Cellular settings mediating Src Substrate switching between Focal Adhesion Kinase Tyrosine 861 and CUB-domain-containing protein 1 (CDCP1) Tyrosine 734

Reciprocal interactions between Src family kinases (SFKs) and focal adhesion kinase (FAK) are critical during changes in cell attachment. Recently it has been recognized that another SFK substrate, CUB-domain-containing protein 1 (CDCP1), is differentially phosphorylated during these events. However, the molecular processes underlying SFK-mediated phosphorylation of CDCP1 are poorly understood. Here we identify a novel mechanism in which FAK tyrosine 861 and CDCP1-Tyr-734 compete as SFK substrates and demonstrate cellular settings in which SFKs switch between these sites. Our results show that stable CDCP1 expression induces robust SFK-mediated phosphorylation of CDCP1-Tyr-734 with concomitant loss of p-FAK-Tyr-861 in adherent HeLa cells. SFK substrate switching in these cells is dependent on the level of expression of CDCP1 and is also dependent on CDCP1-Tyr-734 but is independent of CDCP1-Tyr-743 and -Tyr-762. In HeLa CDCP1 cells, engagement of SFKs with CDCP1 is accompanied by an increase in phosphorylation of Src-Tyr-416 and a change in cell morphology to a fibroblastic appearance dependent on CDCP1-Tyr-734. SFK switching between FAK-Tyr-861 and CDCP1-Tyr-734 also occurs during changes in adhesion of colorectal cancer cell lines endogenously expressing these two proteins. Consistently, increased p-FAK-Tyr-861 levels and a more epithelial morphology are seen in colon cancer SW480 cells silenced for CDCP1. Unlike protein kinase Cδ, FAK does not appear to form a trimeric complex with Src and CDCP1. These data demonstrate novel aspects of the dynamics of SFK-mediated cell signaling that may be relevant during cancer progression.

Microstructural magnetic resonance imaging of articular cartilage

The focus of this Editorial is recent developments in magnetic resonance imaging (MRI) modalities for evaluation of the microstructure and macromolecular organisation of articular cartilage. We place a specific emphasis on three types of measurements: (1) MRI transverse spin-relaxation mapping (T2 mapping); (2) diffusion-tensor imaging; and (3) compression micro-MRI (uMRI) measurements of articular cartilage in vitro. Such studies have a significant role to play in improving the understanding of the fundamental biomechanics of articular cartilage and in the development of in vitro models of early osteoarthritis. We discuss how the supramolecular organisation of the cartilage extracellular matrix and its behaviour under mechanical compression can be inferred from diffusion-tensor and T2 maps with in-plane resolution ~100 um. The emphasis is on in vitro studies performed under controlled physiological conditions but in vivo applications of T2 mapping and DTI are also briefly discussed.

Interactions and consequences of inertia and switching costs

Purpose: Service research typically relates switching costs to customer loyalty, and portrays them as effective switching deterrents that engender harmful word-of-mouth (WOM). Rather than to customer loyalty, this paper aims to relate switching costs to consumer inertia, and show that while switching costs may result in customer retention, they can engender positive and negative WOM. This depends on whether the inertia stems from satisfaction or indifference. Design/methodology/approach: A mall-intercept survey investigated 518 customers' perceptions of their mobile phone service providers. Structural equation modelling fitted the data to the conceptual model. Findings: Switching costs deterred switching and engendered negative WOM, but only with low-inertia customers. With high-inertia customers, retention and WOM behaviours depended on whether the inertia stemmed from satisfaction or indifference. Satisfied customers with high switching costs tended to stay, gave more positive and less negative WOM. With indifferent customers, switching costs were unrelated to retention or WOM behaviours. Research limitations/implications: While they may be perceived negatively, switching costs can engender PWOM. Hence, research should not consider switching costs alone without considering the context that produces them. Practical implications: Service providers should segment their customers into low-inertia, high-inertia/satisfied and high-inertia/indifferent, and target each segment differently. By converting customers into the high-inertia/satisfied segment, service providers can make the best use of switching costs – not only in the traditional sense as a barrier to defection, but also as a way of generating positive WOM. Originality/value: This study is the first to consider the role of inertia with switching costs, positive WOM, and negative WOM. The findings suggest that past studies portraying switching costs as negative impediments that evoke only negative WOM might be misleading.

Natural convection flow in a strong cross magnetic field with radiation

The problem of MHD natural convection boundary layer flow of an electrically conducting and optically dense gray viscous fluid along a heated vertical plate is analyzed in the presence of strong cross magnetic field with radiative heat transfer. In the analysis radiative heat flux is considered by adopting optically thick radiation limit. Attempt is made to obtain the solutions valid for liquid metals by taking Pr≪1. Boundary layer equations are transformed in to a convenient dimensionless form by using stream function formulation (SFF) and primitive variable formulation (PVF). Non-similar equations obtained from SFF are then simulated by implicit finite difference (Keller-box) method whereas parabolic partial differential equations obtained from PVF are integrated numerically by hiring direct finite difference method over the entire range of local Hartmann parameter, $xi$ . Further, asymptotic solutions are also obtained for large and small values of local Hartmann parameter $xi$ . A favorable agreement is found between the results for small, large and all values of $xi$ . Numerical results are also demonstrated graphically by showing the effect of various physical parameters on shear stress, rate of heat transfer, velocity and temperature.

Thermo-magnetic convection of paramagnetic fluids with non-instantaneous heating

The unsteady boundary-layer development for thermomagnetic convection of paramagnetic fluids inside a square cavity has been considered in this study. The cavity is placed in a microgravity condition (no gravitation acceleration) and under a uniform magnetic field which acts vertically. A ramp temperature boundary condition is applied on left vertical side wall of the cavity where the temperature initially increases with time up to some specific time and maintain constant thereafter. A distinct magnetic convection boundary layer is developed adjacent to the left vertical wall due to the effect of the magnetic body force generated on the paramagnetic fluid. An improved scaling analysis has been performed using triple-layer integral method and verified by numerical simulations. The Prandtl number has been chosen greater than unity varied over 5-100. Moreover, the effect of various values of the magnetic parameter and magnetic Rayleigh number on the fluid flow and heat transfer has been shown.

Magnetic flux analysis in superconducting Fault Current Limiters under short-circuit conditions

In order to obtain a more compact Superconducting Fault Current limiter (SFCL), a special geometry of core and AC coil is required. This results in a unique magnetic flux pattern which differs from those associated with conventional round core arrangements. In this paper the magnetic flux density within a Fault Current Limiter (FCL) is described. Both experimental and analytical approaches are considered. A small scale prototype of an FCL was constructed in order to conduct the experiments. This prototype comprises a single phase. The analysis covers both the steady state and the short-circuit condition. Simulation results were obtained using commercial software based on the Finite Element Method (FEM). The magnetic flux saturating the cores, leakage magnetic flux giving rise to electromagnetic forces and leakage magnetic flux flowing in the enclosing tank are computed.

Ventilation distribution in rats : part 2 – a comparison of electrical impedance tomography and hyperpolarised helium magnetic resonance imaging

Background: Hyperpolarised helium MRI (He3 MRI) is a new technique that enables imaging of the air distribution within the lungs. This allows accurate determination of the ventilation distribution in vivo. The technique has the disadvantages of requiring an expensive helium isotope, complex apparatus and moving the patient to a compatible MRI scanner. Electrical impedance tomography (EIT) a non-invasive bedside technique that allows constant monitoring of lung impedance, which is dependent on changes in air space capacity in the lung. We have used He3MRI measurements of ventilation distribution as the gold standard for assessment of EIT. Methods: Seven rats were ventilated in supine, prone, left and right lateral position with 70% helium/30% oxygen for EIT measurements and pure helium for He3 MRI. The same ventilator and settings were used for both measurements. Image dimensions, geometric centre and global in homogeneity index were calculated. Results: EIT images were smaller and of lower resolution and contained less anatomical detail than those from He3 MRI. However, both methods could measure positional induced changes in lung ventilation, as assessed by the geometric centre. The global in homogeneity index were comparable between the techniques. Conclusion: EIT is a suitable technique for monitoring ventilation distribution and inhomgeneity as assessed by comparison with He3 MRI.

Magnetic zeolite NaA : Synthesis, characterization based on metakaolin and its application for the removal of Cu2+, Pb2+

The optimum parameters for synthesis of zeolite NaA based on metakaolin were investigated according to results of cation exchange capacity and static water adsorption of all synthesis products and selected X-ray diffraction (XRD). Magnetic zeolite NaA was synthesized by adding Fe3O4 in the precursor of zeolite. Zeolite NaA and magnetic zeolite NaA were characterized with scanning electron microscopy (SEM) and XRD. Magnetic zeolite NaA with different Fe3O4 loadings was prepared and used for removal of heavy metals (Cu2+, Pb2+). The results show the optimum parameters for synthesis zeolite NaA are SiO2/Al2O3 = 2.3, Na2O/SiO2 = 1.4, H2O/Na2O = 50, crystallization time 8 h, crystallization temperature 95 �C. The addition of Fe3O4 makes the NaA zeolite with good magnetic susceptibility and good magnetic stability regardless of the Fe3O4 loading, confirming the considerable separation efficiency. Additionally, Fe3O4 loading had a little effect on removal of heavy metal by magnetic zeolite, however, the adsorption capacity still reaches 2.3 mmol g�1 for Cu2+, Pb2+ with a removal efficiency of over 95% in spite of 4.7% Fe3O4 loading. This indicates magnetic zeolite can be used to remove metal heavy at least Cu2+, Pb2+ from water with metallic contaminants and can be separated easily after a magnetic process.

Field-effect transistors fabricated from diluted magnetic semiconductor colloidal nanowires

Field-effect transistors (FETs) fabricated from undoped and Co2+-doped CdSe colloidal nanowires show typical n-channel transistor behaviour with gate effect. Exposed to microscope light, a 10 times current enhancement is observed in the doped nanowire-based devices due to the significant modification of the electronic structure of CdSe nanowires induced by Co2+-doping, which is revealed by theoretical calculations from spin-polarized plane-wave density functional theory.

Biomechanics of synthetic elastin : insights from Magnetic Resonance microimaging

We used Magnetic Resonance microimaging (μMRI) to study the compressive behaviour of synthetic elastin. Compression-induced changes in the elastin sample were quantified using longitudinal and transverse spin relaxation rates (R1 and R2, respectively). Spatially-resolved maps of each spin relaxation rate were obtained, allowing the heterogeneous texture of the sample to be observed with and without compression. Compression resulted in an increase of both the mean R1 and the mean R2, but most of this increase was due to sub-locations that exhibited relatively low R1 and R2 in the uncompressed state. This behaviour can be described by differential compression, where local domains in the hydrogel with a relatively low biopolymer content compress more than those with a relatively high biopolymer content.

A study of the diffusion characteristics of normal, delipidized and relipidized articular cartilage using magnetic resonance imaging

This paper assesses the capacity to provide semipermeability of the synthetic layer of surface-active phospholipids created to replace the depleted surface amorphous layer of articular cartilage. The surfaces of articular cartilage specimens in normal, delipidized, and relipidized conditions following incubation in dipalmitoyl-phosphatidylcholine and palmitoyl-oleoyl-phosphatidylcholine components of the joint lipid mixture were characterized nanoscopically with the atomic force microscope and also imaged as deuterium oxide (D2O) diffused transiently through these surfaces in a magnetic resonance imaging enclosure. The MR images were then used to determine the apparent diffusion coefficients in a purpose-built MATLAB®-based algorithm. Our results revealed that all surfaces were permeable to D2O, but that there was a significant difference in the semipermeability of the surfaces under the different conditions, relative to the apparent diffusion coefficients. Based on the results and observations, it can be concluded that the synthetic lipid that is deposited to replace the depleted SAL of articular cartilage is capable of inducing some level of semipermeability.

A method of extracting switching loss from a high efficiency MOSFET based half bridge converter

The measurement of losses in high efficiency / high power converters is difficult. Measuring the losses directly from the difference between the input and output power results in large errors. Calorimetric methods are usually used to bypass this issue but introduce different problems, such as, long measurement times, limited power loss measurement range and/or large set up cost. In this paper the total losses of a converter are measured directly and switching losses are exacted. The measurements can be taken with only three multimeters and a current probe and a standard bench power supply. After acquiring two or three power loss versus output current sweeps, a series of curve fitting processes are applied and the switching losses extracted.