Epidermal growth factor promotes MDA-MB-231 breast cancer cell migration through a phosphatidylinositol 3'-kinase and phospholipase C-dependent mechanism

Epidermal growth factor receptor (EGFR) levels predict a poor outcome in human breast cancer and are most commonly associated with proliferative effects of epidermal growth factor (EGF), with little emphasis placed on motogenic responses to EGF. We found that MDA-MB-231 human breast cancer cells elicited a potent chemotactic response despite their complete lack of a proliferative response to EGF. Antagonists of EGFR ligation, the EGFR kinase, phosphatidylinositol 3'-kinase, and phospholipase C, but not the mitogen- activated protein kinases (extracellular signal-regulated protein kinase 1 and 2), blocked MDA-MB-231 chemotaxis. These findings suggest that EGF may influence human breast cancer progression via migratory pathways, the signaling for which appears to be dissociated, at least in part, from the proliferative pathways.

Isolation and characterization of tumor cells from the ascites of ovarian cancer patients : molecular phenotype of chemoresistant ovarian tumors

Tumor cells in ascites are a major source of disease recurrence in ovarian cancer patients. In an attempt to identify and profile the population of ascites cells obtained from ovarian cancer patients, a novel method was developed to separate adherent (AD) and non-adherent (NAD) cells in culture. Twenty-five patients were recruited to this study; 11 chemonaive (CN) and 14 chemoresistant (CR). AD cells from both CN and CR patients exhibited mesenchymal morphology with an antigen profile of mesenchymal stem cells and fibroblasts. Conversely, NAD cells had an epithelial morphology with enhanced expression of cancer antigen 125 (CA125), epithelial cell adhesion molecule (EpCAM) and cytokeratin 7. NAD cells developed infiltrating tumors and ascites within 12-14 weeks after intraperitoneal (i.p.) injections into nude mice, whereas AD cells remained non-tumorigenic for up to 20 weeks. Subsequent comparison of selective epithelial, mesenchymal and cancer stem cell (CSC) markers between AD and NAD populations of CN and CR patients demonstrated an enhanced trend in mRNA expression of E-cadherin, EpCAM, STAT3 and Oct4 in the NAD population of CR patients. A similar trend of enhanced mRNA expression of CD44, MMP9 and Oct4 was observed in the AD population of CR patients. Hence, using a novel purification method we demonstrate for the first time a distinct separation of ascites cells into epithelial tumorigenic and mesenchymal non-tumorigenic populations. We also demonstrate that cells from the ascites of CR patients are predominantly epithelial and show a trend towards increased mRNA expression of genes associated with CSCs, compared to cells isolated from the ascites of CN patients. As the tumor cells in the ascites of ovarian cancer patients play a dominant role in disease recurrence, a thorough understanding of the biology of the ascites microenvironment from CR and CN patients is essential for effective therapeutic interventions.

Mesenchymal-epithelial transition (MET) as a mechanism for metastatic colonisation in breast cancer

As yet, there is no cure for metastatic breast cancer. Historically, considerable research effort has been concentrated on understanding the processes of metastasis, how a primary tumour locally invades and systemically disseminates using the phenotypic switching mechanism of epithelial to mesenchymal transition (EMT); however, much less is understood about how metastases are then formed. Breast cancer metastases often look (and may even function) as 'normal' breast tissue, a bizarre observation against the backdrop of the organ structure of the lung, liver, bone or brain. Mesenchymal to epithelial transition (MET), the opposite of EMT, has been proposed as a mechanism for establishment of the metastatic neoplasm, leading to questions such as: Can MET be clearly demonstrated in vivo? What factors cause this phenotypic switch within the cancer cell? Are these signals/factors derived from the metastatic site (soil) or expressed by the cancer cells themselves (seed)? How do the cancer cells then grow into a detectable secondary tumour and further disseminate? And finallyCan we design and develop therapies that may combat this dissemination switch? This review aims to address these important questions by evaluating long-standing paradigms and novel emerging concepts in the field of epithelial mesencyhmal plasticity.

A sensor fault detection and isolation method in interior permanent-magnet synchronous motor drives based on an extended Kalman filter

Interior permanent-magnet synchronous motors (IPMSMs) become attractive candidates in modern hybrid electric vehicles and industrial applications. Usually, to obtain good control performance, the electric drives of this kind of motor require one position, one dc link, and at least two current sensors. Failure of any of these sensors might lead to degraded system performance or even instability. As such, sensor fault resilient control becomes a very important issue in modern drive systems. This paper proposes a novel sensor fault detection and isolation algorithm based on an extended Kalman filter. It is robust to system random noise and efficient in real-time implementation. Moreover, the proposed algorithm is compact and can detect and isolate all the sensor faults for IPMSM drives. Thorough theoretical analysis is provided, and the effectiveness of the proposed approach is proven by extensive experimental results.

Selective involvement of TIMP-2 in the second activational cleavage of pro-MMP-2 : refinement of the pro-MMP-2 activation mechanism

A tissue inhibitor of metalloproteinases-2 (TIMP-2)-independent mechanism for generating the first activational cleavage of pro-matrix metalloproteinase-2 (MMP-2) was identified in membrane type-1 MMP (MT1-MMP)-transfected MCF-7 cells and confirmed in TIMP-2-deficient fibroblasts. In contrast, the second MMP-2-activational step was found to be TIMP-2 dependent in both systems. MMP-2 hemopexin C-terminal domain was found to be critical for the first step processing, confirming a need for membrane tethering. We propose that the intermediate species of MMP-2 forms the well-established trimolecular complex (MT1-MMP/TIMP-2/MMP-2) for further TIMP-2-dependent autocatalytic cleavage to the fully active species. This alternate mechanism may supplement the traditional TIMP-2-mediated first step mechanism.

Tunable “Nano-Shearing” : A physical mechanism to displace nonspecific cell adhesion during rare cell detection

We report a tunable alternating current electrohydrodynamic (ac-EHD) force which drives lateran fluid motion within a few nanometers of an electrode surface. Because the magnitude of this fluid shear force can be tuned externally (e.g., via the application of an ac electric field), it provides a new capability to physically displace weakly (nonspecifically) bound cellular analytes. To demonstrate the utility of the tunable nanoshearing phenomenon, we present data on purpose-built microfluidic devices that employ ac-EHD force to remove nonspecific adsorption of molecular and cellular species. Here, we show that an ac-EHD device containing asymmetric planar and microtip electrode pairs resulted in a 4-fold reduction in nonspecific adsorption of blood cells and also captured breast cancer cells in blood, with high efficiency (approximately 87%) and specificity. We therefore feel that this new capability of externally tuning and manipulating fluid flow could have wide applications as an innovative approach to enhance the specific capture of rare cells such as cancer cells in blood.

The effect of temperature on the mechanism of photoluminescence from plasma-nucleated, nitrogenated carbon nanotips

Nitrogenated carbon nanotips (NCNTPs) have been synthesized using customized plasma-enhanced hot filament chemical vapor deposition. The morphological, structural, and photoluminescent properties of the NCNTPs are investigated using scanning and transmission electron microscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, and photoluminescence spectroscopy. The photoluminescence measurements show that the NCNTPs predominantly emit a green band at room temperature while strong blue emission is generated at 77 K. It is shown that these very different emission behaviors are related to the change of the optical band-gap and the concentration of the paramagnetic defects of the carbon nanotips. The studies shed light on the controversies on the photoluminescence mechanisms of carbon-based amorphous films measured at different temperatures. The relevance of the results to the use of nitrogenated carbon nanotips in light-emitting optoelectronic devices is discussed.

Single-step, catalyst-free plasma-assisted synthesis and growth mechanism of single-crystalline aluminum nitride nanorods

Synthesis of one-dimensional AlN nanostructures commonly requires high process temperatures (>900 °C), metal catalyst, and hazardous gas/powder precursors. We report on a simple, single-step, catalyst-free, plasma-assisted growth of dense patterns of size-uniform single-crystalline AlN nanorods at a low substrate temperature (∼650 °C) without any catalyst or hazardous precursors. This unusual growth mechanism is based on highly effective plasma dissociation of N2 molecules, localized species precipitation on AlN islands, and reduced diffusion on the nitrogen-rich surface. This approach can also be used to produce other high-aspect-ratio oxide and nitride nanostructures for applications in energy conversion, sensing, and optoelectronics. © 2010 American Institute of Physics.

Electron transport across magnetic field in low-temperature plasmas : an alternative approach for obtaining evidence of Bohm mechanism

A comparative study involving both experimental and numerical investigations was made to resolve a long-standing problem of understanding electron conductivity mechanism across magnetic field in low-temperature plasmas. We have calculated the plasma parameters from experimentally obtained electric field distribution, and then made a 'back' comparison with the distributions of electron energy and plasma density obtained in the experiment. This approach significantly reduces an influence of the assumption about particular phenomenology of the electron conductivity in plasma. The results of the experiment and calculations made by this technique have showed that the classical conductivity is not capable of providing realistic total current and electron energy, whereas the phenomenological anomalous Bohm mobility has demonstrated a very good agreement with the experiment. These results provide an evidence in favor of the Bohm conductivity, thus making it possible to clarify this pressing long-living question about the main driving mechanism responsible for the electron transport in low-temperature plasmas.

Discharge parameters and dominant electron conductivity mechanism in a low-pressure planar magnetron discharge

Parameters of a discharge sustained in a planar magnetron configuration with crossed electric and magnetic fields are studied experimentally and numerically. By comparing the data obtained in the experiment with the results of calculations made using the proposed theoretical model, conclusion was made about the leading role of the turbulence-driven Bohm electron conductivity in the low-pressure operation mode (up to 1 Pa) of the discharge in crossed electric and magnetic fields. A strong dependence of the width of the cathode sputter trench, associated with the ionization region of the magnetron discharge, on the discharge parameters was observed in the experiments. The experimental data were used as input parameters in the discharge model that describes the motion of secondary electrons across the magnetic field in the ionization region and takes into account the classical, near-wall, and Bohm mechanisms of electron conductivity.

Electron-conduction mechanism and specific heat above transition temperature in LaFeAsO and BaFe2As2 superconductors

The ionization energy theory is used to calculate the evolution of the resistivity and specific heat curves with respect to different doping elements in the recently discovered superconducting pnictide materials. Electron-conduction mechanism in the pnictides above the structural transition temperature is explained unambiguously, which is also consistent with other strongly correlated materials, such as cuprates, manganites, titanates and magnetic semiconductors.

Heating mechanism of self-interaction of surface polaritons at n-type semiconductor-metal interface

The influence of electron heating in the high-frequency surface polariton (SP) field on the dispersion properties of the SPs considered is investigated. High frequency SPs propagate at the interface between an n-type semiconductor with finite electron pressure, and a metal. The nonlinear dispersion relation for the SPs is derived and investigated.

Heating self-interaction mechanism of surface magnetoplasma waves in plasma-like medium bounded by metal

The influence of electron heating in the high-frequency surface magnetoplasma wave(SM) field on dispersion properties of the considered SM is investigated. High frequency SM propagate at the interface between a plasma like medium with a finite electrons pressure and a metal. The nonlinear dispersion relation for the SM is derived and investigated.

Enhanced fast handover triggering mechanism for fast proxy mobile IPv6

Handover performance is critical to support real-time traffic applications in wireless network communications. The longer the handover delay is, the longer an Mobile Node (MN) is prevented from sending and receiving any data packet. In real-time network communication applications, such as VoIP and video-conference, a long handover delay is often unacceptable. In order to achieve better handover performance, Fast Proxy Mobile IPv6 (FPMIPv6) has been standardised as an improvement to the original Proxy Mobile IPv6 (PMIPv6) in the Internet Engineering Task Force (IETF). The FPMIPv6 adopts a link layer triggering mechanism to perform two modes of operation: predictive and reactive modes. Using the link layer triggering, the handover performance of the FPMIPv6 can be improved in the predictive mode. However, an unsuccessful predictive handover operation will lead to activation of a reactive handover. In the reactive mode, MNs still experience long handover delays and a large amount of packet loss, which significantly degrade the handover performance of the FPMIPv6. Addressing this problem, this thesis presents an Enhanced Triggering Mechanism (ETM) in the FPMIPv6 to form an enhanced FPMIPv6 (eFPMIPv6). The ETM reduces the most time consuming processes in the reactive handover: the failed Handover Initiate (HO-Initiate) delay and bidirectional tunnel establishment delay. Consequently, the overall handover performance of the FPMIPv6 is enhanced in the eFPMIPv6. To show the advantages of the proposed eFPMIPv6, a theoretical analysis is carried out to mathematically model the performance of PMIPv6, FPMIPv6 and eFPMIPv6. Extensive case studies are conducted to validate the effectiveness of the presented eFPMIPv6 mechanism. They are carried out under various scenarios with changes in network link delay, traffic load, number of hops and MN moving velocity. The case studies show that the proposed mechanism ETM reduces the reactive handover delay, and the presented eFPMIPv6 outperforms the PMIPv6 and FPMIPv6 in terms of the overall handover performance.

Artemisinin-induced parasite dormancy : a plausible mechanism for treatment failure

Background Artemisinin-combination therapy is a highly effective treatment for uncomplicated falciparum malaria but parasite recrudescence has been commonly reported following artemisinin (ART) monotherapy. The dormancy recovery hypothesis has been proposed to explain this phenomenon, which is different from the slower parasite clearance times reported as the first evidence of the development of ART resistance. Methods In this study, an existing P. falciparum infection model is modified to incorporate the hypothesis of dormancy. Published in vitro data describing the characteristics of dormant parasites is used to explore whether dormancy alone could be responsible for the high recrudescence rates observed in field studies using monotherapy. Several treatment regimens and dormancy rates were simulated to investigate the rate of clinical and parasitological failure following treatment. Results The model output indicates that following a single treatment with ART parasitological and clinical failures occur in up to 77% and 67% of simulations, respectively. These rates rapidly decline with repeated treatment and are sensitive to the assumed dormancy rate. The simulated parasitological and clinical treatment failure rates after 3 and 7 days of treatment are comparable to those reported from several field trials. Conclusions Although further studies are required to confirm dormancy in vivo, this theoretical study adds support for the hypothesis, highlighting the potential role of this parasite sub-population in treatment failure following monotherapy and reinforcing the importance of using ART in combination with other anti-malarials.