Conservation of a microRNA cluster in parasitic nematodes and profiling of miRNAs in excretory-secretory products and microvesicles of Haemonchus contortus

microRNAs are small non-coding RNAs that are important regulators of gene expression in a range of animals, including nematodes. We have analysed a cluster of four miRNAs from the pathogenic nematode species Haemonchus contortus that are closely linked in the genome. We find that the cluster is conserved only in clade V parasitic nematodes and in some ascarids, but not in other clade III species nor in clade V free-living nematodes. Members of the cluster are present in parasite excretory-secretory products and can be detected in the abomasum and draining lymph nodes of infected sheep, indicating their release in vitro and in vivo. As observed for other parasitic nematodes, H. contortus adult worms release extracellular vesicles (EV). Small RNA libraries were prepared from vesicle-enriched and vesicle-depleted supernatants from both adult worms and L4 stage larvae. Comparison of the miRNA species in the different fractions indicated that specific miRNAs are packaged within vesicles, while others are more abundant in vesicle-depleted supernatant. Hierarchical clustering analysis indicated that the gut is the likely source of vesicle-associated miRNAs in the L4 stage, but not in the adult worm. These findings add to the growing body of work demonstrating that miRNAs released from parasitic helminths may play an important role in host-parasite interactions

Active damping of rotating platforms using integral force feedback

peer reviewedThis paper investigates the use of Integral Force Feedback (IFF) for the active damping of rotating mechanical systems. Guaranteed stability, typical benefit of IFF, is lost as soon as the system is rotating due to gyroscopic effects. To overcome this issue, two modifications of the classical IFF control scheme are proposed. The first consists of slightly modifying the control law while the second consists of adding springs in parallel with the force sensors. Conditions for stability and optimal parameters are derived. The results reveal that, despite their different implementations, both modified IFF control scheme have almost identical damping authority on the suspension modes

Active Damping of Rotating Platforms using Integral Force Feedback

This paper investigates the use of Integral Force Feedback (IFF) for the active damping of rotating mechanical systems. Guaranteed stability, typical benefit of IFF, is lost as soon as the system is rotating due to gyroscopic effects. To overcome this issue, two modifications of the classical IFF control scheme are proposed. The first consists of slightly modifying the control law while the second consists of adding springs in parallel with the force sensors. Conditions for stability and optimal parameters are derived. The results reveal that, despite their different implementations, both modified IFF control scheme have almost identical damping authority on suspension modes

SOST Inhibits Prostate Cancer Invasion.

Inhibitors of Wnt signaling have been shown to be involved in prostate cancer (PC) metastasis; however the role of Sclerostin (Sost) has not yet been explored. Here we show that elevated Wnt signaling derived from Sost deficient osteoblasts promotes PC invasion, while rhSOST has an inhibitory effect. In contrast, rhDKK1 promotes PC elongation and filopodia formation, morphological changes characteristic of an invasive phenotype. Furthermore, rhDKK1 was found to activate canonical Wnt signaling in PC3 cells, suggesting that SOST and DKK1 have opposing roles on Wnt signaling in this context. Gene expression analysis of PC3 cells co-cultured with OBs exhibiting varying amounts of Wnt signaling identified CRIM1 as one of the transcripts upregulated under highly invasive conditions. We found CRIM1 overexpression to also promote cell-invasion. These findings suggest that bone-derived Wnt signaling may enhance PC tropism by promoting CRIM1 expression and facilitating cancer cell invasion and adhesion to bone. We concluded that SOST and DKK1 have opposing effects on PC3 cell invasion and that bone-derived Wnt signaling positively contributes to the invasive phenotypes of PC3 cells by activating CRIM1 expression and facilitating PC-OB physical interaction. As such, we investigated the effects of high concentrations of SOST in vivo. We found that PC3-cells overexpressing SOST injected via the tail vein in NSG mice did not readily metastasize, and those injected intrafemorally had significantly reduced osteolysis, suggesting that targeting the molecular bone environment may influence bone metastatic prognosis in clinical settings

Mechatronics Approach for the Development of a Nano-Active-Stabilization-System

With the growing number of fourth generation light sources, there is an increased need of fast positioning end-stations with nanometric precision. Such systems are usually including dedicated control strategies, and many factors may limit their performances. In order to design such complex systems in a predictive way, a mechatronic design approach also known as "model based design", may be utilized. In this paper, we present how this mechatronic design approach was used for the development of a nano-hexapod for the ESRF ID31 beamline. The chosen design approach consists of using models of the mechatronic system (including sensors, actuators and control strategies) to predict its behavior. Based on this behavior and closed-loop simulations, the elements that are limiting the performances can be identified and re-designed accordingly. This allows to make adequate choices concerning the design of the nano-hexapod and the overall mechatronic architecture early in the project and save precious time and resources. Several test benches were used to validate the models and to gain confidence on the predictability of the final system's performances. Measured nano-hexapod's dynamics was shown to be in very good agreement with the models. Further tests should be done in order to confirm that the performances of the system match the predicted one. The presented development approach is foreseen to be applied more frequently to future mechatronic system design at the ESRF.NAS

Nanocomposite Scaffold for Chondrocyte Growth and Cartilage Tissue Engineering: Effects of Carbon Nanotube Surface Functionalization

The goal of this study was to assess the long-term biocompatibility of single-wall carbon nanotubes (SWNTs) for tissue engineering of articular cartilage. We hypothesized that SWNT nanocomposite scaffolds in cartilage tissue engineering can provide an improved molecular-sized substrate for stimulation of chondrocyte growth, as well as structural reinforcement of the scaffold\u27s mechanical properties. The effect of SWNT surface functionalization (-COOH or -PEG) on chondrocyte viability and biochemical matrix deposition was examined in two-dimensional cultures, in three-dimensional (3D) pellet cultures, and in a 3D nanocomposite scaffold consisting of hydrogels + SWNTs. Outcome measures included cell viability, histological and SEM evaluation, GAG biochemical content, compressive and tensile biomechanical properties, and gene expression quantification, including extracellular matrix (ECM) markers aggrecan (Agc), collagen-1 (Col1a1), collagen-2 (Col2a1), collagen-10 (Col10a1), surface adhesion proteins fibronectin (Fn), CD44 antigen (CD44), and tumor marker (Tp53). Our findings indicate that chondrocytes tolerate functionalized SWNTs well, with minimal toxicity of cells in 3D culture systems (pellet and nanocomposite constructs). Both SWNT-PEG and SWNT-COOH groups increased the GAG content in nanocomposites relative to control. The compressive biomechanical properties of cell-laden SWNT-COOH nanocomposites were significantly elevated relative to control. Increases in the tensile modulus and ultimate stress were observed, indicative of a tensile reinforcement of the nanocomposite scaffolds. Surface coating of SWNTs with -COOH also resulted in increased Col2a1 and Fn gene expression throughout the culture in nanocomposite constructs, indicative of increased chondrocyte metabolic activity. In contrast, surface coating of SWNTs with a neutral -PEG moiety had no significant effect on Col2a1 or Fn gene expression, suggesting that the charged nature of the -COOH surface functionalization may promote ECM expression in this culture system. The results of this study indicate that SWNTs exhibit a unique potential for cartilage tissue engineering, where functionalization with bioactive molecules may provide an improved substrate for stimulation of cellular growth and repair

Virtual sensor fusion for high precision control

peer reviewedHigh performance control requires high loop gain and large control bandwidth. However, the spurious resonances at the higher frequencies can limit the performance of such type of systems. This drawback can be overcome by using sensor fusion technique. In sensor fusion, two or more sensors are combined in synergy such that good performance is achieved at lower frequencies while ensuring robustness of the system at higher frequen- cies. This paper presents a new technique, termed as ‘‘virtual sensor fusion”, in which only one of the sensors is physically installed on the system while the other sensor is simulated virtually. The virtual sensor is selected based on desired high frequency response. The effectiveness of the proposed technique is demonstrated numerically for a case of active seismic isolation. A robustness analysis of virtual sensor fusion is also carried out in order to study its stability in the presence of spurious resonances. Finally, the technique is exper- imentally verified on active isolation of pendulum system from ground motion. The results obtained demonstrate good isolation performance at lower frequencies and robustness to plant uncertainties (spurious resonances) at higher frequencies. This technique can be effectively used for high precision control of sensitive instruments

On magnetorheologic elastomers for vibration isolation, damping, and stress reduction in mass-varying structures

This article considers two devices based on a magnetorheological elastomer (MRE): an MRE isolator under a frequency-varying harmonic excitation and a MRE Dynamic Vibration Absorber (DVA) mounted on a frequency-varying structure under a random excitation. In the first case, it is shown that the commandability of the elastomer improves the reduction of the RMS value of the body displacement by 10\%. In the second case, it is shown on a simple example that a MRE DVA, while not optimal, can reduce the stress in the structure about 50 better than a classical DVA when the mass of the structure changes 35\%. This makes them suitable to avoid high stress in mass-varying structures, and delay some damage mechanisms like the emergence of cracks and fatigue. © 2010 The Author(s)