Inhibition of intratracheal lung cancer development by systemic delivery of E1A

Amplification or overexpression of HER-2/neu in human lung cancer has been correlated with poor prognosis and chemoresistance. We have previously reported that the adenovirus type 5 early region 1A (E1A) gene product can suppress HER-2/neu-mediated transformation phenotypes through inhibition of HER-2/neu expression. To find an efficient way to treat HER-2/neu-overexpressing lung cancer with E1A, a replication-deficient adenovirus containing the E1A gene, Ad.E1A(+), was used to transduce E1A into HER-2/neu-overexpressing and low expressing human lung cancer cell lines. Tumour cell growth in vitro and colony formation in soft agarose were greatly inhibited by Ad.E1A(+) transduction in HER-2/neu-overexpressing lung cancer cell lines. In HER-2/neu low expressing cell lines, E1A could not inhibit cell growth in vitro but could reduce the colony formation ability in soft agarose, indicating different effects of E1A in these two types of cancer cells. To test the therapeutic efficacy of E1A to lung cancer by systemic delivery in vivo, tumor-bearing mice were established by intratracheal injection of lung cancer cells and treated by i.v. tail injections of Ad.E1A(+). As a result, Ad.E1A(+) suppressed HER-2/neu overexpression and inhibited intratracheal lung cancer growth. However, no significant tumor suppression effect of Ad.E1A(+) was observed in mice bearing HER-2/neu low expressing cell line when the same therapeutic procedure was followed. Thus, we conclude that systemic delivery of Ad.E1A(+) can efficiently achieve therapeutic effect in HER-2/neu-overexpressing lung cancer in vivo.     

The lattice dynamics of the Fe(tpa) (NCS)2 complex : light-induced excited spin state trapping effect

A light-induced excited spin state trapping (LIESST) experiment for a thermal gradual spin crossover complex, Fetris (2-pyridylmethyl) amine(NCS)2 or Fe(tpa) (NCS)2, was attempted for the first time. The high spin (HS) state after light inducement stayed metastable over a period of days without relaxation at 10 K. Intersystem relaxation from a high to a low spin (LS) complex occurred at 50 K after bleaching at 10 K. Investigation of the Mossbauer spectra of the LIESST and relaxation experiment indicated that the Debye–Waller factor was a correlation parameter of the HS fraction and that the co-operative effect played a role in the relaxation process for such a solid compound. This revised version was published online in November 2006 with corrections to the Cover Date.     

Neural network impedance force control of robot manipulator

The performance of an impedance controller for robot force tracking is affected by the uncertainties in both the robot dynamic model and environment stiffness. The purpose of this paper is to improve the controller robustness by applying the neural network (NN) technique to compensate for the uncertainties in the robot model. NN control techniques are applied to two impedance control methods: torque-based and position-based impedance control, which are distinguished by the way of the impedance functions being implemented. A novel error signal is proposed for the NN training. In addition, a trajectory modification algorithm is developed to determine the reference trajectory when the environment stiffness is unknown. The robustness analysis of this algorithm to force sensor noise and inaccurate environment position measurement is also presented. The performances of the two NN impedance control schemes are compared by computer simulations. Simulation results based on a three-degrees-of-freedom robot show that highly robust position/force tracking can be achieved in the presence of large uncertainties and force sensor noise     

Neurological complications of radiotherapy and chemotherapy

Neurological complications of radiotherapy and chemotherapy can affect the central or peripheral nervous system. Most are dose-dependent and constitute a limiting factor in the administration of treatments. Radiation-induced neurological complications are classified as acute, early-delayed or delayed. The most important are radionecrosis and cognitive dysfunction/leukoencephalopathy. Neurotoxicity of chemotherapy is frequent and depends upon dose, type of drugs (especially cisplatin and methotrexate) and their combination with radiotherapy.     

SCID-Hu mouse as a model for human lung HIV-1 infection

HIV induces a multi-organ infection with a dual tropism for both lymphocytes and monocytes/macrophages. The lung is a target both for HIV infection and HIV-related opportunistic infections. The SCID mouse has provided the opportunity to develop a small animal model for HIV infection. However, HIV-1 infection of the human fetal thymus and liver (SCID Liv/Thy) implanted in these mice occurred only after direct intraimplant injection of HIV-1 and the resultant HIV-1 infection was restricted to the human thymus. Here we report that human foetal lung can develop in SCID Liv/Thy mice resulting in the development of normal human alveolar and bronchiolar lung compartments which can be productively infected with cell-free HIV-1 virus, leading to a systemic and bifocal infection. This SCID-Hu model should be useful for studying AIDS physiopathology, human viruses with lung tropism and for helping to define gene therapy protocols in lung human cells in vivo.     

Air bearing design, optimization, stability analysis andverification for sub-25 nm flying

Three sub-25 nm fly height sliders are presented for near contact recording. The designs are geared towards the goal of achieving 10 Gb/in ² areal density. The optimization procedure presented shows promise for facilitating achievement of this goal. The dynamic simulations show the stability of these designs when disturbed from their steady state conditions     

A new technique for robust control of servo systems

The robust controller has very simple structures and can be divided into two separate parts: a servo controller and an auxiliary controller. The two controllers are designed independently. The function of the auxiliary controller is to cancel out the plant uncertainties directly without the use of the high loop gain principle. Interpretation of robot controller as a signal-synthesis adaptive controller is given. Practical implementation issues of the auxiliary controller are discussed. Simulations of a design example with large parameter uncertainty, nonlinearity, and external disturbance are presented to demonstrate the effectiveness of the design technique. This technique is further tested with success in an experimental study of joint position control of a PUMA 560 robot arm     

Lysis of human monocytic leukemia cells by extracellular adenosine triphosphate: mechanism and characterization of the adenosine triphosphate receptor

The present study shows that extracellular adenosine triphosphate (ATP) has the capacity to mediate dose-dependent lysis of the monocytic leukemia cell line THP-1. The lysis, assessed by 51Cr release, was found to be selective for ATP, because adenosine diphosphate (ADP) or other nucleotides were less effective in their ability to lyse the cells. The amount of 51Cr released was particularly enhanced by the stimulation of the cells with 1,000 U/mL of interferon gamma (IFN-gamma) for 3 days, and the sensitivity was time and dose dependent. Analysis of the mechanism of lysis indicated that the fully ionized form, ATP4-, mediated the lysis, because the addition of cation chelators or the absence of the divalent cations, Ca2+ and Mg2+, in the culture medium of a 6-hour 51Cr release assay increased the percent specific lysis. Therefore, the ATP receptors on THP-1 cells were classified as P2Z purinoceptors. Moreover, it is shown here that the Ca2+/calmodulin complex plays a role in the regulation of the lysis by extracellular ATP of THP-1 cells, because antagonists of this complex, such as trifluoperazine or KN-62, were found to inhibit the ATP-mediated cell lysis.     

Acidity near eroding polylactide-polyglycolide in vitro and in vivo in rabbit tibial bone chambers

Eroding poly(DL-lactide-co-glycolide)(PDLLG) washers were observed chronically in vitro and in vivo following loading in a bone chamber tibial implant (BCI). Images were recorded using intravital microscopy of the implanted rabbit and direct pH measurements were obtained of the tissue in the bone chamber using a combination probe-reference microelectrode. While statistically significant pH differences were found between the control (unloaded) and experimental (PDLLG-bearing) BCIs, they were only of the order of 0.2 pH units. This value proved to be physiologically insignificant as no statistically significant difference in bone defect healing, as indicated by angiogenesis, was detected. It was shown that the measured small pH changes during PDLLG washers erosion would result whether the buffer was phosphate-buffered saline replaced weekly or interstitial fluid subject to vascular exchanges.