthritis. In previous work we showed that part of the photoacoustically induced ultrasound from the epidermis reflects on the bone surface within the finger. These reflected signals could be wrongly interpreted as new photoacoustic sources. In this work we show that a conventional ultrasound reconstruction algorithm, that considers the skin as a collection of ultrasound transmitters and the PA tomography probe as the detector array, can be used to delineate bone surfaces of a finger. This can in the future assist in the localization of the joint gaps. This can provide us with a landmark to localize the region of the inflamed synovial membrane. We test the approach on finger mimicking phantoms.

A Method for Delineation of Bone Surfaces in Photoacoustic Computed Tomography of the Finger

Photoacoustic (PA) imaging of interphalangeal peripheral joints is of interest in the context of using the synovial membrane as a surrogate marker of rheumatoid arthritis. Previous work has shown that ultrasound (US) produced by absorption of light at the epidermis reflects on the bone surfaces within the finger. When the reflected signals are backprojected in the region of interest, artifacts are produced, confounding interpretation of the images. In this work, we present an approach where the PA signals known to originate from the epidermis are treated as virtual US transmitters, and a separate reconstruction is performed as in US reflection imaging. This allows us to identify the bone surfaces. Furthermore, the identification of the joint space is important as this provides a landmark to localize a region-of-interest in seeking the inflamed synovial membrane. The ability to delineate bone surfaces allows us to identify not only the artifacts but also the interphalangeal joint space without recourse to new US hardware or a new measurement. We test the approach on phantoms and on a healthy human finger.

Conceptual design of three-dimensional scaffolds of powder-based materials for bone tissue engineering applications

Purpose - The purpose of this paper is to investigate the possibility to construct tissue-engineered bone repair scaffolds with pore size distributions using rapid prototyping techniques. Design/methodology/approach - The fabrication of porous scaffolds with complex porous architectures represents a major challenge in tissue engineering and the design aspects to mimic complex pore shape as well as spatial distribution of pore sizes of natural hard tissue remain unexplored. In this context, this work aims to evaluate the three-dimensional printing process to study its potential for scaffold fabrication as well as some innovative design of homogeneously porous or gradient porous scaffolds is described and such design has wider implication in the field of bone tissue engineering. Findings - The present work discusses biomedically relevant various design strategies with spatial/radial gradient in pore sizes as well as with different pore sizes and with different pore geometries. Originality/value - One of the important implications of the proposed novel design scheme would be the development of porous bioactive/biodegradable composites with gradient pore size, porosity, composition and with spatially distributed biochemical stimuli so that stem cells loaded into scaffolds would develop into complex tissues such as those at the bone-cartilage interface.