Harmonic force and torque, which are caused by rotor imbalance and sensor runout, are the dominant disturbances in active magnetic bearing (AMB) systems. To eliminate the harmonic force and torque, a novel control method based on repetitive control and notch filters is proposed. Firstly, the dynamics of a four radial degrees of freedom AMB system is described, and the AMB model can be described in terms of the translational and rotational motions, respectively. Next, a closed-loop generalized notch filter is utilized to identify the synchronous displacement resulting from the rotor imbalance, and a feed-forward compensation of the synchronous force and torque related to the AMB displacement stiffness is formulated by using the identified synchronous displacement. Then, a plug-in repetitive controller is designed to track the synchronous feed-forward compensation adaptively and to suppress the harmonic vibrations due to the sensor runout. Finally, the proposed control method is verified by simulations and experiments. The control algorithm is insensitive to the parameter variations of the power amplifiers and can precisely suppress the harmonic force and torque. Its practicality stems from its low computational load.

Integrin receptors connect the extracellular matrix to the cell cytoskeleton to provide essential forces and signals. To examine the contributions of the β1 integrin cytoplasmic tail to adhesive forces, we generated cell lines expressing wild-type and tail mutant β1 integrins in β1-null fibroblasts. Deletion of β1 significantly reduced cell spreading, focal adhesion assembly, and adhesive forces, and expression of human β1 (hβ1) integrin in these cells restored adhesive functions. Cells expressing a truncated tail mutant had impaired spreading, fewer and smaller focal adhesions, reduced integrin binding to fibronectin, and lower adhesion strength and traction forces compared to hβ1-expressing cells. All these metrics were equivalent to those for β1-null cells, demonstrating that the β1 tail is essential to these adhesive functions. Expression of the constitutively-active D759A hβ1 mutant restored many of these adhesive functions in β1-null cells, although with important differences when compared to wild-type β1. Even though there were no differences in integrin-fibronectin binding and adhesion strength between hβ1- and hβ1-D759A-expressing cells, hβ1-D759A-expressing cells assembled more but smaller adhesions than hβ1-expressing cells. Importantly, hβ1-D759A-expressing cells generated lower traction forces compared to hβ1-expressing cells. These differences between hβ1- and hβ1-D759A-expressing cells suggest that regulation of integrin activation is important for fine-tuning cell spreading, focal adhesion assembly, and traction force generation.
Copyright © 2014 Elsevier Inc. All rights reserved.

It is becoming increasingly clear that the T-cell-mediated immune response is important in many diseases. In this study, we used concanavalin A (Con A) -induced hepatitis to investigate the role of CD49a in the molecular and cellular mechanism of the T-cell-mediated immune response. We found that CD49a(-/-) mice had significantly reduced levels of serum alanine aminotransferase and were protected from Con A-induced hepatitis. CD49a deficiency led to decreased production of interferon-γ (IFN-γ) and interleukin-17A (IL-17A) after Con A injection. Furthermore, we found that hepatic CD4(+) T cells and invariant natural killer T cells up-regulated CD49a expression, along with enhanced activation after Con A injection, leading to production of inflammatory cytokines by these T cells. Blockade of CD49a in vivo ameliorated Con A-induced hepatitis with reduced production of IFN-γ and IL-17A. Hence, CD49a promoted Con A-induced hepatitis through enhancing inflammatory cytokine production (IFN-γ and IL-17A) by CD4(+) T and invariant natural killer T cells. The protective effect of CD49a blockade antibody suggested a new target therapeutic molecule for intervention of T-cell-mediated liver injury.
© 2013 John Wiley & Sons Ltd.

Mechanical forces are critical for normal fetal lung development. However, the mechanisms regulating this process are not well-characterized. We hypothesized that strain-induced release of HB-EGF and TGF-α is mediated via integrin-ADAM17/TACE interactions. Employing an in vitro system to simulate mechanical forces in fetal lung development, we showed that mechanical strain of fetal epithelial cells actives TACE, releases HB-EGF and TGF-α, and promotes differentiation. In contrast, in samples incubated with the TACE inhibitor IC-3 or in cells isolated from TACE knock-out mice, mechanical strain did not release ligands or promote cell differentiation, which were both rescued after transfection of ADAM17. Cell adhesion assay and co-immunoprecipitation experiments in wild-type and TACE knock-out cells using several TACE constructs demonstrated not only that integrins α6 and β1 bind to TACE via the disintegrin domain but also that mechanical strain enhances these interactions. Furthermore, force applied to these integrin receptors by magnetic beads activated TACE and shed HB-EGF and TGF-α. The contribution of integrins α6 and β1 to differentiation of fetal epithelial cells by strain was demonstrated by blocking their binding site with specific antibodies and by culturing the cells on membranes coated with anti-integrin α6 and β1 antibodies. In conclusion, mechanical strain releases HB-EGF and TGF-α and promotes fetal type II cell differentiation via α6β1 integrin-ADAM17/TACE signaling pathway. These investigations provide novel mechanistic information on how mechanical forces promote fetal lung development and specifically differentiation of epithelial cells. This information could be also relevant to other tissues exposed to mechanical forces.

Tumor-initiating cells have been suggested to be rare in many cancers. We tested this in mouse malignant peripheral nerve sheath tumors (MPNSTs) and found that 18% of primary and 49% of passaged MPNST cells from Nf1(+/-); Ink4a/Arf(-/-) mice formed tumors upon transplantation, whereas only 1.8% to 2.6% of MPNST cells from Nf1(+/-); p53(+/-) mice did. MPNST cells of both genotypes require laminin binding to β1-integrin for clonogenic growth. Most MPNST cells from Nf1(+/-); Ink4a/Arf(-/-) mice expressed laminin, whereas most MPNST cells from Nf1(+/-); p53(+/-) mice did not. Exogenous laminin increased the percentage of MPNST cells from Nf1(+/-); p53(+/-) but not Nf1(+/-); Ink4a/Arf(-/-) mice that formed tumorigenic colonies. Tumor-forming potential is common among MPNST cells, but the assay conditions required to detect it vary with tumor genotype.
Copyright © 2012 Elsevier Inc. All rights reserved.